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

International Nuclear Information System (INIS)

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

2007-01-01

analysis in large families using high-density SNP arrays and validated this workflow in a family with colorectal cancer. Linkage disequilibrium has to be removed when using SNP arrays, because it can falsely inflate the LOD score. Haplotype analysis is adequate and can predict the carrier status of the family members

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

Science.gov (United States)

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

2015-01-01

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.

High-density SNP genotyping of tomato (Solanum lycopersicum L. reveals patterns of genetic variation due to breeding.

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Sung-Chur Sim

Full Text Available The effects of selection on genome variation were investigated and visualized in tomato using a high-density single nucleotide polymorphism (SNP array. 7,720 SNPs were genotyped on a collection of 426 tomato accessions (410 inbreds and 16 hybrids and over 97% of the markers were polymorphic in the entire collection. Principal component analysis (PCA and pairwise estimates of F(st supported that the inbred accessions represented seven sub-populations including processing, large-fruited fresh market, large-fruited vintage, cultivated cherry, landrace, wild cherry, and S. pimpinellifolium. Further divisions were found within both the contemporary processing and fresh market sub-populations. These sub-populations showed higher levels of genetic diversity relative to the vintage sub-population. The array provided a large number of polymorphic SNP markers across each sub-population, ranging from 3,159 in the vintage accessions to 6,234 in the cultivated cherry accessions. Visualization of minor allele frequency revealed regions of the genome that distinguished three representative sub-populations of cultivated tomato (processing, fresh market, and vintage, particularly on chromosomes 2, 4, 5, 6, and 11. The PCA loadings and F(st outlier analysis between these three sub-populations identified a large number of candidate loci under positive selection on chromosomes 4, 5, and 11. The extent of linkage disequilibrium (LD was examined within each chromosome for these sub-populations. LD decay varied between chromosomes and sub-populations, with large differences reflective of breeding history. For example, on chromosome 11, decay occurred over 0.8 cM for processing accessions and over 19.7 cM for fresh market accessions. The observed SNP variation and LD decay suggest that different patterns of genetic variation in cultivated tomato are due to introgression from wild species and selection for market specialization.

High-throughput SNP genotyping in the highly heterozygous genome of Eucalyptus: assay success, polymorphism and transferability across species

Science.gov (United States)

2011-01-01

Background High-throughput SNP genotyping has become an essential requirement for molecular breeding and population genomics studies in plant species. Large scale SNP developments have been reported for several mainstream crops. A growing interest now exists to expand the speed and resolution of genetic analysis to outbred species with highly heterozygous genomes. When nucleotide diversity is high, a refined diagnosis of the target SNP sequence context is needed to convert queried SNPs into high-quality genotypes using the Golden Gate Genotyping Technology (GGGT). This issue becomes exacerbated when attempting to transfer SNPs across species, a scarcely explored topic in plants, and likely to become significant for population genomics and inter specific breeding applications in less domesticated and less funded plant genera. Results We have successfully developed the first set of 768 SNPs assayed by the GGGT for the highly heterozygous genome of Eucalyptus from a mixed Sanger/454 database with 1,164,695 ESTs and the preliminary 4.5X draft genome sequence for E. grandis. A systematic assessment of in silico SNP filtering requirements showed that stringent constraints on the SNP surrounding sequences have a significant impact on SNP genotyping performance and polymorphism. SNP assay success was high for the 288 SNPs selected with more rigorous in silico constraints; 93% of them provided high quality genotype calls and 71% of them were polymorphic in a diverse panel of 96 individuals of five different species. SNP reliability was high across nine Eucalyptus species belonging to three sections within subgenus Symphomyrtus and still satisfactory across species of two additional subgenera, although polymorphism declined as phylogenetic distance increased. Conclusions This study indicates that the GGGT performs well both within and across species of Eucalyptus notwithstanding its nucleotide diversity ≥2%. The development of a much larger array of informative SNPs across

Construction of a high-density DArTseq SNP-based genetic map and identification of genomic regions with segregation distortion in a genetic population derived from a cross between feral and cultivated-type watermelon.

Science.gov (United States)

Ren, Runsheng; Ray, Rumiana; Li, Pingfang; Xu, Jinhua; Zhang, Man; Liu, Guang; Yao, Xiefeng; Kilian, Andrzej; Yang, Xingping

2015-08-01

Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important vegetable crop grown extensively worldwide. To facilitate the identification of agronomically important traits and provide new information for genetic and genomic research on this species, a high-density genetic linkage map of watermelon was constructed using an F2 population derived from a cross between elite watermelon cultivar K3 and wild watermelon germplasm PI 189225. Based on a sliding window approach, a total of 1,161 bin markers representing 3,465 SNP markers were mapped onto 11 linkage groups corresponding to the chromosome pair number of watermelon. The total length of the genetic map is 1,099.2 cM, with an average distance between bins of 1.0 cM. The number of markers in each chromosome varies from 62 in chromosome 07 to 160 in chromosome 05. The length of individual chromosomes ranged between 61.8 cM for chromosome 07 and 140.2 cM for chromosome 05. A total of 616 SNP bin markers showed significant (P watermelon cultivar K3 allele and 103 were skewed toward PI 189225. The number of SNPs and InDels per Mb varied considerably across the segregation distorted regions (SDRs) on each chromosome, and a mixture of dense and sparse SNPs and InDel SDRs coexisted on some chromosomes suggesting that SDRs were randomly distributed throughout the genome. Recombination rates varied greatly among each chromosome, from 2.0 to 4.2 centimorgans per megabase (cM/Mb). An inconsistency was found between the genetic and physical positions on the map for a segment on chromosome 11. The high-density genetic map described in the present study will facilitate fine mapping of quantitative trait loci, the identification of candidate genes, map-based cloning, as well as marker-assisted selection (MAS) in watermelon breeding programs.

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

Science.gov (United States)

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

A low-density SNP array for analyzing differential selection in freshwater and marine populations of threespine stickleback (Gasterosteus aculeatus).

Science.gov (United States)

Ferchaud, Anne-Laure; Pedersen, Susanne H; Bekkevold, Dorte; Jian, Jianbo; Niu, Yongchao; Hansen, Michael M

2014-10-06

The threespine stickleback (Gasterosteus aculeatus) has become an important model species for studying both contemporary and parallel evolution. In particular, differential adaptation to freshwater and marine environments has led to high differentiation between freshwater and marine stickleback populations at the phenotypic trait of lateral plate morphology and the underlying candidate gene Ectodysplacin (EDA). Many studies have focused on this trait and candidate gene, although other genes involved in marine-freshwater adaptation may be equally important. In order to develop a resource for rapid and cost efficient analysis of genetic divergence between freshwater and marine sticklebacks, we generated a low-density SNP (Single Nucleotide Polymorphism) array encompassing markers of chromosome regions under putative directional selection, along with neutral markers for background. RAD (Restriction site Associated DNA) sequencing of sixty individuals representing two freshwater and one marine population led to the identification of 33,993 SNP markers. Ninety-six of these were chosen for the low-density SNP array, among which 70 represented SNPs under putatively directional selection in freshwater vs. marine environments, whereas 26 SNPs were assumed to be neutral. Annotation of these regions revealed several genes that are candidates for affecting stickleback phenotypic variation, some of which have been observed in previous studies whereas others are new. We have developed a cost-efficient low-density SNP array that allows for rapid screening of polymorphisms in threespine stickleback. The array provides a valuable tool for analyzing adaptive divergence between freshwater and marine stickleback populations beyond the well-established candidate gene Ectodysplacin (EDA).

SNP calling using genotype model selection on high-throughput sequencing data

KAUST Repository

You, Na

2012-01-16

Motivation: A review of the available single nucleotide polymorphism (SNP) calling procedures for Illumina high-throughput sequencing (HTS) platform data reveals that most rely mainly on base-calling and mapping qualities as sources of error when calling SNPs. Thus, errors not involved in base-calling or alignment, such as those in genomic sample preparation, are not accounted for.Results: A novel method of consensus and SNP calling, Genotype Model Selection (GeMS), is given which accounts for the errors that occur during the preparation of the genomic sample. Simulations and real data analyses indicate that GeMS has the best performance balance of sensitivity and positive predictive value among the tested SNP callers. © The Author 2012. Published by Oxford University Press. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

SacconePhD, Scott F [Washington University, St. Louis; Chesler, Elissa J [ORNL; Bierut, Laura J [Washington University, St. Louis; Kalivas, Peter J [Medical College of South Carolina, Charleston; Lerman, Caryn [University of Pennsylvania; Saccone, Nancy L [Washington University, St. Louis; Uhl, George R [Johns Hopkins University; Li, Chuan-Yun [Peking University; Philip, Vivek M [ORNL; Edenberg, Howard [Indiana University; Sherry, Steven [National Center for Biotechnology Information; Feolo, Michael [National Center for Biotechnology Information; Moyzis, Robert K [Johns Hopkins University; Rutter, Joni L [National Institute of Drug Abuse

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.

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

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LiFeng Gao

Full Text Available 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.

Association between SNP and haplotypes in PPARGCl and adiponectin genes and bone mineral density in Chinese nuclear families

Institute of Scientific and Technical Information of China (English)

Zhen-lin ZHANG; Jin-wei HE; Yue-juan QIN; Yun-qiu HU; Miao LI; Yu-juan LIU; Hao ZHANG; Wei-wei HU

2007-01-01

Aim: To assess the contribution of single nucleotide polymorphisms (SNP) and haplotypes in the peroxisome proliferator-activated receptor-γ co-activator-1(PPARGC1) and adiponectin genes to normal bone mineral density (BMD) variation in healthy Chinese women and men. Methods: We performed population-based (ANOVA) and family-based (quantitative trait locus transmission disequi-librium test) association studies of PPARGC1 and adiponectin genes. SNP in the 2 genes were genotyped. BMD was measured using dual-energy X-ray absorptiometry in the lumbar spine and hip in 401 nuclear families with a total of1260 subjects, including 458 premenopausal women, 20-40 years of age; 401 post-menopausal women (mothers), 43-74 years of age; and 401 men (fathers), 49-76years of age. Results: Significant within-family association was found between the Thr394Thr polymorphism in the PPGAGC1 gene and peak BMD in the femoral neck (P=0.026). Subsequent permutations were in agreement with this significant within-family association result (P=0.016), but Thr394Thr SNP only accounted for0.7% of the variation in femoral neck peak BMD. However, no significant within-family association was detected between each SNP in the adiponect in gene and peak BMD. Although no significant association was found between BMD and SNP in the PPARGC1 and adiponectin genes in both men and postmenopausal women, haplotype 2 (T-T) in the adiponect in gene was associated with lumbar spine BMD in postmenopausal women (P=0.019). Conclusion: Our findings sug-gest that Thr394Thr SNP in the PPARGC1 gene was associated with peak BMD in the femoral neck in Chinese women. Confirmation of our results is needed in other populations and with more functional markers within and flanking the PPARGC1 or adiponectin genes region.

SNP based heritability estimation using a Bayesian approach

DEFF Research Database (Denmark)

Krag, Kristian; Janss, Luc; Mahdi Shariati, Mohammad

2013-01-01

. Differences in family structure were in general not found to influence the estimation of the heritability. For the sample sizes used in this study, a 10-fold increase of SNP density did not improve precision estimates compared with set-ups with a less dense distribution of SNPs. The methods used in this study...

A low-density SNP array for analyzing differential selection in freshwater and marine populations of threespine stickleback (Gasterosteus aculeatus)

DEFF Research Database (Denmark)

Ferchaud, Anne-Laure; Pedersen, Susanne H.; Bekkevold, Dorte

2014-01-01

for rapid and cost efficient analysis of genetic divergence between freshwater and marine sticklebacks, we generated a low-density SNP (Single Nucleotide Polymorphism) array encompassing markers of chromosome regions under putative directional selection, along with neutral markers for background. Results......: RAD (Restriction site Associated DNA) sequencing of sixty individuals representing two freshwater and one marine population led to the identification of 33,993 SNP markers. Ninety-six of these were chosen for the low-density SNP array, among which 70 represented SNPs under putatively directional...... selection in freshwater vs. marine environments, whereas 26 SNPs were assumed to be neutral. Annotation of these regions revealed several genes that are candidates for affecting stickleback phenotypic variation, some of which have been observed in previous studies whereas others are new. Conclusions: We...

Genome-wide linkage mapping of yield-related traits in three Chinese bread wheat populations using high-density SNP markers.

Science.gov (United States)

Li, Faji; Wen, Weie; He, Zhonghu; Liu, Jindong; Jin, Hui; Cao, Shuanghe; Geng, Hongwei; Yan, Jun; Zhang, Pingzhi; Wan, Yingxiu; Xia, Xianchun

2018-06-01

We identified 21 new and stable QTL, and 11 QTL clusters for yield-related traits in three bread wheat populations using the wheat 90 K SNP assay. Identification of quantitative trait loci (QTL) for yield-related traits and closely linked molecular markers is important in order to identify gene/QTL for marker-assisted selection (MAS) in wheat breeding. The objectives of the present study were to identify QTL for yield-related traits and dissect the relationships among different traits in three wheat recombinant inbred line (RIL) populations derived from crosses Doumai × Shi 4185 (D × S), Gaocheng 8901 × Zhoumai 16 (G × Z) and Linmai 2 × Zhong 892 (L × Z). Using the available high-density linkage maps previously constructed with the wheat 90 K iSelect single nucleotide polymorphism (SNP) array, 65, 46 and 53 QTL for 12 traits were identified in the three RIL populations, respectively. Among them, 34, 23 and 27 were likely to be new QTL. Eighteen common QTL were detected across two or three populations. Eleven QTL clusters harboring multiple QTL were detected in different populations, and the interval 15.5-32.3 cM around the Rht-B1 locus on chromosome 4BS harboring 20 QTL is an important region determining grain yield (GY). Thousand-kernel weight (TKW) is significantly affected by kernel width and plant height (PH), whereas flag leaf width can be used to select lines with large kernel number per spike. Eleven candidate genes were identified, including eight cloned genes for kernel, heading date (HD) and PH-related traits as well as predicted genes for TKW, spike length and HD. The closest SNP markers of stable QTL or QTL clusters can be used for MAS in wheat breeding using kompetitive allele-specific PCR or semi-thermal asymmetric reverse PCR assays for improvement of GY.

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

Science.gov (United States)

Esteras, Cristina; Gómez, Pedro; Monforte, Antonio J; Blanca, José; Vicente-Dólera, Nelly; Roig, Cristina; Nuez, Fernando; Picó, Belén

2012-02-22

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). 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. 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 of these markers are located in

Design of a bovine low-density SNP array optimized for imputation.

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Didier Boichard

Full Text Available The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle.

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

Science.gov (United States)

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Alkali-developable silicone-based negative photoresist (SNP) for deep UV, electron beam, and X-ray lithographies

International Nuclear Information System (INIS)

Ban, Hiroshi; Tanaka, Akinobu; Kawai, Yoshio; Deguchi, Kimiyoshi

1989-01-01

A new silicone-based negative photoresist (SNP) developable with alkaline aqueous solutions is prepared. SNP composed of acetylated phenylsilsesquioxane oligomer and azidopyrene is applied to deep UV, electron beam (EB), and X-ray lithographies. SNP slightly swells in alkaline developers, thus exhibiting exceptionally high resolution characteristics for a negative resist. The resistance of SNP to oxygen reactive ion etching is approximately 30 times greater than that of conventional novolac resists. (author)

Development and Applications of a High Throughput Genotyping Tool for Polyploid Crops: Single Nucleotide Polymorphism (SNP Array

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Qian You

2018-02-01

Full Text Available Polypoid species play significant roles in agriculture and food production. Many crop species are polyploid, such as potato, wheat, strawberry, and sugarcane. Genotyping has been a daunting task for genetic studies of polyploid crops, which lags far behind the diploid crop species. Single nucleotide polymorphism (SNP array is considered to be one of, high-throughput, relatively cost-efficient and automated genotyping approaches. However, there are significant challenges for SNP identification in complex, polyploid genomes, which has seriously slowed SNP discovery and array development in polyploid species. Ploidy is a significant factor impacting SNP qualities and validation rates of SNP markers in SNP arrays, which has been proven to be a very important tool for genetic studies and molecular breeding. In this review, we (1 discussed the pros and cons of SNP array in general for high throughput genotyping, (2 presented the challenges of and solutions to SNP calling in polyploid species, (3 summarized the SNP selection criteria and considerations of SNP array design for polyploid species, (4 illustrated SNP array applications in several different polyploid crop species, then (5 discussed challenges, available software, and their accuracy comparisons for genotype calling based on SNP array data in polyploids, and finally (6 provided a series of SNP array design and genotype calling recommendations. This review presents a complete overview of SNP array development and applications in polypoid crops, which will benefit the research in molecular breeding and genetics of crops with complex genomes.

Development of admixture mapping panels for African Americans from commercial high-density SNP arrays

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Dunston Georgia M

2010-07-01

Full Text Available Abstract Background Admixture mapping is a powerful approach for identifying genetic variants involved in human disease that exploits the unique genomic structure in recently admixed populations. To use existing published panels of ancestry-informative markers (AIMs for admixture mapping, markers have to be genotyped de novo for each admixed study sample and samples representing the ancestral parental populations. The increased availability of dense marker data on commercial chips has made it feasible to develop panels wherein the markers need not be predetermined. Results We developed two panels of AIMs (~2,000 markers each based on the Affymetrix Genome-Wide Human SNP Array 6.0 for admixture mapping with African American samples. These two AIM panels had good map power that was higher than that of a denser panel of ~20,000 random markers as well as other published panels of AIMs. As a test case, we applied the panels in an admixture mapping study of hypertension in African Americans in the Washington, D.C. metropolitan area. Conclusions Developing marker panels for admixture mapping from existing genome-wide genotype data offers two major advantages: (1 no de novo genotyping needs to be done, thereby saving costs, and (2 markers can be filtered for various quality measures and replacement markers (to minimize gaps can be selected at no additional cost. Panels of carefully selected AIMs have two major advantages over panels of random markers: (1 the map power from sparser panels of AIMs is higher than that of ~10-fold denser panels of random markers, and (2 clusters can be labeled based on information from the parental populations. With current technology, chip-based genome-wide genotyping is less expensive than genotyping ~20,000 random markers. The major advantage of using random markers is the absence of ascertainment effects resulting from the process of selecting markers. The ability to develop marker panels informative for ancestry from

SNP high-throughput screening in grapevine using the SNPlex™ genotyping system

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Velasco Riccardo

2008-01-01

Full Text Available Abstract Background Until recently, only a small number of low- and mid-throughput methods have been used for single nucleotide polymorphism (SNP discovery and genotyping in grapevine (Vitis vinifera L.. However, following completion of the sequence of the highly heterozygous genome of Pinot Noir, it has been possible to identify millions of electronic SNPs (eSNPs thus providing a valuable source for high-throughput genotyping methods. Results Herein we report the first application of the SNPlex™ genotyping system in grapevine aiming at the anchoring of an eukaryotic genome. This approach combines robust SNP detection with automated assay readout and data analysis. 813 candidate eSNPs were developed from non-repetitive contigs of the assembled genome of Pinot Noir and tested in 90 progeny of Syrah × Pinot Noir cross. 563 new SNP-based markers were obtained and mapped. The efficiency rate of 69% was enhanced to 80% when multiple displacement amplification (MDA methods were used for preparation of genomic DNA for the SNPlex assay. Conclusion Unlike other SNP genotyping methods used to investigate thousands of SNPs in a few genotypes, or a few SNPs in around a thousand genotypes, the SNPlex genotyping system represents a good compromise to investigate several hundred SNPs in a hundred or more samples simultaneously. Therefore, the use of the SNPlex assay, coupled with whole genome amplification (WGA, is a good solution for future applications in well-equipped laboratories.

SNP-based typing: a useful tool to study Bordetella pertussis populations.

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Marjolein van Gent

Full Text Available To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA. In this study, a single nucleotide polymorphism (SNP typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in The Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis.

SNP-Based Typing: A Useful Tool to Study Bordetella pertussis Populations

Science.gov (United States)

van der Heide, Han G. J.; Heuvelman, Kees J.; Kallonen, Teemu; He, Qiushui; Mertsola, Jussi; Advani, Abdolreza; Hallander, Hans O.; Janssens, Koen; Hermans, Peter W.; Mooi, Frits R.

2011-01-01

To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in the Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis. PMID:21647370

Development of high-throughput SNP-based genotyping in Acacia auriculiformis x A. mangium hybrids using short-read transcriptome data

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Wong Melissa ML

2012-12-01

Full Text Available Abstract Background Next Generation Sequencing has provided comprehensive, affordable and high-throughput DNA sequences for Single Nucleotide Polymorphism (SNP discovery in Acacia auriculiformis and Acacia mangium. Like other non-model species, SNP detection and genotyping in Acacia are challenging due to lack of genome sequences. The main objective of this study is to develop the first high-throughput SNP genotyping assay for linkage map construction of A. auriculiformis x A. mangium hybrids. Results We identified a total of 37,786 putative SNPs by aligning short read transcriptome data from four parents of two Acacia hybrid mapping populations using Bowtie against 7,839 de novo transcriptome contigs. Given a set of 10 validated SNPs from two lignin genes, our in silico SNP detection approach is highly accurate (100% compared to the traditional in vitro approach (44%. Further validation of 96 SNPs using Illumina GoldenGate Assay gave an overall assay success rate of 89.6% and conversion rate of 37.5%. We explored possible factors lowering assay success rate by predicting exon-intron boundaries and paralogous genes of Acacia contigs using Medicago truncatula genome as reference. This assessment revealed that presence of exon-intron boundary is the main cause (50% of assay failure. Subsequent SNPs filtering and improved assay design resulted in assay success and conversion rate of 92.4% and 57.4%, respectively based on 768 SNPs genotyping. Analysis of clustering patterns revealed that 27.6% of the assays were not reproducible and flanking sequence might play a role in determining cluster compression. In addition, we identified a total of 258 and 319 polymorphic SNPs in A. auriculiformis and A. mangium natural germplasms, respectively. Conclusion We have successfully discovered a large number of SNP markers in A. auriculiformis x A. mangium hybrids using next generation transcriptome sequencing. By using a reference genome from the most closely

Association test based on SNP set: logistic kernel machine based test vs. principal component analysis.

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Yang Zhao

Full Text Available GWAS has facilitated greatly the discovery of risk SNPs associated with complex diseases. Traditional methods analyze SNP individually and are limited by low power and reproducibility since correction for multiple comparisons is necessary. Several methods have been proposed based on grouping SNPs into SNP sets using biological knowledge and/or genomic features. In this article, we compare the linear kernel machine based test (LKM and principal components analysis based approach (PCA using simulated datasets under the scenarios of 0 to 3 causal SNPs, as well as simple and complex linkage disequilibrium (LD structures of the simulated regions. Our simulation study demonstrates that both LKM and PCA can control the type I error at the significance level of 0.05. If the causal SNP is in strong LD with the genotyped SNPs, both the PCA with a small number of principal components (PCs and the LKM with kernel of linear or identical-by-state function are valid tests. However, if the LD structure is complex, such as several LD blocks in the SNP set, or when the causal SNP is not in the LD block in which most of the genotyped SNPs reside, more PCs should be included to capture the information of the causal SNP. Simulation studies also demonstrate the ability of LKM and PCA to combine information from multiple causal SNPs and to provide increased power over individual SNP analysis. We also apply LKM and PCA to analyze two SNP sets extracted from an actual GWAS dataset on non-small cell lung cancer.

Whole genome DNA copy number changes identified by high density oligonucleotide arrays

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Huang Jing

2004-05-01

Full Text Available Abstract Changes in DNA copy number are one of the hallmarks of the genetic instability common to most human cancers. Previous micro-array-based methods have been used to identify chromosomal gains and losses; however, they are unable to genotype alleles at the level of single nucleotide polymorphisms (SNPs. Here we describe a novel algorithm that uses a recently developed high-density oligonucleotide array-based SNP genotyping method, whole genome sampling analysis (WGSA, to identify genome-wide chromosomal gains and losses at high resolution. WGSA simultaneously genotypes over 10,000 SNPs by allele-specific hybridisation to perfect match (PM and mismatch (MM probes synthesised on a single array. The copy number algorithm jointly uses PM intensity and discrimination ratios between paired PM and MM intensity values to identify and estimate genetic copy number changes. Values from an experimental sample are compared with SNP-specific distributions derived from a reference set containing over 100 normal individuals to gain statistical power. Genomic regions with statistically significant copy number changes can be identified using both single point analysis and contiguous point analysis of SNP intensities. We identified multiple regions of amplification and deletion using a panel of human breast cancer cell lines. We verified these results using an independent method based on quantitative polymerase chain reaction and found that our approach is both sensitive and specific and can tolerate samples which contain a mixture of both tumour and normal DNA. In addition, by using known allele frequencies from the reference set, statistically significant genomic intervals can be identified containing contiguous stretches of homozygous markers, potentially allowing the detection of regions undergoing loss of heterozygosity (LOH without the need for a matched normal control sample. The coupling of LOH analysis, via SNP genotyping, with copy number

A high-density SNP genetic linkage map for the silver-lipped pearl oyster, Pinctada maxima: a valuable resource for gene localisation and marker-assisted selection.

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Jones, David B; Jerry, Dean R; Khatkar, Mehar S; Raadsma, Herman W; Zenger, Kyall R

2013-11-20

The silver-lipped pearl oyster, Pinctada maxima, is an important tropical aquaculture species extensively farmed for the highly sought "South Sea" pearls. Traditional breeding programs have been initiated for this species in order to select for improved pearl quality, but many economic traits under selection are complex, polygenic and confounded with environmental factors, limiting the accuracy of selection. The incorporation of a marker-assisted selection (MAS) breeding approach would greatly benefit pearl breeding programs by allowing the direct selection of genes responsible for pearl quality. However, before MAS can be incorporated, substantial genomic resources such as genetic linkage maps need to be generated. The construction of a high-density genetic linkage map for P. maxima is not only essential for unravelling the genomic architecture of complex pearl quality traits, but also provides indispensable information on the genome structure of pearl oysters. A total of 1,189 informative genome-wide single nucleotide polymorphisms (SNPs) were incorporated into linkage map construction. The final linkage map consisted of 887 SNPs in 14 linkage groups, spans a total genetic distance of 831.7 centimorgans (cM), and covers an estimated 96% of the P. maxima genome. Assessment of sex-specific recombination across all linkage groups revealed limited overall heterochiasmy between the sexes (i.e. 1.15:1 F/M map length ratio). However, there were pronounced localised differences throughout the linkage groups, whereby male recombination was suppressed near the centromeres compared to female recombination, but inflated towards telomeric regions. Mean values of LD for adjacent SNP pairs suggest that a higher density of markers will be required for powerful genome-wide association studies. Finally, numerous nacre biomineralization genes were localised providing novel positional information for these genes. This high-density SNP genetic map is the first comprehensive linkage

A SNP and SSR based genetic map of asparagus bean (Vigna. unguiculata ssp. sesquipedialis and comparison with the broader species.

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Pei Xu

Full Text Available Asparagus bean (Vigna. unguiculata ssp. sesquipedialis is a distinctive subspecies of cowpea [Vigna. unguiculata (L. Walp.] that apparently originated in East Asia and is characterized by extremely long and thin pods and an aggressive climbing growth habit. The crop is widely cultivated throughout Asia for the production of immature pods known as 'long beans' or 'asparagus beans'. While the genome of cowpea ssp. unguiculata has been characterized recently by high-density genetic mapping and partial sequencing, little is known about the genome of asparagus bean. We report here the first genetic map of asparagus bean based on SNP and SSR markers. The current map consists of 375 loci mapped onto 11 linkage groups (LGs, with 191 loci detected by SNP markers and 184 loci by SSR markers. The overall map length is 745 cM, with an average marker distance of 1.98 cM. There are four high marker-density blocks distributed on three LGs and three regions of segregation distortion (SDRs identified on two other LGs, two of which co-locate in chromosomal regions syntenic to SDRs in soybean. Synteny between asparagus bean and the model legume Lotus. japonica was also established. This work provides the basis for mapping and functional analysis of genes/QTLs of particular interest in asparagus bean, as well as for comparative genomics study of cowpea at the subspecies level.

A SNP and SSR Based Genetic Map of Asparagus Bean (Vigna. unguiculata ssp. sesquipedialis) and Comparison with the Broader Species

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Xu, Pei; Wu, Xiaohua; Wang, Baogen; Liu, Yonghua; Ehlers, Jeffery D.; Close, Timothy J.; Roberts, Philip A.; Diop, Ndeye-Ndack; Qin, Dehui; Hu, Tingting; Lu, Zhongfu; Li, Guojing

2011-01-01

Asparagus bean (Vigna. unguiculata ssp. sesquipedialis) is a distinctive subspecies of cowpea [Vigna. unguiculata (L.) Walp.] that apparently originated in East Asia and is characterized by extremely long and thin pods and an aggressive climbing growth habit. The crop is widely cultivated throughout Asia for the production of immature pods known as ‘long beans’ or ‘asparagus beans’. While the genome of cowpea ssp. unguiculata has been characterized recently by high-density genetic mapping and partial sequencing, little is known about the genome of asparagus bean. We report here the first genetic map of asparagus bean based on SNP and SSR markers. The current map consists of 375 loci mapped onto 11 linkage groups (LGs), with 191 loci detected by SNP markers and 184 loci by SSR markers. The overall map length is 745 cM, with an average marker distance of 1.98 cM. There are four high marker-density blocks distributed on three LGs and three regions of segregation distortion (SDRs) identified on two other LGs, two of which co-locate in chromosomal regions syntenic to SDRs in soybean. Synteny between asparagus bean and the model legume Lotus. japonica was also established. This work provides the basis for mapping and functional analysis of genes/QTLs of particular interest in asparagus bean, as well as for comparative genomics study of cowpea at the subspecies level. PMID:21253606

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

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Gray Joanna

2010-11-01

Full Text Available Abstract Background We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism microarrays and DNA pooling (SNP-MaP employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations. The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred.

Switchgrass genomic diversity, ploidy, and evolution: novel insights from a network-based SNP discovery protocol.

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Fei Lu

Full Text Available Switchgrass (Panicum virgatum L. is a perennial grass that has been designated as an herbaceous model biofuel crop for the United States of America. To facilitate accelerated breeding programs of switchgrass, we developed both an association panel and linkage populations for genome-wide association study (GWAS and genomic selection (GS. All of the 840 individuals were then genotyped using genotyping by sequencing (GBS, generating 350 GB of sequence in total. As a highly heterozygous polyploid (tetraploid and octoploid species lacking a reference genome, switchgrass is highly intractable with earlier methodologies of single nucleotide polymorphism (SNP discovery. To access the genetic diversity of species like switchgrass, we developed a SNP discovery pipeline based on a network approach called the Universal Network-Enabled Analysis Kit (UNEAK. Complexities that hinder single nucleotide polymorphism discovery, such as repeats, paralogs, and sequencing errors, are easily resolved with UNEAK. Here, 1.2 million putative SNPs were discovered in a diverse collection of primarily upland, northern-adapted switchgrass populations. Further analysis of this data set revealed the fundamentally diploid nature of tetraploid switchgrass. Taking advantage of the high conservation of genome structure between switchgrass and foxtail millet (Setaria italica (L. P. Beauv., two parent-specific, synteny-based, ultra high-density linkage maps containing a total of 88,217 SNPs were constructed. Also, our results showed clear patterns of isolation-by-distance and isolation-by-ploidy in natural populations of switchgrass. Phylogenetic analysis supported a general south-to-north migration path of switchgrass. In addition, this analysis suggested that upland tetraploid arose from upland octoploid. All together, this study provides unparalleled insights into the diversity, genomic complexity, population structure, phylogeny, phylogeography, ploidy, and evolutionary dynamics

Development and validation of a 20K single nucleotide polymorphism (SNP) whole genome genotyping array for apple (Malus × domestica Borkh).

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Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

2014-01-01

High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.

Development and validation of a 20K single nucleotide polymorphism (SNP whole genome genotyping array for apple (Malus × domestica Borkh.

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Luca Bianco

Full Text Available High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus. A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs. Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.

Development and Validation of a 20K Single Nucleotide Polymorphism (SNP) Whole Genome Genotyping Array for Apple (Malus × domestica Borkh)

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Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

2014-01-01

High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs. PMID:25303088

Two combinatorial optimization problems for SNP discovery using base-specific cleavage and mass spectrometry.

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Chen, Xin; Wu, Qiong; Sun, Ruimin; Zhang, Louxin

2012-01-01

The discovery of single-nucleotide polymorphisms (SNPs) has important implications in a variety of genetic studies on human diseases and biological functions. One valuable approach proposed for SNP discovery is based on base-specific cleavage and mass spectrometry. However, it is still very challenging to achieve the full potential of this SNP discovery approach. In this study, we formulate two new combinatorial optimization problems. While both problems are aimed at reconstructing the sample sequence that would attain the minimum number of SNPs, they search over different candidate sequence spaces. The first problem, denoted as SNP - MSP, limits its search to sequences whose in silico predicted mass spectra have all their signals contained in the measured mass spectra. In contrast, the second problem, denoted as SNP - MSQ, limits its search to sequences whose in silico predicted mass spectra instead contain all the signals of the measured mass spectra. We present an exact dynamic programming algorithm for solving the SNP - MSP problem and also show that the SNP - MSQ problem is NP-hard by a reduction from a restricted variation of the 3-partition problem. We believe that an efficient solution to either problem above could offer a seamless integration of information in four complementary base-specific cleavage reactions, thereby improving the capability of the underlying biotechnology for sensitive and accurate SNP discovery.

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

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Gwenola Tosser-Klopp

Full Text Available 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.

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

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Chang Hsueh-Wei

2010-04-01

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

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

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

2010-04-08

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

SNP discovery in the transcriptome of white Pacific shrimp Litopenaeus vannamei by next generation sequencing.

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Yang Yu

Full Text Available 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.

Comprehensive evaluation of SNP identification with the Restriction Enzyme-based Reduced Representation Library (RRL method

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Du Ye

2012-02-01

Full Text Available Abstract Background Restriction Enzyme-based Reduced Representation Library (RRL method represents a relatively feasible and flexible strategy used for Single Nucleotide Polymorphism (SNP identification in different species. It has remarkable advantage of reducing the complexity of the genome by orders of magnitude. However, comprehensive evaluation for actual efficacy of SNP identification by this method is still unavailable. Results In order to evaluate the efficacy of Restriction Enzyme-based RRL method, we selected Tsp 45I enzyme which covers 266 Mb flanking region of the enzyme recognition site according to in silico simulation on human reference genome, then we sequenced YH RRL after Tsp 45I treatment and obtained reads of which 80.8% were mapped to target region with an 20-fold average coverage, about 96.8% of target region was covered by at least one read and 257 K SNPs were identified in the region using SOAPsnp software. Compared with whole genome resequencing data, we observed false discovery rate (FDR of 13.95% and false negative rate (FNR of 25.90%. The concordance rate of homozygote loci was over 99.8%, but that of heterozygote were only 92.56%. Repeat sequences and bases quality were proved to have a great effect on the accuracy of SNP calling, SNPs in recognition sites contributed evidently to the high FNR and the low concordance rate of heterozygote. Our results indicated that repeat masking and high stringent filter criteria could significantly decrease both FDR and FNR. Conclusions This study demonstrates that Restriction Enzyme-based RRL method was effective for SNP identification. The results highlight the important role of bias and the method-derived defects represented in this method and emphasize the special attentions noteworthy.

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

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Gonzalez-Neira Anna

2007-08-01

Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

An improved PSO algorithm for generating protective SNP barcodes in breast cancer.

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Li-Yeh Chuang

Full Text Available BACKGROUND: Possible single nucleotide polymorphism (SNP interactions in breast cancer are usually not investigated in genome-wide association studies. Previously, we proposed a particle swarm optimization (PSO method to compute these kinds of SNP interactions. However, this PSO does not guarantee to find the best result in every implement, especially when high-dimensional data is investigated for SNP-SNP interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we propose IPSO algorithm to improve the reliability of PSO for the identification of the best protective SNP barcodes (SNP combinations and genotypes with maximum difference between cases and controls associated with breast cancer. SNP barcodes containing different numbers of SNPs were computed. The top five SNP barcode results are retained for computing the next SNP barcode with a one-SNP-increase for each processing step. Based on the simulated data for 23 SNPs of six steroid hormone metabolisms and signalling-related genes, the performance of our proposed IPSO algorithm is evaluated. Among 23 SNPs, 13 SNPs displayed significant odds ratio (OR values (1.268 to 0.848; p<0.05 for breast cancer. Based on IPSO algorithm, the jointed effect in terms of SNP barcodes with two to seven SNPs show significantly decreasing OR values (0.84 to 0.57; p<0.05 to 0.001. Using PSO algorithm, two to four SNPs show significantly decreasing OR values (0.84 to 0.77; p<0.05 to 0.001. Based on the results of 20 simulations, medians of the maximum differences for each SNP barcode generated by IPSO are higher than by PSO. The interquartile ranges of the boxplot, as well as the upper and lower hinges for each n-SNP barcode (n = 3∼10 are more narrow in IPSO than in PSO, suggesting that IPSO is highly reliable for SNP barcode identification. CONCLUSIONS/SIGNIFICANCE: Overall, the proposed IPSO algorithm is robust to provide exact identification of the best protective SNP barcodes for breast cancer.

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array.

Science.gov (United States)

Antanaviciute, Laima; Fernández-Fernández, Felicidad; Jansen, Johannes; Banchi, Elisa; Evans, Katherine M; Viola, Roberto; Velasco, Riccardo; Dunwell, Jim M; Troggio, Michela; Sargent, Daniel J

2012-05-25

A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the 'Golden Delicious' genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been

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

Science.gov (United States)

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

2017-10-06

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

QTL Mapping of Adult-Plant Resistance to Leaf Rust in the Wheat Cross Zhou 8425B/Chinese Spring Using High-Density SNP Markers

Directory of Open Access Journals (Sweden)

Peipei Zhang

2017-05-01

Full Text Available Wheat leaf rust is an important disease worldwide. Growing resistant cultivars is an effective means to control the disease. In the present study, 244 recombinant inbred lines from Zhou 8425B/Chinese Spring cross were phenotyped for leaf rust severities during the 2011–2012, 2012–2013, 2013–2014, and 2014–2015 cropping seasons at Baoding, Hebei province, and 2012–2013 and 2013–2014 cropping seasons in Zhoukou, Henan province. The population was genotyped using the high-density Illumina iSelect 90K SNP assay and SSR markers. Inclusive composite interval mapping identified eight QTL, designated as QLr.hebau-2AL, QLr.hebau-2BS, QLr.hebau-3A, QLr.hebau-3BS, QLr.hebau-4AL, QLr.hebau-4B, QLr.hebau-5BL, and QLr.hebau-7DS, respectively. QLr.hebau-2BS, QLr.hebau-3A, QLr.hebau-3BS, and QLr.hebau-5BL were derived from Zhou 8425B, whereas the other four were from Chinese Spring. Three stable QTL on chromosomes 2BS, 4B and 7DS explained 7.5–10.6%, 5.5–24.4%, and 11.2–20.9% of the phenotypic variance, respectively. QLr.hebau-2BS in Zhou 8425B might be the same as LrZH22 in Zhoumai 22; QLr.hebau-4B might be the residual resistance of Lr12, and QLr.hebau-7DS is Lr34. QLr.hebau-2AL, QLr.hebau-3BS, QLr.hebau-4AL, and QLr.hebau-5BL are likely to be novel QTL for leaf rust. These QTL and their closely linked SNP and SSR markers can be used for fine mapping, candidate gene discovery, and marker-assisted selection in wheat breeding.

Affymetrix SNP array data for wild Dutch great tits (Parus major)

NARCIS (Netherlands)

Silva, Da Vinicius; Laine, Veronika N.; Bosse, M.; Oers, C.H.J.; Dibbits, B.W.; Visser, M.E.; Crooijmans, R.P.M.A.; Groenen, M.

2018-01-01

The great tit is a widely studied passerine bird species in ecology that, in the past decades, has provided important insights into speciation, phenology, behavior and microevolution. After completion of the great tit genome sequence, a customized high density 650k SNP array was developed enabling

SAQC: SNP Array Quality Control

Directory of Open Access Journals (Sweden)

Li Ling-Hui

2011-04-01

Full Text Available Abstract Background Genome-wide single-nucleotide polymorphism (SNP arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed. Results We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples. Conclusions This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC. SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm.

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

Energy Technology Data Exchange (ETDEWEB)

Yoshimura, Yoshinaga; Ohtake, Tomoko; Okada, Hajime; Fujimoto, Kenzo [School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292 (Japan); Ami, Takehiro [Innovation Plaza Ishikawa, Japan Science and Technology Agency, 2-13 Asahidai, Nomi, Ishikawa 923-1211 (Japan); Tsukaguchi, Tadashi, E-mail: kenzo@jaist.ac.j [Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa 921-8836 (Japan)

2009-06-15

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.

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

Directory of Open Access Journals (Sweden)

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

2009-01-01

Full Text Available 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.

Construction of a high-density genetic map for grape using next generation restriction-site associated DNA sequencing

Directory of Open Access Journals (Sweden)

Wang Nian

2012-08-01

Full Text Available Abstract Background Genetic mapping and QTL detection are powerful methodologies in plant improvement and breeding. Construction of a high-density and high-quality genetic map would be of great benefit in the production of superior grapes to meet human demand. High throughput and low cost of the recently developed next generation sequencing (NGS technology have resulted in its wide application in genome research. Sequencing restriction-site associated DNA (RAD might be an efficient strategy to simplify genotyping. Combining NGS with RAD has proven to be powerful for single nucleotide polymorphism (SNP marker development. Results An F1 population of 100 individual plants was developed. In-silico digestion-site prediction was used to select an appropriate restriction enzyme for construction of a RAD sequencing library. Next generation RAD sequencing was applied to genotype the F1 population and its parents. Applying a cluster strategy for SNP modulation, a total of 1,814 high-quality SNP markers were developed: 1,121 of these were mapped to the female genetic map, 759 to the male map, and 1,646 to the integrated map. A comparison of the genetic maps to the published Vitis vinifera genome revealed both conservation and variations. Conclusions The applicability of next generation RAD sequencing for genotyping a grape F1 population was demonstrated, leading to the successful development of a genetic map with high density and quality using our designed SNP markers. Detailed analysis revealed that this newly developed genetic map can be used for a variety of genome investigations, such as QTL detection, sequence assembly and genome comparison.

Application of high resolution SNP arrays in patients with congenital ...

Indian Academy of Sciences (India)

clinical experience in implementing whole-genome high-resolution SNP arrays to investigate 33 patients with syndromic and .... Online Mendelian Inheritance in Man database (OMIM, ..... of damaged mitochondria through either autophagy or mito- ..... malformations: associations with maternal and infant character- istics in a ...

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

NARCIS (Netherlands)

Chagné, D.; Crowhurst, R.N.; Troggio, M.; Davey, M.W.; Gilmore, B.; Lawley, C.; Vanderzande, S.; Hellens, R.P.; Kumar, S.; Cestaro, A.; Velasco, R.; Main, D.; Rees, J.D.; Iezzoni, A.F.; Mockler, T.; Wilhelm, L.; Weg, van de W.E.; Gardiner, S.E.; Bassil, N.; Peace, C.

2012-01-01

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

Lithium-Based High Energy Density Flow Batteries

Science.gov (United States)

Bugga, Ratnakumar V. (Inventor); West, William C. (Inventor); Kindler, Andrew (Inventor); Smart, Marshall C. (Inventor)

2014-01-01

Systems and methods in accordance with embodiments of the invention implement a lithium-based high energy density flow battery. In one embodiment, a lithium-based high energy density flow battery includes a first anodic conductive solution that includes a lithium polyaromatic hydrocarbon complex dissolved in a solvent, a second cathodic conductive solution that includes a cathodic complex dissolved in a solvent, a solid lithium ion conductor disposed so as to separate the first solution from the second solution, such that the first conductive solution, the second conductive solution, and the solid lithium ionic conductor define a circuit, where when the circuit is closed, lithium from the lithium polyaromatic hydrocarbon complex in the first conductive solution dissociates from the lithium polyaromatic hydrocarbon complex, migrates through the solid lithium ionic conductor, and associates with the cathodic complex of the second conductive solution, and a current is generated.

SNP calling using genotype model selection on high-throughput sequencing data

KAUST Repository

You, Na; Murillo, Gabriel; Su, Xiaoquan; Zeng, Xiaowei; Xu, Jian; Ning, Kang; Zhang, ShouDong; Zhu, Jian-Kang; Cui, Xinping

2012-01-01

calling SNPs. Thus, errors not involved in base-calling or alignment, such as those in genomic sample preparation, are not accounted for.Results: A novel method of consensus and SNP calling, Genotype Model Selection (GeMS), is given which accounts

Light whole genome sequence for SNP discovery across domestic cat breeds

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Driscoll Carlos

2010-06-01

Full Text Available Abstract 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.

Detecting selection signatures between Duroc and Duroc synthetic pig populations using high-density SNP chip.

Science.gov (United States)

Edea, Z; Hong, J-K; Jung, J-H; Kim, D-W; Kim, Y-M; Kim, E-S; Shin, S S; Jung, Y C; Kim, K-S

2017-08-01

The development of high throughput genotyping techniques has facilitated the identification of selection signatures of pigs. The detection of genomic selection signals in a population subjected to differential selection pressures may provide insights into the genes associated with economically and biologically important traits. To identify genomic regions under selection, we genotyped 488 Duroc (D) pigs and 155 D × Korean native pigs (DKNPs) using the Porcine SNP70K BeadChip. By applying the F ST and extended haplotype homozygosity (EHH-Rsb) methods, we detected genes under directional selection associated with growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG, COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159 and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly near or at fixation. These results could be a basis for investigating the underlying mutations associated with observed phenotypic variation. Validation using genome-wide association analysis would also facilitate the inclusion of some of these markers in genetic evaluation programs. © 2017 Stichting International Foundation for Animal Genetics.

CFSAN SNP Pipeline: an automated method for constructing SNP matrices from next-generation sequence data

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Steve Davis

2015-08-01

Full Text Available The analysis of next-generation sequence (NGS data is often a fragmented step-wise process. For example, multiple pieces of software are typically needed to map NGS reads, extract variant sites, and construct a DNA sequence matrix containing only single nucleotide polymorphisms (i.e., a SNP matrix for a set of individuals. The management and chaining of these software pieces and their outputs can often be a cumbersome and difficult task. Here, we present CFSAN SNP Pipeline, which combines into a single package the mapping of NGS reads to a reference genome with Bowtie2, processing of those mapping (BAM files using SAMtools, identification of variant sites using VarScan, and production of a SNP matrix using custom Python scripts. We also introduce a Python package (CFSAN SNP Mutator that when given a reference genome will generate variants of known position against which we validate our pipeline. We created 1,000 simulated Salmonella enterica sp. enterica Serovar Agona genomes at 100× and 20× coverage, each containing 500 SNPs, 20 single-base insertions and 20 single-base deletions. For the 100× dataset, the CFSAN SNP Pipeline recovered 98.9% of the introduced SNPs and had a false positive rate of 1.04 × 10−6; for the 20× dataset 98.8% of SNPs were recovered and the false positive rate was 8.34 × 10−7. Based on these results, CFSAN SNP Pipeline is a robust and accurate tool that it is among the first to combine into a single executable the myriad steps required to produce a SNP matrix from NGS data. Such a tool is useful to those working in an applied setting (e.g., food safety traceback investigations as well as for those interested in evolutionary questions.

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

NARCIS (Netherlands)

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

2007-01-01

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

SNP-based pathway enrichment analysis for genome-wide association studies

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Potkin Steven G

2011-04-01

Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

Direct inference of SNP heterozygosity rates and resolution of LOH detection.

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Xiaohong Li

2007-11-01

Full Text Available Single nucleotide polymorphisms (SNPs have been increasingly utilized to investigate somatic genetic abnormalities in premalignancy and cancer. LOH is a common alteration observed during cancer development, and SNP assays have been used to identify LOH at specific chromosomal regions. The design of such studies requires consideration of the resolution for detecting LOH throughout the genome and identification of the number and location of SNPs required to detect genetic alterations in specific genomic regions. Our study evaluated SNP distribution patterns and used probability models, Monte Carlo simulation, and real human subject genotype data to investigate the relationships between the number of SNPs, SNP HET rates, and the sensitivity (resolution for detecting LOH. We report that variances of SNP heterozygosity rate in dbSNP are high for a large proportion of SNPs. Two statistical methods proposed for directly inferring SNP heterozygosity rates require much smaller sample sizes (intermediate sizes and are feasible for practical use in SNP selection or verification. Using HapMap data, we showed that a region of LOH greater than 200 kb can be reliably detected, with losses smaller than 50 kb having a substantially lower detection probability when using all SNPs currently in the HapMap database. Higher densities of SNPs may exist in certain local chromosomal regions that provide some opportunities for reliably detecting LOH of segment sizes smaller than 50 kb. These results suggest that the interpretation of the results from genome-wide scans for LOH using commercial arrays need to consider the relationships among inter-SNP distance, detection probability, and sample size for a specific study. New experimental designs for LOH studies would also benefit from considering the power of detection and sample sizes required to accomplish the proposed aims.

Application of high resolution SNP arrays in patients with congenital ...

Indian Academy of Sciences (India)

TING-YING LEI

lent oligonucleotide-based array-CGH to determine the exact breakpoints in 14 patients with partial deletions of chromo- some 13q21.1-qter. They were able to refine the smallest deletion region linked to cleft lip/palate (13q31.3–13q33.1). Except for the arrays that measure DNA copy number differ- ences only, SNP arrays, ...

Meta-analysis diagnostic accuracy of SNP-based pathogenicity detection tools: a case of UTG1A1 gene mutations.

Science.gov (United States)

Galehdari, Hamid; Saki, Najmaldin; Mohammadi-Asl, Javad; Rahim, Fakher

2013-01-01

Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene. The main objective of the present review is to summarize results of all available evidence on the accuracy of SNP-based pathogenicity detection tools compared to published clinical result for the prediction of in nsSNPs that leads to disease using prediction performance method. A comprehensive search was performed to find all mutations related to CNS. Database searches included dbSNP, SNPdbe, HGMD, Swissvar, ensemble, and OMIM. All the mutation related to CNS was extracted. The pathogenicity prediction was done using SNP-based pathogenicity detection tools include SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59 different SNPs related to missense mutations in the UGT1A1 gene, were reviewed. Comparing the diagnostic OR, PolyPhen2 and Mutpred have the highest detection 4.983 (95% CI: 1.24 - 20.02) in both, following by SIFT (diagnostic OR: 3.25, 95% CI: 1.07 - 9.83). The highest MCC of SNP-based pathogenicity detection tools, was belong to SIFT (34.19%) followed by Provean, PolyPhen2, and Mutpred (29.99%, 29.89%, and 29.89%, respectively). Hence the highest SNP-based pathogenicity detection tools ACC, was fit to SIFT (62.71%) followed by PolyPhen2, and Mutpred (61.02%, in both). Our results suggest that some of the well-established SNP-based pathogenicity detection tools can appropriately reflect the role of a disease-associated SNP in both local and global structures.

Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

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Claudia Coronnello

Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

Improving accuracy of genomic prediction in Brangus cattle by adding animals with imputed low-density SNP genotypes.

Science.gov (United States)

Lopes, F B; Wu, X-L; Li, H; Xu, J; Perkins, T; Genho, J; Ferretti, R; Tait, R G; Bauck, S; Rosa, G J M

2018-02-01

Reliable genomic prediction of breeding values for quantitative traits requires the availability of sufficient number of animals with genotypes and phenotypes in the training set. As of 31 October 2016, there were 3,797 Brangus animals with genotypes and phenotypes. These Brangus animals were genotyped using different commercial SNP chips. Of them, the largest group consisted of 1,535 animals genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to the SNP content of the GGP-LDV4 chip, so that the number of animals available for training the genomic prediction models was more than doubled. The present study showed that the pooling of animals with both original or imputed 40K SNP genotypes substantially increased genomic prediction accuracies on the ten traits. By supplementing imputed genotypes, the relative gains in genomic prediction accuracies on estimated breeding values (EBV) were from 12.60% to 31.27%, and the relative gain in genomic prediction accuracies on de-regressed EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the performance of five genomic prediction models and two cross-validation methods. The five genomic models predicted EBV and de-regressed EBV of the ten traits similarly well. Of the two cross-validation methods, leave-one-out cross-validation maximized the number of animals at the stage of training for genomic prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was validated in 1,106 newly genotyped Brangus animals based on the SNP effects estimated in the previous set of 3,797 Brangus animals, and they were slightly lower than GPA in the original data. The present study was the first to leverage currently available genotype and phenotype resources in order to harness genomic prediction in Brangus beef cattle. © 2018 Blackwell Verlag GmbH.

SNP Arrays

Directory of Open Access Journals (Sweden)

Jari Louhelainen

2016-10-01

Full Text Available 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.

Dissection of Genetic Factors underlying Wheat Kernel Shape and Size in an Elite × Nonadapted Cross using a High Density SNP Linkage Map

Directory of Open Access Journals (Sweden)

Ajay Kumar

2016-03-01

Full Text Available Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL, developed using an elite (ND 705 and a nonadapted genotype (PI 414566, was extensively phenotyped in replicated field trials and genotyped using Infinium iSelect 90K assay to gain insight into the genetic architecture of kernel shape and size. A high density genetic map consisting of 10,172 single nucleotide polymorphism (SNP markers, with an average marker density of 0.39 cM/marker, identified a total of 29 genomic regions associated with six grain shape and size traits; ∼80% of these regions were associated with multiple traits. The analyses showed that kernel length (KL and width (KW are genetically independent, while a large number (∼59% of the quantitative trait loci (QTL for kernel shape traits were in common with genomic regions associated with kernel size traits. The most significant QTL was identified on chromosome 4B, and could be an ortholog of major rice grain size and shape gene or . Major and stable loci also were identified on the homeologous regions of Group 5 chromosomes, and in the regions of (6A and (7A genes. Both parental genotypes contributed equivalent positive QTL alleles, suggesting that the nonadapted germplasm has a great potential for enhancing the gene pool for grain shape and size. This study provides new knowledge on the genetic dissection of kernel morphology, with a much higher resolution, which may aid further improvement in wheat yield and quality using genomic tools.

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

Directory of Open Access Journals (Sweden)

David Chagné

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

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

Science.gov (United States)

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

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of ‘Golden Delicious’, SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple. PMID:22363718

saSNP Approach for Scalable SNP Analyses of Multiple Bacterial or Viral Genomes

Energy Technology Data Exchange (ETDEWEB)

Gardner, Shea [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Slezak, Tom [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2010-07-27

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. The method is fast to compute, finding SNPs and building a SNP phylogeny in seconds to hours. We use it to identify thousands of putative SNPs from all publicly available Filoviridae, Poxviridae, foot-and-mouth disease virus, Bacillus, and Escherichia coli genomes and plasmids. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle as input hundreds of gigabases of sequence in a single run. The algorithm is based on k-mer analysis using a suffix array, so we call it saSNP.

SNP discovery in nonmodel organisms: strand bias and base-substitution errors reduce conversion rates.

Science.gov (United States)

Gonçalves da Silva, Anders; Barendse, William; Kijas, James W; Barris, Wes C; McWilliam, Sean; Bunch, Rowan J; McCullough, Russell; Harrison, Blair; Hoelzel, A Rus; England, Phillip R

2015-07-01

Single nucleotide polymorphisms (SNPs) have become the marker of choice for genetic studies in organisms of conservation, commercial or biological interest. Most SNP discovery projects in nonmodel organisms apply a strategy for identifying putative SNPs based on filtering rules that account for random sequencing errors. Here, we analyse data used to develop 4723 novel SNPs for the commercially important deep-sea fish, orange roughy (Hoplostethus atlanticus), to assess the impact of not accounting for systematic sequencing errors when filtering identified polymorphisms when discovering SNPs. We used SAMtools to identify polymorphisms in a velvet assembly of genomic DNA sequence data from seven individuals. The resulting set of polymorphisms were filtered to minimize 'bycatch'-polymorphisms caused by sequencing or assembly error. An Illumina Infinium SNP chip was used to genotype a final set of 7714 polymorphisms across 1734 individuals. Five predictors were examined for their effect on the probability of obtaining an assayable SNP: depth of coverage, number of reads that support a variant, polymorphism type (e.g. A/C), strand-bias and Illumina SNP probe design score. Our results indicate that filtering out systematic sequencing errors could substantially improve the efficiency of SNP discovery. We show that BLASTX can be used as an efficient tool to identify single-copy genomic regions in the absence of a reference genome. The results have implications for research aiming to identify assayable SNPs and build SNP genotyping assays for nonmodel organisms. © 2014 John Wiley & Sons Ltd.

Multiplex target enrichment using DNA indexing for ultra-high throughput SNP detection.

LENUS (Irish Health Repository)

Kenny, Elaine M

2011-02-01

Screening large numbers of target regions in multiple DNA samples for sequence variation is an important application of next-generation sequencing but an efficient method to enrich the samples in parallel has yet to be reported. We describe an advanced method that combines DNA samples using indexes or barcodes prior to target enrichment to facilitate this type of experiment. Sequencing libraries for multiple individual DNA samples, each incorporating a unique 6-bp index, are combined in equal quantities, enriched using a single in-solution target enrichment assay and sequenced in a single reaction. Sequence reads are parsed based on the index, allowing sequence analysis of individual samples. We show that the use of indexed samples does not impact on the efficiency of the enrichment reaction. For three- and nine-indexed HapMap DNA samples, the method was found to be highly accurate for SNP identification. Even with sequence coverage as low as 8x, 99% of sequence SNP calls were concordant with known genotypes. Within a single experiment, this method can sequence the exonic regions of hundreds of genes in tens of samples for sequence and structural variation using as little as 1 μg of input DNA per sample.

Population genetic analysis of ascertained SNP data

Directory of Open Access Journals (Sweden)

Nielsen Rasmus

2004-03-01

Full Text Available Abstract The large single nucleotide polymorphism (SNP typing projects have provided an invaluable data resource for human population geneticists. Almost all of the available SNP loci, however, have been identified through a SNP discovery protocol that will influence the allelic distributions in the sampled loci. Standard methods for population genetic analysis based on the available SNP data will, therefore, be biased. This paper discusses the effect of this ascertainment bias on allelic distributions and on methods for quantifying linkage disequilibrium and estimating demographic parameters. Several recently developed methods for correcting for the ascertainment bias will also be discussed.

fcGENE: a versatile tool for processing and transforming SNP datasets.

Directory of Open Access Journals (Sweden)

Nab Raj Roshyara

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

V-MitoSNP: visualization of human mitochondrial SNPs

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Tsui Ke-Hung

2006-08-01

Full Text Available Abstract Background Mitochondrial single nucleotide polymorphisms (mtSNPs constitute important data when trying to shed some light on human diseases and cancers. Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases in a neatly organized and transparent visual manner still remains a challenge. Amongst the many methods reported for SNP genotyping, determining the restriction fragment length polymorphisms (RFLPs is still one of the most convenient and cost-saving methods. In this study, we prepared the visualization of the mtDNA genome in a way, which integrates the RFLP genotyping information with mitochondria related cancers and diseases in a user-friendly, intuitive and interactive manner. The inherent problem associated with mtDNA sequences in BLAST of the NCBI database was also solved. Description V-MitoSNP provides complete mtSNP information for four different kinds of inputs: (1 color-coded visual input by selecting genes of interest on the genome graph, (2 keyword search by locus, disease and mtSNP rs# ID, (3 visualized input of nucleotide range by clicking the selected region of the mtDNA sequence, and (4 sequences mtBLAST. The V-MitoSNP output provides 500 bp (base pairs flanking sequences for each SNP coupled with the RFLP enzyme and the corresponding natural or mismatched primer sets. The output format enables users to see the SNP genotype pattern of the RFLP by virtual electrophoresis of each mtSNP. The rate of successful design of enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was validated by actual agarose electrophoresis and showed successful results for all mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information within the input sequence rather than providing the complete mitochondrial chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in NCBI are integrated in the corresponding SNP in V-MitoSNP. Conclusion V-MitoSNP is a web-based

Dissection of Genetic Factors underlying Wheat Kernel Shape and Size in an Elite × Nonadapted Cross using a High Density SNP Linkage Map.

Science.gov (United States)

Kumar, Ajay; Mantovani, E E; Seetan, R; Soltani, A; Echeverry-Solarte, M; Jain, S; Simsek, S; Doehlert, D; Alamri, M S; Elias, E M; Kianian, S F; Mergoum, M

2016-03-01

Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL), developed using an elite (ND 705) and a nonadapted genotype (PI 414566), was extensively phenotyped in replicated field trials and genotyped using Infinium iSelect 90K assay to gain insight into the genetic architecture of kernel shape and size. A high density genetic map consisting of 10,172 single nucleotide polymorphism (SNP) markers, with an average marker density of 0.39 cM/marker, identified a total of 29 genomic regions associated with six grain shape and size traits; ∼80% of these regions were associated with multiple traits. The analyses showed that kernel length (KL) and width (KW) are genetically independent, while a large number (∼59%) of the quantitative trait loci (QTL) for kernel shape traits were in common with genomic regions associated with kernel size traits. The most significant QTL was identified on chromosome 4B, and could be an ortholog of major rice grain size and shape gene or . Major and stable loci also were identified on the homeologous regions of Group 5 chromosomes, and in the regions of (6A) and (7A) genes. Both parental genotypes contributed equivalent positive QTL alleles, suggesting that the nonadapted germplasm has a great potential for enhancing the gene pool for grain shape and size. This study provides new knowledge on the genetic dissection of kernel morphology, with a much higher resolution, which may aid further improvement in wheat yield and quality using genomic tools. Copyright © 2016 Crop Science Society of America.

Metal hydrides based high energy density thermal battery

International Nuclear Information System (INIS)

Fang, Zhigang Zak; Zhou, Chengshang; Fan, Peng; Udell, Kent S.; Bowman, Robert C.; Vajo, John J.; Purewal, Justin J.; Kekelia, Bidzina

2015-01-01

Highlights: • The principle of the thermal battery using advanced metal hydrides was demonstrated. • The thermal battery used MgH 2 and TiMnV as a working pair. • High energy density can be achieved by the use of MgH 2 to store thermal energy. - Abstract: A concept of thermal battery based on advanced metal hydrides was studied for heating and cooling of cabins in electric vehicles. The system utilized a pair of thermodynamically matched metal hydrides as energy storage media. The pair of hydrides that was identified and developed was: (1) catalyzed MgH 2 as the high temperature hydride material, due to its high energy density and enhanced kinetics; and (2) TiV 0.62 Mn 1.5 alloy as the matching low temperature hydride. Further, a proof-of-concept prototype was built and tested, demonstrating the potential of the system as HVAC for transportation vehicles

SNP interaction pattern identifier (SIPI)

DEFF Research Database (Denmark)

Lin, Hui Yi; Chen, Dung Tsa; Huang, Po Yu

2017-01-01

Motivation: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...

TEMPO-based catholyte for high-energy density nonaqueous redox flow batteries.

Science.gov (United States)

Wei, Xiaoliang; Xu, Wu; Vijayakumar, Murugesan; Cosimbescu, Lelia; Liu, Tianbiao; Sprenkle, Vincent; Wang, Wei

2014-12-03

A TEMPO-based non-aqueous electrolyte with the TEMPO concentration as high as 2.0 m is demonstrated as a high-energy-density catholyte for redox flow battery applications. With a hybrid anode, Li|TEMPO flow cells using this electrolyte deliver an energy efficiency of ca. 70% and an impressively high energy density of 126 W h L(-1) . © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metal hydrides based high energy density thermal battery

Energy Technology Data Exchange (ETDEWEB)

Fang, Zhigang Zak, E-mail: zak.fang@utah.edu [Department of Metallurgical Engineering, The University of Utah, 135 South 1460 East, Room 412, Salt Lake City, UT 84112-0114 (United States); Zhou, Chengshang; Fan, Peng [Department of Metallurgical Engineering, The University of Utah, 135 South 1460 East, Room 412, Salt Lake City, UT 84112-0114 (United States); Udell, Kent S. [Department of Metallurgical Engineering, The University of Utah, 50 S. Central Campus Dr., Room 2110, Salt Lake City, UT 84112-0114 (United States); Bowman, Robert C. [Department of Metallurgical Engineering, The University of Utah, 135 South 1460 East, Room 412, Salt Lake City, UT 84112-0114 (United States); Vajo, John J.; Purewal, Justin J. [HRL Laboratories, LLC, 3011 Malibu Canyon Road, Malibu, CA 90265 (United States); Kekelia, Bidzina [Department of Metallurgical Engineering, The University of Utah, 50 S. Central Campus Dr., Room 2110, Salt Lake City, UT 84112-0114 (United States)

2015-10-05

Highlights: • The principle of the thermal battery using advanced metal hydrides was demonstrated. • The thermal battery used MgH{sub 2} and TiMnV as a working pair. • High energy density can be achieved by the use of MgH{sub 2} to store thermal energy. - Abstract: A concept of thermal battery based on advanced metal hydrides was studied for heating and cooling of cabins in electric vehicles. The system utilized a pair of thermodynamically matched metal hydrides as energy storage media. The pair of hydrides that was identified and developed was: (1) catalyzed MgH{sub 2} as the high temperature hydride material, due to its high energy density and enhanced kinetics; and (2) TiV{sub 0.62}Mn{sub 1.5} alloy as the matching low temperature hydride. Further, a proof-of-concept prototype was built and tested, demonstrating the potential of the system as HVAC for transportation vehicles.

Heap: a highly sensitive and accurate SNP detection tool for low-coverage high-throughput sequencing data

KAUST Repository

Kobayashi, Masaaki; Ohyanagi, Hajime; Takanashi, Hideki; Asano, Satomi; Kudo, Toru; Kajiya-Kanegae, Hiromi; Nagano, Atsushi J.; Tainaka, Hitoshi; Tokunaga, Tsuyoshi; Sazuka, Takashi; Iwata, Hiroyoshi; Tsutsumi, Nobuhiro; Yano, Kentaro

2017-01-01

and GP depends on not only their mathematical models, but the quality and quantity of variants employed in the analysis. In NGS single nucleotide polymorphism (SNP) calling, conventional tools ideally require more reads for higher SNP sensitivity

High-resolution SNP array analysis of patients with developmental disorder and normal array CGH results

Directory of Open Access Journals (Sweden)

Siggberg Linda

2012-09-01

Full Text Available Abstract Background Diagnostic analysis of patients with developmental disorders has improved over recent years largely due to the use of microarray technology. Array methods that facilitate copy number analysis have enabled the diagnosis of up to 20% more patients with previously normal karyotyping results. A substantial number of patients remain undiagnosed, however. Methods and Results Using the Genome-Wide Human SNP array 6.0, we analyzed 35 patients with a developmental disorder of unknown cause and normal array comparative genomic hybridization (array CGH results, in order to characterize previously undefined genomic aberrations. We detected no seemingly pathogenic copy number aberrations. Most of the vast amount of data produced by the array was polymorphic and non-informative. Filtering of this data, based on copy number variant (CNV population frequencies as well as phenotypically relevant genes, enabled pinpointing regions of allelic homozygosity that included candidate genes correlating to the phenotypic features in four patients, but results could not be confirmed. Conclusions In this study, the use of an ultra high-resolution SNP array did not contribute to further diagnose patients with developmental disorders of unknown cause. The statistical power of these results is limited by the small size of the patient cohort, and interpretation of these negative results can only be applied to the patients studied here. We present the results of our study and the recurrence of clustered allelic homozygosity present in this material, as detected by the SNP 6.0 array.

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

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Wang Wanxing

2012-10-01

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

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

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Rosen David

2008-10-01

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

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

Science.gov (United States)

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.

Forensic SNP genotyping with SNaPshot

DEFF Research Database (Denmark)

Fondevila, M; Børsting, C; Phillips, C

2017-01-01

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......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...... 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...

HRM and SNaPshot as alternative forensic SNP genotyping methods.

Science.gov (United States)

Mehta, Bhavik; Daniel, Runa; McNevin, Dennis

2017-09-01

Single nucleotide polymorphisms (SNPs) have been widely used in forensics for prediction of identity, biogeographical ancestry (BGA) and externally visible characteristics (EVCs). Single base extension (SBE) assays, most notably SNaPshot® (Thermo Fisher Scientific), are commonly used for forensic SNP genotyping as they can be employed on standard instrumentation in forensic laboratories (e.g. capillary electrophoresis). High resolution melt (HRM) analysis is an alternative method and is a simple, fast, single tube assay for low throughput SNP typing. This study compares HRM and SNaPshot®. HRM produced reproducible and concordant genotypes at 500 pg, however, difficulties were encountered when genotyping SNPs with high GC content in flanking regions and differentiating variants of symmetrical SNPs. SNaPshot® was reproducible at 100 pg and is less dependent on SNP choice. HRM has a shorter processing time in comparison to SNaPshot®, avoids post PCR contamination risk and has potential as a screening tool for many forensic applications.

The Brachyury Gly177Asp SNP Is not Associated with a Risk of Skull Base Chordoma in the Chinese Population

Directory of Open Access Journals (Sweden)

Zhen Wu

2013-10-01

Full Text Available A recent chordoma cancer genotyping study reveals that the rs2305089, a single nucleotide polymorphism (SNP located in brachyury gene and a key gene in the development of notochord, is significantly associated with chordoma risk. The brachyury gene is believed to be one of the key genes involved in the pathogenesis of chordoma, a rare primary bone tumor originating along the spinal column or at the base of the skull. The association between the brachyury Gly177Asp single nucleotide polymorphism (SNP and the risk of skull base chordoma in Chinese populations is currently unknown. We investigated the genotype distribution of this SNP in 65 skull-base chordoma cases and 120 healthy subjects. Comparisons of the genotype distributions and allele frequencies did not reveal any significant difference between the groups. Our data suggest that the brachyury Gly177Asp SNP is not involved in the risks of skull-base chordoma, at least in the Chinese population.

Network-based regularization for high dimensional SNP data in the case-control study of Type 2 diabetes.

Science.gov (United States)

Ren, Jie; He, Tao; Li, Ye; Liu, Sai; Du, Yinhao; Jiang, Yu; Wu, Cen

2017-05-16

Over the past decades, the prevalence of type 2 diabetes mellitus (T2D) has been steadily increasing around the world. Despite large efforts devoted to better understand the genetic basis of the disease, the identified susceptibility loci can only account for a small portion of the T2D heritability. Some of the existing approaches proposed for the high dimensional genetic data from the T2D case-control study are limited by analyzing a few number of SNPs at a time from a large pool of SNPs, by ignoring the correlations among SNPs and by adopting inefficient selection techniques. We propose a network constrained regularization method to select important SNPs by taking the linkage disequilibrium into account. To accomodate the case control study, an iteratively reweighted least square algorithm has been developed within the coordinate descent framework where optimization of the regularized logistic loss function is performed with respect to one parameter at a time and iteratively cycle through all the parameters until convergence. In this article, a novel approach is developed to identify important SNPs more effectively through incorporating the interconnections among them in the regularized selection. A coordinate descent based iteratively reweighed least squares (IRLS) algorithm has been proposed. Both the simulation study and the analysis of the Nurses's Health Study, a case-control study of type 2 diabetes data with high dimensional SNP measurements, demonstrate the advantage of the network based approach over the competing alternatives.

SNP-SNP interactions in breast cancer susceptibility

Directory of Open Access Journals (Sweden)

Wang Yuanyuan

2006-05-01

Full Text Available Abstract Background Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2 are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. Methods In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR principle. Results None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082A], cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val], cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln], and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val] pathways. Conclusion The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their

SNP-SNP interactions in breast cancer susceptibility

International Nuclear Information System (INIS)

Onay, Venüs Ümmiye; Ozcelik, Hilmi; Briollais, Laurent; Knight, Julia A; Shi, Ellen; Wang, Yuanyuan; Wells, Sean; Li, Hong; Rajendram, Isaac; Andrulis, Irene L

2006-01-01

Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle. None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways. The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described

SNP markers retrieval for a non-model species: a practical approach

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Shahin Arwa

2012-01-01

Full Text Available Abstract Background SNP (Single Nucleotide Polymorphism markers are rapidly becoming the markers of choice for applications in breeding because of next generation sequencing technology developments. For SNP development by NGS technologies, correct assembly of the huge amounts of sequence data generated is essential. Little is known about assembler's performance, especially when dealing with highly heterogeneous species that show a high genome complexity and what the possible consequences are of differences in assemblies on SNP retrieval. This study tested two assemblers (CAP3 and CLC on 454 data from four lily genotypes and compared results with respect to SNP retrieval. Results CAP3 assembly resulted in higher numbers of contigs, lower numbers of reads per contig, and shorter average read lengths compared to CLC. Blast comparisons showed that CAP3 contigs were highly redundant. Contrastingly, CLC in rare cases combined paralogs in one contig. Redundant and chimeric contigs may lead to erroneous SNPs. Filtering for redundancy can be done by blasting selected SNP markers to the contigs and discarding all the SNP markers that show more than one blast hit. Results on chimeric contigs showed that only four out of 2,421 SNP markers were selected from chimeric contigs. Conclusion In practice, CLC performs better in assembling highly heterogeneous genome sequences compared to CAP3, and consequently SNP retrieval is more efficient. Additionally a simple flow scheme is suggested for SNP marker retrieval that can be valid for all non-model species.

Combining target enrichment with barcode multiplexing for high throughput SNP discovery

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Lunke Sebastian

2010-11-01

Full Text Available Abstract Background The primary goal of genetic linkage analysis is to identify genes affecting a phenotypic trait. After localisation of the linkage region, efficient genetic dissection of the disease linked loci requires that functional variants are identified across the loci. These functional variations are difficult to detect due to extent of genetic diversity and, to date, incomplete cataloguing of the large number of variants present both within and between populations. Massively parallel sequencing platforms offer unprecedented capacity for variant discovery, however the number of samples analysed are still limited by cost per sample. Some progress has been made in reducing the cost of resequencing using either multiplexing methodologies or through the utilisation of targeted enrichment technologies which provide the ability to resequence genomic areas of interest rather that full genome sequencing. Results We developed a method that combines current multiplexing methodologies with a solution-based target enrichment method to further reduce the cost of resequencing where region-specific sequencing is required. Our multiplex/enrichment strategy produced high quality data with nominal reduction of sequencing depth. We undertook a genotyping study and were successful in the discovery of novel SNP alleles in all samples at uniplex, duplex and pentaplex levels. Conclusion Our work describes the successful combination of a targeted enrichment method and index barcode multiplexing to reduce costs, time and labour associated with processing large sample sets. Furthermore, we have shown that the sequencing depth obtained is adequate for credible SNP genotyping analysis at uniplex, duplex and pentaplex levels.

SNP Discovery In Marine Fish Species By 454 Sequencing

DEFF Research Database (Denmark)

Panitz, Frank; Nielsen, Rasmus Ory; van Houdt, Jeroen K J

2011-01-01

Based on the 454 Next-Generation-Sequencing technology (Roche) a high throughput screening method was devised in order to generate novel genetic markers (SNPs). SNP discovery was performed for three target species of marine fish: hake (Merluccius merluccius), herring (Clupea harengus) and sole...

SNP mining porcine ESTs with MAVIANT, a novel tool for SNP evaluation and annotation

DEFF Research Database (Denmark)

Panitz, Frank; Stengaard, Henrik; Hornshoj, Henrik

2007-01-01

MOTIVATION: Single nucleotide polymorphisms (SNPs) analysis is an important means to study genetic variation. A fast and cost-efficient approach to identify large numbers of novel candidates is the SNP mining of large scale sequencing projects. The increasing availability of sequence trace data...... manual annotation, which is immediately accessible and can be easily shared with external collaborators. RESULTS: Large-scale SNP mining of polymorphisms bases on porcine EST sequences yielded more than 7900 candidate SNPs in coding regions (cSNPs), which were annotated relative to the human genome. Non...

Dynamic variable selection in SNP genotype autocalling from APEX microarray data

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Zamar Ruben H

2006-11-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are DNA sequence variations, occurring when a single nucleotide – adenine (A, thymine (T, cytosine (C or guanine (G – is altered. Arguably, SNPs account for more than 90% of human genetic variation. Our laboratory has developed a highly redundant SNP genotyping assay consisting of multiple probes with signals from multiple channels for a single SNP, based on arrayed primer extension (APEX. This mini-sequencing method is a powerful combination of a highly parallel microarray with distinctive Sanger-based dideoxy terminator sequencing chemistry. Using this microarray platform, our current genotype calling system (known as SNP Chart is capable of calling single SNP genotypes by manual inspection of the APEX data, which is time-consuming and exposed to user subjectivity bias. Results Using a set of 32 Coriell DNA samples plus three negative PCR controls as a training data set, we have developed a fully-automated genotyping algorithm based on simple linear discriminant analysis (LDA using dynamic variable selection. The algorithm combines separate analyses based on the multiple probe sets to give a final posterior probability for each candidate genotype. We have tested our algorithm on a completely independent data set of 270 DNA samples, with validated genotypes, from patients admitted to the intensive care unit (ICU of St. Paul's Hospital (plus one negative PCR control sample. Our method achieves a concordance rate of 98.9% with a 99.6% call rate for a set of 96 SNPs. By adjusting the threshold value for the final posterior probability of the called genotype, the call rate reduces to 94.9% with a higher concordance rate of 99.6%. We also reversed the two independent data sets in their training and testing roles, achieving a concordance rate up to 99.8%. Conclusion The strength of this APEX chemistry-based platform is its unique redundancy having multiple probes for a single SNP. Our

Ultra-low-density genotype panels for breed assignment of Angus and Hereford cattle.

Science.gov (United States)

Judge, M M; Kelleher, M M; Kearney, J F; Sleator, R D; Berry, D P

2017-06-01

Angus and Hereford beef is marketed internationally for apparent superior meat quality attributes; DNA-based breed authenticity could be a useful instrument to ensure consumer confidence on premium meat products. The objective of this study was to develop an ultra-low-density genotype panel to accurately quantify the Angus and Hereford breed proportion in biological samples. Medium-density genotypes (13 306 single nucleotide polymorphisms (SNPs)) were available on 54 703 commercial and 4042 purebred animals. The breed proportion of the commercial animals was generated from the medium-density genotypes and this estimate was regarded as the gold-standard breed composition. Ten genotype panels (100 to 1000 SNPs) were developed from the medium-density genotypes; five methods were used to identify the most informative SNPs and these included the Delta statistic, the fixation (F st) statistic and an index of both. Breed assignment analyses were undertaken for each breed, panel density and SNP selection method separately with a programme to infer population structure using the entire 13 306 SNP panel (representing the gold-standard measure). Breed assignment was undertaken for all commercial animals (n=54 703), animals deemed to contain some proportion of Angus based on pedigree (n=5740) and animals deemed to contain some proportion of Hereford based on pedigree (n=5187). The predicted breed proportion of all animals from the lower density panels was then compared with the gold-standard breed prediction. Panel density, SNP selection method and breed all had a significant effect on the correlation of predicted and actual breed proportion. Regardless of breed, the Index method of SNP selection numerically (but not significantly) outperformed all other selection methods in accuracy (i.e. correlation and root mean square of prediction) when panel density was ⩾300 SNPs. The correlation between actual and predicted breed proportion increased as panel density increased. Using

Detection of genomic signatures for pig hairlessness using high-density SNP data

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Ying SU,Yi LONG,Xinjun LIAO,Huashui AI,Zhiyan ZHANG,Bin YANG,Shijun XIAO,Jianhong TANG,Wenshui XIN,Lusheng HUANG,Jun REN,Nengshui DING

2014-12-01

Full Text Available Hair provides thermal regulation for mammals and protects the skin from wounds, bites and ultraviolet (UV radiation, and is important in adaptation to volatile environments. Pigs in nature are divided into hairy and hairless, which provide a good model for deciphering the molecular mechanisms of hairlessness. We conducted a genomic scan for genetically differentiated regions between hairy and hairless pigs using 60K SNP data, with the aim to better understand the genetic basis for the hairless phenotype in pigs. A total of 38405 SNPs in 498 animals from 36 diverse breeds were used to detect genomic signatures for pig hairlessness by estimating between-population (FST values. Seven diversifying signatures between Yucatan hairless pig and hairy pigs were identified on pig chromosomes (SSC 1, 3, 7, 8, 10, 11 and 16, and the biological functions of two notable genes, RGS17 and RB1, were revealed. When Mexican hairless pigs were contrasted with hairypigs, strong signatures were detected on SSC1 and SSC10, which harbor two functionally plausible genes, REV3L and BAMBI. KEGG pathway analysis showed a subset of overrepresented genes involved in the T cell receptor signaling pathway, MAPK signaling pathway and the tight junction pathways. All of these pathways may be important in local adaptability of hairless pigs. The potential mechanisms underlying the hairless phenotype in pigs are reported for the first time. RB1 and BAMBI are interesting candidate genes for the hairless phenotype in Yucatan hairless and Mexico hairless pigs, respectively. RGS17, REV3L, ICOS and RASGRP1 as well as other genes involved in the MAPK and T cell receptor signaling pathways may be important in environmental adaption by improved tolerance to UV damage in hairless pigs. These findings improve our understanding of the genetic basis for inherited hairlessness in pigs.

Partitioned learning of deep Boltzmann machines for SNP data.

Science.gov (United States)

Hess, Moritz; Lenz, Stefan; Blätte, Tamara J; Bullinger, Lars; Binder, Harald

2017-10-15

Learning the joint distributions of measurements, and in particular identification of an appropriate low-dimensional manifold, has been found to be a powerful ingredient of deep leaning approaches. Yet, such approaches have hardly been applied to single nucleotide polymorphism (SNP) data, probably due to the high number of features typically exceeding the number of studied individuals. After a brief overview of how deep Boltzmann machines (DBMs), a deep learning approach, can be adapted to SNP data in principle, we specifically present a way to alleviate the dimensionality problem by partitioned learning. We propose a sparse regression approach to coarsely screen the joint distribution of SNPs, followed by training several DBMs on SNP partitions that were identified by the screening. Aggregate features representing SNP patterns and the corresponding SNPs are extracted from the DBMs by a combination of statistical tests and sparse regression. In simulated case-control data, we show how this can uncover complex SNP patterns and augment results from univariate approaches, while maintaining type 1 error control. Time-to-event endpoints are considered in an application with acute myeloid leukemia patients, where SNP patterns are modeled after a pre-screening based on gene expression data. The proposed approach identified three SNPs that seem to jointly influence survival in a validation dataset. This indicates the added value of jointly investigating SNPs compared to standard univariate analyses and makes partitioned learning of DBMs an interesting complementary approach when analyzing SNP data. A Julia package is provided at 'http://github.com/binderh/BoltzmannMachines.jl'. binderh@imbi.uni-freiburg.de. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Vitis phylogenomics: hybridization intensities from a SNP array outperform genotype calls.

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Allison J Miller

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

Genome-wide SNP discovery in tetraploid alfalfa using 454 sequencing and high resolution melting analysis

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Zhao Patrick X

2011-07-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most common type of sequence variation among plants and are often functionally important. We describe the use of 454 technology and high resolution melting analysis (HRM for high throughput SNP discovery in tetraploid alfalfa (Medicago sativa L., a species with high economic value but limited genomic resources. Results The alfalfa genotypes selected from M. sativa subsp. sativa var. 'Chilean' and M. sativa subsp. falcata var. 'Wisfal', which differ in water stress sensitivity, were used to prepare cDNA from tissue of clonally-propagated plants grown under either well-watered or water-stressed conditions, and then pooled for 454 sequencing. Based on 125.2 Mb of raw sequence, a total of 54,216 unique sequences were obtained including 24,144 tentative consensus (TCs sequences and 30,072 singletons, ranging from 100 bp to 6,662 bp in length, with an average length of 541 bp. We identified 40,661 candidate SNPs distributed throughout the genome. A sample of candidate SNPs were evaluated and validated using high resolution melting (HRM analysis. A total of 3,491 TCs harboring 20,270 candidate SNPs were located on the M. truncatula (MT 3.5.1 chromosomes. Gene Ontology assignments indicate that sequences obtained cover a broad range of GO categories. Conclusions We describe an efficient method to identify thousands of SNPs distributed throughout the alfalfa genome covering a broad range of GO categories. Validated SNPs represent valuable molecular marker resources that can be used to enhance marker density in linkage maps, identify potential factors involved in heterosis and genetic variation, and as tools for association mapping and genomic selection in alfalfa.

High-density lipoproteins and adrenal steroidogenesis : A population-based study

NARCIS (Netherlands)

Buitenwerf, Edward; Kerstens, Michiel N.; Links, Thera P.; Kema, Ido P.; Dullaart, Robin P. F.

BACKGROUND: Cholesterol trafficked within plasma lipoproteins, in particular high-density lipoproteins (HDL), may represent an important source of cholesterol that is required for adrenal steroidogenesis. Based on a urinary gas chromatography method, compromised adrenal function has been suggested

Individual tree detection based on densities of high points of high resolution airborne lidar

NARCIS (Netherlands)

Abd Rahman, M.Z.; Gorte, B.G.H.

2008-01-01

The retrieval of individual tree location from Airborne LiDAR has focused largely on utilizing canopy height. However, high resolution Airborne LiDAR offers another source of information for tree detection. This paper presents a new method for tree detection based on high points’ densities from a

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

Science.gov (United States)

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.

SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

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Sarah L. Nickerson

2015-10-01

Full Text Available Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*, establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS. Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

A high-density genetic map of Arachis duranensis, a diploid ancestor of cultivated peanut

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Nagy Ervin D

2012-09-01

Full Text Available Abstract Background Cultivated peanut (Arachis hypogaea is an allotetraploid species whose ancestral genomes are most likely derived from the A-genome species, A. duranensis, and the B-genome species, A. ipaensis. The very recent (several millennia evolutionary origin of A. hypogaea has imposed a bottleneck for allelic and phenotypic diversity within the cultigen. However, wild diploid relatives are a rich source of alleles that could be used for crop improvement and their simpler genomes can be more easily analyzed while providing insight into the structure of the allotetraploid peanut genome. The objective of this research was to establish a high-density genetic map of the diploid species A. duranensis based on de novo generated EST databases. Arachis duranensis was chosen for mapping because it is the A-genome progenitor of cultivated peanut and also in order to circumvent the confounding effects of gene duplication associated with allopolyploidy in A. hypogaea. Results More than one million expressed sequence tag (EST sequences generated from normalized cDNA libraries of A. duranensis were assembled into 81,116 unique transcripts. Mining this dataset, 1236 EST-SNP markers were developed between two A. duranensis accessions, PI 475887 and Grif 15036. An additional 300 SNP markers also were developed from genomic sequences representing conserved legume orthologs. Of the 1536 SNP markers, 1054 were placed on a genetic map. In addition, 598 EST-SSR markers identified in A. hypogaea assemblies were included in the map along with 37 disease resistance gene candidate (RGC and 35 other previously published markers. In total, 1724 markers spanning 1081.3 cM over 10 linkage groups were mapped. Gene sequences that provided mapped markers were annotated using similarity searches in three different databases, and gene ontology descriptions were determined using the Medicago Gene Atlas and TAIR databases. Synteny analysis between A. duranensis, Medicago

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

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William Murk

2016-07-01

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

High-density 3D graphene-based monolith and related materials, methods, and devices

Energy Technology Data Exchange (ETDEWEB)

Worsley, Marcus A.; Baumann, Theodore F.; Biener, Juergen; Charnvanichborikarn, Supakit; Kucheyev, Sergei; Montalvo, Elizabeth; Shin, Swanee; Tylski, Elijah

2017-03-21

A composition comprising at least one high-density graphene-based monolith, said monolith comprising a three-dimensional structure of graphene sheets crosslinked by covalent carbon bonds and having a density of at least 0.1 g/cm.sup.3. Also provided is a method comprising: preparing a reaction mixture comprising a suspension and at least one catalyst, said suspension selected from a graphene oxide (GO) suspension and a carbon nanotube suspension; curing the reaction mixture to produce a wet gel; drying the wet gel to produce a dry gel, said drying step is substantially free of supercritical drying and freeze drying; and pyrolyzing the dry gel to produce a high-density graphene-based monolith. Exceptional combinations of properties are achieved including high conductive and mechanical properties.

SNP genotyping technologies

DEFF Research Database (Denmark)

Studer, Bruno; Kölliker, Roland

2013-01-01

In the recent years, single nucleotide polymorphism (SNP) markers have emerged as the marker technology of choice for plant genetics and breeding applications. Besides the efficient technologies available for SNP discovery even in complex genomes, one of the main reasons for this is the availabil...

Association between genetic subgroups of pancreatic ductal adenocarcinoma defined by high density 500 K SNP-arrays and tumor histopathology.

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María Laura Gutiérrez

Full Text Available The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP-arrays to define those chromosomal regions which most commonly harbour copy number (CN alterations and loss of heterozygozity (LOH in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70% extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9 versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11. From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterozygozity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC.

Detecting imbalanced expression of SNP alleles by minisequencing on microarrays

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Dahlgren Andreas

2004-10-01

Full Text Available Abstract Background Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system. Results The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1–9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and

Effect of Co-segregating Markers on High-Density Genetic Maps and Prediction of Map Expansion Using Machine Learning Algorithms.

Science.gov (United States)

N'Diaye, Amidou; Haile, Jemanesh K; Fowler, D Brian; Ammar, Karim; Pozniak, Curtis J

2017-01-01

Advances in sequencing and genotyping methods have enable cost-effective production of high throughput single nucleotide polymorphism (SNP) markers, making them the choice for linkage mapping. As a result, many laboratories have developed high-throughput SNP assays and built high-density genetic maps. However, the number of markers may, by orders of magnitude, exceed the resolution of recombination for a given population size so that only a minority of markers can accurately be ordered. Another issue attached to the so-called 'large p, small n' problem is that high-density genetic maps inevitably result in many markers clustering at the same position (co-segregating markers). While there are a number of related papers, none have addressed the impact of co-segregating markers on genetic maps. In the present study, we investigated the effects of co-segregating markers on high-density genetic map length and marker order using empirical data from two populations of wheat, Mohawk × Cocorit (durum wheat) and Norstar × Cappelle Desprez (bread wheat). The maps of both populations consisted of 85% co-segregating markers. Our study clearly showed that excess of co-segregating markers can lead to map expansion, but has little effect on markers order. To estimate the inflation factor (IF), we generated a total of 24,473 linkage maps (8,203 maps for Mohawk × Cocorit and 16,270 maps for Norstar × Cappelle Desprez). Using seven machine learning algorithms, we were able to predict with an accuracy of 0.7 the map expansion due to the proportion of co-segregating markers. For example in Mohawk × Cocorit, with 10 and 80% co-segregating markers the length of the map inflated by 4.5 and 16.6%, respectively. Similarly, the map of Norstar × Cappelle Desprez expanded by 3.8 and 11.7% with 10 and 80% co-segregating markers. With the increasing number of markers on SNP-chips, the proportion of co-segregating markers in high-density maps will continue to increase making map expansion

Effect of Co-segregating Markers on High-Density Genetic Maps and Prediction of Map Expansion Using Machine Learning Algorithms

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Amidou N’Diaye

2017-08-01

Full Text Available Advances in sequencing and genotyping methods have enable cost-effective production of high throughput single nucleotide polymorphism (SNP markers, making them the choice for linkage mapping. As a result, many laboratories have developed high-throughput SNP assays and built high-density genetic maps. However, the number of markers may, by orders of magnitude, exceed the resolution of recombination for a given population size so that only a minority of markers can accurately be ordered. Another issue attached to the so-called ‘large p, small n’ problem is that high-density genetic maps inevitably result in many markers clustering at the same position (co-segregating markers. While there are a number of related papers, none have addressed the impact of co-segregating markers on genetic maps. In the present study, we investigated the effects of co-segregating markers on high-density genetic map length and marker order using empirical data from two populations of wheat, Mohawk × Cocorit (durum wheat and Norstar × Cappelle Desprez (bread wheat. The maps of both populations consisted of 85% co-segregating markers. Our study clearly showed that excess of co-segregating markers can lead to map expansion, but has little effect on markers order. To estimate the inflation factor (IF, we generated a total of 24,473 linkage maps (8,203 maps for Mohawk × Cocorit and 16,270 maps for Norstar × Cappelle Desprez. Using seven machine learning algorithms, we were able to predict with an accuracy of 0.7 the map expansion due to the proportion of co-segregating markers. For example in Mohawk × Cocorit, with 10 and 80% co-segregating markers the length of the map inflated by 4.5 and 16.6%, respectively. Similarly, the map of Norstar × Cappelle Desprez expanded by 3.8 and 11.7% with 10 and 80% co-segregating markers. With the increasing number of markers on SNP-chips, the proportion of co-segregating markers in high-density maps will continue to increase

Survey of SSC12 regions affecting fatty acid composition of intramuscular fat using high density SNP data

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María eMuñoz

2012-01-01

Full Text Available Fatty acid composition is a critical aspect of pork because it affects sensorial and technological aspects of meat quality and it is relevant for human health. Previous studies identified significant QTLs in porcine chromosome 12 for fatty acid profile of backfat and intramuscular fat. In the present study, 374 SNPs mapped in SSC12 from the 60K Porcine SNP Beadchip were used. We have combined linkage and association analyses with expression data analysis in order to identify regions of SSC12 that could affect fatty acid composition of intramuscular fat in longissimus muscle. The QTL scan showed a region around the 60 cM position that significantly affects palmitic fatty acid and two related fatty acid indexes. The Iberian QTL allele increased the palmitic content (+2.6% of mean trait. This QTL does not match any of those reported in the previous study on fatty acid composition of backfat, suggesting different genetic control acting at both tissues. The SNP association analyses showed significant associations with linolenic and palmitic acids besides several indexes. Among the polymorphisms that affect palmitic fatty acid and match the QTL region at 60 cM, there were three that mapped in the Phosphatidylcholine Transfer Protein (PCTP gene and one in the Acetyl-CoA Carboxylase  gene (ACACA. Interestingly one of the PCTP SNPs also affected significantly unsaturated and double bound indexes and the ratio between polyunsaturated/monounsaturated fatty acids. Differential expression was assessed on longissimus muscle conditional on the genotype of the QTL and on the most significant SNPs, according to the results obtained in the former analyses. Results from the microarray expression analyses, validated by RT-qPCR, showed that PCTP expression levels significantly vary depending on the QTL as well as on the own PCTP genotype. The results obtained with the different approaches point out the PCTP gene as a powerful candidate underlying the QTL for

Imputation of microsatellite alleles from dense SNP genotypes for parental verification

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Matthew eMcclure

2012-08-01

Full Text Available Microsatellite (MS markers have recently been used for parental verification and are still the international standard despite higher cost, error rate, and turnaround time compared with Single Nucleotide Polymorphisms (SNP-based assays. Despite domestic and international interest from producers and research communities, no viable means currently exist to verify parentage for an individual unless all familial connections were analyzed using the same DNA marker type (MS or SNP. A simple and cost-effective method was devised to impute MS alleles from SNP haplotypes within breeds. For some MS, imputation results may allow inference across breeds. A total of 347 dairy cattle representing 4 dairy breeds (Brown Swiss, Guernsey, Holstein, and Jersey were used to generate reference haplotypes. This approach has been verified (>98% accurate for imputing the International Society of Animal Genetics (ISAG recommended panel of 12 MS for cattle parentage verification across a validation set of 1,307 dairy animals.. Implementation of this method will allow producers and breed associations to transition to SNP-based parentage verification utilizing MS genotypes from historical data on parents where SNP genotypes are missing. This approach may be applicable to additional cattle breeds and other species that wish to migrate from MS- to SNP- based parental verification.

Frontiers in pulse-power-based high energy density plasma physics and its applications

International Nuclear Information System (INIS)

Horioka, Kazuhiko

2008-03-01

The papers in this volume of report were presented at the Symposium on Frontiers in Pulse-power-based High Energy Density Physics' held by National Institute for Fusion Science. The topics include the present status of high energy density plasma researches, extreme ultraviolet sources, intense radiation sources, high power ion beams, and R and D of related pulse power technologies. The 13 of the presented papers are indexed individually. (J.P.N.)

LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures.

Science.gov (United States)

Ryan, Michael; Diekhans, Mark; Lien, Stephanie; Liu, Yun; Karchin, Rachel

2009-06-01

LS-SNP/PDB is a new WWW resource for genome-wide annotation of human non-synonymous (amino acid changing) SNPs. It serves high-quality protein graphics rendered with UCSF Chimera molecular visualization software. The system is kept up-to-date by an automated, high-throughput build pipeline that systematically maps human nsSNPs onto Protein Data Bank structures and annotates several biologically relevant features. LS-SNP/PDB is available at (http://ls-snp.icm.jhu.edu/ls-snp-pdb) and via links from protein data bank (PDB) biology and chemistry tabs, UCSC Genome Browser Gene Details and SNP Details pages and PharmGKB Gene Variants Downloads/Cross-References pages.

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

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ShiGang Yu

Full Text Available 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

Imputation Accuracy from Low to Moderate Density Single Nucleotide Polymorphism Chips in a Thai Multibreed Dairy Cattle Population

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Danai Jattawa

2016-04-01

Full Text Available The objective of this study was to investigate the accuracy of imputation from low density (LDC to moderate density SNP chips (MDC in a Thai Holstein-Other multibreed dairy cattle population. Dairy cattle with complete pedigree information (n = 1,244 from 145 dairy farms were genotyped with GeneSeek GGP20K (n = 570, GGP26K (n = 540 and GGP80K (n = 134 chips. After checking for single nucleotide polymorphism (SNP quality, 17,779 SNP markers in common between the GGP20K, GGP26K, and GGP80K were used to represent MDC. Animals were divided into two groups, a reference group (n = 912 and a test group (n = 332. The SNP markers chosen for the test group were those located in positions corresponding to GeneSeek GGP9K (n = 7,652. The LDC to MDC genotype imputation was carried out using three different software packages, namely Beagle 3.3 (population-based algorithm, FImpute 2.2 (combined family- and population-based algorithms and Findhap 4 (combined family- and population-based algorithms. Imputation accuracies within and across chromosomes were calculated as ratios of correctly imputed SNP markers to overall imputed SNP markers. Imputation accuracy for the three software packages ranged from 76.79% to 93.94%. FImpute had higher imputation accuracy (93.94% than Findhap (84.64% and Beagle (76.79%. Imputation accuracies were similar and consistent across chromosomes for FImpute, but not for Findhap and Beagle. Most chromosomes that showed either high (73% or low (80% imputation accuracies were the same chromosomes that had above and below average linkage disequilibrium (LD; defined here as the correlation between pairs of adjacent SNP within chromosomes less than or equal to 1 Mb apart. Results indicated that FImpute was more suitable than Findhap and Beagle for genotype imputation in this Thai multibreed population. Perhaps additional increments in imputation accuracy could be achieved by increasing the completeness of pedigree information.

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

Science.gov (United States)

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

Construction of High Density Sweet Cherry (Prunus avium L. Linkage Maps Using Microsatellite Markers and SNPs Detected by Genotyping-by-Sequencing (GBS.

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Verónica Guajardo

Full Text Available Linkage maps are valuable tools in genetic and genomic studies. For sweet cherry, linkage maps have been constructed using mainly microsatellite markers (SSRs and, recently, using single nucleotide polymorphism markers (SNPs from a cherry 6K SNP array. Genotyping-by-sequencing (GBS, a new methodology based on high-throughput sequencing, holds great promise for identification of high number of SNPs and construction of high density linkage maps. In this study, GBS was used to identify SNPs from an intra-specific sweet cherry cross. A total of 8,476 high quality SNPs were selected for mapping. The physical position for each SNP was determined using the peach genome, Peach v1.0, as reference, and a homogeneous distribution of markers along the eight peach scaffolds was obtained. On average, 65.6% of the SNPs were present in genic regions and 49.8% were located in exonic regions. In addition to the SNPs, a group of SSRs was also used for construction of linkage maps. Parental and consensus high density maps were constructed by genotyping 166 siblings from a 'Rainier' x 'Rivedel' (Ra x Ri cross. Using Ra x Ri population, 462, 489 and 985 markers were mapped into eight linkage groups in 'Rainier', 'Rivedel' and the Ra x Ri map, respectively, with 80% of mapped SNPs located in genic regions. Obtained maps spanned 549.5, 582.6 and 731.3 cM for 'Rainier', 'Rivedel' and consensus maps, respectively, with an average distance of 1.2 cM between adjacent markers for both 'Rainier' and 'Rivedel' maps and of 0.7 cM for Ra x Ri map. High synteny and co-linearity was observed between obtained maps and with Peach v1.0. These new high density linkage maps provide valuable information on the sweet cherry genome, and serve as the basis for identification of QTLs and genes relevant for the breeding of the species.

The clinical application of single-sperm-based SNP haplotyping for PGD of osteogenesis imperfecta.

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Chen, Linjun; Diao, Zhenyu; Xu, Zhipeng; Zhou, Jianjun; Yan, Guijun; Sun, Haixiang

2018-05-15

Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder, presenting either autosomal dominant, autosomal recessive or X-linked inheritance patterns. The majority of OI cases are autosomal dominant and are caused by heterozygous mutations in either the COL1A1 or COL1A2 gene. In these dominant disorders, allele dropout (ADO) can lead to misdiagnosis in preimplantation genetic diagnosis (PGD). Polymorphic markers linked to the mutated genes have been used to establish haplotypes for identifying ADO and ensuring the accuracy of PGD. However, the haplotype of male patients cannot be determined without data from affected relatives. Here, we developed a method for single-sperm-based single-nucleotide polymorphism (SNP) haplotyping via next-generation sequencing (NGS) for the PGD of OI. After NGS, 10 informative polymorphic SNP markers located upstream and downstream of the COL1A1 gene and its pathogenic mutation site were linked to individual alleles in a single sperm from an affected male. After haplotyping, a normal blastocyst was transferred to the uterus for a subsequent frozen embryo transfer cycle. The accuracy of PGD was confirmed by amniocentesis at 19 weeks of gestation. A healthy infant weighing 4,250 g was born via vaginal delivery at the 40th week of gestation. Single-sperm-based SNP haplotyping can be applied for PGD of any monogenic disorders or de novo mutations in males in whom the haplotype of paternal mutations cannot be determined due to a lack of affected relatives. ADO: allele dropout; DI: dentinogenesis imperfect; ESHRE: European Society of Human Reproduction and Embryology; FET: frozen embryo transfer; gDNA: genomic DNA; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MDA: multiple displacement amplification; NGS: next-generation sequencing; OI: osteogenesis imperfect; PBS: phosphate buffer saline; PCR: polymerase chain reaction; PGD: preimplantation genetic diagnosis; SNP: single-nucleotide polymorphism; STR

Identification of SNP barcode biomarkers for genes associated with facial emotion perception using particle swarm optimization algorithm.

Science.gov (United States)

Chuang, Li-Yeh; Lane, Hsien-Yuan; Lin, Yu-Da; Lin, Ming-Teng; Yang, Cheng-Hong; Chang, Hsueh-Wei

2014-01-01

Facial emotion perception (FEP) can affect social function. We previously reported that parts of five tested single-nucleotide polymorphisms (SNPs) in the MET and AKT1 genes may individually affect FEP performance. However, the effects of SNP-SNP interactions on FEP performance remain unclear. This study compared patients with high and low FEP performances (n = 89 and 93, respectively). A particle swarm optimization (PSO) algorithm was used to identify the best SNP barcodes (i.e., the SNP combinations and genotypes that revealed the largest differences between the high and low FEP groups). The analyses of individual SNPs showed no significant differences between the high and low FEP groups. However, comparisons of multiple SNP-SNP interactions involving different combinations of two to five SNPs showed that the best PSO-generated SNP barcodes were significantly associated with high FEP score. The analyses of the joint effects of the best SNP barcodes for two to five interacting SNPs also showed that the best SNP barcodes had significantly higher odds ratios (2.119 to 3.138; P < 0.05) compared to other SNP barcodes. In conclusion, the proposed PSO algorithm effectively identifies the best SNP barcodes that have the strongest associations with FEP performance. This study also proposes a computational methodology for analyzing complex SNP-SNP interactions in social cognition domains such as recognition of facial emotion.

Genetic dissection of maize plant architecture with an ultra-high density bin map based on recombinant inbred lines.

Science.gov (United States)

Zhou, Zhiqiang; Zhang, Chaoshu; Zhou, Yu; Hao, Zhuanfang; Wang, Zhenhua; Zeng, Xing; Di, Hong; Li, Mingshun; Zhang, Degui; Yong, Hongjun; Zhang, Shihuang; Weng, Jianfeng; Li, Xinhai

2016-03-03

Plant architecture attributes, such as plant height, ear height, and internode number, have played an important role in the historical increases in grain yield, lodging resistance, and biomass in maize (Zea mays L.). Analyzing the genetic basis of variation in plant architecture using high density QTL mapping will be of benefit for the breeding of maize for many traits. However, the low density of molecular markers in existing genetic maps has limited the efficiency and accuracy of QTL mapping. Genotyping by sequencing (GBS) is an improved strategy for addressing a complex genome via next-generation sequencing technology. GBS has been a powerful tool for SNP discovery and high-density genetic map construction. The creation of ultra-high density genetic maps using large populations of advanced recombinant inbred lines (RILs) is an efficient way to identify QTL for complex agronomic traits. A set of 314 RILs derived from inbreds Ye478 and Qi319 were generated and subjected to GBS. A total of 137,699,000 reads with an average of 357,376 reads per individual RIL were generated, which is equivalent to approximately 0.07-fold coverage of the maize B73 RefGen_V3 genome for each individual RIL. A high-density genetic map was constructed using 4183 bin markers (100-Kb intervals with no recombination events). The total genetic distance covered by the linkage map was 1545.65 cM and the average distance between adjacent markers was 0.37 cM with a physical distance of about 0.51 Mb. Our results demonstrated a relatively high degree of collinearity between the genetic map and the B73 reference genome. The quality and accuracy of the bin map for QTL detection was verified by the mapping of a known gene, pericarp color 1 (P1), which controls the color of the cob, with a high LOD value of 80.78 on chromosome 1. Using this high-density bin map, 35 QTL affecting plant architecture, including 14 for plant height, 14 for ear height, and seven for internode number were detected

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq.

Science.gov (United States)

Wang, Jun; Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet.

A large-scale chromosome-specific SNP discovery guideline.

Science.gov (United States)

Akpinar, Bala Ani; Lucas, Stuart; Budak, Hikmet

2017-01-01

Single-nucleotide polymorphisms (SNPs) are the most prevalent type of variation in genomes that are increasingly being used as molecular markers in diversity analyses, mapping and cloning of genes, and germplasm characterization. However, only a few studies reported large-scale SNP discovery in Aegilops tauschii, restricting their potential use as markers for the low-polymorphic D genome. Here, we report 68,592 SNPs found on the gene-related sequences of the 5D chromosome of Ae. tauschii genotype MvGB589 using genomic and transcriptomic sequences from seven Ae. tauschii accessions, including AL8/78, the only genotype for which a draft genome sequence is available at present. We also suggest a workflow to compare SNP positions in homologous regions on the 5D chromosome of Triticum aestivum, bread wheat, to mark single nucleotide variations between these closely related species. Overall, the identified SNPs define a density of 4.49 SNPs per kilobyte, among the highest reported for the genic regions of Ae. tauschii so far. To our knowledge, this study also presents the first chromosome-specific SNP catalog in Ae. tauschii that should facilitate the association of these SNPs with morphological traits on chromosome 5D to be ultimately targeted for wheat improvement.

Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein (HDL) in an asymptomatic Brazilian population.

Science.gov (United States)

Zago, V H S; Scherrer, D Z; Parra, E S; Panzoldo, N B; Alexandre, F; Nakandakare, E R; Quintão, E C R; de Faria, E C

2015-03-01

ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high-density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to investigate the relationships of SNP rs1893590 with plasma lipids and lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and normolipidemic volunteers from both genders. Clinical and anthropometrical data were taken and blood samples were drawn after 12 h fasting. Plasma lipids and lipoproteins, as well as HDL particle size and volume were determined. Genomic DNA was isolated for SNP rs1893590 detection by TaqMan(®) OpenArray(®) Real-Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way ANOVA were the used statistical tests. No significant differences were found in the comparison analyses between the allele groups for all studied parameters. Conversely, significant interactions were observed between SNP and age over plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C (p = 0.048). Similar results were observed in the group with body mass index (BMI) m(2), where volunteers with AA genotype had higher HDL-C levels (p = 0.0034), plus an increased HDL particle size (p = 0.01). These findings indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under asymptomatic clinical conditions in an age and BMI dependent way.

A SNP-centric database for the investigation of the human genome

Directory of Open Access Journals (Sweden)

Kohane Isaac S

2004-03-01

Full Text Available Abstract Background Single Nucleotide Polymorphisms (SNPs are an increasingly important tool for genetic and biomedical research. Although current genomic databases contain information on several million SNPs and are growing at a very fast rate, the true value of a SNP in this context is a function of the quality of the annotations that characterize it. Retrieving and analyzing such data for a large number of SNPs often represents a major bottleneck in the design of large-scale association studies. Description SNPper is a web-based application designed to facilitate the retrieval and use of human SNPs for high-throughput research purposes. It provides a rich local database generated by combining SNP data with the Human Genome sequence and with several other data sources, and offers the user a variety of querying, visualization and data export tools. In this paper we describe the structure and organization of the SNPper database, we review the available data export and visualization options, and we describe how the architecture of SNPper and its specialized data structures support high-volume SNP analysis. Conclusions The rich annotation database and the powerful data manipulation and presentation facilities it offers make SNPper a very useful online resource for SNP research. Its success proves the great need for integrated and interoperable resources in the field of computational biology, and shows how such systems may play a critical role in supporting the large-scale computational analysis of our genome.

The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease

NARCIS (Netherlands)

Clee, S. M.; Loubser, O.; Collins, J.; Kastelein, J. J.; Hayden, M. R.

2001-01-01

Linkage of the lipoprotein lipase (LPL) gene to blood pressure levels has been reported. The LPL S447X single nucleotide polymorphism (cSNP) has been associated with decreased triglycerides (TG), increased high density lipoprotein cholesterol, and a decreased risk of coronary artery disease (CAD),

SNPServer: a real-time SNP discovery tool.

Science.gov (United States)

Savage, David; Batley, Jacqueline; Erwin, Tim; Logan, Erica; Love, Christopher G; Lim, Geraldine A C; Mongin, Emmanuel; Barker, Gary; Spangenberg, German C; Edwards, David

2005-07-01

SNPServer is a real-time flexible tool for the discovery of SNPs (single nucleotide polymorphisms) within DNA sequence data. The program uses BLAST, to identify related sequences, and CAP3, to cluster and align these sequences. The alignments are parsed to the SNP discovery software autoSNP, a program that detects SNPs and insertion/deletion polymorphisms (indels). Alternatively, lists of related sequences or pre-assembled sequences may be entered for SNP discovery. SNPServer and autoSNP use redundancy to differentiate between candidate SNPs and sequence errors. For each candidate SNP, two measures of confidence are calculated, the redundancy of the polymorphism at a SNP locus and the co-segregation of the candidate SNP with other SNPs in the alignment. SNPServer is available at http://hornbill.cspp.latrobe.edu.au/snpdiscovery.html.

Series asymmetric supercapacitors based on free-standing inner-connection electrodes for high energy density and high output voltage

Science.gov (United States)

Tao, Jiayou; Liu, Nishuang; Rao, Jiangyu; Ding, Longwei; Al Bahrani, Majid Raissan; Li, Luying; Su, Jun; Gao, Yihua

2014-11-01

Asymmetric supercapacitors (ASCs) based on free-standing membranes with high energy density and high output voltage are reported. MnO2 nanowire/carbon nanotube (CNT) composites and MoO3 nanobelt/CNT composites are selected as the anode and the cathode materials of the devices, respectively. The ASC has a high volumetric capacitance of 50.2 F cm-3 at a scan rate of 2 mV s-1 and a high operation voltage window of 2.0 V. Especially, after a middle layer with an inner-connection structure was inserted between the anode and the cathode, the output voltage of the whole device can achieve 4.0 V. The full cell of series ASCs (SASC) with an inner-connection middle layer has a high energy density of 28.6 mW h cm-3 at a power density of 261.4 mW cm-3, and exhibits excellent cycling performance of 99.6% capacitance retention over 10 000 cycles. This strategy of designing the hybridized structure for SASCs provides a promising route for next-generation SCs with high energy density and high output voltage.Asymmetric supercapacitors (ASCs) based on free-standing membranes with high energy density and high output voltage are reported. MnO2 nanowire/carbon nanotube (CNT) composites and MoO3 nanobelt/CNT composites are selected as the anode and the cathode materials of the devices, respectively. The ASC has a high volumetric capacitance of 50.2 F cm-3 at a scan rate of 2 mV s-1 and a high operation voltage window of 2.0 V. Especially, after a middle layer with an inner-connection structure was inserted between the anode and the cathode, the output voltage of the whole device can achieve 4.0 V. The full cell of series ASCs (SASC) with an inner-connection middle layer has a high energy density of 28.6 mW h cm-3 at a power density of 261.4 mW cm-3, and exhibits excellent cycling performance of 99.6% capacitance retention over 10 000 cycles. This strategy of designing the hybridized structure for SASCs provides a promising route for next-generation SCs with high energy density and high

FunctSNP: an R package to link SNPs to functional knowledge and dbAutoMaker: a suite of Perl scripts to build SNP databases

Directory of Open Access Journals (Sweden)

Watson-Haigh Nathan S

2010-06-01

Full Text Available Abstract Background Whole genome association studies using highly dense single nucleotide polymorphisms (SNPs are a set of methods to identify DNA markers associated with variation in a particular complex trait of interest. One of the main outcomes from these studies is a subset of statistically significant SNPs. Finding the potential biological functions of such SNPs can be an important step towards further use in human and agricultural populations (e.g., for identifying genes related to susceptibility to complex diseases or genes playing key roles in development or performance. The current challenge is that the information holding the clues to SNP functions is distributed across many different databases. Efficient bioinformatics tools are therefore needed to seamlessly integrate up-to-date functional information on SNPs. Many web services have arisen to meet the challenge but most work only within the framework of human medical research. Although we acknowledge the importance of human research, we identify there is a need for SNP annotation tools for other organisms. Description We introduce an R package called FunctSNP, which is the user interface to custom built species-specific databases. The local relational databases contain SNP data together with functional annotations extracted from online resources. FunctSNP provides a unified bioinformatics resource to link SNPs with functional knowledge (e.g., genes, pathways, ontologies. We also introduce dbAutoMaker, a suite of Perl scripts, which can be scheduled to run periodically to automatically create/update the customised SNP databases. We illustrate the use of FunctSNP with a livestock example, but the approach and software tools presented here can be applied also to human and other organisms. Conclusions Finding the potential functional significance of SNPs is important when further using the outcomes from whole genome association studies. FunctSNP is unique in that it is the only R

Typing of 48 autosomal SNPs and amelogenin with GenPlex SNP genotyping system in forensic genetics

DEFF Research Database (Denmark)

Tomas Mas, Carmen; Stangegaard, Michael; Børsting, Claus

2008-01-01

, Somalia and Greenland were investigated with GenPlex using a Biomek 3000 (Beckman Coulter) robot. The results were compared to results obtained with an ISO 17025 accredited SNP typing assay based on single base extension (SBE). With the GenPlex SNP genotyping system, full SNP profiles were obtained in 97.......6% of the investigations. Perfect concordance was obtained in duplicate investigations and the SNP genotypes obtained with the GenPlex system were concordant with those of the accredited SBE based SNP typing system except for one result in rs901398 in one of 286 individuals most likely due to a mutation 6 bp downstream...

Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol.

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Dhanasekaran Bodhini

Full Text Available Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R and Transcription Factor 7-Like 2 (TCF7L2 gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP (rs17782313 and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146 and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT (n = 821 and participants with type 2 diabetes (T2D (n = 861 recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES. A validated food frequency questionnaire (FFQ was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day (Pinteraction = 0.0001 on high-density lipoprotein cholesterol (HDL-C, where the 'T' allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008 and those in the highest tertile (P = 0.017 had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day (Pinteraction<0.0001 on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024 and those in the highest PUFA tertile had lower HDL-C (P = 0.028 than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day on HDL

Genome-wide SNP identification in multiple morphotypes of allohexaploid tall fescue (Festuca arundinacea Schreb

Directory of Open Access Journals (Sweden)

Hand Melanie L

2012-06-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs provide essential tools for the advancement of research in plant genomics, and the development of SNP resources for many species has been accelerated by the capabilities of second-generation sequencing technologies. The current study aimed to develop and use a novel bioinformatic pipeline to generate a comprehensive collection of SNP markers within the agriculturally important pasture grass tall fescue; an outbreeding allopolyploid species displaying three distinct morphotypes: Continental, Mediterranean and rhizomatous. Results A bioinformatic pipeline was developed that successfully identified SNPs within genotypes from distinct tall fescue morphotypes, following the sequencing of 414 polymerase chain reaction (PCR – generated amplicons using 454 GS FLX technology. Equivalent amplicon sets were derived from representative genotypes of each morphotype, including six Continental, five Mediterranean and one rhizomatous. A total of 8,584 and 2,292 SNPs were identified with high confidence within the Continental and Mediterranean morphotypes respectively. The success of the bioinformatic approach was demonstrated through validation (at a rate of 70% of a subset of 141 SNPs using both SNaPshot™ and GoldenGate™ assay chemistries. Furthermore, the quantitative genotyping capability of the GoldenGate™ assay revealed that approximately 30% of the putative SNPs were accessible to co-dominant scoring, despite the hexaploid genome structure. The sub-genome-specific origin of each SNP validated from Continental tall fescue was predicted using a phylogenetic approach based on comparison with orthologous sequences from predicted progenitor species. Conclusions Using the appropriate bioinformatic approach, amplicon resequencing based on 454 GS FLX technology is an effective method for the identification of polymorphic SNPs within the genomes of Continental and Mediterranean tall fescue. The

RASSF1A and the rs2073498 Cancer Associated SNP

International Nuclear Information System (INIS)

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.

Weavable, Conductive Yarn-Based NiCo//Zn Textile Battery with High Energy Density and Rate Capability.

Science.gov (United States)

Huang, Yan; Ip, Wing Shan; Lau, Yuen Ying; Sun, Jinfeng; Zeng, Jie; Yeung, Nga Sze Sea; Ng, Wing Sum; Li, Hongfei; Pei, Zengxia; Xue, Qi; Wang, Yukun; Yu, Jie; Hu, Hong; Zhi, Chunyi

2017-09-26

With intrinsic safety and much higher energy densities than supercapacitors, rechargeable nickel/cobalt-zinc-based textile batteries are promising power sources for next generation personalized wearable electronics. However, high-performance wearable nickel/cobalt-zinc-based batteries are rarely reported because there is a lack of industrially weavable and knittable highly conductive yarns. Here, we use scalably produced highly conductive yarns uniformly covered with zinc (as anode) and nickel cobalt hydroxide nanosheets (as cathode) to fabricate rechargeable yarn batteries. They possess a battery level capacity and energy density, as well as a supercapacitor level power density. They deliver high specific capacity of 5 mAh cm -3 and energy densities of 0.12 mWh cm -2 and 8 mWh cm -3 (based on the whole solid battery). They exhibit ultrahigh rate capabilities of 232 C (liquid electrolyte) and 116 C (solid electrolyte), which endows the batteries excellent power densities of 32.8 mW cm -2 and 2.2 W cm -3 (based on the whole solid battery). These are among the highest values reported so far. A wrist band battery is further constructed by using a large conductive cloth woven from the conductive yarns by a commercial weaving machine. It powers various electronic devices successfully, enabling dual functions of wearability and energy storage.

Conclusive evidence for hexasomic inheritance in chrysanthemum based on analysis of a 183 k SNP array.

Science.gov (United States)

van Geest, Geert; Voorrips, Roeland E; Esselink, Danny; Post, Aike; Visser, Richard Gf; Arens, Paul

2017-08-07

Cultivated chrysanthemum is an outcrossing hexaploid (2n = 6× = 54) with a disputed mode of inheritance. In this paper, we present a single nucleotide polymorphism (SNP) selection pipeline that was used to design an Affymetrix Axiom array with 183 k SNPs from RNA sequencing data (1). With this array, we genotyped four bi-parental populations (with sizes of 405, 53, 76 and 37 offspring plants respectively), and a cultivar panel of 63 genotypes. Further, we present a method for dosage scoring in hexaploids from signal intensities of the array based on mixture models (2) and validation of selection steps in the SNP selection pipeline (3). The resulting genotypic data is used to draw conclusions on the mode of inheritance in chrysanthemum (4), and to make an inference on allelic expression bias (5). With use of the mixture model approach, we successfully called the dosage of 73,936 out of 183,130 SNPs (40.4%) that segregated in any of the bi-parental populations. To investigate the mode of inheritance, we analysed markers that segregated in the large bi-parental population (n = 405). Analysis of segregation of duplex x nulliplex SNPs resulted in evidence for genome-wide hexasomic inheritance. This evidence was substantiated by the absence of strong linkage between markers in repulsion, which indicated absence of full disomic inheritance. We present the success rate of SNP discovery out of RNA sequencing data as affected by different selection steps, among which SNP coverage over genotypes and use of different types of sequence read mapping software. Genomic dosage highly correlated with relative allele coverage from the RNA sequencing data, indicating that most alleles are expressed according to their genomic dosage. The large population, genotyped with a very large number of markers, is a unique framework for extensive genetic analyses in hexaploid chrysanthemum. As starting point, we show conclusive evidence for genome-wide hexasomic inheritance.

Using SNP array to identify aneuploidy and segmental imbalance in translocation carriers

Directory of Open Access Journals (Sweden)

B. Xiong

2014-12-01

In addition to genetic testing techniques, the embryo biopsy stage (polar body, cleavage embryo or blastocyst and the mode of embryo transfer (fresh or frozen embryos can affect the outcome of PGD. It is now generally recommended that blastomere biopsy should be replaced by blastocyst biopsy to avoid a high mosaic rate and biopsy-related damage to cleavage-stage embryos, which might affect embryo development. However, more clinical data are required to confirm that the technique of SNP array-based PGD (SNP-PGD combined with trophectoderm (TE biopsy and frozen embryo transfer (FET is superior to traditional FISH-PGD combined with Day 3 (D3 blastomere biopsy and fresh embryo transfer.

MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients

Science.gov (United States)

Deben, Christophe; Op de Beeck, Ken; Van den Bossche, Jolien; Jacobs, Julie; Lardon, Filip; Wouters, An; Peeters, Marc; Van Camp, Guy; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

2017-01-01

Objectives: Two functional polymorphisms in the MDM2 promoter region, SNP309T>G and SNP285G>C, have been shown to impact MDM2 expression and cancer risk. Currently available data on the prognostic value of MDM2 SNP309 in non-small cell lung cancer (NSCLC) is contradictory and unavailable for SNP285. The goal of this study was to clarify the role of these MDM2 SNPs in the outcome of NSCLC patients. Materials and Methods: In this study we genotyped SNP309 and SNP285 in 98 NSCLC adenocarcinoma patients and determined MDM2 mRNA and protein levels. In addition, we assessed the prognostic value of these common SNPs on overall and progression free survival, taking into account the TP53 status of the tumor. Results and Conclusion: We found that the SNP285C allele, but not the SNP309G allele, was significantly associated with increased MDM2 mRNA expression levels (p = 0.025). However, we did not observe an association with MDM2 protein levels for SNP285. The SNP309G allele was significantly associated with the presence of wild type TP53 (p = 0.047) and showed a strong trend towards increased MDM2 protein levels (p = 0.068). In addition, patients harboring the SNP309G allele showed a worse overall survival, but only in the presence of wild type TP53. The SNP285C allele was significantly associated with an early age of diagnosis and metastasis. Additionally, the SNP285C allele acted as an independent predictor for worse progression free survival (HR = 3.97; 95% CI = 1.51 - 10.42; p = 0.005). Our data showed that both SNP309 (in the presence of wild type TP53) and SNP285 act as negative prognostic markers for NSCLC patients, implicating a prominent role for these variants in the outcome of these patients. PMID:28819417

Ultra-high Density SNParray in Neuroblastoma Molecular Diagnostics

Directory of Open Access Journals (Sweden)

Inge M. Ambros

2014-08-01

Full Text Available Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e. amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses: so called segmental chromosomal aberrations, i.e. gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as chromothripsis are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism (SNP arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

Ascertainment biases in SNP chips affect measures of population divergence

DEFF Research Database (Denmark)

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

2010-01-01

Chip-based high-throughput genotyping has facilitated genome-wide studies of genetic diversity. Many studies have utilized these large data sets to make inferences about the demographic history of human populations using measures of genetic differentiation such as F(ST) or principal component...... on direct sequencing. In addition, we also analyze publicly available genome-wide data. We demonstrate that the ascertainment biases will distort measures of human diversity and possibly change conclusions drawn from these measures in some times unexpected ways. We also show that details of the genotyping...... analyses. However, the single nucleotide polymorphism (SNP) chip data suffer from ascertainment biases caused by the SNP discovery process in which a small number of individuals from selected populations are used as discovery panels. In this study, we investigate the effect of the ascertainment bias...

UPD detection using homozygosity profiling with a SNP genotyping microarray.

Science.gov (United States)

Papenhausen, Peter; Schwartz, Stuart; Risheg, Hiba; Keitges, Elisabeth; Gadi, Inder; Burnside, Rachel D; Jaswaney, Vikram; Pappas, John; Pasion, Romela; Friedman, Kenneth; Tepperberg, James

2011-04-01

Single nucleotide polymorphism (SNP) based chromosome microarrays provide both a high-density whole genome analysis of copy number and genotype. In the past 21 months we have analyzed over 13,000 samples primarily referred for developmental delay using the Affymetrix SNP/CN 6.0 version array platform. In addition to copy number, we have focused on the relative distribution of allele homozygosity (HZ) throughout the genome to confirm a strong association of uniparental disomy (UPD) with regions of isoallelism found in most confirmed cases of UPD. We sought to determine whether a long contiguous stretch of HZ (LCSH) greater than a threshold value found only in a single chromosome would correlate with UPD of that chromosome. Nine confirmed UPD cases were retrospectively analyzed with the array in the study, each showing the anticipated LCSH with the smallest 13.5 Mb in length. This length is well above the average longest run of HZ in a set of control patients and was then set as the prospective threshold for reporting possible UPD correlation. Ninety-two cases qualified at that threshold, 46 of those had molecular UPD testing and 29 were positive. Including retrospective cases, 16 showed complete HZ across the chromosome, consistent with total isoUPD. The average size LCSH in the 19 cases that were not completely HZ was 46.3 Mb with a range of 13.5-127.8 Mb. Three patients showed only segmental UPD. Both the size and location of the LCSH are relevant to correlation with UPD. Further studies will continue to delineate an optimal threshold for LCSH/UPD correlation. Copyright © 2011 Wiley-Liss, Inc.

Performance of the SNPforID 52 SNP-plex assay in paternity testing

DEFF Research Database (Denmark)

Børsting, Claus; Sanchez, Juan Jose; Hansen, Hanna E

2008-01-01

(VNTRs). The typical PIs based on 15 STRs or seven VNTRs were 5-50 times higher than the typical PIs based on 52 SNPs. Six mutations in tandem repeats were detected among the randomly selected trios. In contrast, there was not found any mutations in the SNP loci. The results showed that the 52 SNP...

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

Science.gov (United States)

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. © 2012 Blackwell Publishing Ltd/University College London.

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

Science.gov (United States)

Hall, Michael J; Ruth, Karen J; Chen, David Yt; Gross, Laura M; Giri, Veda N

2015-01-01

Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population. Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy. Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016). Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

Heterogeneous computing architecture for fast detection of SNP-SNP interactions.

Science.gov (United States)

Sluga, Davor; Curk, Tomaz; Zupan, Blaz; Lotric, Uros

2014-06-25

The extent of data in a typical genome-wide association study (GWAS) poses considerable computational challenges to software tools for gene-gene interaction discovery. Exhaustive evaluation of all interactions among hundreds of thousands to millions of single nucleotide polymorphisms (SNPs) may require weeks or even months of computation. Massively parallel hardware within a modern Graphic Processing Unit (GPU) and Many Integrated Core (MIC) coprocessors can shorten the run time considerably. While the utility of GPU-based implementations in bioinformatics has been well studied, MIC architecture has been introduced only recently and may provide a number of comparative advantages that have yet to be explored and tested. We have developed a heterogeneous, GPU and Intel MIC-accelerated software module for SNP-SNP interaction discovery to replace the previously single-threaded computational core in the interactive web-based data exploration program SNPsyn. We report on differences between these two modern massively parallel architectures and their software environments. Their utility resulted in an order of magnitude shorter execution times when compared to the single-threaded CPU implementation. GPU implementation on a single Nvidia Tesla K20 runs twice as fast as that for the MIC architecture-based Xeon Phi P5110 coprocessor, but also requires considerably more programming effort. General purpose GPUs are a mature platform with large amounts of computing power capable of tackling inherently parallel problems, but can prove demanding for the programmer. On the other hand the new MIC architecture, albeit lacking in performance reduces the programming effort and makes it up with a more general architecture suitable for a wider range of problems.

dbSNP

Data.gov (United States)

U.S. Department of Health & Human Services — dbSNP is a database of single nucleotide polymorphisms (SNPs) and multiple small-scale variations that include insertions/deletions, microsatellites, and...

Novel density-based and hierarchical density-based clustering algorithms for uncertain data.

Science.gov (United States)

Zhang, Xianchao; Liu, Han; Zhang, Xiaotong

2017-09-01

Uncertain data has posed a great challenge to traditional clustering algorithms. Recently, several algorithms have been proposed for clustering uncertain data, and among them density-based techniques seem promising for handling data uncertainty. However, some issues like losing uncertain information, high time complexity and nonadaptive threshold have not been addressed well in the previous density-based algorithm FDBSCAN and hierarchical density-based algorithm FOPTICS. In this paper, we firstly propose a novel density-based algorithm PDBSCAN, which improves the previous FDBSCAN from the following aspects: (1) it employs a more accurate method to compute the probability that the distance between two uncertain objects is less than or equal to a boundary value, instead of the sampling-based method in FDBSCAN; (2) it introduces new definitions of probability neighborhood, support degree, core object probability, direct reachability probability, thus reducing the complexity and solving the issue of nonadaptive threshold (for core object judgement) in FDBSCAN. Then, we modify the algorithm PDBSCAN to an improved version (PDBSCANi), by using a better cluster assignment strategy to ensure that every object will be assigned to the most appropriate cluster, thus solving the issue of nonadaptive threshold (for direct density reachability judgement) in FDBSCAN. Furthermore, as PDBSCAN and PDBSCANi have difficulties for clustering uncertain data with non-uniform cluster density, we propose a novel hierarchical density-based algorithm POPTICS by extending the definitions of PDBSCAN, adding new definitions of fuzzy core distance and fuzzy reachability distance, and employing a new clustering framework. POPTICS can reveal the cluster structures of the datasets with different local densities in different regions better than PDBSCAN and PDBSCANi, and it addresses the issues in FOPTICS. Experimental results demonstrate the superiority of our proposed algorithms over the existing

Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

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Yadav Sapkota

Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

High power density reactors based on direct cooled particle beds

Science.gov (United States)

Powell, J. R.; Horn, F. L.

Reactors based on direct cooled High Temperature Gas Cooled Reactor (HTGR) type particle fuel are described. The small diameter particle fuel is packed between concentric porous cylinders to make annular fuel elements, with the inlet coolant gas flowing inwards. Hot exit gas flows out along the central channel of each element. Because of the very large heat transfer area in the packed beds, power densities in particle bed reactors (PBRs) are extremely high resulting in compact, lightweight systems. Coolant exit temperatures are high, because of the ceramic fuel temperature capabilities, and the reactors can be ramped to full power and temperature very rapidly. PBR systems can generate very high burst power levels using open cycle hydrogen coolant, or high continuous powers using closed cycle helium coolant. PBR technology is described and development requirements assessed.

Application of LogitBoost Classifier for Traceability Using SNP Chip Data.

Science.gov (United States)

Kim, Kwondo; Seo, Minseok; Kang, Hyunsung; Cho, Seoae; Kim, Heebal; Seo, Kang-Seok

2015-01-01

Consumer attention to food safety has increased rapidly due to animal-related diseases; therefore, it is important to identify their places of origin (POO) for safety purposes. However, only a few studies have addressed this issue and focused on machine learning-based approaches. In the present study, classification analyses were performed using a customized SNP chip for POO prediction. To accomplish this, 4,122 pigs originating from 104 farms were genotyped using the SNP chip. Several factors were considered to establish the best prediction model based on these data. We also assessed the applicability of the suggested model using a kinship coefficient-filtering approach. Our results showed that the LogitBoost-based prediction model outperformed other classifiers in terms of classification performance under most conditions. Specifically, a greater level of accuracy was observed when a higher kinship-based cutoff was employed. These results demonstrated the applicability of a machine learning-based approach using SNP chip data for practical traceability.

Development and evaluation of the first high-throughput SNP array for common carp (Cyprinus carpio).

Science.gov (United States)

Xu, Jian; Zhao, Zixia; Zhang, Xiaofeng; Zheng, Xianhu; Li, Jiongtang; Jiang, Yanliang; Kuang, Youyi; Zhang, Yan; Feng, Jianxin; Li, Chuangju; Yu, Juhua; Li, Qiang; Zhu, Yuanyuan; Liu, Yuanyuan; Xu, Peng; Sun, Xiaowen

2014-04-24

A large number of single nucleotide polymorphisms (SNPs) have been identified in common carp (Cyprinus carpio) but, as yet, no high-throughput genotyping platform is available for this species. C. carpio is an important aquaculture species that accounts for nearly 14% of freshwater aquaculture production worldwide. We have developed an array for C. carpio with 250,000 SNPs and evaluated its performance using samples from various strains of C. carpio. The SNPs used on the array were selected from two resources: the transcribed sequences from RNA-seq data of four strains of C. carpio, and the genome re-sequencing data of five strains of C. carpio. The 250,000 SNPs on the resulting array are distributed evenly across the reference C.carpio genome with an average spacing of 6.6 kb. To evaluate the SNP array, 1,072 C. carpio samples were collected and tested. Of the 250,000 SNPs on the array, 185,150 (74.06%) were found to be polymorphic sites. Genotyping accuracy was checked using genotyping data from a group of full-siblings and their parents, and over 99.8% of the qualified SNPs were found to be reliable. Analysis of the linkage disequilibrium on all samples and on three domestic C.carpio strains revealed that the latter had the longer haplotype blocks. We also evaluated our SNP array on 80 samples from eight species related to C. carpio, with from 53,526 to 71,984 polymorphic SNPs. An identity by state analysis divided all the samples into three clusters; most of the C. carpio strains formed the largest cluster. The Carp SNP array described here is the first high-throughput genotyping platform for C. carpio. Our evaluation of this array indicates that it will be valuable for farmed carp and for genetic and population biology studies in C. carpio and related species.

SNP discovery and High Resolution Melting Analysis from massive transcriptome sequencing in the California red abalone Haliotis rufescens.

Science.gov (United States)

Valenzuela-Muñoz, Valentina; Araya-Garay, José Miguel; Gallardo-Escárate, Cristian

2013-06-01

The California red abalone, Haliotis rufescens that belongs to the Haliotidae family, is the largest species of abalone in the world that has sustained the major fishery and aquaculture production in the USA and Mexico. This native mollusk has not been evaluated or assigned a conservation category even though in the last few decades it was heavily exploited until it disappeared in some areas along the California coast. In Chile, the red abalone was introduced in the 1970s from California wild abalone stocks for the purposes of aquaculture. Considering the number of years that the red abalone has been cultivated in Chile crucial genetic information is scarce and critical issues remain unresolved. This study reports and validates novel single nucleotide polymorphisms (SNP) markers for the red abalone H. rufescens using cDNA pyrosequencing. A total of 622 high quality SNPs were identified in 146 sequences with an estimated frequency of 1 SNP each 1000bp. Forty-five SNPs markers with functional information for gene ontology were selected. Of these, 8 were polymorphic among the individuals screened: Heat shock protein 70 (HSP70), vitellogenin (VTG), lysin, alginate lyase enzyme (AL), Glucose-regulated protein 94 (GRP94), fructose-bisphosphate aldolase (FBA), sulfatase 1A precursor (S1AP) and ornithine decarboxylase antizyme (ODC). Two additional sequences were also identified with polymorphisms but no similarities with known proteins were achieved. To validate the putative SNP markers, High Resolution Melting Analysis (HRMA) was conducted in a wild and hatchery-bred population. Additionally, SNP cross-amplifications were tested in two further native abalone species, Haliotis fulgens and Haliotis corrugata. This study provides novel candidate genes that could be used to evaluate loss of genetic diversity due to hatchery selection or inbreeding effects. Copyright © 2013 Elsevier B.V. All rights reserved.

New Insights on Water Buffalo Genomic Diversity and Post-Domestication Migration Routes From Medium Density SNP Chip Data

Directory of Open Access Journals (Sweden)

Licia Colli

2018-03-01

Full Text Available The domestic water buffalo is native to the Asian continent but through historical migrations and recent importations, nowadays has a worldwide distribution. The two types of water buffalo, i.e., river and swamp, display distinct morphological and behavioral traits, different karyotypes and also have different purposes and geographical distributions. River buffaloes from Pakistan, Iran, Turkey, Egypt, Romania, Bulgaria, Italy, Mozambique, Brazil and Colombia, and swamp buffaloes from China, Thailand, Philippines, Indonesia and Brazil were genotyped with a species-specific medium-density 90K SNP panel. We estimated the levels of molecular diversity and described population structure, which revealed historical relationships between populations and migration events. Three distinct gene pools were identified in pure river as well as in pure swamp buffalo populations. Genomic admixture was seen in the Philippines and in Brazil, resulting from importations of animals for breed improvement. Our results were largely consistent with previous archeological, historical and molecular-based evidence for two independent domestication events for river- and swamp-type buffaloes, which occurred in the Indo-Pakistani region and close to the China/Indochina border, respectively. Based on a geographical analysis of the distribution of diversity, our evidence also indicated that the water buffalo spread out of the domestication centers followed two major divergent migration directions: river buffaloes migrated west from the Indian sub-continent while swamp buffaloes migrated from northern Indochina via an east-south-eastern route. These data suggest that the current distribution of water buffalo diversity has been shaped by the combined effects of multiple migration events occurred at different stages of the post-domestication history of the species.

Compression and fast retrieval of SNP data.

Science.gov (United States)

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

2014-11-01

The increasing interest in rare genetic variants and epistatic genetic effects on complex phenotypic traits is currently pushing genome-wide association study design towards datasets of increasing size, both in the number of studied subjects and in the number of genotyped single nucleotide polymorphisms (SNPs). This, in turn, is leading to a compelling need for new methods for compression and fast retrieval of SNP data. We present a novel algorithm and file format for compressing and retrieving SNP data, specifically designed for large-scale association studies. Our algorithm is based on two main ideas: (i) compress linkage disequilibrium blocks in terms of differences with a reference SNP and (ii) compress reference SNPs exploiting information on their call rate and minor allele frequency. Tested on two SNP datasets and compared with several state-of-the-art software tools, our compression algorithm is shown to be competitive in terms of compression rate and to outperform all tools in terms of time to load compressed data. Our compression and decompression algorithms are implemented in a C++ library, are released under the GNU General Public License and are freely downloadable from http://www.dei.unipd.it/~sambofra/snpack.html. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Snap: an integrated SNP annotation platform

DEFF Research Database (Denmark)

Li, Shengting; Ma, Lijia; Li, Heng

2007-01-01

Snap (Single Nucleotide Polymorphism Annotation Platform) is a server designed to comprehensively analyze single genes and relationships between genes basing on SNPs in the human genome. The aim of the platform is to facilitate the study of SNP finding and analysis within the framework of medical...

High power density reactors based on direct cooled particle beds

International Nuclear Information System (INIS)

Powell, J.R.; Horn, F.L.

1985-01-01

Reactors based on direct cooled HTGR type particle fuel are described. The small diameter particle fuel is packed between concentric porous cylinders to make annular fuel elements, with the inlet coolant gas flowing inwards. Hot exit gas flows out long the central channel of each element. Because of the very large heat transfer area in the packed beds, power densities in particle bed reactors (PBR's) are extremely high resulting in compact, lightweight systems. Coolant exit temperatures are high, because of the ceramic fuel temperature capabilities, and the reactors can be ramped to full power and temperature very rapidly. PBR systems can generate very high burst power levels using open cycle hydrogen coolant, or high continuous powers using closed cycle helium coolant. PBR technology is described and development requirements assessed. 12 figs

Activated Biomass-derived Graphene-based Carbons for Supercapacitors with High Energy and Power Density.

Science.gov (United States)

Jung, SungHoon; Myung, Yusik; Kim, Bit Na; Kim, In Gyoo; You, In-Kyu; Kim, TaeYoung

2018-01-30

Here, we present a facile and low-cost method to produce hierarchically porous graphene-based carbons from a biomass source. Three-dimensional (3D) graphene-based carbons were produced through continuous sequential steps such as the formation and transformation of glucose-based polymers into 3D foam-like structures and their subsequent carbonization to form the corresponding macroporous carbons with thin graphene-based carbon walls of macropores and intersectional carbon skeletons. Physical and chemical activation was then performed on this carbon to create micro- and meso-pores, thereby producing hierarchically porous biomass-derived graphene-based carbons with a high Brunauer-Emmett-Teller specific surface area of 3,657 m 2  g -1 . Owing to its exceptionally high surface area, interconnected hierarchical pore networks, and a high degree of graphitization, this carbon exhibited a high specific capacitance of 175 F g -1 in ionic liquid electrolyte. A supercapacitor constructed with this carbon yielded a maximum energy density of 74 Wh kg -1 and a maximum power density of 408 kW kg -1 , based on the total mass of electrodes, which is comparable to those of the state-of-the-art graphene-based carbons. This approach holds promise for the low-cost and readily scalable production of high performance electrode materials for supercapacitors.

Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

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Calus Mario PL

2011-10-01

Full Text Available Abstract 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

Whole-genome single-nucleotide polymorphism (SNP marker discovery and association analysis with the eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA content in Larimichthys crocea

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Shijun Xiao

2016-12-01

Full Text Available Whole-genome single-nucleotide polymorphism (SNP markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms.

Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

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Aung H. Naing

2017-11-01

Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

Robust Demographic Inference from Genomic and SNP Data

Science.gov (United States)

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

2013-01-01

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

snpTree - a web-server to identify and construct SNP trees from whole genome sequence data

DEFF Research Database (Denmark)

Leekitcharoenphon, Pimlapas; Kaas, Rolf Sommer; Thomsen, Martin Christen Frølund

2012-01-01

identify SNPs and construct phylogenetic trees from WGS as well as from assembled genomes or contigs. WGS data in fastq format are aligned to reference genomes by BWA while contigs in fasta format are processed by Nucmer. SNPs are concatenated based on position on reference genome and a tree is constructed...... to differentiate and classify isolates. One of the successfully and broadly used methods is analysis of single nucletide polymorphisms (SNPs). Currently, there are different tools and methods to identify SNPs including various options and cut-off values. Furthermore, all current methods require bioinformatic...... skills. Thus, we lack a standard and simple automatic tool to determine SNPs and construct phylogenetic tree from WGS data. Results Here we introduce snpTree, a server for online-automatic SNPs analysis. This tool is composed of different SNPs analysis suites, perl and python scripts. snpTree can...

Marcadores SNP: conceitos básicos, aplicações no manejo e no melhoramento animal e perspectivas para o futuro SNP markers: basic concepts, applications in animal breeding and management and perspectives for the future

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Alexandre Rodrigues Caetano

2009-07-01

molecular markers to characterize genetic resources and generate tools for animal breeding and management date from the end of the 80s. In the last 20 years the technologies to generate molecular data went through several innovation cycles. The last wave of technological innovations represents a true revolution, bringing methods to identify and genotype SNP (Single Nucleotide Polymorphism markers in large scale. High density DNA chips were generated to genotype from tens of thousands to hundreds of thousands of SNPs in a single assay. Furthermore, other medium density technologies allow for the genotyping of tens to hundreds of makers, in high numbers of samples, with very high speed and automation. These new technologies allowed for the generation of new applications, such as the methods to genetically evaluate and select animals based on their Genomic Value (Genomic Estimated Breeding Value - GEBV. The statistical methods for genomic evaluation and selection are in full development, but the technology already became reality with the release of the first bull summary for the Holstein breed with GEBVs for milk production and quality traits in January 2009. In addition, these technologies brought new options for development of diagnostic tests for paternity testing, individual identification, traceability, etc. Also, these new technologies to genotype SNP markers facilitated the development of outsourcing companies to generate molecular data, allowing any group to conduct advanced experiments, always using the most advanced technologies, without the need of investments into equipment.

A set of 14 DIP-SNP markers to detect unbalanced DNA mixtures.

Science.gov (United States)

Liu, Zhizhen; Liu, Jinding; Wang, Jiaqi; Chen, Deqing; Liu, Zidong; Shi, Jie; Li, Zeqin; Li, Wenyan; Zhang, Gengqian; Du, Bing

2018-03-04

Unbalanced DNA mixture is still a difficult problem for forensic practice. DIP-STRs are useful markers for detection of minor DNA but they are not widespread in the human genome and having long amplicons. In this study, we proposed a novel type of genetic marker, termed DIP-SNP. DIP-SNP refers to the combination of INDEL and SNP in less than 300bp length of human genome. The multiplex PCR and SNaPshot assay were established for 14 DIP-SNP markers in a Chinese Han population from Shanxi, China. This novel compound marker allows detection of the minor DNA contributor with sensitivity from 1:50 to 1:1000 in a DNA mixture of any gender with 1 ng-10 ng DNA template. Most of the DIP-SNP markers had a relatively high probability of informative alleles with an average I value of 0.33. In all, we proposed DIP-SNP as a novel kind of genetic marker for detection of minor contributor from unbalanced DNA mixture and established the detection method by associating the multiplex PCR and SNaPshot assay. DIP-SNP polymorphisms are promising markers for forensic or clinical mixture examination because they are shorter, widespread and higher sensitive. Copyright © 2018 Elsevier Inc. All rights reserved.

Development and dissection of diagnostic SNP markers for the downy mildew resistance genes Pl Arg and Pl 8 and maker-assisted gene pyramiding in sunflower (Helianthus annuus L.).

Science.gov (United States)

Qi, L L; Talukder, Z I; Hulke, B S; Foley, M E

2017-06-01

Diagnostic DNA markers are an invaluable resource in breeding programs for successful introgression and pyramiding of disease resistance genes. Resistance to downy mildew (DM) disease in sunflower is mediated by Pl genes which are known to be effective against the causal fungus, Plasmopara halstedii. Two DM resistance genes, Pl Arg and Pl 8 , are highly effective against P. halstedii races in the USA, and have been previously mapped to the sunflower linkage groups (LGs) 1 and 13, respectively, using simple sequence repeat (SSR) markers. In this study, we developed high-density single nucleotide polymorphism (SNP) maps encompassing the Pl arg and Pl 8 genes and identified diagnostic SNP markers closely linked to these genes. The specificity of the diagnostic markers was validated in a highly diverse panel of 548 sunflower lines. Dissection of a large marker cluster co-segregated with Pl Arg revealed that the closest SNP markers NSA_007595 and NSA_001835 delimited Pl Arg to an interval of 2.83 Mb on the LG1 physical map. The SNP markers SFW01497 and SFW06597 delimited Pl 8 to an interval of 2.85 Mb on the LG13 physical map. We also developed sunflower lines with homozygous, three gene pyramids carrying Pl Arg , Pl 8 , and the sunflower rust resistance gene R 12 using the linked SNP markers from a segregating F 2 population of RHA 340 (carrying Pl 8 )/RHA 464 (carrying Pl Arg and R 12 ). The high-throughput diagnostic SNP markers developed in this study will facilitate marker-assisted selection breeding, and the pyramided sunflower lines will provide durable resistance to downy mildew and rust diseases.

Development of a rapid SNP-typing assay to differentiate Bifidobacterium animalis ssp. lactis strains used in probiotic-supplemented dairy products.

Science.gov (United States)

Lomonaco, Sara; Furumoto, Emily J; Loquasto, Joseph R; Morra, Patrizia; Grassi, Ausilia; Roberts, Robert F

2015-02-01

Identification at the genus, species, and strain levels is desirable when a probiotic microorganism is added to foods. Strains of Bifidobacterium animalis ssp. lactis (BAL) are commonly used worldwide in dairy products supplemented with probiotic strains. However, strain discrimination is difficult because of the high degree of genome identity (99.975%) between different genomes of this subspecies. Typing of monomorphic species can be carried out efficiently by targeting informative single nucleotide polymorphisms (SNP). Findings from a previous study analyzing both reference and commercial strains of BAL identified SNP that could be used to discriminate common strains into 8 groups. This paper describes development of a minisequencing assay based on the primer extension reaction (PER) targeting multiple SNP that can allow strain differentiation of BAL. Based on previous data, 6 informative SNP were selected for further testing, and a multiplex preliminary PCR was optimized to amplify the DNA regions containing the selected SNP. Extension primers (EP) annealing immediately adjacent to the selected SNP were developed and tested in simplex and multiplex PER to evaluate their performance. Twenty-five strains belonging to 9 distinct genomic clusters of B. animalis ssp. lactis were selected and analyzed using the developed minisequencing assay, simultaneously targeting the 6 selected SNP. Fragment analysis was subsequently carried out in duplicate and demonstrated that the assay yielded 8 specific profiles separating the most commonly used commercial strains. This novel multiplex PER approach provides a simple, rapid, flexible SNP-based subtyping method for proper characterization and identification of commercial probiotic strains of BAL from fermented dairy products. To assess the usefulness of this method, DNA was extracted from yogurt manufactured with and without the addition of B. animalis ssp. lactis BB-12. Extracted DNA was then subjected to the minisequencing

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

KAUST Repository

Coll, Francesc

2014-09-01

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ∼92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ∼7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type. © 2014 Macmillan Publishers Limited.

Report on ISFG SNP Panel Discussion

DEFF Research Database (Denmark)

Butler, John M.; Budowle, B.; Gill, P.

2008-01-01

Six scientists presented their views and experience with single nucleotide polymorphism (SNP) markers, multiplexes, and methods regarding their potential application in forensic identity and relationship testing. Benefits and limitations of SNPs were reviewed, as were different SNP marker...

The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

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Molly B. Sheridan

2015-01-01

Full Text Available Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC. Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.

SNPhylo: a pipeline to construct a phylogenetic tree from huge SNP data.

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Lee, Tae-Ho; Guo, Hui; Wang, Xiyin; Kim, Changsoo; Paterson, Andrew H

2014-02-26

Phylogenetic trees are widely used for genetic and evolutionary studies in various organisms. Advanced sequencing technology has dramatically enriched data available for constructing phylogenetic trees based on single nucleotide polymorphisms (SNPs). However, massive SNP data makes it difficult to perform reliable analysis, and there has been no ready-to-use pipeline to generate phylogenetic trees from these data. We developed a new pipeline, SNPhylo, to construct phylogenetic trees based on large SNP datasets. The pipeline may enable users to construct a phylogenetic tree from three representative SNP data file formats. In addition, in order to increase reliability of a tree, the pipeline has steps such as removing low quality data and considering linkage disequilibrium. A maximum likelihood method for the inference of phylogeny is also adopted in generation of a tree in our pipeline. Using SNPhylo, users can easily produce a reliable phylogenetic tree from a large SNP data file. Thus, this pipeline can help a researcher focus more on interpretation of the results of analysis of voluminous data sets, rather than manipulations necessary to accomplish the analysis.

Identification of QTLs for 14 Agronomically Important Traits in Setaria italica Based on SNPs Generated from High-Throughput Sequencing

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Kai Zhang

2017-05-01

Full Text Available Foxtail millet (Setaria italica is an important crop possessing C4 photosynthesis capability. The S. italica genome was de novo sequenced in 2012, but the sequence lacked high-density genetic maps with agronomic and yield trait linkages. In the present study, we resequenced a foxtail millet population of 439 recombinant inbred lines (RILs and developed high-resolution bin map and high-density SNP markers, which could provide an effective approach for gene identification. A total of 59 QTL for 14 agronomic traits in plants grown under long- and short-day photoperiods were identified. The phenotypic variation explained ranged from 4.9 to 43.94%. In addition, we suggested that there may be segregation distortion on chromosome 6 that is significantly distorted toward Zhang gu. The newly identified QTL will provide a platform for sequence-based research on the S. italica genome, and for molecular marker-assisted breeding.

Genome wide SNP discovery in flax through next generation sequencing of reduced representation libraries

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Kumar Santosh

2012-12-01

Full Text Available Abstract Background Flax (Linum usitatissimum L. is a significant fibre and oilseed crop. Current flax molecular markers, including isozymes, RAPDs, AFLPs and SSRs are of limited use in the construction of high density linkage maps and for association mapping applications due to factors such as low reproducibility, intense labour requirements and/or limited numbers. We report here on the use of a reduced representation library strategy combined with next generation Illumina sequencing for rapid and large scale discovery of SNPs in eight flax genotypes. SNP discovery was performed through in silico analysis of the sequencing data against the whole genome shotgun sequence assembly of flax genotype CDC Bethune. Genotyping-by-sequencing of an F6-derived recombinant inbred line population provided validation of the SNPs. Results Reduced representation libraries of eight flax genotypes were sequenced on the Illumina sequencing platform resulting in sequence coverage ranging from 4.33 to 15.64X (genome equivalents. Depending on the relatedness of the genotypes and the number and length of the reads, between 78% and 93% of the reads mapped onto the CDC Bethune whole genome shotgun sequence assembly. A total of 55,465 SNPs were discovered with the largest number of SNPs belonging to the genotypes with the highest mapping coverage percentage. Approximately 84% of the SNPs discovered were identified in a single genotype, 13% were shared between any two genotypes and the remaining 3% in three or more. Nearly a quarter of the SNPs were found in genic regions. A total of 4,706 out of 4,863 SNPs discovered in Macbeth were validated using genotyping-by-sequencing of 96 F6 individuals from a recombinant inbred line population derived from a cross between CDC Bethune and Macbeth, corresponding to a validation rate of 96.8%. Conclusions Next generation sequencing of reduced representation libraries was successfully implemented for genome-wide SNP discovery from

Photoionization and High Density Gas

Science.gov (United States)

Kallman, T.; Bautista, M.; White, Nicholas E. (Technical Monitor)

2002-01-01

We present results of calculations using the XSTAR version 2 computer code. This code is loosely based on the XSTAR v.1 code which has been available for public use for some time. However it represents an improvement and update in several major respects, including atomic data, code structure, user interface, and improved physical description of ionization/excitation. In particular, it now is applicable to high density situations in which significant excited atomic level populations are likely to occur. We describe the computational techniques and assumptions, and present sample runs with particular emphasis on high density situations.

Tag SNP selection via a genetic algorithm.

Science.gov (United States)

Mahdevar, Ghasem; Zahiri, Javad; Sadeghi, Mehdi; Nowzari-Dalini, Abbas; Ahrabian, Hayedeh

2010-10-01

Single Nucleotide Polymorphisms (SNPs) provide valuable information on human evolutionary history and may lead us to identify genetic variants responsible for human complex diseases. Unfortunately, molecular haplotyping methods are costly, laborious, and time consuming; therefore, algorithms for constructing full haplotype patterns from small available data through computational methods, Tag SNP selection problem, are convenient and attractive. This problem is proved to be an NP-hard problem, so heuristic methods may be useful. In this paper we present a heuristic method based on genetic algorithm to find reasonable solution within acceptable time. The algorithm was tested on a variety of simulated and experimental data. In comparison with the exact algorithm, based on brute force approach, results show that our method can obtain optimal solutions in almost all cases and runs much faster than exact algorithm when the number of SNP sites is large. Our software is available upon request to the corresponding author.

A conceptual fusion reactor based on the high-plasma-density Z-pinch

International Nuclear Information System (INIS)

Hartman, C.W.; Carlson, G.; Hoffman, M.; Werner, R.

1977-01-01

Conceptual DT and DD fusion reactors are discussed based on magnetic confinement with the high-plasma-density Z-pinch. The reactor concepts have no ''first wall'', the fusion neutrons and plasma energy being absorbed directly into a surrounding lithium vortex blanket. Efficient systems with low re-circulated power are projected, based on a flow-through pinch cycle for which overall Q values can approach 10. The conceptual reactors are characterized by simplicity, small minimum size (100MW(e)) and by the potential for minimal radioactivity hazards. (author)

A 50 SNP-multiplex mass spectrometry assay for human identification

DEFF Research Database (Denmark)

Wächter, Andrea; Mengel-From, Jonas; Børsting, Claus

2008-01-01

We developed a 50 SNP-multiplex assay for detection on a MALDI-TOF MS platform based on the SNPs in the 52 SNP-multiplex assay recently developed by the SNPforID Consortium. After PCR amplification, the products were purified on Qiagen columns and used as templates in one single base extension (SBE...... primers were extended with biotin labelled ddNTPs and purified on avidin beads ensuring that only the extended SBE primers were isolated and spotted on the MALDI-TOF anchor target. Detection of the 50 extended primers from the SBE reaction was performed in a mass range between 3000 and 10,000 m/z...

Toward allotetraploid cotton genome assembly: integration of a high-density molecular genetic linkage map with DNA sequence information

Science.gov (United States)

2012-01-01

Background Cotton is the world’s most important natural textile fiber and a significant oilseed crop. Decoding cotton genomes will provide the ultimate reference and resource for research and utilization of the species. Integration of high-density genetic maps with genomic sequence information will largely accelerate the process of whole-genome assembly in cotton. Results In this paper, we update a high-density interspecific genetic linkage map of allotetraploid cultivated cotton. An additional 1,167 marker loci have been added to our previously published map of 2,247 loci. Three new marker types, InDel (insertion-deletion) and SNP (single nucleotide polymorphism) developed from gene information, and REMAP (retrotransposon-microsatellite amplified polymorphism), were used to increase map density. The updated map consists of 3,414 loci in 26 linkage groups covering 3,667.62 cM with an average inter-locus distance of 1.08 cM. Furthermore, genome-wide sequence analysis was finished using 3,324 informative sequence-based markers and publicly-available Gossypium DNA sequence information. A total of 413,113 EST and 195 BAC sequences were physically anchored and clustered by 3,324 sequence-based markers. Of these, 14,243 ESTs and 188 BACs from different species of Gossypium were clustered and specifically anchored to the high-density genetic map. A total of 2,748 candidate unigenes from 2,111 ESTs clusters and 63 BACs were mined for functional annotation and classification. The 337 ESTs/genes related to fiber quality traits were integrated with 132 previously reported cotton fiber quality quantitative trait loci, which demonstrated the important roles in fiber quality of these genes. Higher-level sequence conservation between different cotton species and between the A- and D-subgenomes in tetraploid cotton was found, indicating a common evolutionary origin for orthologous and paralogous loci in Gossypium. Conclusion This study will serve as a valuable genomic resource

SNPdetector: a software tool for sensitive and accurate SNP detection.

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Jinghui Zhang

2005-10-01

Full Text Available Identification of single nucleotide polymorphisms (SNPs and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool, and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozygosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://lpg.nci.nih.gov.

A high-energy-density redox flow battery based on zinc/polyhalide chemistry.

Science.gov (United States)

Zhang, Liqun; Lai, Qinzhi; Zhang, Jianlu; Zhang, Huamin

2012-05-01

Zn and the Art of Battery Development: A zinc/polyhalide redox flow battery employs Br(-) /ClBr(2-) and Zn/Zn(2+) redox couples in its positive and negative half-cells, respectively. The performance of the battery is evaluated by charge-discharge cycling tests and reveals a high energy efficiency of 81%, based on a Coulombic efficiency of 96% and voltage efficiency of 84%. The new battery technology can provide high performance and energy density at an acceptable cost. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantification of within-sample genetic heterogeneity from SNP-array data

DEFF Research Database (Denmark)

Martinez, Pierre; Kimberley, Christopher; Birkbak, Nicolai Juul

2017-01-01

Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using...... standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples. We created in-silico and in-vitro mixtures...... sequencing data but heterogeneity in the fraction of tumour cells present across samples hampered accurate quantification. The prognostic potential of both scores was moderate but significantly predictive of survival in several tumour types (corrected p = 0.03). Our work thus shows how individual SNP...

Prediction of disease causing non-synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP.

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Morten Bo Johansen

Full Text Available We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP.

SNP discovery and chromosome anchoring provide the first physically-anchored hexaploid oat map and reveal synteny with model species.

Directory of Open Access Journals (Sweden)

Rebekah E Oliver

Full Text Available A physically anchored consensus map is foundational to modern genomics research; however, construction of such a map in oat (Avena sativa L., 2n = 6x = 42 has been hindered by the size and complexity of the genome, the scarcity of robust molecular markers, and the lack of aneuploid stocks. Resources developed in this study include a modified SNP discovery method for complex genomes, a diverse set of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy. These resources were applied to build the first complete, physically-anchored consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico SNPs were discovered based on nine million inter-varietal sequence reads of genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311 robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six bi-parental mapping populations ranging in size from 49 to 97 progeny. The consensus map included 985 SNPs and 68 previously-published markers, resolving 21 linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups were assigned to 21 chromosomes using SNP deletion analysis of chromosome-deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and Brachypodium provide evidence for extensive conservation of genomic regions, and renewed encouragement for orthology-based genomic discovery in this important hexaploid species. These results also provide a framework for high-resolution genetic analysis in oat, and a model for marker development and map construction in other species with complex genomes and limited resources.

Scalable Density-Based Subspace Clustering

DEFF Research Database (Denmark)

Müller, Emmanuel; Assent, Ira; Günnemann, Stephan

2011-01-01

For knowledge discovery in high dimensional databases, subspace clustering detects clusters in arbitrary subspace projections. Scalability is a crucial issue, as the number of possible projections is exponential in the number of dimensions. We propose a scalable density-based subspace clustering...... method that steers mining to few selected subspace clusters. Our novel steering technique reduces subspace processing by identifying and clustering promising subspaces and their combinations directly. Thereby, it narrows down the search space while maintaining accuracy. Thorough experiments on real...... and synthetic databases show that steering is efficient and scalable, with high quality results. For future work, our steering paradigm for density-based subspace clustering opens research potential for speeding up other subspace clustering approaches as well....

Feedback controlled, reactor relevant, high-density, high-confinement scenarios at ASDEX Upgrade

Science.gov (United States)

Lang, P. T.; Blanken, T. C.; Dunne, M.; McDermott, R. M.; Wolfrum, E.; Bobkov, V.; Felici, F.; Fischer, R.; Janky, F.; Kallenbach, A.; Kardaun, O.; Kudlacek, O.; Mertens, V.; Mlynek, A.; Ploeckl, B.; Stober, J. K.; Treutterer, W.; Zohm, H.; ASDEX Upgrade Team

2018-03-01

One main programme topic at the ASDEX Upgrade all-metal-wall tokamak is development of a high-density regime with central densities at reactor grade level while retaining high-confinement properties. This required development of appropriate control techniques capable of coping with the pellet tool, a powerful means of fuelling but one which presented challenges to the control system for handling of related perturbations. Real-time density profile control was demonstrated, raising the core density well above the Greenwald density while retaining the edge density in order to avoid confinement losses. Recently, a new model-based approach was implemented that allows direct control of the central density. Investigations focussed first on the N-seeding scenario owing to its proven potential to yield confinement enhancements. Combining pellets and N seeding was found to improve the divertor buffering further and enhance the operational range accessible. For core densities up to about the Greenwald density, a clear improvement with respect to the non-seeding reference was achieved; however, at higher densities this benefit is reduced. This behaviour is attributed to recurrence of an outward shift of the edge density profile, resulting in a reduced peeling-ballooning stability. This is similar to the shift seen during strong gas puffing, which is required to prevent impurity influx in ASDEX Upgrade. First tests indicate that highly-shaped plasma configurations like the ITER base-line scenario, respond very well to pellet injection, showing efficient fuelling with no measurable impact on the edge density profile.

Identification of QTLs for 14 Agronomically Important Traits in Setaria italica Based on SNPs Generated from High-Throughput Sequencing.

Science.gov (United States)

Zhang, Kai; Fan, Guangyu; Zhang, Xinxin; Zhao, Fang; Wei, Wei; Du, Guohua; Feng, Xiaolei; Wang, Xiaoming; Wang, Feng; Song, Guoliang; Zou, Hongfeng; Zhang, Xiaolei; Li, Shuangdong; Ni, Xuemei; Zhang, Gengyun; Zhao, Zhihai

2017-05-05

Foxtail millet ( Setaria italica ) is an important crop possessing C4 photosynthesis capability. The S. italica genome was de novo sequenced in 2012, but the sequence lacked high-density genetic maps with agronomic and yield trait linkages. In the present study, we resequenced a foxtail millet population of 439 recombinant inbred lines (RILs) and developed high-resolution bin map and high-density SNP markers, which could provide an effective approach for gene identification. A total of 59 QTL for 14 agronomic traits in plants grown under long- and short-day photoperiods were identified. The phenotypic variation explained ranged from 4.9 to 43.94%. In addition, we suggested that there may be segregation distortion on chromosome 6 that is significantly distorted toward Zhang gu. The newly identified QTL will provide a platform for sequence-based research on the S. italica genome, and for molecular marker-assisted breeding. Copyright © 2017 Zhang et al.

Flexible asymmetric supercapacitors with high energy and high power density in aqueous electrolytes

Science.gov (United States)

Cheng, Yingwen; Zhang, Hongbo; Lu, Songtao; Varanasi, Chakrapani V.; Liu, Jie

2013-01-01

Supercapacitors with both high energy and high power densities are critical for many practical applications. In this paper, we discuss the design and demonstrate the fabrication of flexible asymmetric supercapacitors based on nanocomposite electrodes of MnO2, activated carbon, carbon nanotubes and graphene. The combined unique properties of each of these components enable highly flexible and mechanically strong films that can serve as electrodes directly without using any current collectors or binders. Using these flexible electrodes and a roll-up approach, asymmetric supercapacitors with 2 V working voltage were successfully fabricated. The fabricated device showed excellent rate capability, with 78% of the original capacitance retained when the scan rate was increased from 2 mV s-1 to 500 mV s-1. Owing to the unique composite structure, these supercapacitors were able to deliver high energy density (24 W h kg-1) under high power density (7.8 kW kg-1) conditions. These features could enable supercapacitor based energy storage systems to be very attractive for a variety of critical applications, such as the power sources in hybrid electric vehicles and the back-up powers for wind and solar energy, where both high energy density and high power density are required.Supercapacitors with both high energy and high power densities are critical for many practical applications. In this paper, we discuss the design and demonstrate the fabrication of flexible asymmetric supercapacitors based on nanocomposite electrodes of MnO2, activated carbon, carbon nanotubes and graphene. The combined unique properties of each of these components enable highly flexible and mechanically strong films that can serve as electrodes directly without using any current collectors or binders. Using these flexible electrodes and a roll-up approach, asymmetric supercapacitors with 2 V working voltage were successfully fabricated. The fabricated device showed excellent rate capability, with 78% of

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Directory of Open Access Journals (Sweden)

Dana B Hancock

Full Text Available Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1, and its ratio to forced vital capacity (FEV(1/FVC. Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA of single nucleotide polymorphism (SNP and SNP-by-smoking (ever-smoking or pack-years associations on FEV(1 and FEV(1/FVC across 19 studies (total N = 50,047. We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = 5.00×10(-11, HLA-DQB1 and HLA-DQA2 (smallest P(JMA = 4.35×10(-9, and KCNJ2 and SOX9 (smallest P(JMA = 1.28×10(-8 were associated with FEV(1/FVC or FEV(1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

High-Power-Density, High-Energy-Density Fluorinated Graphene for Primary Lithium Batteries

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Guiming Zhong

2018-03-01

Full Text Available Li/CFx is one of the highest-energy-density primary batteries; however, poor rate capability hinders its practical applications in high-power devices. Here we report a preparation of fluorinated graphene (GFx with superior performance through a direct gas fluorination method. We find that the so-called “semi-ionic” C-F bond content in all C-F bonds presents a more critical impact on rate performance of the GFx in comparison with sp2 C content in the GFx, morphology, structure, and specific surface area of the materials. The rate capability remains excellent before the semi-ionic C-F bond proportion in the GFx decreases. Thus, by optimizing semi-ionic C-F content in our GFx, we obtain the optimal x of 0.8, with which the GF0.8 exhibits a very high energy density of 1,073 Wh kg−1 and an excellent power density of 21,460 W kg−1 at a high current density of 10 A g−1. More importantly, our approach opens a new avenue to obtain fluorinated carbon with high energy densities without compromising high power densities.

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

Science.gov (United States)

Howe, Glenn T; Yu, Jianbin; Knaus, Brian; Cronn, Richard; Kolpak, Scott; Dolan, Peter; Lorenz, W Walter; Dean, Jeffrey F D

2013-02-28

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. 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. 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 and potential responses to

Comparison of SNP-based subtyping workflows for bacterial isolates using WGS data, applied to Salmonella enterica serotype Typhimurium and serotype 1,4,[5],12:i:-

Science.gov (United States)

Saltykova, Assia; Wuyts, Véronique; Mattheus, Wesley; Bertrand, Sophie; Roosens, Nancy H. C.; Marchal, Kathleen

2018-01-01

Whole genome sequencing represents a promising new technology for subtyping of bacterial pathogens. Besides the technological advances which have pushed the approach forward, the last years have been marked by considerable evolution of the whole genome sequencing data analysis methods. Prior to application of the technology as a routine epidemiological typing tool, however, reliable and efficient data analysis strategies need to be identified among the wide variety of the emerged methodologies. In this work, we have compared three existing SNP-based subtyping workflows using a benchmark dataset of 32 Salmonella enterica subsp. enterica serovar Typhimurium and serovar 1,4,[5],12:i:- isolates including five isolates from a confirmed outbreak and three isolates obtained from the same patient at different time points. The analysis was carried out using the original (high-coverage) and a down-sampled (low-coverage) datasets and two different reference genomes. All three tested workflows, namely CSI Phylogeny-based workflow, CFSAN-based workflow and PHEnix-based workflow, were able to correctly group the confirmed outbreak isolates and isolates from the same patient with all combinations of reference genomes and datasets. However, the workflows differed strongly with respect to the SNP distances between isolates and sensitivity towards sequencing coverage, which could be linked to the specific data analysis strategies used therein. To demonstrate the effect of particular data analysis steps, several modifications of the existing workflows were also tested. This allowed us to propose data analysis schemes most suitable for routine SNP-based subtyping applied to S. Typhimurium and S. 1,4,[5],12:i:-. Results presented in this study illustrate the importance of using correct data analysis strategies and to define benchmark and fine-tune parameters applied within routine data analysis pipelines to obtain optimal results. PMID:29408896

A SNP Genotyping Array for Hexaploid Oat

Directory of Open Access Journals (Sweden)

Nicholas A. Tinker

2014-11-01

Full Text Available Recognizing a need in cultivated hexaploid oat ( L. for a reliable set of reference single nucleotide polymorphisms (SNPs, we have developed a 6000 (6K BeadChip design containing 257 Infinium I and 5486 Infinium II designs corresponding to 5743 SNPs. Of those, 4975 SNPs yielded successful assays after array manufacturing. These SNPs were discovered based on a variety of bioinformatics pipelines in complementary DNA (cDNA and genomic DNA originating from 20 or more diverse oat cultivars. The array was validated in 1100 samples from six recombinant inbred line (RIL mapping populations and sets of diverse oat cultivars and breeding lines, and provided approximately 3500 discernible Mendelian polymorphisms. Here, we present an annotation of these SNPs, including methods of discovery, gene identification and orthology, population-genetic characteristics, and tentative positions on an oat consensus map. We also evaluate a new cluster-based method of calling SNPs. The SNP design sequences are made publicly available, and the full SNP genotyping platform is available for commercial purchase from an independent third party.

SNP-based linkage mapping for validation of QTLs for resistance to ascochyta blight in lentil

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Shimna Sudheesh

2016-11-01

Full Text Available Lentil (Lens culinaris Medik. is a self-pollinating, diploid, annual, cool-season, food legume crop that is cultivated throughout the world. Ascochyta blight (AB, caused by Ascochyta lentis Vassilievsky, is an economically important and widespread disease of lentil. Development of cultivars with high levels of durable resistance provides an environmentally acceptable and economically feasible method for AB control. A detailed understanding of the genetic basis of AB resistance is hence highly desirable, in order to obtain insight into the number and influence of resistance genes. Genetic linkage maps based on single nucleotide polymorphisms (SNP and simple sequence repeat (SSR markers have been developed from three recombinant inbred line (RIL populations. The IH x NF map contained 460 loci across 1461.6 cM, while the IH x DIG map contained 329 loci across 1302.5 cM and the third map, NF x DIG contained 330 loci across 1914.1 cM. Data from these maps were combined with a map from a previously published study through use of bridging markers to generate a consensus linkage map containing 689 loci distributed across 7 linkage groups (LGs, with a cumulative length of 2429.61 cM at an average density of one marker per 3.5 cM. Trait dissection of AB resistance was performed for the RIL populations, identifying totals of two and three quantitative trait loci (QTLs explaining 52% and 69% of phenotypic variation for resistance to infection in the IH x DIG and IH x NF populations, respectively. Presence of common markers in the vicinity of the AB_IH1- and AB_IH2.1/AB_IH2.2-containing regions on both maps supports the inference that a common genomic region is responsible for conferring resistance and is associated with the resistant parent, Indianhead. The third QTL was derived from Northfield. Evaluation of markers associated with AB resistance across a diverse lentil germplasm panel revealed that the identity of alleles associated with AB_IH1 predicted

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Directory of Open Access Journals (Sweden)

Ariel M Pani

2010-08-01

Full Text Available Intellectual disability (ID affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450 region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications, one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information

Polygenic analysis of genome-wide SNP data identifies common variants on allergic rhinitis

DEFF Research Database (Denmark)

Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette

Background: Allergic Rhinitis (AR) is a complex disorder that affects many people around the world. There is a high genetic contribution to the development of the AR, as twins and family studies have estimated heritability of more than 33%. Due to the complex nature of the disease, single SNP...... analysis has limited power in identifying the genetic variations for AR. We combined genome-wide association analysis (GWAS) with polygenic risk score (PRS) in exploring the genetic basis underlying the disease. Methods: We collected clinical data on 631 Danish subjects with AR cases consisting of 434...... sibling pairs and unrelated individuals and control subjects of 197 unrelated individuals. SNP genotyping was done by Affymetrix Genome-Wide Human SNP Array 5.0. SNP imputation was performed using "IMPUTE2". Using additive effect model, GWAS was conducted in discovery sample, the genotypes...

Wireless sEMG System with a Microneedle-Based High-Density Electrode Array on a Flexible Substrate.

Science.gov (United States)

Kim, Minjae; Gu, Gangyong; Cha, Kyoung Je; Kim, Dong Sung; Chung, Wan Kyun

2017-12-30

Surface electromyography (sEMG) signals reflect muscle contraction and hence, can provide information regarding a user's movement intention. High-density sEMG systems have been proposed to measure muscle activity in small areas and to estimate complex motion using spatial patterns. However, conventional systems based on wet electrodes have several limitations. For example, the electrolyte enclosed in wet electrodes restricts spatial resolution, and these conventional bulky systems limit natural movements. In this paper, a microneedle-based high-density electrode array on a circuit integrated flexible substrate for sEMG is proposed. Microneedles allow for high spatial resolution without requiring conductive substances, and flexible substrates guarantee stable skin-electrode contact. Moreover, a compact signal processing system is integrated with the electrode array. Therefore, sEMG measurements are comfortable to the user and do not interfere with the movement. The system performance was demonstrated by testing its operation and estimating motion using a Gaussian mixture model-based, simplified 2D spatial pattern.

A High-Density Integrated DArTseq SNP-Based Genetic Map of Pisum fulvum and Identification of QTLs Controlling Rust Resistance

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Eleonora Barilli

2018-02-01

Full Text Available Pisum fulvum, a wild relative of pea is an important source of allelic diversity to improve the genetic resistance of cultivated species against fungal diseases of economic importance like the pea rust caused by Uromyces pisi. To unravel the genetic control underlying resistance to this fungal disease, a recombinant inbred line (RIL population was generated from a cross between two P. fulvum accessions, IFPI3260 and IFPI3251, and genotyped using Diversity Arrays Technology. A total of 9,569 high-quality DArT-Seq and 8,514 SNPs markers were generated. Finally, a total of 12,058 markers were assembled into seven linkage groups, equivalent to the number of haploid chromosomes of P. fulvum and P. sativum. The newly constructed integrated genetic linkage map of P. fulvum covered an accumulated distance of 1,877.45 cM, an average density of 1.19 markers cM−1 and an average distance between adjacent markers of 1.85 cM. The composite interval mapping revealed three QTLs distributed over two linkage groups that were associated with the percentage of rust disease severity (DS%. QTLs UpDSII and UpDSIV were located in the LGs II and IV respectively and were consistently identified both in adult plants over 3 years at the field (Córdoba, Spain and in seedling plants under controlled conditions. Whenever they were detected, their contribution to the total phenotypic variance varied between 19.8 and 29.2. A third QTL (UpDSIV.2 was also located in the LGIVand was environmentally specific as was only detected for DS % in seedlings under controlled conditions. It accounted more than 14% of the phenotypic variation studied. Taking together the data obtained in the study, it could be concluded that the expression of resistance to fungal diseases in P. fulvum originates from the resistant parent IFPI3260.

Large SNP arrays for genotyping in crop plants

Indian Academy of Sciences (India)

Genotyping with large numbers of molecular markers is now an indispensable tool within plant genetics and breeding. Especially through the identification of large numbers of single nucleotide polymorphism (SNP) markers using the novel high-throughput sequencing technologies, it is now possible to reliably identify many ...

Comparison of three PCR-based assays for SNP genotyping in sugar beet

Science.gov (United States)

Background: PCR allelic discrimination technologies have broad applications in the detection of single nucleotide polymorphisms (SNPs) in genetics and genomics. The use of fluorescence-tagged probes is the leading method for targeted SNP detection, but assay costs and error rates could be improved t...

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

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Daniel Zanetti Scherrer

2015-07-01

Full Text Available Background:Evidences suggest that paraoxonase 1 (PON1 confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL.Objective:To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age. Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA. Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317.Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38; RQ = 46.96 (22.35; QQ = 85.35 (24.83 μmol/min; p Conclusion:In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Breast density estimation from high spectral and spatial resolution MRI

Science.gov (United States)

Li, Hui; Weiss, William A.; Medved, Milica; Abe, Hiroyuki; Newstead, Gillian M.; Karczmar, Gregory S.; Giger, Maryellen L.

2016-01-01

Abstract. A three-dimensional breast density estimation method is presented for high spectral and spatial resolution (HiSS) MR imaging. Twenty-two patients were recruited (under an Institutional Review Board--approved Health Insurance Portability and Accountability Act-compliant protocol) for high-risk breast cancer screening. Each patient received standard-of-care clinical digital x-ray mammograms and MR scans, as well as HiSS scans. The algorithm for breast density estimation includes breast mask generating, breast skin removal, and breast percentage density calculation. The inter- and intra-user variabilities of the HiSS-based density estimation were determined using correlation analysis and limits of agreement. Correlation analysis was also performed between the HiSS-based density estimation and radiologists’ breast imaging-reporting and data system (BI-RADS) density ratings. A correlation coefficient of 0.91 (pdensity estimations. An interclass correlation coefficient of 0.99 (pdensity estimations. A moderate correlation coefficient of 0.55 (p=0.0076) was observed between HiSS-based breast density estimations and radiologists’ BI-RADS. In summary, an objective density estimation method using HiSS spectral data from breast MRI was developed. The high reproducibility with low inter- and low intra-user variabilities shown in this preliminary study suggest that such a HiSS-based density metric may be potentially beneficial in programs requiring breast density such as in breast cancer risk assessment and monitoring effects of therapy. PMID:28042590

(SNP) markers for the Chinese black sleeper, Bostrychus sinensis

African Journals Online (AJOL)

ajl yemi

2011-04-25

Apr 25, 2011 ... Polynesia, north to Japan and south to Australia (Kottelat et al., 1993; Masuda ... developed the first set of SNP markers for Chinese black sleeper which can ... Then, the. 44 primer pairs were designed based on all the cloning.

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

Science.gov (United States)

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

2013-08-01

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/].

High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

LENUS (Irish Health Repository)

Holt, Kathryn E

2010-05-31

Abstract Background Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

Development of a single nucleotide polymorphism (SNP) marker for ...

African Journals Online (AJOL)

The nature of the single nucleotide polymorphism (SNP) marker was validated by DNA sequencing of the parental PCR products. Using high resolution melt (HRM) profiles and normalised difference plots, we successfully differentiated the homozygous dominant (wild type), homozygous recessive (LPA) and heterozygous ...

Nanofluidic crystal: a facile, high-efficiency and high-power-density scaling up scheme for energy harvesting based on nanofluidic reverse electrodialysis

International Nuclear Information System (INIS)

Ouyang Wei; Wang Wei; Zhang Haixia; Wu Wengang; Li Zhihong

2013-01-01

The great advances in nanotechnology call for advances in miniaturized power sources for micro/nano-scale systems. Nanofluidic channels have received great attention as promising high-power-density substitutes for ion exchange membranes for use in energy harvesting from ambient ionic concentration gradient, namely reverse electrodialysis. This paper proposes the nanofluidic crystal (NFC), of packed nanoparticles in micro-meter-sized confined space, as a facile, high-efficiency and high-power-density scaling-up scheme for energy harvesting by nanofluidic reverse electrodialysis (NRED). Obtained from the self-assembly of nanoparticles in a micropore, the NFC forms an ion-selective network with enormous nanochannels due to electrical double-layer overlap in the nanoparticle interstices. As a proof-of-concept demonstration, a maximum efficiency of 42.3 ± 1.84%, a maximum power density of 2.82 ± 0.22 W m −2 , and a maximum output power of 1.17 ± 0.09 nW/unit (nearly three orders of magnitude of amplification compared to other NREDs) were achieved in our prototype cell, which was prepared within 30 min. The current NFC-based prototype cell can be parallelized and cascaded to achieve the desired output power and open circuit voltage. This NFC-based scaling-up scheme for energy harvesting based on NRED is promising for the building of self-powered micro/nano-scale systems. (paper)

A Whole Genome Association Study on Meat Quality Traits Using High Density SNP Chips in a Cross between Korean Native Pig and Landrace

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K.-T Lee

2012-11-01

Full Text Available A whole genome association (WGA study was performed to detect significant polymorphisms for meat quality traits in an F2 cross population (N = 478 that were generated with Korean native pig sires and Landrace dams in National Livestock Research Institute, Songwhan, Korea. The animals were genotyped using Illumina porcine 60k SNP beadchips, in which a set of 46,865 SNPs were available for the WGA analyses on ten carcass quality traits; live weight, crude protein, crude lipids, crude ash, water holding capacity, drip loss, shear force, CIE L, CIE a and CIE b. Phenotypes were regressed on additive and dominance effects for each SNP using a simple linear regression model, after adjusting for sex, sire and slaughter stage as fixed effects. With the significant SNPs for each trait (p<0.001, a stepwise regression procedure was applied to determine the best set of SNPs with the additive and/or dominance effects. A total of 106 SNPs, or quantitative trait loci (QTL were detected, and about 32 to 66% of the total phenotypic variation was explained by the significant SNPs for each trait. The QTL were identified in most porcine chromosomes (SSCs, in which majority of the QTL were detected in SSCs 1, 2, 12, 13, 14 and 16. Several QTL clusters were identified on SSCs 12, 16 and 17, and a cluster of QTL influencing crude protein, crude lipid, drip loss, shear force, CIE a and CIE b were located between 20 and 29 Mb of SSC12. A pleiotropic QTL for drip loss, CIE L and CIE b was also detected on SSC16. These QTL need to be validated in commercial pig populations for genetic improvement in meat quality via marker-assisted selection.

Proper joint analysis of summary association statistics requires the adjustment of heterogeneity in SNP coverage pattern.

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Zhang, Han; Wheeler, William; Song, Lei; Yu, Kai

2017-07-07

As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

High density data recording for SSCL linac

International Nuclear Information System (INIS)

VanDeusen, A.L.; Crist, C.

1993-01-01

The Superconducting Super Collider Laboratory and AlliedSignal Aerospace have collaboratively developed a high density data monitoring system for beam diagnostic activities. The 128 channel data system is based on a custom multi-channel high speed digitizer card for the VXI bus. The card is referred to as a Modular Input VXI (MIX) digitizer. Multiple MIX cards are used in the complete system to achieve the necessary high channel density requirements. Each MIX digitizer card also contains programmable signal conditioning, and enough local memory to complete an entire beam scan without assistance from the host processor

Family-based multi-SNP X chromosome analysis using parental information

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Alison S. Wise

2016-02-01

Full Text Available We propose a method for association analysis of haplotypes on the X chromosome that offers both improved power and robustness to population stratification in studies of affected offspring and their parents if all three have been genotyped. The method makes use of assumed parental haplotype exchangeability, a weaker assumption than Hardy-Weinberg equilibrium. Parental haplotype exchangeability requires that in the source population, of the three X chromosome haplotypes carried by the two parents, each is equally likely to be carried by the father. We propose a pseudo-sibling approach that exploits that exchangeability assumption. Our method extends the single-SNP PIX-LRT method to multiple SNPs in a high linkage block. We describe methods for testing the parental haplotype exchangeability assumption and also for determining how apparent violations can be distinguished from true fetal effects or maternally-mediated effects. We show results of simulations that demonstrate nominal type I error rate and good power. The methods are then applied to dbGaP data on the birth defect oral cleft, using both Asian and Caucasian families with cleft.

GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets.

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Dozmorov, Mikhail G; Cara, Lukas R; Giles, Cory B; Wren, Jonathan D

2016-08-01

The growing amount of regulatory data from the ENCODE, Roadmap Epigenomics and other consortia provides a wealth of opportunities to investigate the functional impact of single nucleotide polymorphisms (SNPs). Yet, given the large number of regulatory datasets, researchers are posed with a challenge of how to efficiently utilize them to interpret the functional impact of SNP sets. We developed the GenomeRunner web server to automate systematic statistical analysis of SNP sets within a regulatory context. Besides defining the functional impact of SNP sets, GenomeRunner implements novel regulatory similarity/differential analyses, and cell type-specific regulatory enrichment analysis. Validated against literature- and disease ontology-based approaches, analysis of 39 disease/trait-associated SNP sets demonstrated that the functional impact of SNP sets corresponds to known disease relationships. We identified a group of autoimmune diseases with SNPs distinctly enriched in the enhancers of T helper cell subpopulations, and demonstrated relevant cell type-specificity of the functional impact of other SNP sets. In summary, we show how systematic analysis of genomic data within a regulatory context can help interpreting the functional impact of SNP sets. GenomeRunner web server is freely available at http://www.integrativegenomics.org/ mikhail.dozmorov@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Laser fusion and high energy density science

International Nuclear Information System (INIS)

Kodama, Ryosuke

2005-01-01

High-power laser technology is now opening a variety of new fields of science and technology using laser-produced plasmas. The laser plasma is now recognized as one of the important tools for the investigation and application of matter under extreme conditions, which is called high energy density science. This chapter shows a variety of applications of laser-produced plasmas as high energy density science. One of the more attractive industrial and science applications is the generation of intense pulse-radiation sources, such as the generation of electro-magnetic waves in the ranges of EUV (Extreme Ultra Violet) to gamma rays and laser acceleration of charged particles. The laser plasma is used as an energy converter in this regime. The fundamental science applications of high energy density physics are shown by introducing laboratory astrophysics, the equation of state of high pressure matter, including warm dense matter and nuclear science. Other applications are also presented, such as femto-second laser propulsion and light guiding. Finally, a new systematization is proposed to explore the possibility of the high energy density plasma application, which is called high energy plasma photonics''. This is also exploration of the boundary regions between laser technology and beam optics based on plasma physics. (author)

An Improved Consensus Linkage Map of Barley Based on Flow-Sorted Chromosomes and Single Nucleotide Polymorphism Markers

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María Muñoz-Amatriaín

2011-11-01

Full Text Available 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 single nucleotide polymorphism (SNP-based genotyping platform was developed and used to genotype 373 individuals in four barley ( L. mapping populations. This led to a 2943 SNP consensus genetic map with 975 unique positions. In this work, we add data from six additional populations and more individuals from one of the original populations to develop an improved consensus map from 1133 individuals. A stringent and systematic analysis of each of the 10 populations was performed to achieve uniformity. This involved reexamination of the four populations included in the previous map. As a consequence, we present a robust consensus genetic map that contains 2994 SNP loci mapped to 1163 unique positions. The map spans 1137.3 cM with an average density of one marker bin per 0.99 cM. A novel application of the genotyping platform for gene detection allowed the assignment of 2930 genes to flow-sorted chromosomes or arms, confirmed the position of 2545 SNP-mapped loci, added chromosome or arm allocations to an additional 370 SNP loci, and delineated pericentromeric regions for chromosomes 2H to 7H. Marker order has been improved and map resolution has been increased by almost 20%. These increased precision outcomes enable more optimized SNP selection for marker-assisted breeding and support association genetic analysis and map-based cloning. It will also improve the anchoring of DNA sequence scaffolds and the barley physical map to the genetic map.

Development and implementation of a highly-multiplexed SNP array for genetic mapping in maritime pine and comparative mapping with loblolly pine

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Garnier-Géré Pauline

2011-07-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most abundant source of genetic variation among individuals of a species. New genotyping technologies allow examining hundreds to thousands of SNPs in a single reaction for a wide range of applications such as genetic diversity analysis, linkage mapping, fine QTL mapping, association studies, marker-assisted or genome-wide selection. In this paper, we evaluated the potential of highly-multiplexed SNP genotyping for genetic mapping in maritime pine (Pinus pinaster Ait., the main conifer used for commercial plantation in southwestern Europe. Results We designed a custom GoldenGate assay for 1,536 SNPs detected through the resequencing of gene fragments (707 in vitro SNPs/Indels and from Sanger-derived Expressed Sequenced Tags assembled into a unigene set (829 in silico SNPs/Indels. Offspring from three-generation outbred (G2 and inbred (F2 pedigrees were genotyped. The success rate of the assay was 63.6% and 74.8% for in silico and in vitro SNPs, respectively. A genotyping error rate of 0.4% was further estimated from segregating data of SNPs belonging to the same gene. Overall, 394 SNPs were available for mapping. A total of 287 SNPs were integrated with previously mapped markers in the G2 parental maps, while 179 SNPs were localized on the map generated from the analysis of the F2 progeny. Based on 98 markers segregating in both pedigrees, we were able to generate a consensus map comprising 357 SNPs from 292 different loci. Finally, the analysis of sequence homology between mapped markers and their orthologs in a Pinus taeda linkage map, made it possible to align the 12 linkage groups of both species. Conclusions Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in maritime pine, a conifer species that has a genome seven times the size of the human genome. This SNP-array will be extended thanks to recent sequencing effort using

Underestimated effect sizes in GWAS: fundamental limitations of single SNP analysis for dichotomous phenotypes.

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Sven Stringer

Full Text Available Complex diseases are often highly heritable. However, for many complex traits only a small proportion of the heritability can be explained by observed genetic variants in traditional genome-wide association (GWA studies. Moreover, for some of those traits few significant SNPs have been identified. Single SNP association methods test for association at a single SNP, ignoring the effect of other SNPs. We show using a simple multi-locus odds model of complex disease that moderate to large effect sizes of causal variants may be estimated as relatively small effect sizes in single SNP association testing. This underestimation effect is most severe for diseases influenced by numerous risk variants. We relate the underestimation effect to the concept of non-collapsibility found in the statistics literature. As described, continuous phenotypes generated with linear genetic models are not affected by this underestimation effect. Since many GWA studies apply single SNP analysis to dichotomous phenotypes, previously reported results potentially underestimate true effect sizes, thereby impeding identification of true effect SNPs. Therefore, when a multi-locus model of disease risk is assumed, a multi SNP analysis may be more appropriate.

Extensive variation in the density and distribution of DNA polymorphism in sorghum genomes.

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Joseph Evans

Full Text Available Sorghum genotypes currently used for grain production in the United States were developed from African landraces that were imported starting in the mid-to-late 19(th century. Farmers and plant breeders selected genotypes for grain production with reduced plant height, early flowering, increased grain yield, adaptation to drought, and improved resistance to lodging, diseases and pests. DNA polymorphisms that distinguish three historically important grain sorghum genotypes, BTx623, BTx642 and Tx7000, were characterized by genome sequencing, genotyping by sequencing, genetic mapping, and pedigree-based haplotype analysis. The distribution and density of DNA polymorphisms in the sequenced genomes varied widely, in part because the lines were derived through breeding and selection from diverse Kafir, Durra, and Caudatum race accessions. Genomic DNA spanning dw1 (SBI-09 and dw3 (SBI-07 had identical haplotypes due to selection for reduced height. Lower SNP density in genes located in pericentromeric regions compared with genes located in euchromatic regions is consistent with background selection in these regions of low recombination. SNP density was higher in euchromatic DNA and varied >100-fold in contiguous intervals that spanned up to 300 Kbp. The localized variation in DNA polymorphism density occurred throughout euchromatic regions where recombination is elevated, however, polymorphism density was not correlated with gene density or DNA methylation. Overall, sorghum chromosomes contain distal euchromatic regions characterized by extensive, localized variation in DNA polymorphism density, and large pericentromeric regions of low gene density, diversity, and recombination.

Small-mammal density estimation: A field comparison of grid-based vs. web-based density estimators

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Parmenter, R.R.; Yates, Terry L.; Anderson, D.R.; Burnham, K.P.; Dunnum, J.L.; Franklin, A.B.; Friggens, M.T.; Lubow, B.C.; Miller, M.; Olson, G.S.; Parmenter, Cheryl A.; Pollard, J.; Rexstad, E.; Shenk, T.M.; Stanley, T.R.; White, Gary C.

2003-01-01

��blind” test allowed us to evaluate the influence of expertise and experience in calculating density estimates in comparison to simply using default values in programs CAPTURE and DISTANCE. While the rodent sample sizes were considerably smaller than the recommended minimum for good model results, we found that several models performed well empirically, including the web-based uniform and half-normal models in program DISTANCE, and the grid-based models Mb and Mbh in program CAPTURE (with AÌ‚ adjusted by species-specific full mean maximum distance moved (MMDM) values). These models produced accurate DÌ‚ values (with 95% confidence intervals that included the true D values) and exhibited acceptable bias but poor precision. However, in linear regression analyses comparing each model's DÌ‚ values to the true D values over the range of observed test densities, only the web-based uniform model exhibited a regression slope near 1.0; all other models showed substantial slope deviations, indicating biased estimates at higher or lower density values. In addition, the grid-based DÌ‚ analyses using full MMDM values for WÌ‚ area adjustments required a number of theoretical assumptions of uncertain validity, and we therefore viewed their empirical successes with caution. Finally, density estimates from the independent analysts were highly variable, but estimates from web-based approaches had smaller mean square errors and better achieved confidence-interval coverage of D than did grid-based approaches. Our results support the contention that web-based approaches for density estimation of small-mammal populations are both theoretically and empirically superior to grid-based approaches, even when sample size is far less than often recommended. In view of the increasing need for standardized environmental measures for comparisons among ecosystems and through time, analytical models based on distance sampling appear to offer accurate density estimation approaches for research

[Relationship between genetic polymorphisms of 3 SNP loci in 5-HTT gene and paranoid schizophrenia].

Science.gov (United States)

Xuan, Jin-Feng; Ding, Mei; Pang, Hao; Xing, Jia-Xin; Sun, Yi-Hua; Yao, Jun; Zhao, Yi; Li, Chun-Mei; Wang, Bao-Jie

2012-12-01

To investigate the population genetic data of 3 SNP loci (rs25533, rs34388196 and rs1042173) of 5-hydroxytryptamine transporter (5-HTT) gene and the association with paranoid schizophrenia. Three SNP loci of 5-HTT gene were examined in 132 paranoid schizophrenia patients and 150 unrelated healthy individuals of Northern Chinese Han population by PCR-RFLP technique. The Hardy-Weinberg equilibrium test was performed using the chi-square test and the data of haplotype frequency and population genetics parameters were statistically analyzed. Among these three SNP loci, four haplotypes were obtained. There were no statistically significant differences between the patient group and the control group (P > 0.05). The DP values of the 3 SNP loci were 0.276, 0.502 and 0.502. The PIC of them were 0.151, 0.281 and 0.281. The PE of them were 0.014, 0.072 and 0.072. The three SNP loci and four haplotypes of 5-HTT gene have no association with paranoid schizophrenia, while the polymorphism still have high potential application in forensic practice.

High-resolution melting genotyping of Enterococcus faecium based on multilocus sequence typing derived single nucleotide polymorphisms.

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Steven Y C Tong

Full Text Available We have developed a single nucleotide polymorphism (SNP nucleated high-resolution melting (HRM technique to genotype Enterococcus faecium. Eight SNPs were derived from the E. faecium multilocus sequence typing (MLST database and amplified fragments containing these SNPs were interrogated by HRM. We tested the HRM genotyping scheme on 85 E. faecium bloodstream isolates and compared the results with MLST, pulsed-field gel electrophoresis (PFGE and an allele specific real-time PCR (AS kinetic PCR SNP typing method. In silico analysis based on predicted HRM curves according to the G+C content of each fragment for all 567 sequence types (STs in the MLST database together with empiric data from the 85 isolates demonstrated that HRM analysis resolves E. faecium into 231 "melting types" (MelTs and provides a Simpson's Index of Diversity (D of 0.991 with respect to MLST. This is a significant improvement on the AS kinetic PCR SNP typing scheme that resolves 61 SNP types with D of 0.95. The MelTs were concordant with the known ST of the isolates. For the 85 isolates, there were 13 PFGE patterns, 17 STs, 14 MelTs and eight SNP types. There was excellent concordance between PFGE, MLST and MelTs with Adjusted Rand Indices of PFGE to MelT 0.936 and ST to MelT 0.973. In conclusion, this HRM based method appears rapid and reproducible. The results are concordant with MLST and the MLST based population structure.

Genome-wide ENU mutagenesis in combination with high density SNP analysis and exome sequencing provides rapid identification of novel mouse models of developmental disease.

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Georgina Caruana

Full Text Available Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking gene function to normal development and human disorders. To generate mouse models harbouring novel alleles that are involved in organogenesis we conducted a phenotype-driven, genome-wide mutagenesis screen in mice using the mutagen N-ethyl-N-nitrosourea (ENU.ENU was injected into male C57BL/6 mice and the mutations transmitted through the germ-line. ENU-induced mutations were bred to homozygosity and G3 embryos screened at embryonic day (E 13.5 and E18.5 for abnormalities in limb and craniofacial structures, skin, blood, vasculature, lungs, gut, kidneys, ureters and gonads. From 52 pedigrees screened 15 were detected with anomalies in one or more of the structures/organs screened. Using single nucleotide polymorphism (SNP-based linkage analysis in conjunction with candidate gene or next-generation sequencing (NGS we identified novel recessive alleles for Fras1, Ift140 and Lig1.In this study we have generated mouse models in which the anomalies closely mimic those seen in human disorders. The association between novel mutant alleles and phenotypes will lead to a better understanding of gene function in normal development and establish how their dysfunction causes human anomalies and disease.

Single tube genotyping of sickle cell anaemia using PCR-based SNP analysis.

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Waterfall, C M; Cobb, B D

2001-12-01

Allele-specific amplification (ASA) is a generally applicable technique for the detection of known single nucleotide polymorphisms (SNPs), deletions, insertions and other sequence variations. Conventionally, two reactions are required to determine the zygosity of DNA in a two-allele system, along with significant upstream optimisation to define the specific test conditions. Here, we combine single tube bi-directional ASA with a 'matrix-based' optimisation strategy, speeding up the whole process in a reduced reaction set. We use sickle cell anaemia as our model SNP system, a genetic disease that is currently screened using ASA methods. Discriminatory conditions were rapidly optimised enabling the unambiguous identification of DNA from homozygous sickle cell patients (HbS/S), heterozygous carriers (HbA/S) or normal DNA in a single tube. Simple downstream mathematical analyses based on product yield across the optimisation set allow an insight into the important aspects of priming competition and component interactions in this competitive PCR. This strategy can be applied to any polymorphism, defining specific conditions using a multifactorial approach. The inherent simplicity and low cost of this PCR-based method validates bi-directional ASA as an effective tool in future clinical screening and pharmacogenomic research where more expensive fluorescence-based approaches may not be desirable.

MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

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Landt Olfert

2008-04-01

Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

Repairability of CAD/CAM high-density PMMA- and composite-based polymers.

Science.gov (United States)

Wiegand, Annette; Stucki, Lukas; Hoffmann, Robin; Attin, Thomas; Stawarczyk, Bogna

2015-11-01

The study aimed to analyse the shear bond strength of computer-aided design and computer-aided manufacturing (CAD/CAM) polymethyl methacrylate (PMMA)- and composite-based polymer materials repaired with a conventional methacrylate-based composite after different surface pretreatments. Each 48 specimens was prepared from six different CAD/CAM polymer materials (Ambarino high-class, artBloc Temp, CAD-Temp, Lava Ultimate, Telio CAD, Everest C-Temp) and a conventional dimethacrylate-based composite (Filtek Supreme XTE, control) and aged by thermal cycling (5000 cycles, 5-55 °C). The surfaces were left untreated or were pretreated by mechanical roughening, aluminium oxide air abrasion or silica coating/silanization (each subgroup n = 12). The surfaces were further conditioned with an etch&rinse adhesive (OptiBond FL) before the repair composite (Filtek Supreme XTE) was adhered to the surface. After further thermal cycling, shear bond strength was tested, and failure modes were assessed. Shear bond strength was statistically analysed by two- and one-way ANOVAs and Weibull statistics, failure mode by chi(2) test (p ≤ 0.05). Shear bond strength was highest for silica coating/silanization > aluminium oxide air abrasion = mechanical roughening > no surface pretreatment. Independently of the repair pretreatment, highest bond strength values were observed in the control group and for the composite-based Everest C-Temp and Ambarino high-class, while PMMA-based materials (artBloc Temp, CAD-Temp and Telio CAD) presented significantly lowest values. For all materials, repair without any surface pretreatment resulted in adhesive failures only, which mostly were reduced when surface pretreatment was performed. Repair of CAD/CAM high-density polymers requires surface pretreatment prior to adhesive and composite application. However, four out of six of the tested CAD/CAM materials did not achieve the repair bond strength of a conventional dimethacrylate-based

High-Current-Density Vertical-Tunneling Transistors from Graphene/Highly Doped Silicon Heterostructures.

Science.gov (United States)

Liu, Yuan; Sheng, Jiming; Wu, Hao; He, Qiyuan; Cheng, Hung-Chieh; Shakir, Muhammad Imran; Huang, Yu; Duan, Xiangfeng

2016-06-01

Scalable fabrication of vertical-tunneling transistors is presented based on heterostructures formed between graphene, highly doped silicon, and its native oxide. Benefiting from the large density of states of highly doped silicon, the tunneling transistors can deliver a current density over 20 A cm(-2) . This study demonstrates that the interfacial native oxide plays a crucial role in governing the carrier transport in graphene-silicon heterostructures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SNP discovery in the bovine milk transcriptome using RNA-Seq technology.

Science.gov (United States)

Cánovas, Angela; Rincon, Gonzalo; Islas-Trejo, Alma; Wickramasinghe, Saumya; Medrano, Juan F

2010-12-01

High-throughput sequencing of RNA (RNA-Seq) was developed primarily to analyze global gene expression in different tissues. However, it also is an efficient way to discover coding SNPs. The objective of this study was to perform a SNP discovery analysis in the milk transcriptome using RNA-Seq. Seven milk samples from Holstein cows were analyzed by sequencing cDNAs using the Illumina Genome Analyzer system. We detected 19,175 genes expressed in milk samples corresponding to approximately 70% of the total number of genes analyzed. The SNP detection analysis revealed 100,734 SNPs in Holstein samples, and a large number of those corresponded to differences between the Holstein breed and the Hereford bovine genome assembly Btau4.0. The number of polymorphic SNPs within Holstein cows was 33,045. The accuracy of RNA-Seq SNP discovery was tested by comparing SNPs detected in a set of 42 candidate genes expressed in milk that had been resequenced earlier using Sanger sequencing technology. Seventy of 86 SNPs were detected using both RNA-Seq and Sanger sequencing technologies. The KASPar Genotyping System was used to validate unique SNPs found by RNA-Seq but not observed by Sanger technology. Our results confirm that analyzing the transcriptome using RNA-Seq technology is an efficient and cost-effective method to identify SNPs in transcribed regions. This study creates guidelines to maximize the accuracy of SNP discovery and prevention of false-positive SNP detection, and provides more than 33,000 SNPs located in coding regions of genes expressed during lactation that can be used to develop genotyping platforms to perform marker-trait association studies in Holstein cattle.

High baryon density from relativistic heavy ion collisions

Energy Technology Data Exchange (ETDEWEB)

Pang, Y.; Kahana, S.H. [Brookhaven National Lab., Upton, NY (United States); Schlagel, T.J. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

1993-10-01

A quantitative model, based on hadronic physics, is developed and applied to heavy ion collisions at BNL-AGS energies. This model is in excellent agreement with observed particle spectra in heavy ion collisions using Si beams, where baryon densities of three and four times the normal nuclear matter density ({rho}{sub 0}) are reached. For Au on Au collisions, the authors predict the formation of matter at very high densities (up to 10 {rho}{sub 0}).

Forensic typing of autosomal SNPs with a 29 SNP-multiplex--results of a collaborative EDNAP exercise.

Science.gov (United States)

Sanchez, J J; Børsting, C; Balogh, K; Berger, B; Bogus, M; Butler, J M; Carracedo, A; Court, D Syndercombe; Dixon, L A; Filipović, B; Fondevila, M; Gill, P; Harrison, C D; Hohoff, C; Huel, R; Ludes, B; Parson, W; Parsons, T J; Petkovski, E; Phillips, C; Schmitter, H; Schneider, P M; Vallone, P M; Morling, N

2008-06-01

We report the results of an inter-laboratory exercise on typing of autosomal single nucleotide polymorphisms (SNP) for forensic genetic investigations in crime cases. The European DNA Profiling Group (EDNAP), a working group under the International Society for Forensic Genetics (ISFG), organised the exercise. A total of 11 European and one US forensic genetic laboratories tested a subset of a 52 SNP-multiplex PCR kit developed by the SNPforID consortium. The 52 SNP-multiplex kit amplifies 52 DNA fragments with 52 autosomal SNP loci in one multiplex PCR. The 52 SNPs are detected in two separate single base extension (SBE) multiplex reactions with 29 and 23 SNPs, respectively, using SNaPshot kit, capillary electrophoresis and multicolour fluorescence detection. For practical reasons, only the 29 SBE multiplex reaction was carried out by the participating laboratories. A total of 11 bloodstains on FTA cards including a sample of poor quality and a negative control were sent to the laboratories together with the essential reagents for the initial multiplex PCR and the multiplex SBE reaction. The total SNP locus dropout rate was 2.8% and more than 50% of the dropouts were observed with the poor quality sample. The overall rate of discrepant SNP allele assignments was 2.0%. Two laboratories reported 60% of all the discrepancies. Two laboratories reported all 29 SNP alleles in all 10 positive samples correctly. The results of the collaborative exercise were surprisingly good and demonstrate that SNP typing with SBE, capillary electrophoresis and multicolour detection methods can be developed for forensic genetics.

Models for Experimental High Density Housing

Science.gov (United States)

Bradecki, Tomasz; Swoboda, Julia; Nowak, Katarzyna; Dziechciarz, Klaudia

2017-10-01

The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio - housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.

High-density hybrid interconnect methodologies

International Nuclear Information System (INIS)

John, J.; Zimmermann, L.; Moor, P.De; Hoof, C.Van

2003-01-01

Full text: The presentation gives an overview of the state-of-the-art of hybrid integration and in particular the IMEC technological approaches that will be able to address future hybrid detector needs. The dense hybrid flip-chip integration of an array of detectors and its dedicated readout electronics can be achieved with a variety of solderbump techniques such as pure Indium or Indium alloys, Ph-In, Ni/PbSn, but also conducting polymers... Particularly for cooled applications or ultra-high density applications, Indium solderbump technology (electroplated or evaporated) is the method of choice. The state-of-the-art of solderbump technologies that are to a high degree independent of the underlying detector material will be presented and examples of interconnect densities between 5x1E4cm-2 and 1x1E6 cm-2 will be demonstrated. For several classes of detectors, flip-chip integration is not allowed since the detectors have to be illuminated from the top. This applies to image sensors for EUV applications such as GaN/AlGaN based detectors and to MEMS-based sensors. In such cases, the only viable interconnection method has to be through the (thinned) detector wafer followed by a solderbump-based integration. The approaches for dense and ultra-dense through-the-wafer interconnect 'vias' will be presented and wafer thinning approaches will be shown

Genetic dissection of powdery mildew resistance in interspecific half-sib grapevine families using SNP-based maps.

Science.gov (United States)

Teh, Soon Li; Fresnedo-Ramírez, Jonathan; Clark, Matthew D; Gadoury, David M; Sun, Qi; Cadle-Davidson, Lance; Luby, James J

2017-01-01

Quantitative trait locus (QTL) identification in perennial fruit crops is impeded largely by their lengthy generation time, resulting in costly and labor-intensive maintenance of breeding programs. In a grapevine (genus Vitis ) breeding program, although experimental families are typically unreplicated, the genetic backgrounds may contain similar progenitors previously selected due to their contribution of favorable alleles. In this study, we investigated the utility of joint QTL identification provided by analyzing half-sib families. The genetic control of powdery mildew was studied using two half-sib F 1 families, namely GE0711/1009 (MN1264 × MN1214; N  = 147) and GE1025 (MN1264 × MN1246; N  = 125) with multiple species in their ancestry. Maternal genetic maps consisting of 1077 and 1641 single nucleotide polymorphism (SNP) markers, respectively, were constructed using a pseudo-testcross strategy. Ratings of field resistance to powdery mildew were obtained based on whole-plant evaluation of disease severity. This 2-year analysis uncovered two QTLs that were validated on a consensus map in these half-sib families with improved precision relative to the parental maps. Examination of haplotype combinations based on the two QTL regions identified strong association of haplotypes inherited from 'Seyval blanc', through MN1264, with powdery mildew resistance. This investigation also encompassed the use of microsatellite markers to establish a correlation between 206-bp (UDV-015b) and 357-bp (VViv67) fragment sizes with resistance-carrying haplotypes. Our work is one of the first reports in grapevine demonstrating the use of SNP-based maps and haplotypes for QTL identification and tagging of powdery mildew resistance in half-sib families.

Fine-scaled human genetic structure revealed by SNP microarrays.

Science.gov (United States)

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.

MAFsnp: A Multi-Sample Accurate and Flexible SNP Caller Using Next-Generation Sequencing Data

Science.gov (United States)

Hu, Jiyuan; Li, Tengfei; Xiu, Zidi; Zhang, Hong

2015-01-01

Most existing statistical methods developed for calling single nucleotide polymorphisms (SNPs) using next-generation sequencing (NGS) data are based on Bayesian frameworks, and there does not exist any SNP caller that produces p-values for calling SNPs in a frequentist framework. To fill in this gap, we develop a new method MAFsnp, a Multiple-sample based Accurate and Flexible algorithm for calling SNPs with NGS data. MAFsnp is based on an estimated likelihood ratio test (eLRT) statistic. In practical situation, the involved parameter is very close to the boundary of the parametric space, so the standard large sample property is not suitable to evaluate the finite-sample distribution of the eLRT statistic. Observing that the distribution of the test statistic is a mixture of zero and a continuous part, we propose to model the test statistic with a novel two-parameter mixture distribution. Once the parameters in the mixture distribution are estimated, p-values can be easily calculated for detecting SNPs, and the multiple-testing corrected p-values can be used to control false discovery rate (FDR) at any pre-specified level. With simulated data, MAFsnp is shown to have much better control of FDR than the existing SNP callers. Through the application to two real datasets, MAFsnp is also shown to outperform the existing SNP callers in terms of calling accuracy. An R package “MAFsnp” implementing the new SNP caller is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/. PMID:26309201

Development of COS-SNP and HRM markers for high-throughput and reliable haplotype-based detection of Lr14a in durum wheat (Triticum durum Desf.).

Science.gov (United States)

Terracciano, Irma; Maccaferri, Marco; Bassi, Filippo; Mantovani, Paola; Sanguineti, Maria C; Salvi, Silvio; Simková, Hana; Doležel, Jaroslav; Massi, Andrea; Ammar, Karim; Kolmer, James; Tuberosa, Roberto

2013-04-01

Leaf rust (Puccinia triticina Eriks. & Henn.) is a major disease affecting durum wheat production. The Lr14a-resistant gene present in the durum wheat cv. Creso and its derivative cv. Colosseo is one of the best characterized leaf-rust resistance sources deployed in durum wheat breeding. Lr14a has been mapped close to the simple sequence repeat markers gwm146, gwm344 and wmc10 in the distal portion of the chromosome arm 7BL, a gene-dense region. The objectives of this study were: (1) to enrich the Lr14a region with single nucleotide polymorphisms (SNPs) and high-resolution melting (HRM)-based markers developed from conserved ortholog set (COS) genes and from sequenced Diversity Array Technology (DArT(®)) markers; (2) to further investigate the gene content and colinearity of this region with the Brachypodium and rice genomes. Ten new COS-SNP and five HRM markers were mapped within an 8.0 cM interval spanning Lr14a. Two HRM markers pinpointed the locus in an interval of HRM designed for agarose gel electrophoresis/KASPar(®) assays and high-resolution melting analysis, respectively, as well as the double-marker combinations ubw14/ubw18, ubw14/ubw35 and wPt-4038-HRM-ubw35 will be useful for germplasm haplotyping and for molecular-assisted breeding.

Genome wide in silico SNP-tumor association analysis

International Nuclear Information System (INIS)

Qiu, Ping; Wang, Luquan; Kostich, Mitch; Ding, Wei; Simon, Jason S; Greene, Jonathan R

2004-01-01

Carcinogenesis occurs, at least in part, due to the accumulation of mutations in critical genes that control the mechanisms of cell proliferation, differentiation and death. Publicly accessible databases contain millions of expressed sequence tag (EST) and single nucleotide polymorphism (SNP) records, which have the potential to assist in the identification of SNPs overrepresented in tumor tissue. An in silico SNP-tumor association study was performed utilizing tissue library and SNP information available in NCBI's dbEST (release 092002) and dbSNP (build 106). A total of 4865 SNPs were identified which were present at higher allele frequencies in tumor compared to normal tissues. A subset of 327 (6.7%) SNPs induce amino acid changes to the protein coding sequences. This approach identified several SNPs which have been previously associated with carcinogenesis, as well as a number of SNPs that now warrant further investigation This novel in silico approach can assist in prioritization of genes and SNPs in the effort to elucidate the genetic mechanisms underlying the development of cancer

Unidirectional threshold switching in Ag/Si-based electrochemical metallization cells for high-density bipolar RRAM applications

Science.gov (United States)

Wang, Chao; Song, Bing; Li, Qingjiang; Zeng, Zhongming

2018-03-01

We herein present a novel unidirectional threshold selector for cross-point bipolar RRAM array. The proposed Ag/amorphous Si based threshold selector showed excellent threshold characteristics in positive field, such as high selectivity ( 105), steep slope (type RRAM. By integrating a bipolar RRAM device with the selector, experiments showed that the undesired sneak was significantly suppressed, indicating its potentiality for high-density integrated nonvolatile memory applications.

Use of genotyping by sequencing data to develop a high-throughput and multifunctional SNP panel for conservation applications in Pacific lamprey.

Science.gov (United States)

Hess, Jon E; Campbell, Nathan R; Docker, Margaret F; Baker, Cyndi; Jackson, Aaron; Lampman, Ralph; McIlraith, Brian; Moser, Mary L; Statler, David P; Young, William P; Wildbill, Andrew J; Narum, Shawn R

2015-01-01

Next-generation sequencing data can be mined for highly informative single nucleotide polymorphisms (SNPs) to develop high-throughput genomic assays for nonmodel organisms. However, choosing a set of SNPs to address a variety of objectives can be difficult because SNPs are often not equally informative. We developed an optimal combination of 96 high-throughput SNP assays from a total of 4439 SNPs identified in a previous study of Pacific lamprey (Entosphenus tridentatus) and used them to address four disparate objectives: parentage analysis, species identification and characterization of neutral and adaptive variation. Nine of these SNPs are FST outliers, and five of these outliers are localized within genes and significantly associated with geography, run-timing and dwarf life history. Two of the 96 SNPs were diagnostic for two other lamprey species that were morphologically indistinguishable at early larval stages and were sympatric in the Pacific Northwest. The majority (85) of SNPs in the panel were highly informative for parentage analysis, that is, putatively neutral with high minor allele frequency across the species' range. Results from three case studies are presented to demonstrate the broad utility of this panel of SNP markers in this species. As Pacific lamprey populations are undergoing rapid decline, these SNPs provide an important resource to address critical uncertainties associated with the conservation and recovery of this imperiled species. © 2014 John Wiley & Sons Ltd.

High performance H-mode plasmas at densities above the Greenwald limit

International Nuclear Information System (INIS)

Mahdavi, M.A.; Osborne, T.H.; Leonard, A.W.

2001-01-01

Densities up to 40 percent above the Greenwald limit are reproducibly achieved in high confinement (H ITER89p =2) ELMing H-mode discharges. Simultaneous gas fueling and divertor pumping were used to obtain these results. Confinement of these discharges, similar to moderate density H-mode, is characterized by a stiff temperature profile, and therefore sensitive to the density profile. A particle transport model is presented that explains the roles of divertor pumping and geometry for access to high densities. Energy loss per ELM at high density is a factor of five lower than predictions of an earlier scaling, based on data from lower density discharges. (author)

OpenADAM: an open source genome-wide association data management system for Affymetrix SNP arrays

Directory of Open Access Journals (Sweden)

Sham P C

2008-12-01

Full Text Available Abstract Background Large scale genome-wide association studies have become popular since the introduction of high throughput genotyping platforms. Efficient management of the vast array of data generated poses many challenges. Description We have developed an open source web-based data management system for the large amount of genotype data generated from the Affymetrix GeneChip® Mapping Array and Affymetrix Genome-Wide Human SNP Array platforms. The database supports genotype calling using DM, BRLMM, BRLMM-P or Birdseed algorithms provided by the Affymetrix Power Tools. The genotype and corresponding pedigree data are stored in a relational database for efficient downstream data manipulation and analysis, such as calculation of allele and genotype frequencies, sample identity checking, and export of genotype data in various file formats for analysis using commonly-available software. A novel method for genotyping error estimation is implemented using linkage disequilibrium information from the HapMap project. All functionalities are accessible via a web-based user interface. Conclusion OpenADAM provides an open source database system for management of Affymetrix genome-wide association SNP data.

SUPLEMENTASI Lactobacillus acidophilus SNP-2 PADA TAPE DAN PENGARUHNYA PADA RELAWAN [Supplementation of Lactocbacillus acidophilus SNP-2 Into Tape and its Effect to the Volunteer

Directory of Open Access Journals (Sweden)

Endang S Rahayu1

2004-08-01

Full Text Available Functional food is defined as any potentially healthful food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains. Many researches have been conducted on the health benefit of probiotic (life bacterial cells, one of the ingredient of functional foods. One of the potential bacteria used for probiotic agent and also involved in traditional fermented foods are lactic acid bacteria (LAB. Previous research showed that Lactobacillus acidophilus SNP-2 isolated from faecal material of healthy infant is resistant to acid and bile salt, and has an antagonistic effect against several enteric bacterial pathogens. The objective of this research was to study the effect of L. acidophilus SNP-2 as probiotic agent to the health benefits. These bacteria were supplemented into tape ketan (fermented sticky rice, the indigenous Indonesian fermented food. Tape ketan was chosen as the carrier of probiotic biomass based on the high population of LAB in this product, i.e., 1.3 x 108 CFU/g. Addition of L. acidophilus SNP-2 biomass prior to fermentation of tape ketan resulted in a higher total of LAB cells, i.e. 2.1 x 109 CFU/g compared to the amount of 1.5 x 108 CFU/g when the addition was done after fermentation. Consumption of tape ketan containing probiotic agent by the volunteers increased the population of lactobacilli (from 1.7x107 CFU/g to 9.9x107 CFU/g and decreased the population of enterobacteriacea (from 5.4x109 CFU/g to 4.4x108 in their faecal material. This phenomenon revealed that probiotic agent was able to colonize and inhibit the growth of enterobacteriaceae in the gastrointestinal tract. The result implied that tape ketan can be used as a carrier for probiotic agent and it can be categorized as functional food

Heap: a highly sensitive and accurate SNP detection tool for low-coverage high-throughput sequencing data

KAUST Repository

Kobayashi, Masaaki

2017-04-20

Recent availability of large-scale genomic resources enables us to conduct so called genome-wide association studies (GWAS) and genomic prediction (GP) studies, particularly with next-generation sequencing (NGS) data. The effectiveness of GWAS and GP depends on not only their mathematical models, but the quality and quantity of variants employed in the analysis. In NGS single nucleotide polymorphism (SNP) calling, conventional tools ideally require more reads for higher SNP sensitivity and accuracy. In this study, we aimed to develop a tool, Heap, that enables robustly sensitive and accurate calling of SNPs, particularly with a low coverage NGS data, which must be aligned to the reference genome sequences in advance. To reduce false positive SNPs, Heap determines genotypes and calls SNPs at each site except for sites at the both ends of reads or containing a minor allele supported by only one read. Performance comparison with existing tools showed that Heap achieved the highest F-scores with low coverage (7X) restriction-site associated DNA sequencing reads of sorghum and rice individuals. This will facilitate cost-effective GWAS and GP studies in this NGS era. Code and documentation of Heap are freely available from https://github.com/meiji-bioinf/heap (29 March 2017, date last accessed) and our web site (http://bioinf.mind.meiji.ac.jp/lab/en/tools.html (29 March 2017, date last accessed)).

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce

Science.gov (United States)

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W.

2013-01-01

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa. The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. PMID:23550116

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.

Science.gov (United States)

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W

2013-04-09

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F 7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. Copyright © 2013 Truco et al.

High-Density Genetic Map Construction and Stem Total Polysaccharide Content-Related QTL Exploration for Chinese Endemic Dendrobium (Orchidaceae)

Science.gov (United States)

Lu, Jiangjie; Liu, Yuyang; Xu, Jing; Mei, Ziwei; Shi, Yujun; Liu, Pengli; He, Jianbo; Wang, Xiaotong; Meng, Yijun; Feng, Shangguo; Shen, Chenjia; Wang, Huizhong

2018-01-01

Plants of the Dendrobium genus are orchids with not only ornamental value but also high medicinal value. To understand the genetic basis of variations in active ingredients of the stem total polysaccharide contents (STPCs) among different Dendrobium species, it is of paramount importance to understand the mechanism of STPC formation and identify genes affecting its process at the whole genome level. Here, we report the first high-density single-nucleotide polymorphism (SNP) integrated genetic map with a good genome coverage of Dendrobium. The specific-locus amplified fragment sequencing (SLAF-seq) technology led to identification of 7,013,400 SNPs from 1,503,626 high-quality SLAF markers from two parents (Dendrobium moniliforme ♀ × Dendrobium officinale ♂) and their interspecific F1 hybrid population. The final genetic map contained 8, 573 SLAF markers, covering 19 linkage groups (LGs). This genetic map spanned a length of 2,737.49 cM, where the average distance between markers is 0.32 cM. In total, 5 quantitative trait loci (QTL) related to STPC were identified, 3 of which have candidate genes within the confidence intervals of these stable QTLs based on the D. officinale genome sequence. This study will build a foundation up for the mapping of other medicinal-related traits and provide an important reference for the molecular breeding of these Chinese herb. PMID:29636767

High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

DEFF Research Database (Denmark)

Goyette, Philippe; Boucher, Gabrielle; Mallon, Dermot

2015-01-01

high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA......Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including...

Evaluation of the Ion Torrent™ HID SNP 169-plex

DEFF Research Database (Denmark)

Børsting, Claus; Fordyce, Sarah L; Olofsson, Jill Katharina

2014-01-01

The Ion Torrent™ HID SNP assay amplified 136 autosomal SNPs and 33 Y-chromosome markers in one PCR and the markers were subsequently typed using the Ion PGM™ second generation sequencing platform. A total of 51 of the autosomal SNPs were selected from the SNPforID panel that is routinely used...... in our ISO 17025 accredited laboratory. Concordance between the Ion Torrent™ HID SNP assay and the SNPforID assay was tested by typing 44 Iraqis twice with the Ion Torrent™ HID SNP assay. The same samples were previously typed with the SNPforID assay and the Y-chromosome haplogroups of the individuals...

Common genetic variation and novel loci associated with volumetric mammographic density.

Science.gov (United States)

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Identification, Characterization, and Mapping of a Novel SNP Associated with Body Color Transparency in Juvenile Red Sea Bream (Pagrus major).

Science.gov (United States)

Sawayama, Eitaro; Noguchi, Daiki; Nakayama, Kei; Takagi, Motohiro

2018-03-23

We previously reported a body color deformity in juvenile red sea bream, which shows transparency in the juvenile stage because of delayed chromatophore development compared with normal individuals, and this finding suggested a genetic cause based on parentage assessments. To conduct marker-assisted selection to eliminate broodstock inheriting the causative gene, developing DNA markers associated with the phenotype was needed. We first conducted SNP mining based on AFLP analysis using bulked-DNA from normal and transparent individuals. One SNP was identified from a transparent-specific AFLP fragment, which significantly associated with transparent individuals. Two alleles (A/G) were observed in this locus, and the genotype G/G was dominantly observed in the transparent groups (97.1%) collected from several production lots produced from different broodstock populations. A few normal individuals inherited the G/G genotype (5.0%), but the A/A and A/G genotypes were dominantly observed in the normal groups. The homologs region of the SNP was searched using a medaka genome database, and intron 12 of the Nell2a gene (located on chromosome 6 of the medaka genome) was highly matched. We also mapped the red sea bream Nell2a gene on the previously developed linkage maps, and this gene was mapped on a male linkage group, LG4-M. The newly found SNP was useful in eliminating broodstock possessing the causative gene of the body color transparency observed in juvenile stage of red sea bream.

The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies

Science.gov (United States)

Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong

2017-01-01

It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online. PMID:28736464

Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

KAUST Repository

Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

2012-01-01

Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

KAUST Repository

Cui, Peng

2012-03-23

Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

High density data storage principle, technology, and materials

CERN Document Server

Zhu, Daoben

2009-01-01

The explosive increase in information and the miniaturization of electronic devices demand new recording technologies and materials that combine high density, fast response, long retention time and rewriting capability. As predicted, the current silicon-based computer circuits are reaching their physical limits. Further miniaturization of the electronic components and increase in data storage density are vital for the next generation of IT equipment such as ultra high-speed mobile computing, communication devices and sophisticated sensors. This original book presents a comprehensive introduction to the significant research achievements on high-density data storage from the aspects of recording mechanisms, materials and fabrication technologies, which are promising for overcoming the physical limits of current data storage systems. The book serves as an useful guide for the development of optimized materials, technologies and device structures for future information storage, and will lead readers to the fascin...

(SNP) markers for the Chinese black sleeper, Bostrychus sinensis

African Journals Online (AJOL)

We characterized 11 single nucleotide ploymorphism (SNP) markers for the Chinese black sleeper, Bostrychus sinensis. These markers were isolated from a genomic library and tested in ten geographically distant individuals of B. sinensis. Polymorphisms of these SNP loci were assessed using a wild population including ...

High throughput nonparametric probability density estimation.

Science.gov (United States)

Farmer, Jenny; Jacobs, Donald

2018-01-01

In high throughput applications, such as those found in bioinformatics and finance, it is important to determine accurate probability distribution functions despite only minimal information about data characteristics, and without using human subjectivity. Such an automated process for univariate data is implemented to achieve this goal by merging the maximum entropy method with single order statistics and maximum likelihood. The only required properties of the random variables are that they are continuous and that they are, or can be approximated as, independent and identically distributed. A quasi-log-likelihood function based on single order statistics for sampled uniform random data is used to empirically construct a sample size invariant universal scoring function. Then a probability density estimate is determined by iteratively improving trial cumulative distribution functions, where better estimates are quantified by the scoring function that identifies atypical fluctuations. This criterion resists under and over fitting data as an alternative to employing the Bayesian or Akaike information criterion. Multiple estimates for the probability density reflect uncertainties due to statistical fluctuations in random samples. Scaled quantile residual plots are also introduced as an effective diagnostic to visualize the quality of the estimated probability densities. Benchmark tests show that estimates for the probability density function (PDF) converge to the true PDF as sample size increases on particularly difficult test probability densities that include cases with discontinuities, multi-resolution scales, heavy tails, and singularities. These results indicate the method has general applicability for high throughput statistical inference.

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

Science.gov (United States)

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

Multiplexed, high density electrophysiology with nanofabricated neural probes.

Directory of Open Access Journals (Sweden)

Jiangang Du

Full Text Available Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable.

Genome Wide Association Study of SNP-, Gene-, and Pathway-based Approaches to Identify Genes Influencing Susceptibility to Staphylococcus aureus Infections

Directory of Open Access Journals (Sweden)

Zhan eYe

2014-05-01

Full Text Available Background: We conducted a genome-wide association study (GWAS to identify specific genetic variants that underlie susceptibility to disease caused by Staphylococcus aureus in humans. Methods: Cases (n=309 and controls (n=2,925 were genotyped at 508,921 single nucleotide polymorphisms (SNPs. Cases had at least one laboratory and clinician confirmed disease caused by S. aureus whereas controls did not. R-package (for SNP association, EIGENSOFT (to estimate and adjust for population stratification and gene- (VEGAS and pathway-based (DAVID, PANTHER, and Ingenuity Pathway Analysis analyses were performed.Results: No SNP reached genome-wide significance. Four SNPs exceeded the pConclusion: We identified potential susceptibility genes for S. aureus diseases in this preliminary study but confirmation by other studies is needed. The observed associations could be relevant given the complexity of S. aureus as a pathogen and its ability to exploit multiple biological pathways to cause infections in humans.

Importing low-density ideas to high-density revitalisation

DEFF Research Database (Denmark)

Arnholtz, Jens; Ibsen, Christian Lyhne; Ibsen, Flemming

2016-01-01

Why did union officials from a high-union-density country like Denmark choose to import an organising strategy from low-density countries such as the US and the UK? Drawing on in-depth interviews with key union officials and internal documents, the authors of this article argue two key points. Fi...

Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses

NARCIS (Netherlands)

Orr, J.L.; Back, W.; Gu, J.; Leegwater, P.H.; Govindarajan, P.; Conroy, J.; Ducro, B.J.; Arendonk, van J.A.M.

2010-01-01

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

Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses.

Science.gov (United States)

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. © 2010 The Authors, Journal compilation © 2010 Stichting International Foundation for Animal Genetics.

A mitochondrial DNA SNP multiplex assigning Caucasians into 36 haplo- and subhaplogroups

DEFF Research Database (Denmark)

Mikkelsen, Martin; Rockenbauer, Eszter; Sørensen, Erik

2008-01-01

Mitochondrial DNA (mtDNA) is maternally inherited without recombination events and has a high copy number, which makes mtDNA analysis feasible even when genomic DNA is sparse or degraded. Here, we present a SNP typing assay with 33 previously described mtDNA coding region SNPs for haplogroup...... previously typed by sequencing of the mitochondrial HV1 and HV2 regions. Haplogroup assignments based on mtDNA coding region SNPs and sequencing of HV1 and HV2 regions gave identical results for 27% of the samples, and except for one sample, differences in haplogroup assignments were at the subhaplogroup...

Comparative analysis of core genome MLST and SNP typing within a European Salmonella serovar Enteritidis outbreak.

Science.gov (United States)

Pearce, Madison E; Alikhan, Nabil-Fareed; Dallman, Timothy J; Zhou, Zhemin; Grant, Kathie; Maiden, Martin C J

2018-06-02

Multi-country outbreaks of foodborne bacterial disease present challenges in their detection, tracking, and notification. As food is increasingly distributed across borders, such outbreaks are becoming more common. This increases the need for high-resolution, accessible, and replicable isolate typing schemes. Here we evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution reproducible typing of Salmonella enterica (S. enterica) isolates, by its application to a large European outbreak of S. enterica serovar Enteritidis. This outbreak had been extensively characterised using single nucleotide polymorphism (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP-based analysis, the epidemiological data, and whole genome MLST (wgMLST) analysis. Combination of the cgMLST and epidemiological data confirmed that the genetic diversity among the isolates predated the outbreak, and was likely present at the infection source. There was consequently no link between country of isolation and genetic diversity, but the cgMLST clusters were congruent with date of isolation. Furthermore, comparison with publicly available Enteritidis isolate data demonstrated that the cgMLST scheme presented is highly scalable, enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST scheme is therefore shown to be a standardised and scalable typing method, which allows Salmonella outbreaks to be analysed and compared across laboratories and jurisdictions. Copyright © 2018. Published by Elsevier B.V.

High Energy Density Laboratory Astrophysics

CERN Document Server

Lebedev, Sergey V

2007-01-01

During the past decade, research teams around the world have developed astrophysics-relevant research utilizing high energy-density facilities such as intense lasers and z-pinches. Every two years, at the International conference on High Energy Density Laboratory Astrophysics, scientists interested in this emerging field discuss the progress in topics covering: - Stellar evolution, stellar envelopes, opacities, radiation transport - Planetary Interiors, high-pressure EOS, dense plasma atomic physics - Supernovae, gamma-ray bursts, exploding systems, strong shocks, turbulent mixing - Supernova remnants, shock processing, radiative shocks - Astrophysical jets, high-Mach-number flows, magnetized radiative jets, magnetic reconnection - Compact object accretion disks, x-ray photoionized plasmas - Ultrastrong fields, particle acceleration, collisionless shocks. These proceedings cover many of the invited and contributed papers presented at the 6th International Conference on High Energy Density Laboratory Astrophys...

Giant energy density and high efficiency achieved in bismuth ferrite-based film capacitors via domain engineering.

Science.gov (United States)

Pan, Hao; Ma, Jing; Ma, Ji; Zhang, Qinghua; Liu, Xiaozhi; Guan, Bo; Gu, Lin; Zhang, Xin; Zhang, Yu-Jun; Li, Liangliang; Shen, Yang; Lin, Yuan-Hua; Nan, Ce-Wen

2018-05-08

Developing high-performance film dielectrics for capacitive energy storage has been a great challenge for modern electrical devices. Despite good results obtained in lead titanate-based dielectrics, lead-free alternatives are strongly desirable due to environmental concerns. Here we demonstrate that giant energy densities of ~70 J cm -3 , together with high efficiency as well as excellent cycling and thermal stability, can be achieved in lead-free bismuth ferrite-strontium titanate solid-solution films through domain engineering. It is revealed that the incorporation of strontium titanate transforms the ferroelectric micro-domains of bismuth ferrite into highly-dynamic polar nano-regions, resulting in a ferroelectric to relaxor-ferroelectric transition with concurrently improved energy density and efficiency. Additionally, the introduction of strontium titanate greatly improves the electrical insulation and breakdown strength of the films by suppressing the formation of oxygen vacancies. This work opens up a feasible and propagable route, i.e., domain engineering, to systematically develop new lead-free dielectrics for energy storage.

WSN-Based Space Charge Density Measurement System.

Science.gov (United States)

Deng, Dawei; Yuan, Haiwen; Lv, Jianxun; Ju, Yong

2017-01-01

It is generally acknowledged that high voltage direct current (HVDC) transmission line endures the drawback of large area, because of which the utilization of cable for space charge density monitoring system is of inconvenience. Compared with the traditional communication network, wireless sensor network (WSN) shows advantages in small volume, high flexibility and strong self-organization, thereby presenting great potential in solving the problem. Additionally, WSN is more suitable for the construction of distributed space charge density monitoring system as it has longer distance and higher mobility. A distributed wireless system is designed for collecting and monitoring the space charge density under HVDC transmission lines, which has been widely applied in both Chinese state grid HVDC test base and power transmission projects. Experimental results of the measuring system demonstrated its adaptability in the complex electromagnetic environment under the transmission lines and the ability in realizing accurate, flexible, and stable demands for the measurement of space charge density.

Relativistic density functional theory with picture-change corrected electron density based on infinite-order Douglas-Kroll-Hess method

Science.gov (United States)

Oyama, Takuro; Ikabata, Yasuhiro; Seino, Junji; Nakai, Hiromi

2017-07-01

This Letter proposes a density functional treatment based on the two-component relativistic scheme at the infinite-order Douglas-Kroll-Hess (IODKH) level. The exchange-correlation energy and potential are calculated using the electron density based on the picture-change corrected density operator transformed by the IODKH method. Numerical assessments indicated that the picture-change uncorrected density functional terms generate significant errors, on the order of hartree for heavy atoms. The present scheme was found to reproduce the energetics in the four-component treatment with high accuracy.

Analysis of SNP rs16754 of WT1 gene in a series of de novo acute myeloid leukemia patients.

Science.gov (United States)

Luna, Irene; Such, Esperanza; Cervera, Jose; Barragán, Eva; Jiménez-Velasco, Antonio; Dolz, Sandra; Ibáñez, Mariam; Gómez-Seguí, Inés; López-Pavía, María; Llop, Marta; Fuster, Óscar; Oltra, Silvestre; Moscardó, Federico; Martínez-Cuadrón, David; Senent, M Leonor; Gascón, Adriana; Montesinos, Pau; Martín, Guillermo; Bolufer, Pascual; Sanz, Miguel A

2012-12-01

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been previously described as a possible prognostic marker in normal karyotype acute myeloid leukemia (AML) patients. Nevertheless, the findings in this field are not always reproducible in different series. One hundred and seventy-five adult de novo AML patients were screened with two different methods for the detection of SNP rs16754: high-resolution melting (HRM) and FRET hybridization probes. Direct sequencing was used to validate both techniques. The SNP was detected in 52 out of 175 patients (30 %), both by HRM and hybridization probes. Direct sequencing confirmed that every positive sample in the screening methods had a variation in the DNA sequence. Patients with the wild-type genotype (WT1(AA)) for the SNP rs16754 were significantly younger than those with the heterozygous WT1(AG) genotype. No other difference was observed for baseline characteristic or outcome between patients with or without the SNP. Both techniques are equally reliable and reproducible as screening methods for the detection of the SNP rs16754, allowing for the selection of those samples that will need to be sequenced. We were unable to confirm the suggested favorable outcome of SNP rs16754 in de novo AML.

High-density multicore fibers

DEFF Research Database (Denmark)

Takenaga, K.; Matsuo, S.; Saitoh, K.

2016-01-01

High-density single-mode multicore fibers were designed and fabricated. A heterogeneous 30-core fiber realized a low crosstalk of −55 dB. A quasi-single-mode homogeneous 31-core fiber attained the highest core count as a single-mode multicore fiber.......High-density single-mode multicore fibers were designed and fabricated. A heterogeneous 30-core fiber realized a low crosstalk of −55 dB. A quasi-single-mode homogeneous 31-core fiber attained the highest core count as a single-mode multicore fiber....

High-field, high-density tokamak power reactor

International Nuclear Information System (INIS)

Cohn, D.R.; Cook, D.L.; Hay, R.D.; Kaplan, D.; Kreischer, K.; Lidskii, L.M.; Stephany, W.; Williams, J.E.C.; Jassby, D.L.; Okabayashi, M.

1977-11-01

A conceptual design of a compact (R 0 = 6.0 m) high power density (average P/sub f/ = 7.7 MW/m 3 ) tokamak demonstration power reactor has been developed. High magnetic field (B/sub t/ = 7.4 T) and moderate elongation (b/a = 1.6) permit operation at the high density (n(0) approximately 5 x 10 14 cm -3 ) needed for ignition in a relatively small plasma, with a spatially-averaged toroidal beta of only 4%. A unique design for the Nb 3 Sn toroidal-field magnet system reduces the stress in the high-field trunk region, and allows modularization for simpler disassembly. The modest value of toroidal beta permits a simple, modularized plasma-shaping coil system, located inside the TF coil trunk. Heating of the dense central plasma is attained by the use of ripple-assisted injection of 120-keV D 0 beams. The ripple-coil system also affords dynamic control of the plasma temperature during the burn period. A FLIBE-lithium blanket is designed especially for high-power-density operation in a high-field environment, and gives an overall tritium breeding ratio of 1.05 in the slowly pumped lithium

Biopolymer-nanocarbon composite electrodes for use as high-energy high-power density electrodes

Science.gov (United States)

Karakaya, Mehmet; Roberts, Mark; Arcilla-Velez, Margarita; Zhu, Jingyi; Podila, Ramakrishna; Rao, Apparao

2014-03-01

Supercapacitors (SCs) address our current energy storage and delivery needs by combining the high power, rapid switching, and exceptional cycle life of a capacitor with the high energy density of a battery. Although activated carbon is extensively used as a supercapacitor electrode due to its inexpensive nature, its low specific capacitance (100-120 F/g) fundamentally limits the energy density of SCs. We demonstrate that a nano-carbon based mechanically robust, electrically conducting, free-standing buckypaper electrode modified with an inexpensive biorenewable polymer, viz., lignin increases the electrode's specific capacitance (~ 600-700 F/g) while maintaining rapid discharge rates. In these systems, the carbon nanomaterials provide the high surface area, electrical conductivity and porosity, while the redox polymers provide a mechanism for charge storage through Faradaic charge transfer. The design of redox polymers and their incorporation into nanomaterial electrodes will be discussed with a focus on enabling high power and high energy density electrodes. Research supported by US NSF CMMI Grant 1246800.

Design and Characterization of a 52K SNP Chip for Goats

NARCIS (Netherlands)

Tosser-klopp, G.; Bardou, P.; Bouchez, O.; Cabau, C.; Crooijmans, R.P.M.A.; Dong, Y.; Donnadieu-Tonon, C.; Eggen, A.; Heuven, H.C.M.; Jamli, S.; Jiken, A.J.; Klopp, C.; Lawley, C.T.; McEwen, J.; Martin, P.; Moreno, C.R.; Mulsant, P.; Nabihoudine, I.; Pailhoux, E.; Palhiere, I.; Rupp, R.; Sarry, J.; Sayre, B.L.; Tircazes, A.; Wang, J.; Wang, W.; Zhang, W.G.

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

Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.

Science.gov (United States)

Xu, Li-Xin; Holland, Heidrun; Kirsten, Holger; Ahnert, Peter; Krupp, Wolfgang; Bauer, Manfred; Schober, Ralf; Mueller, Wolf; Fritzsch, Dominik; Meixensberger, Jürgen; Koschny, Ronald

2015-04-01

According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas. © 2014 Japanese Society of Neuropathology.

High density harp for SSCL linac

International Nuclear Information System (INIS)

Fritsche, C.T.; Krogh, M.L.; Crist, C.E.

1993-01-01

AlliedSignal Inc., Kansas City Division, and the Superconducting Super Collider Laboratory (SSCL) are collaboratively developing a high density harp for the SSCL linac. This harp is designed using hybrid microcircuit (HMC) technology to obtain a higher wire density than previously available. The developed harp contains one hundred twenty-eight 33-micron-diameter carbon wires on 0.38-mm centers. The harp features an onboard broken wire detection circuit. Carbon wire preparation and attachment processes were developed. High density surface mount connectors were located. The status of high density harp development will be presented along with planned future activities

High density harp for SSCL linac

International Nuclear Information System (INIS)

Fritsche, C.T.; Krogh, M.L.

1993-05-01

AlliedSignal Inc., Kansas City Division, and the Superconducting Super Collider Laboratory (SSCL) are collaboratively developing a high density harp for the SSCL linac. This harp is designed using hybrid microcircuit (HMC) technology to obtain a higher wire density than previously available. The developed harp contains one hundred twenty-eight 33-micron-diameter carbon wires on 0.38-mm centers. The harp features an onboard broken wire detection circuit. Carbon wire preparation and attachment processes were developed. High density surface mount connectors were located. The status of high density harp development will be presented along with planned future activities

High density dispersion fuel

International Nuclear Information System (INIS)

Hofman, G.L.

1996-01-01

A fuel development campaign that results in an aluminum plate-type fuel of unlimited LEU burnup capability with an uranium loading of 9 grams per cm 3 of meat should be considered an unqualified success. The current worldwide approved and accepted highest loading is 4.8 g cm -3 with U 3 Si 2 as fuel. High-density uranium compounds offer no real density advantage over U 3 Si 2 and have less desirable fabrication and performance characteristics as well. Of the higher-density compounds, U 3 Si has approximately a 30% higher uranium density but the density of the U 6 X compounds would yield the factor 1.5 needed to achieve 9 g cm -3 uranium loading. Unfortunately, irradiation tests proved these peritectic compounds have poor swelling behavior. It is for this reason that the authors are turning to uranium alloys. The reason pure uranium was not seriously considered as a dispersion fuel is mainly due to its high rate of growth and swelling at low temperatures. This problem was solved at least for relatively low burnup application in non-dispersion fuel elements with small additions of Si, Fe, and Al. This so called adjusted uranium has nearly the same density as pure α-uranium and it seems prudent to reconsider this alloy as a dispersant. Further modifications of uranium metal to achieve higher burnup swelling stability involve stabilization of the cubic γ phase at low temperatures where normally α phase exists. Several low neutron capture cross section elements such as Zr, Nb, Ti and Mo accomplish this in various degrees. The challenge is to produce a suitable form of fuel powder and develop a plate fabrication procedure, as well as obtain high burnup capability through irradiation testing

High regression rate, high density hybrid fuels, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — This SBIR program will investigate high energy density novel nanofuels combined with high density binders for use with an N2O oxidizer. Terves has developed...

Workshop on High Power ICH Antenna Designs for High Density Tokamaks

Science.gov (United States)

Aamodt, R. E.

1990-02-01

A workshop in high power ICH antenna designs for high density tokamaks was held to: (1) review the data base relevant to the high power heating of high density tokamaks; (2) identify the important issues which need to be addressed in order to ensure the success of the ICRF programs on CIT and Alcator C-MOD; and (3) recommend approaches for resolving the issues in a timely realistic manner. Some specific performance goals for the antenna system define a successful design effort. Simply stated these goals are: couple the specified power per antenna into the desired ion species; produce no more than an acceptable level of RF auxiliary power induced impurities; and have a mechanical structure which safely survives the thermal, mechanical and radiation stresses in the relevant environment. These goals are intimately coupled and difficult tradeoffs between scientific and engineering constraints have to be made.

SNP detection for massively parallel whole-genome resequencing

DEFF Research Database (Denmark)

Li, Ruiqiang; Li, Yingrui; Fang, Xiaodong

2009-01-01

-genome or target region resequencing. Here, we have developed a consensus-calling and SNP-detection method for sequencing-by-synthesis Illumina Genome Analyzer technology. We designed this method by carefully considering the data quality, alignment, and experimental errors common to this technology. All...... of this information was integrated into a single quality score for each base under Bayesian theory to measure the accuracy of consensus calling. We tested this methodology using a large-scale human resequencing data set of 36x coverage and assembled a high-quality nonrepetitive consensus sequence for 92.......25% of the diploid autosomes and 88.07% of the haploid X chromosome. Comparison of the consensus sequence with Illumina human 1M BeadChip genotyped alleles from the same DNA sample showed that 98.6% of the 37,933 genotyped alleles on the X chromosome and 98% of 999,981 genotyped alleles on autosomes were covered...

High-Density Renewable Fuels Based on the Selective Dimerization of Pinenes

Science.gov (United States)

2009-01-01

RJ-5, significant ring strain contributing to a high heat of combustion (Table 1). Bulk agricultural waste products, such as cellulose and lignin , are...compact structures and reactive olefin functionalities, these molecules have sig- nificant potential as feedstocks for high-density renewable fuels.2b,7...potential to have heating values exceeding that of JP-10. Given the favorable potential net heat of combustion for these pinene dimers, reactivity

Dissecting tocopherols content in maize (Zea mays L.), using two segregating populations and high-density single nucleotide polymorphism markers

Science.gov (United States)

2012-01-01

Background Tocopherols, which are vitamin E compounds, play an important role in maintaining human health. Compared with other staple foods, maize grains contain high level of tocopherols. Results Two F2 populations (K22/CI7 and K22/Dan340, referred to as POP-1 and POP-2, respectively), which share a common parent (K22), were developed and genotyped using a GoldenGate assay containing 1,536 single nucleotide polymorphism (SNP) markers. An integrated genetic linkage map was constructed using 619 SNP markers, spanning a total of 1649.03 cM of the maize genome with an average interval of 2.67 cM. Seventeen quantitative trait loci (QTLs) for all the traits were detected in the first map and 13 in the second. In these two maps, QTLs for different traits were localized to the same genomic regions and some were co-located with candidate genes in the tocopherol biosynthesis pathway. Single QTL was responsible for 3.03% to 52.75% of the phenotypic variation and the QTLs in sum explained23.4% to 66.52% of the total phenotypic variation. A major QTL (qc5-1/qd5-1) affecting α-tocopherol (αT) was identified on chromosome 5 between the PZA03161.1 and PZA02068.1 in the POP-2. The QTL region was narrowed down from 18.7 Mb to 5.4 Mb by estimating the recombination using high-density markers of the QTL region. This allowed the identification of the candidate gene VTE4 which encodes γ-tocopherol methyltransferase, an enzyme that transforms γ-tocopherol (γT)to αT. Conclusions These results demonstrate that a few QTLs with major effects and several QTLs with medium to minor effects might contribute to the natural variation of tocopherols in maize grain. The high-density markers will help to fine map and identify the QTLs with major effects even in the preliminary segregating populations. Furthermore, this study provides a simple guide line for the breeders to improve traits that minimize the risk of malnutrition, especially in developing countries. PMID:23122295

Psoriasis prediction from genome-wide SNP profiles

Directory of Open Access Journals (Sweden)

Fang Xiangzhong

2011-01-01

Full Text Available Abstract Background With the availability of large-scale genome-wide association study (GWAS data, choosing an optimal set of SNPs for disease susceptibility prediction is a challenging task. This study aimed to use single nucleotide polymorphisms (SNPs to predict psoriasis from searching GWAS data. Methods Totally we had 2,798 samples and 451,724 SNPs. Process for searching a set of SNPs to predict susceptibility for psoriasis consisted of two steps. The first one was to search top 1,000 SNPs with high accuracy for prediction of psoriasis from GWAS dataset. The second one was to search for an optimal SNP subset for predicting psoriasis. The sequential information bottleneck (sIB method was compared with classical linear discriminant analysis(LDA for classification performance. Results The best test harmonic mean of sensitivity and specificity for predicting psoriasis by sIB was 0.674(95% CI: 0.650-0.698, while only 0.520(95% CI: 0.472-0.524 was reported for predicting disease by LDA. Our results indicate that the new classifier sIB performs better than LDA in the study. Conclusions The fact that a small set of SNPs can predict disease status with average accuracy of 68% makes it possible to use SNP data for psoriasis prediction.

Workshop on high power ICH antenna designs for high density tokamaks

International Nuclear Information System (INIS)

Aamodt, R.E.

1990-01-01

A workshop in high power ICH antenna designs for high density tokamaks was held in Boulder, Colorado on January 31 through February 2, 1990. The purposes of the workshop were to: (1) review the data base relevant to the high power heating of high density tokamaks; (2) identify the important issues which need to be addressed in order to ensure the success of the ICRF programs on CIT and Alcator C-MOD; and (3) recommend approaches for resolving the issues in a timely realistic manner. Some specific performance goals for the antenna system define a successful design effort. Simply stated these goals are: couple the specified power per antenna into the desired ion species; produce no more than an acceptable level of rf auxiliary power induced impurities; and have a mechanical structure which safely survives the thermal, mechanical and radiation stresses in the relevant environment. These goals are intimately coupled and difficult tradeoffs between scientific and engineering constraints have to be made

Edge-enriched, porous carbon-based, high energy density supercapacitors for hybrid electric vehicles.

Science.gov (United States)

Kim, Yong Jung; Yang, Cheol-Min; Park, Ki Chul; Kaneko, Katsumi; Kim, Yoong Ahm; Noguchi, Minoru; Fujino, Takeshi; Oyama, Shigeki; Endo, Morinobu

2012-03-12

Supercapacitors can store and deliver energy by a simple charge separation, and thus they could be an attractive option to meet transient high energy density in operating fuel cells and in electric and hybrid electric vehicles. To achieve such requirements, intensive studies have been carried out to improve the volumetric capacitance in supercapacitors using various types and forms of carbons including carbon nanotubes and graphenes. However, conventional porous carbons are not suitable for use as electrode material in supercapacitors for such high energy density applications. Here, we show that edge-enriched porous carbons are the best electrode material for high energy density supercapacitors to be used in vehicles as an auxiliary powertrain. Molten potassium hydroxide penetrates well-aligned graphene layers vertically and consequently generates both suitable pores that are easily accessible to the electrolyte and a large fraction of electrochemically active edge sites. We expect that our findings will motivate further research related to energy storage devices and also environmentally friendly electric vehicles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advanced Cathode Material For High Energy Density Lithium-Batteries, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Advanced cathode materials having high red-ox potential and high specific capacity offer great promise to the development of high energy density lithium-based...

Magnetization of High Density Hadronic Fluid

DEFF Research Database (Denmark)

Bohr, Henrik; Providencia, Constanca; da Providencia, João

2012-01-01

In the present paper the magnetization of a high density relativistic fluid of elementary particles is studied. At very high densities, such as may be found in the interior of a neutron star, when the external magnetic field is gradually increased, the energy of the normal phase of the fluid...... in the particle fluid. For nuclear densities above 2 to 3 rho(0), where rho(0) is the equilibrium nuclear density, the resulting magnetic field turns out to be rather huge, of the order of 10(17) Gauss....

Grouping and clustering of maize Lancaster germplasm inbreds according to the results of SNP-analysis

Directory of Open Access Journals (Sweden)

K. V. Derkach

2017-08-01

Full Text Available The objective of this article is the grouping and clustering of maize inbred lines based on the results of SNP-genotyping for the verification of a separate cluster of Lancaster germplasm inbred lines. As material for the study, we used 91 maize (Zea mays L. inbred lines, including 31 Lancaster germplasm lines and 60 inbred lines of other germplasms (23 Iodent inbreds, 15 Reid inbreds, 7 Lacon inbreds, 12 Mix inbreds and 3 exotic inbreds. The majority of the given inbred lines are included in the Dnipro breeding programme. The SNP-genotyping of these inbred lines was conducted using BDI-III panel of 384 SNP-markers developed by BioDiagnostics, Inc. (USA on the base of Illumina VeraCode Bead Plate. The SNP-markers of this panel are biallelic and are located on all 10 maize chromosomes. Their range of conductivity was >0.6. The SNP-analysis was made in completely automated regime on Illumina BeadStation equipment at BioDiagnostics, Inc. (USA. A principal component analysis was applied to group a general set of 91 inbreds according to allelic states of SNP-markers and to identify a cluster of Lancaster inbreds. The clustering and determining hierarchy in 31 Lancaster germplasm inbreds used quantitative cluster analysis. The share of monomorphic markers in the studied set of 91 inbred lines equaled 0.7%, and the share of dimorphic markers equaled 99.3%. Minor allele frequency (MAF > 0.2 was observed for 80.6% of dimorphic markers, the average index of shift of gene diversity equaled 0.2984, PIC on average reached 0.3144. The index of gene diversity of markers varied from 0.1701 to 0.1901, pairwise genetic distances between inbred lines ranged from 0.0316–0.8000, the frequencies of major alleles of SNP-markers were within 0.5085–0.9821, and the frequencies of minor alleles were within 0.0179–0.4915. The average homozygosity of inbred lines was 98.8%. The principal component analysis of SNP-distances confirmed the isolation of the Lancaster

Towards a consensus Y-chromosomal phylogeny and Y-SNP set in forensics in the next-generation sequencing era.

Science.gov (United States)

Larmuseau, Maarten H D; Van Geystelen, Anneleen; Kayser, Manfred; van Oven, Mannis; Decorte, Ronny

2015-03-01

Currently, several different Y-chromosomal phylogenies and haplogroup nomenclatures are presented in scientific literature and at conferences demonstrating the present diversity in Y-chromosomal phylogenetic trees and Y-SNP sets used within forensic and anthropological research. This situation can be ascribed to the exponential growth of the number of Y-SNPs discovered due to mostly next-generation sequencing (NGS) studies. As Y-SNPs and their respective phylogenetic positions are important in forensics, such as for male lineage characterization and paternal bio-geographic ancestry inference, there is a need for forensic geneticists to know how to deal with these newly identified Y-SNPs and phylogenies, especially since these phylogenies are often created with other aims than to carry out forensic genetic research. Therefore, we give here an overview of four categories of currently used Y-chromosomal phylogenies and the associated Y-SNP sets in scientific research in the current NGS era. We compare these categories based on the construction method, their advantages and disadvantages, the disciplines wherein the phylogenetic tree can be used, and their specific relevance for forensic geneticists. Based on this overview, it is clear that an up-to-date reduced tree with a consensus Y-SNP set and a stable nomenclature will be the most appropriate reference resource for forensic research. Initiatives to reach such an international consensus are therefore highly recommended. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Molecular phylogeny and SNP variation of polar bears (Ursus maritimus), brown bears (U. arctos), and black bears (U. americanus) derived from genome sequences.

Science.gov (United States)

Cronin, Matthew A; Rincon, Gonzalo; Meredith, Robert W; MacNeil, Michael D; Islas-Trejo, Alma; Cánovas, Angela; Medrano, Juan F

2014-01-01

We assessed the relationships of polar bears (Ursus maritimus), brown bears (U. arctos), and black bears (U. americanus) with high throughput genomic sequencing data with an average coverage of 25× for each species. A total of 1.4 billion 100-bp paired-end reads were assembled using the polar bear and annotated giant panda (Ailuropoda melanoleuca) genome sequences as references. We identified 13.8 million single nucleotide polymorphisms (SNP) in the 3 species aligned to the polar bear genome. These data indicate that polar bears and brown bears share more SNP with each other than either does with black bears. Concatenation and coalescence-based analysis of consensus sequences of approximately 1 million base pairs of ultraconserved elements in the nuclear genome resulted in a phylogeny with black bears as the sister group to brown and polar bears, and all brown bears are in a separate clade from polar bears. Genotypes for 162 SNP loci of 336 bears from Alaska and Montana showed that the species are genetically differentiated and there is geographic population structure of brown and black bears but not polar bears.

High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification

Directory of Open Access Journals (Sweden)

Sun Zhenyu

2001-08-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the foundation of powerful complex trait and pharmacogenomic analyses. The availability of large SNP databases, however, has emphasized a need for inexpensive SNP genotyping methods of commensurate simplicity, robustness, and scalability. We describe a solution-based, microtiter plate method for SNP genotyping of human genomic DNA. The method is based upon allele discrimination by ligation of open circle probes followed by rolling circle amplification of the signal using fluorescent primers. Only the probe with a 3' base complementary to the SNP is circularized by ligation. Results SNP scoring by ligation was optimized to a 100,000 fold discrimination against probe mismatched to the SNP. The assay was used to genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput format. Assay directly from genomic DNA eliminates the need to preamplify the target as done for many other genotyping methods. The sensitivity of the assay was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the assay can detect a single molecule of the circularized probe. Conclusions Compatibility with homogeneous formats and the ability to assay small amounts of genomic DNA meets the exacting requirements of automated, high-throughput SNP scoring.

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

DEFF Research Database (Denmark)

Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia

2015-01-01

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...

High-energy-density physics researches based on pulse power technology

International Nuclear Information System (INIS)

Horioka, Kazuhiko; Nakajima, Mitsuo; Kawamura, Tohru; Sasaki, Toru; Kondo, Kotaro; Yano, Yuuri

2006-01-01

Plasmas driven by pulse power device are of interest, concerning the researches on high-energy-density (HED) physics. Dense plasmas are produced using pulse power driven exploding discharges in water. Experimental results show that the wire plasma is tamped and stabilized by the surrounding water and it evolves through a strongly coupled plasma state. A shock-wave-heated, high temperature plasma is produced in a compact pulse power device. Experimental results show that strong shock waves can be produced in the device. In particular, at low initial pressure condition, the shock Mach number reaches 250 and this indicates that the shock heated region is dominated by radiation processes. (author)

Tin phosphide-based anodes for sodium-ion batteries: synthesis via solvothermal transformation of Sn metal and phase-dependent Na storage performance

Science.gov (United States)

Shin, Hyun-Seop; Jung, Kyu-Nam; Jo, Yong Nam; Park, Min-Sik; Kim, Hansung; Lee, Jong-Won

2016-01-01

There is a great deal of current interest in the development of rechargeable sodium (Na)-ion batteries (SIBs) for low-cost, large-scale stationary energy storage systems. For the commercial success of this technology, significant progress should be made in developing robust anode (negative electrode) materials with high capacity and long cycle life. Sn-P compounds are considered promising anode materials that have considerable potential to meet the required performance of SIBs, and they have been typically prepared by high-energy mechanical milling. Here, we report Sn-P-based anodes synthesised through solvothermal transformation of Sn metal and their electrochemical Na storage properties. The temperature and time period used for solvothermal treatment play a crucial role in determining the phase, microstructure, and composition of the Sn-P compound and thus its electrochemical performance. The Sn-P compound prepared under an optimised solvothermal condition shows excellent electrochemical performance as an SIB anode, as evidenced by a high reversible capacity of ~560 mAh g−1 at a current density of 100 mA g−1 and cycling stability for 100 cycles. The solvothermal route provides an effective approach to synthesising Sn-P anodes with controlled phases and compositions, thus tailoring their Na storage behaviour. PMID:27189834

A Larger Chocolate Chip—Development of a 15K Theobroma cacao L. SNP Array to Create High-Density Linkage Maps

Directory of Open Access Journals (Sweden)

Donald Livingstone

2017-12-01

Full Text Available Cacao (Theobroma cacao L. is an important cash crop in tropical regions around the world and has a rich agronomic history in South America. As a key component in the cosmetic and confectionary industries, millions of people worldwide use products made from cacao, ranging from shampoo to chocolate. An Illumina Infinity II array was created using 13,530 SNPs identified within a small diversity panel of cacao. Of these SNPs, 12,643 derive from variation within annotated cacao genes. The genotypes of 3,072 trees were obtained, including two mapping populations from Ecuador. High-density linkage maps for these two populations were generated and compared to the cacao genome assembly. Phenotypic data from these populations were combined with the linkage maps to identify the QTLs for yield and disease resistance.

A Larger Chocolate Chip-Development of a 15K Theobroma cacao L. SNP Array to Create High-Density Linkage Maps.

Science.gov (United States)

Livingstone, Donald; Stack, Conrad; Mustiga, Guiliana M; Rodezno, Dayana C; Suarez, Carmen; Amores, Freddy; Feltus, Frank A; Mockaitis, Keithanne; Cornejo, Omar E; Motamayor, Juan C

2017-01-01

Cacao ( Theobroma cacao L.) is an important cash crop in tropical regions around the world and has a rich agronomic history in South America. As a key component in the cosmetic and confectionary industries, millions of people worldwide use products made from cacao, ranging from shampoo to chocolate. An Illumina Infinity II array was created using 13,530 SNPs identified within a small diversity panel of cacao. Of these SNPs, 12,643 derive from variation within annotated cacao genes. The genotypes of 3,072 trees were obtained, including two mapping populations from Ecuador. High-density linkage maps for these two populations were generated and compared to the cacao genome assembly. Phenotypic data from these populations were combined with the linkage maps to identify the QTLs for yield and disease resistance.

A novel wood flour-filled composite based on microfibrillar high-density polyethylene (HDPE)/Nylon-6 blends.

Science.gov (United States)

Liu, Hongzhi; Yao, Fei; Xu, Yanjun; Wu, Qinglin

2010-05-01

A novel wood flour (WF)-filled composite based on the microfibrillar high-density polyethylene (HDPE) and Nylon-6 co-blend, in which both in situ formed Nylon-6 microfibrils and WF acted as reinforcing elements, was successfully developed using a two-step extrusion method. At the 30wt.% WF loading level, WF-filled composite based on the microfibrillized HDPE/Nylon-6 blend exhibited higher strengths and moduli than the corresponding HDPE-based composite. The incorporation of WF reduced short-term creep response of HDPE matrix and the presence of Nylon-6 microfibrils further contributed to the creep reduction. Copyright 2009 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2013-03-01

New cases of leprosy are still being detected in Colombia after the country declared achievement of the WHO defined 'elimination' status. To study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. The location (latitude and longitude) of patient residences were mapped. Slit skin smears and/or skin biopsies were collected and DNA was extracted. Standard agarose gel electrophoresis following a multiplex PCR-was developed for rapid and inexpensive strain typing of Mycobacterium leprae based on copy numbers of two VNTR minisatellite loci 27-5 and 12-5. A SNP (C/T) in gyrA (SNP7614) was mapped by introducing a novel PCR-RFLP into an ongoing drug resistance surveillance effort. Multiple genotypes were detected combining the three molecular markers. The two frequent genotypes in Colombia were SNP7614(C)/27-5(5)/12-5(4) [C54] predominantly distributed in the Atlantic departments and SNP7614 (T)/27-5(4)/12-5(5) [T45] associated with the Andean departments. A novel genotype SNP7614 (C)/27-5(6)/12-5(4) [C64] was detected in cities along the Magdalena river which separates the Andean from Atlantic departments; a subset was further characterized showing association with a rare allele of minisatellite 23-3 and the SNP type 1 of M. leprae. The genotypes within intra-family cases were conserved. Overall, this is the first large scale study that utilized simple and rapid assay formats for identification of major strain types and their distribution in Colombia. It provides the framework for further strain type discrimination and geographic information systems as tools for tracing transmission of leprosy. Copyright © 2012 Elsevier B.V. All rights reserved.

The Association of FTO SNP rs9939609 with Weight Gain at University

NARCIS (Netherlands)

Meisel, S.F.; Beeken, R.J.; Jaarsveld, C.H.M. van; Wardle, J.

2015-01-01

AIM: We tested the hypothesis that the obesity-associated FTO SNP rs9939609 would be associated with clinically significant weight gain (>/= 5% of initial body weight) in the first year of university; a time identified as high risk for weight gain. METHODS: We collected anthropometric data from

A SNP resource for studying North American moose [version 1; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Theodore S. Kalbfleisch

2018-01-01

Full Text Available Background: Moose (Alces alces colonized the North American continent from Asia less than 15,000 years ago, and spread across the boreal forest regions of Canada and the northern United States (US.  Contemporary populations have low genetic diversity, due either to low number of individuals in the original migration (founder effect, and/or subsequent population bottlenecks in North America.  Genetic tests based on informative single nucleotide polymorphism (SNP markers are helpful in forensic and wildlife conservation activities, but have been difficult to develop for moose, due to the lack of a reference genome assembly and whole genome sequence (WGS data. Methods:  WGS data were generated for four individual moose from the US states of Alaska, Idaho, Wyoming, and Vermont with minimum and average genome coverage depths of 14- and 19-fold, respectively.  Cattle and sheep reference genomes were used for aligning sequence reads and identifying moose SNPs. Results:  Approximately 11% and 9% of moose WGS reads aligned to cattle and sheep genomes, respectively.  The reads clustered at genomic segments, where sequence identity between these species was greater than 95%.  In these segments, average mapped read depth was approximately 19-fold.  Sets of 46,005 and 36,934 high-confidence SNPs were identified from cattle and sheep comparisons, respectively, with 773 and 552 of those having minor allele frequency of 0.5 and conserved flanking sequences in all three species.  Among the four moose, heterozygosity and allele sharing of SNP genotypes were consistent with decreasing levels of moose genetic diversity from west to east.  A minimum set of 317 SNPs, informative across all four moose, was selected as a resource for future SNP assay design. Conclusions:  All SNPs and associated information are available, without restriction, to support development of SNP-based tests for animal identification, parentage determination, and estimating

Genetic Polymorphism of MDM2 SNP309 in Patients with Helicobacter Pylori-Associated Gastritis.

Science.gov (United States)

Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

2015-01-01

Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population.

High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Science.gov (United States)

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-01-01

Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

Renewable carbohydrates are a potential high-density hydrogen carrier

Energy Technology Data Exchange (ETDEWEB)

Zhang, Y.-H. Percival [Biological Systems Engineering Department, 210-A Seitz Hall, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Institute for Critical Technology and Applied Sciences (ICTAS), Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); DOE BioEnergy Science Center (BESC), Oak Ridge, TN 37831 (United States)

2010-10-15

The possibility of using renewable biomass carbohydrates as a potential high-density hydrogen carrier is discussed here. Gravimetric density of polysaccharides is 14.8 H{sub 2} mass% where water can be recycled from PEM fuel cells or 8.33% H{sub 2} mass% without water recycling; volumetric densities of polysaccharides are >100 kg of H{sup 2}/m{sup 3}. Renewable carbohydrates (e.g., cellulosic materials and starch) are less expensive based on GJ than are other hydrogen carriers, such as hydrocarbons, biodiesel, methanol, ethanol, and ammonia. Biotransformation of carbohydrates to hydrogen by cell-free synthetic (enzymatic) pathway biotransformation (SyPaB) has numerous advantages, such as high product yield (12 H{sub 2}/glucose unit), 100% selectivity, high energy conversion efficiency (122%, based on combustion energy), high-purity hydrogen generated, mild reaction conditions, low-cost of bioreactor, few safety concerns, and nearly no toxicity hazards. Although SyPaB may suffer from current low reaction rates, numerous approaches for accelerating hydrogen production rates are proposed and discussed. Potential applications of carbohydrate-based hydrogen/electricity generation would include hydrogen bioreactors, home-size electricity generators, sugar batteries for portable electronics, sugar-powered passenger vehicles, and so on. Developments in thermostable enzymes as standardized building blocks for cell-free SyPaB projects, use of stable and low-cost biomimetic NAD cofactors, and accelerating reaction rates are among the top research and development priorities. International collaborations are urgently needed to solve the above obstacles within a short time. (author)

SNPsnap: a Web-based tool for identification and annotation of matched SNPs

DEFF Research Database (Denmark)

Pers, Tune Hannes; Timshel, Pascal; Hirschhorn, Joel N.

2015-01-01

-localization of GWAS signals to gene-dense and high linkage disequilibrium (LD) regions, and correlations of gene size, location and function. The SNPsnap Web server enables SNP-based enrichment analysis by providing matched sets of SNPs that can be used to calibrate background expectations. Specifically, SNPsnap...... efficiently identifies sets of randomly drawn SNPs that are matched to a set of query SNPs based on allele frequency, number of SNPs in LD, distance to nearest gene and gene density. Availability and implementation : SNPsnap server is available at http://www.broadinstitute.org/mpg/snpsnap/. Contact: joelh...

Serum osteoprotegerin levels and mammographic density among high-risk women.

Science.gov (United States)

Moran, Olivia; Zaman, Tasnim; Eisen, Andrea; Demsky, Rochelle; Blackmore, Kristina; Knight, Julia A; Elser, Christine; Ginsburg, Ophira; Zbuk, Kevin; Yaffe, Martin; Narod, Steven A; Salmena, Leonardo; Kotsopoulos, Joanne

2018-06-01

Mammographic density is a risk factor for breast cancer but the mechanism behind this association is unclear. The receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) pathway has been implicated in the development of breast cancer. Given the role of RANK signaling in mammary epithelial cell proliferation, we hypothesized this pathway may also be associated with mammographic density. Osteoprotegerin (OPG), a decoy receptor for RANKL, is known to inhibit RANK signaling. Thus, it is of interest to evaluate whether OPG levels modify breast cancer risk through mammographic density. We quantified serum OPG levels in 57 premenopausal and 43 postmenopausal women using an enzyme-linked immunosorbent assay (ELISA). Cumulus was used to measure percent density, dense area, and non-dense area for each mammographic image. Subjects were classified into high versus low OPG levels based on the median serum OPG level in the entire cohort (115.1 pg/mL). Multivariate models were used to assess the relationship between serum OPG levels and the measures of mammographic density. Serum OPG levels were not associated with mammographic density among premenopausal women (P ≥ 0.42). Among postmenopausal women, those with low serum OPG levels had higher mean percent mammographic density (20.9% vs. 13.7%; P = 0.04) and mean dense area (23.4 cm 2 vs. 15.2 cm 2 ; P = 0.02) compared to those with high serum OPG levels after covariate adjustment. These findings suggest that low OPG levels may be associated with high mammographic density, particularly in postmenopausal women. Targeting RANK signaling may represent a plausible, non-surgical prevention option for high-risk women with high mammographic density, especially those with low circulating OPG levels.

High Density Hydrogen Storage System Demonstration Using NaAlH4 Based Complex Compound Hydrides

Energy Technology Data Exchange (ETDEWEB)

Daniel A. Mosher; Xia Tang; Ronald J. Brown; Sarah Arsenault; Salvatore Saitta; Bruce L. Laube; Robert H. Dold; Donald L. Anton

2007-07-27

This final report describes the motivations, activities and results of the hydrogen storage independent project "High Density Hydrogen Storage System Demonstration Using NaAlH4 Based Complex Compound Hydrides" performed by the United Technologies Research Center under the Department of Energy Hydrogen Program, contract # DE-FC36-02AL67610. The objectives of the project were to identify and address the key systems technologies associated with applying complex hydride materials, particularly ones which differ from those for conventional metal hydride based storage. This involved the design, fabrication and testing of two prototype systems based on the hydrogen storage material NaAlH4. Safety testing, catalysis studies, heat exchanger optimization, reaction kinetics modeling, thermochemical finite element analysis, powder densification development and material neutralization were elements included in the effort.

Fine-mapping additive and dominant SNP effects using group-LASSO and Fractional Resample Model Averaging

Science.gov (United States)

Sabourin, Jeremy; Nobel, Andrew B.; Valdar, William

2014-01-01

Genomewide association studies sometimes identify loci at which both the number and identities of the underlying causal variants are ambiguous. In such cases, statistical methods that model effects of multiple SNPs simultaneously can help disentangle the observed patterns of association and provide information about how those SNPs could be prioritized for follow-up studies. Current multi-SNP methods, however, tend to assume that SNP effects are well captured by additive genetics; yet when genetic dominance is present, this assumption translates to reduced power and faulty prioritizations. We describe a statistical procedure for prioritizing SNPs at GWAS loci that efficiently models both additive and dominance effects. Our method, LLARRMA-dawg, combines a group LASSO procedure for sparse modeling of multiple SNP effects with a resampling procedure based on fractional observation weights; it estimates for each SNP the robustness of association with the phenotype both to sampling variation and to competing explanations from other SNPs. In producing a SNP prioritization that best identifies underlying true signals, we show that: our method easily outperforms a single marker analysis; when additive-only signals are present, our joint model for additive and dominance is equivalent to or only slightly less powerful than modeling additive-only effects; and, when dominance signals are present, even in combination with substantial additive effects, our joint model is unequivocally more powerful than a model assuming additivity. We also describe how performance can be improved through calibrated randomized penalization, and discuss how dominance in ungenotyped SNPs can be incorporated through either heterozygote dosage or multiple imputation. PMID:25417853

Development and application of a 20K SNP array in potato

NARCIS (Netherlands)

Vos, Peter

2016-01-01

In this thesis the results are described of investigations of various application of genome wide SNP (single nucleotide polymorphism) markers. The set of SNP markers was identified by GBS (genotyping by sequencing) strategy. The resulting dataset of 129,156 SNPs across 83 tetraploid varieties was

A genetic linkage map with 178 SSR and 1 901 SNP markers constructed using a RIL population in wheat （Triticum aestivum L.）

Institute of Scientific and Technical Information of China (English)

ZHAI Hui-jie; FENG Zhi-yu; LIU Xin-ye; CHENG Xue-jiao; PENG Hui-ru; YAO Ying-yin; SUN Qi-xin; NI Zhong-fu

2015-01-01

The construction of high density genetic linkage map provides a powerful tool to detect and map quantitative trait loci （QTLs） controlling agronomically important traits. In this study, simple sequence repeat （SSR） markers and Illumina 9K iSelect single nucleotide polymorphism （SNP） genechip were employed to construct one genetic linkage map of common wheat （Triticum aestivum L.） using 191 recombinant inbred lines （RILs） derived from cross Yu 8679xJing 411. This map included 1 901 SNP loci and 178 SSR loci, covering 1 659.9 cM and 1 000 marker bins, with an average interval distance of 1.66 cM. A, B and D genomes covered 719.1,703.5 and 237.3 cM, with an average interval distance of 1.66, 1.45 and 2.9 cM, respectively. Notably, the genetic linkage map covered 20 chromosomes, with the exception of chromosome 5D. Bioinformatics analysis revealed that 1 754 （92.27%） of 1 901 mapped SNP loci could be aligned to 1 215 distinct wheat unigenes, among which 1 184 （97.4%） were located on one single chromosome, and the rest 31 （2.6%） were located on 2 to 3 chromosomes. By performing in silico comparison, 214 chromosome deletion bin-mapped expressed sequence tags （ESTs）, 1 043 Brachypodium genes and 1 033 rice genes were further added onto the genetic linkage map. This map not only integrated genetic and physical maps, SSR and SNP loci, respectively, but also provided the information of Brachypodium and rice genes corresponding to 1 754 SNP loci. Therefore, it will be a useful tool for comparative genomics analysis, fine mapping of QTL/gene controlling agronomically important traits and marker-assisted selection breeding in wheat.

High-energy density physics at Los Alamos

International Nuclear Information System (INIS)

Byrnes, P.; Younger, S.M.

1993-03-01

This brochure describes the facilities of the Above Ground Experiments II (AGEX II) and the Inertial Confinement Fusion (ICF) programs at Los Alamo. Combined, these programs represent, an unparalleled capability to address important issues in high-energy density physics that are critical to the future defense, energy, and research needs of th e United States. The mission of the AGEX II program at Los Alamos is to provide additional experimental opportunities for the nuclear weapons program. For this purpose we have assembled at Los Alamos the broadest array of high-energy density physics facilities of any laboratory in the world. Inertial confinement fusion seeks to achieve thermonuclear burn on a laboratory scale through the implosion of a small quantity of deuterium and tritium fuel to very high Pressure and temperature.The Los Alamos ICF program is focused on target physics. With the largest scientific computing center in the world, We can perform calculations of unprecedented sophistication and precision. We field experiments at facilities worldwide-including our own Trident and Mercury lasers-to confirm our understanding and to provide the necessary data base to proceed toward the historic goal of controlled fusion in the laboratory. In addition to direct programmatic high-energy density physics is a nc scientific endeavor in itself. The ultrahigh magnetic fields produced in our high explosive pulsed-power generators can be used in awide variety of solid state physics and temperature superconductor studies. The structure and dynamics of planetary atmospheres can be simulated through the compression of gas mixtures

RS-SNP: a random-set method for genome-wide association studies

Directory of Open Access Journals (Sweden)

Mukherjee Sayan

2011-03-01

Full Text Available Abstract Background The typical objective of Genome-wide association (GWA studies is to identify single-nucleotide polymorphisms (SNPs and corresponding genes with the strongest evidence of association (the 'most-significant SNPs/genes' approach. Borrowing ideas from micro-array data analysis, we propose a new method, named RS-SNP, for detecting sets of genes enriched in SNPs moderately associated to the phenotype. RS-SNP assesses whether the number of significant SNPs, with p-value P ≤ α, belonging to a given SNP set is statistically significant. The rationale of proposed method is that two kinds of null hypotheses are taken into account simultaneously. In the first null model the genotype and the phenotype are assumed to be independent random variables and the null distribution is the probability of the number of significant SNPs in greater than observed by chance. The second null model assumes the number of significant SNPs in depends on the size of and not on the identity of the SNPs in . Statistical significance is assessed using non-parametric permutation tests. Results We applied RS-SNP to the Crohn's disease (CD data set collected by the Wellcome Trust Case Control Consortium (WTCCC and compared the results with GENGEN, an approach recently proposed in literature. The enrichment analysis using RS-SNP and the set of pathways contained in the MSigDB C2 CP pathway collection highlighted 86 pathways rich in SNPs weakly associated to CD. Of these, 47 were also indicated to be significant by GENGEN. Similar results were obtained using the MSigDB C5 pathway collection. Many of the pathways found to be enriched by RS-SNP have a well-known connection to CD and often with inflammatory diseases. Conclusions The proposed method is a valuable alternative to other techniques for enrichment analysis of SNP sets. It is well founded from a theoretical and statistical perspective. Moreover, the experimental comparison with GENGEN highlights that it is

Noise reduction in muon tomography for detecting high density objects

International Nuclear Information System (INIS)

Benettoni, M; Checchia, P; Cossutta, L; Furlan, M; Gonella, F; Pegoraro, M; Garola, A Rigoni; Ronchese, P; Vanini, S; Viesti, G; Bettella, G; Bonomi, G; Donzella, A; Subieta, M; Zenoni, A; Calvagno, G; Cortelazzo, G; Zanuttigh, P; Calvini, P; Squarcia, S

2013-01-01

The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. In this paper a new and innovative method is presented to handle the density fluctuations (noise) of reconstructed images, a well known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at the Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect high density materials, such as lead, albeit surrounded by light or medium density material, in short times. A comparison with algorithms published in literature is also presented

Density-dependent squeezing of excitons in highly excited semiconductors

International Nuclear Information System (INIS)

Nguyen Hong Quang.

1995-07-01

The time evolution from coherent states to squeezed states of high density excitons is studied theoretically based on the boson formalism and within the Random Phase Approximation. Both the mutual interaction between excitons and the anharmonic exciton-photon interaction due to phase-space filling of excitons are taken into account. It is shown that the exciton squeezing depends strongly on the exciton density in semiconductors and becomes smaller with increasing the latter. (author). 16 refs, 2 figs

Discrimination of relationships with the same degree of kinship using chromosomal sharing patterns estimated from high-density SNPs.

Science.gov (United States)

Morimoto, Chie; Manabe, Sho; Fujimoto, Shuntaro; Hamano, Yuya; Tamaki, Keiji

2018-03-01

Distinguishing relationships with the same degree of kinship (e.g., uncle-nephew and grandfather-grandson) is generally difficult in forensic genetics by using the commonly employed short tandem repeat loci. In this study, we developed a new method for discerning such relationships between two individuals by examining the number of chromosomal shared segments estimated from high-density single nucleotide polymorphisms (SNPs). We computationally generated second-degree kinships (i.e., uncle-nephew and grandfather-grandson) and third-degree kinships (i.e., first cousins and great-grandfather-great-grandson) for 174,254 autosomal SNPs considering the effect of linkage disequilibrium and recombination for each SNP. We investigated shared chromosomal segments between two individuals that were estimated based on identity by state regions. We then counted the number of segments in each pair. Based on our results, the number of shared chromosomal segments in collateral relationships was larger than that in lineal relationships with both the second-degree and third-degree kinships. This was probably caused by differences involving chromosomal transitions and recombination between relationships. As we probabilistically evaluated the relationships between simulated pairs based on the number of shared segments using logistic regression, we could determine accurate relationships in >90% of second-degree relatives and >70% of third-degree relatives, using a probability criterion for the relationship ≥0.9. Furthermore, we could judge the true relationships of actual sample pairs from volunteers, as well as simulated data. Therefore, this method can be useful for discerning relationships between two individuals with the same degree of kinship. Copyright © 2017 Elsevier B.V. All rights reserved.

Interference of Homologous Sequences on the SNP Study of CYP2A13 Gene

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Qinghua ZHOU

2010-02-01

Full Text Available Background and objective It has been proven that cytochrome P450 enzyme 2A13 (CYP2A13 played an important role in the association between single nucleotide polymorphisms (SNP and human diseases. Cytochrome P450 enzymes are a group of isoenzymes, whose sequence homology may interfere with the study for SNP. The aim of this study is to explore the interference on the SNP study of CYP2A13 caused by homologous sequences. Methods Taqman probe was applied to detect distribution of rs8192789 sites in 573 subjects, and BLAST method was used to analyze the amplified sequences. Partial sequences of CYP2A13 were emplified by PCR from 60 cases. The emplified sequences were TA cloned and sequenced. Results For rs8192789 loci in 573 cases, only 3 cases were TT, while the rest were CT heterozygotes, which was caused by homologous sequences. There are a large number of overlapping peaks in identical sequences of 60 cases, and the SNP of 101 amino acid site reported in the SNP database is not found. The cloned sequences are 247 bp, 235 bp fragments. Conclusion The homologous sequences may interfere the study for SNP of CYP2A13, and some SNP may not exist.

Ubiquitin-conjugating enzyme E2-like gene associated to pathogen response in Concholepas concholepas: SNP identification and transcription expression.

Science.gov (United States)

Núñez-Acuña, Gustavo; Aguilar-Espinoza, Andrea; Chávez-Mardones, Jacqueline; Gallardo-Escárate, Cristian

2012-10-01

Ubiquitin-conjugated E2 enzyme (UBE2) is one of the main components of the proteasome degradation cascade. Previous studies have shown an increase of expression levels in individuals challenged to some pathogen organism such as virus and bacteria. The study was to characterize the immune response of UBE2 gene in the gastropod Concholepas concholepas through expression analysis and single nucleotide polymorphisms (SNP) discovery. Hence, UBE2 was identified from a cDNA library by 454 pyrosequencing, while SNP identification and validation were performed using De novo assembly and high resolution melting analysis. Challenge trials with Vibrio anguillarum was carried out to evaluate the relative transcript abundance of UBE2 gene from two to thirty-three hours post-treatment. The results showed a partial UBE2 sequence of 889 base pair (bp) with a partial coding region of 291 bp. SNP variation (A/C) was observed at the 546th position. Individuals challenged by V. anguillarum showed an overexpression of the UBE2 gene, the expression being significantly higher in homozygous individuals (AA) than (CC) or heterozygous individuals (A/C). This study contributes useful information relating to the UBE2 gene and its association with innate immune response in marine invertebrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low-enriched uranium high-density target project. Compendium report

Energy Technology Data Exchange (ETDEWEB)

Vandegrift, George; Brown, M. Alex; Jerden, James L.; Gelis, Artem V.; Stepinski, Dominique C.; Wiedmeyer, Stanley; Youker, Amanda; Hebden, Andrew; Solbrekken, G; Allen, C; Robertson., D; El-Gizawy, Sherif; Govindarajan, Srisharan; Hoyer, Annemarie; Makarewicz, Philip; Harris, Jacob; Graybill, Brian; Gunn, Andy; Berlin, James; Bryan, Chris; Sherman, Steven; Hobbs, Randy; Griffin, F. P.; Chandler, David; Hurt, C. J.; Williams, Paul; Creasy, John; Tjader, Barak; McFall, Danielle; Longmire, Hollie

2016-09-01

At present, most ⁹⁹Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassembly of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.

Density measurements of small amounts of high-density solids by a floatation method

International Nuclear Information System (INIS)

Akabori, Mitsuo; Shiba, Koreyuki

1984-09-01

A floatation method for determining the density of small amounts of high-density solids is described. The use of a float combined with an appropriate floatation liquid allows us to measure the density of high-density substances in small amounts. Using the sample of 0.1 g in weight, the floatation liquid of 3.0 g cm -3 in density and the float of 1.5 g cm -3 in apparent density, the sample densities of 5, 10 and 20 g cm -3 are determined to an accuracy better than +-0.002, +-0.01 and +-0.05 g cm -3 , respectively that correspond to about +-1 x 10 -5 cm 3 in volume. By means of appropriate degassing treatments, the densities of (Th,U)O 2 pellets of --0.1 g in weight and --9.55 g cm -3 in density were determined with an accuracy better than +-0.05 %. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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.

Pulse Power Capability Of High Energy Density Capacitors Based on a New Dielectric Material

Science.gov (United States)

Winsor, Paul; Scholz, Tim; Hudis, Martin; Slenes, Kirk M.

1999-01-01

A new dielectric composite consisting of a polymer coated onto a high-density metallized Kraft has been developed for application in high energy density pulse power capacitors. The polymer coating is custom formulated for high dielectric constant and strength with minimum dielectric losses. The composite can be wound and processed using conventional wound film capacitor manufacturing equipment. This new system has the potential to achieve 2 to 3 J/cu cm whole capacitor energy density at voltage levels above 3.0 kV, and can maintain its mechanical properties to temperatures above 150 C. The technical and manufacturing development of the composite material and fabrication into capacitors are summarized in this paper. Energy discharge testing, including capacitance and charge-discharge efficiency at normal and elevated temperatures, as well as DC life testing were performed on capacitors manufactured using this material. TPL (Albuquerque, NM) has developed the material and Aerovox (New Bedford, MA) has used the material to build and test actual capacitors. The results of the testing will focus on pulse power applications specifically those found in electro-magnetic armor and guns, high power microwave sources and defibrillators.

High Energy Density Li-ion Cells for EV’s Based on Novel, High Voltage Cathode Material Systems

Energy Technology Data Exchange (ETDEWEB)

Kepler, Keith [Farasis Energy Inc; Slater, Michael [Farasis Energy Inc

2018-03-14

This Li-ion cell technology development project had three objectives: to develop advanced electrode materials and cell components to enable stable high-voltage operation; to design and demonstrate a Li-ion cell using these materials that meets the PHEV40 performance targets; and to design and demonstrate a Li-ion cell using these materials that meets the EV performance targets. The major challenge to creating stable high energy cells with long cycle life is system integration. Although materials that can give high energy cells are known, stabilizing them towards long-term cycling in the presence of other novel cell components is a major challenge. The major technical barriers addressed by this work include low cathode specific energy, poor electrolyte stability during high voltage operation, and insufficient capacity retention during deep discharge for Si-containing anodes. Through the course of this project, Farasis was able to improve capacity retention of NCM materials for 4.4+ V operation, through both surface treatment and bulk-doping approaches. Other material advances include increased rate capability and of HE-NCM materials through novel synthesis approach, doubling the relative capacity at 1C over materials synthesized using standard methods. Silicon active materials proved challenging throughout the project and ultimately were the limiting factor in the energy density vs. cycle life trade off. By avoiding silicon anodes for the lower energy PHEV design, we manufactured cells with intermediate energy density and long cycle life under high voltage operation for PHEV applications. Cells with high energy density for EV applications were manufactured targeting a 300 Wh/kg design and were able to achieve > 200 cycles.

A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff

Science.gov (United States)

Cingolani, Pablo; Platts, Adrian; Wang, Le Lily; Coon, Melissa; Nguyen, Tung; Wang, Luan; Land, Susan J.; Lu, Xiangyi; Ruden, Douglas M.

2012-01-01

We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in the 5′UTR. We found, as expected, that the SNP frequency is proportional to the recombination frequency (i.e., highest in the middle of chromosome arms). We also found that start-gain or stop-lost SNPs in Drosophila melanogaster often result in additions of N-terminal or C-terminal amino acids that are conserved in other Drosophila species. It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus. As genome sequencing is becoming inexpensive and routine, SnpEff enables rapid analyses of whole-genome sequencing data to be performed by an individual laboratory. PMID:22728672

Research on high energy density plasmas and applications

International Nuclear Information System (INIS)

1999-01-01

Recently, technologies on lasers, accelerators, and pulse power machines have been significantly advanced and input power density covers the intensity range from 10 10 W/cm 2 to higher than 10 20 W/cm 2 . As the results, high pressure gas and solid targets can be heated up to very high temperature to create hot dense plasmas which have never appeared on the earth. The high energy density plasmas opened up new research fields such as inertial confinement fusion, high brightness X-ray radiation sources, interiors of galactic nucleus,supernova, stars and planets, ultra high pressure condensed matter physics, plasma particle accelerator, X-ray laser, and so on. Furthermore, since these fields are intimately connected with various industrial sciences and technologies, the high energy density plasma is now studied in industries, government institutions, and so on. This special issue of the Journal of Plasma Physics and Nuclear Fusion Research reviews the high energy density plasma science for the comprehensive understanding of such new fields. In May, 1998, the review committee for investigating the present status and the future prospects of high energy density plasma science was established in the Japan Society of Plasma Science and Nuclear Fusion Research. We held three committee meetings to discuss present status and critical issues of research items related to high energy density plasmas. This special issue summarizes the understandings of the committee. This special issue consists of four chapters: They are Chapter 1: Physics important in the high energy density plasmas, Chapter 2: Technologies related to the plasma generation; drivers such as lasers, pulse power machines, particle beams and fabrication of various targets, Chapter 3: Plasma diagnostics important in high energy density plasma experiments, Chapter 4: A variety of applications of high energy density plasmas; X-ray radiation, particle acceleration, inertial confinement fusion, laboratory astrophysics

Achieving High-Energy-High-Power Density in a Flexible Quasi-Solid-State Sodium Ion Capacitor.

Science.gov (United States)

Li, Hongsen; Peng, Lele; Zhu, Yue; Zhang, Xiaogang; Yu, Guihua

2016-09-14

Simultaneous integration of high-energy output with high-power delivery is a major challenge for electrochemical energy storage systems, limiting dual fine attributes on a device. We introduce a quasi-solid-state sodium ion capacitor (NIC) based on a battery type urchin-like Na2Ti3O7 anode and a capacitor type peanut shell derived carbon cathode, using a sodium ion conducting gel polymer as electrolyte, achieving high-energy-high-power characteristics in solid state. Energy densities can reach 111.2 Wh kg(-1) at power density of 800 W kg(-1), and 33.2 Wh kg(-1) at power density of 11200 W kg(-1), which are among the best reported state-of-the-art NICs. The designed device also exhibits long-term cycling stability over 3000 cycles with capacity retention ∼86%. Furthermore, we demonstrate the assembly of a highly flexible quasi-solid-state NIC and it shows no obvious capacity loss under different bending conditions.

Functional characterization of the Thr946Ala SNP at the type 1 diabetes IFIH1 locus.

Science.gov (United States)

Zouk, Hana; Marchand, Luc; Li, Quan; Polychronakos, Constantin

2014-02-01

The Thr allele at the Thr946Ala non-synonymous single-nucleotide polymorphism (nsSNP) in the IFIH1 gene confers risk for type 1 diabetes (T1D). IFIH1 binds viral double-stranded RNA (dsRNA), inducing a type I interferon (IFN) response. Reports of this nsSNP's role in IFIH1 expression regulation have produced conflicting results and a study evaluating transfected Thr946Ala protein alleles in an artificial system overexpressing IFIH1 shows that the SNP does not affect IFH1 function. In this study, we examine the effects of the Thr946Ala polymorphism on IFN-α response in a cell line that endogenously expresses physiological levels of IFIH1. Eleven lymphoblastoid cell lines (LCLs) homozygous for the major predisposing allele (Thr/Thr) and 6 LCLs homozygous for the minor protective allele (Ala/Ala) were electroporated with the viral dsRNA mimic, poly I:C, in three independent experiments. Media were collected 24 hours later and measured for IFN-α production by ELISA. Basal IFN response is minimal in mock-transfected cells from both genotypes and increases by about 8-fold in cells treated with poly I:C. LCLs with the Ala/Ala genotype have slightly higher IFN-α levels than their Thr/Thr counterparts but this did not reach statistical significance because of the large variability of the IFN response, due mostly to two high outliers (biological, not technical). A larger sample size would be needed to determine whether the Thr946Ala SNP affects the poly I:C-driven IFN-α response. Additionally, the possibility that this nsSNP recognizes viral dsRNA specificities cannot be ruled out. Thus, the mechanism of the observed association of this SNP with T1D remains to be determined.

Foldable, High Energy Density Lithium Ion Batteries

Science.gov (United States)

Suresh, Shravan

CNMs (0.7 mg/cm2) as compared to metallic foils (5-10 mg/cm2). We show that the energy density of the fully foldable battery with CMF current collectors can be up to 2-fold higher than conventional LIBs at realistic mass loading (5mg/cm2) of the electrode materials. Therefore, not only does the CMF impart shape conformability, it also significantly boosts the energy density of the device by removing the dead weight of the batteries. Silicon (Si) shows enormous potential as the next generation anode material in Lithium-ion batteries due to its high energy denisty. However, Si is highly brittle, and in an effort to prevent Si from fracturing, the research community has migrated from the use of Si films to Si nanoparticle based electrodes. Such a strategy significantly reduces volumetric energy density due to the porosity of Si nanoparticle electrodes. In Chapters 4 and 5, we propose two solutions to incorporate Si films in foldable batteries. We show that contrary to conventional wisdom, Si films can be stabilized by two strategies: (a) anchoring the Si films to a carbon nanotube macrofilm (CNM) current-collector and (b) draping the films with a graphene monolayer. After electrochemical cycling, the graphene-coated Si films on CNM resembled a tough mud-cracked surface in which the graphene capping layer suppresses delamination and stabilizes the solid electrolyte interface by creating a slippery interface and reducing the stress transfer across the interface. The graphene-draped Si films on CNM exhibit long cycle life (> 1000 charge/discharge steps) with an average specific capacity of 806 mAh/g. The volumetric capacity averaged over 1000 cycles of charge/discharge is 2821 mAh/cm3 which is 2 to 5 times higher than what is reported in the literature for Si nanoparticle based electrodes. The graphene-draped Si anode could also be successfully cycled against commercial cathodes in a full-cell configuration. In Chapter 5, an alternate strategy has been explored to stabilize

Marker-assisted introgression of drought tolerance from wild ancestors into popular Indian rice varieties using a 7K Infinium SNP array

Directory of Open Access Journals (Sweden)

Ravindra Donde

2017-10-01

Full Text Available Recent advances in the area of genomics have led to the development of high throughput genotyping platforms that have immensely contributed to molecular breeding programs. Custom-designed single nucleotide polymorphism (SNP arrays provide an efficient, cost effective, high throughput genotyping tool for QTL/gene mapping, variety identification, marker-assisted selection, etc. In the current study, two interspecific libraries of Chromosome Segment Substitution Lines (CSSLs were evaluated under both drought and control conditions to identify lines with superior yield under drought. The CSSL libraries consisted of 48 BC4F3 lines derived from O. sativa cv. Curinga (tropical japonica x O. rufipogon, and 32 BC4F3 lines derived from O. sativa cv. Curinga (tropical japonica x O. meridionalis. The phenotypic screening of these 80 CSSLs led to the identification of three lines, MER-20, RUF-16, and RUF-44, that yielded well under drought stress. This line was backcrossed with popular rice variety of India, Swarna-Sub1 to introgress wild chromosome segments responsible for reproductive stage drought tolerance. During backcrossing, tracking of wild introgressions and monitoring of recurrent parent genome recovery was facilitated by the use of the Cornell 6K and 7K Infinium rice SNP arrays. The 6K and 7K SNP arrays assayed 5275 SNPs and 7099 SNPs, respectively, distributed across the 12 chromosomes. In our populations of (MER-20X Swarna sub1 BC2F1 lines, 1775 SNPs were polymorphic using the 6K array. The percentage of recurrent parent genome in these backcrossed lines ranged from 33-92% and the percentage of wild donor genome ranged from 8-67%. Using genotypic selection, 5% of plants were identified for further marker assisted backcrossing, based on the presence of the target donor (wild segment and maximum recovery of recurrent parent background. In the next generation, BC3F1 lines were genotyped using the 7K SNP array, which identified 2521 polymorphic SNPs

Toward Low-Cost, High-Energy Density, and High-Power Density Lithium-Ion Batteries

Science.gov (United States)

Li, Jianlin; Du, Zhijia; Ruther, Rose E.; AN, Seong Jin; David, Lamuel Abraham; Hays, Kevin; Wood, Marissa; Phillip, Nathan D.; Sheng, Yangping; Mao, Chengyu; Kalnaus, Sergiy; Daniel, Claus; Wood, David L.

2017-09-01

Reducing cost and increasing energy density are two barriers for widespread application of lithium-ion batteries in electric vehicles. Although the cost of electric vehicle batteries has been reduced by 70% from 2008 to 2015, the current battery pack cost (268/kWh in 2015) is still >2 times what the USABC targets (125/kWh). Even though many advancements in cell chemistry have been realized since the lithium-ion battery was first commercialized in 1991, few major breakthroughs have occurred in the past decade. Therefore, future cost reduction will rely on cell manufacturing and broader market acceptance. This article discusses three major aspects for cost reduction: (1) quality control to minimize scrap rate in cell manufacturing; (2) novel electrode processing and engineering to reduce processing cost and increase energy density and throughputs; and (3) material development and optimization for lithium-ion batteries with high-energy density. Insights on increasing energy and power densities of lithium-ion batteries are also addressed.

Deep-blue efficient OLED based on NPB with little efficiency roll-off under high current density

Science.gov (United States)

Liu, Jian

2017-03-01

NPB usually is used as a hole-transport layer in OLED. In fact, it is a standard pure blue-emission material. However, its light-emitting efficiency in OLED is low due to emissive nature of organic material. Herein, a deep-blue OLDE based on NPB was fabricated. The light-emitting efficiency of the device demonstrates a moderate value, and efficiency roll-off is little under high current density. The device demonstrates that the electroplex's emission decreases with increasing electric field intensity.

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

Science.gov (United States)

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.

Properties of matter at ultra-high densities

International Nuclear Information System (INIS)

Banerjee, B.; Chitre, S.M.

1975-01-01

The recent discovery of pulsars and their subsequent identification with neutron stars has given a great impetus to the study of the behaviour of matter at ultra high densities. The object of these studies is to calculate the equation of state as a function of density. In this paper, the properties of electrically neutral, cold (T=0) matter at unusually high densities has been reviewed. The physics of the equation of state of such matter divides quite naturally in four density ranges. (i) At the very lowest densities the state of minimum energy is a lattice of 56 Fe atoms. This state persists upto 10 7 g/cm 3 . (ii) In the next density region the nuclei at the lattice sites become neutron rich because the high electron Fermi energy makes inverse beta decay possible. (iii) At a density 4.3 x 10 11 the nuclei become so neutron rich that the neutrons start 'dripping' out of the nuclei and form a gas. This density range is characterised by large, neutron-rich nuclei immersed in a neutron gas. (iv) At a density 2.4 x 10 14 g/cm 3 , the nuclei disappear and a fluid of uniform neutron matter with a small percentage of protons and electrons results. The above four density ranges have been discussed in detail as the equation of state is now well established upto the nuclear density 3 x 10 14 g/cm 3 . The problems of extending the equation of state beyond this density are also touched upon. (author)

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Science.gov (United States)

Scherrer, Daniel Zanetti; Zago, Vanessa Helena de Souza; Vieira, Isabela Calanca; Parra, Eliane Soler; Panzoldo, Natália Baratella; Alexandre, Fernanda; Secolin, Rodrigo; Baracat, Jamal; Quintão, Eder Carlos Rocha; de Faria, Eliana Cotta

2015-01-01

Background Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). Objective To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. Methods We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). Results The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. Conclusion In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis. PMID:26039660

Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao.

Science.gov (United States)

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. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Reference genome-independent assessment of mutation density using restriction enzyme-phased sequencing

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Monson-Miller Jennifer

2012-02-01

Full Text Available Abstract Background The availability of low cost sequencing has spurred its application to discovery and typing of variation, including variation induced by mutagenesis. Mutation discovery is challenging as it requires a substantial amount of sequencing and analysis to detect very rare changes and distinguish them from noise. Also challenging are the cases when the organism of interest has not been sequenced or is highly divergent from the reference. Results We describe the development of a simple method for reduced representation sequencing. Input DNA was digested with a single restriction enzyme and ligated to Y adapters modified to contain a sequence barcode and to provide a compatible overhang for ligation. We demonstrated the efficiency of this method at SNP discovery using rice and arabidopsis. To test its suitability for the discovery of very rare SNP, one control and three mutagenized rice individuals (1, 5 and 10 mM sodium azide were used to prepare genomic libraries for Illumina sequencers by ligating barcoded adapters to NlaIII restriction sites. For genome-dependent discovery 15-30 million of 80 base reads per individual were aligned to the reference sequence achieving individual sequencing coverage from 7 to 15×. We identified high-confidence base changes by comparing sequences across individuals and identified instances consistent with mutations, i.e. changes that were found in a single treated individual and were solely GC to AT transitions. For genome-independent discovery 70-mers were extracted from the sequence of the control individual and single-copy sequence was identified by comparing the 70-mers across samples to evaluate copy number and variation. This de novo "genome" was used to align the reads and identify mutations as above. Covering approximately 1/5 of the 380 Mb genome of rice we detected mutation densities ranging from 0.6 to 4 per Mb of diploid DNA depending on the mutagenic treatment. Conclusions The

HLA-C -35kb expression SNP is associated with differential control of β-HPV infection in squamous cell carcinoma cases and controls.

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Karin A Vineretsky

Full Text Available A single nucleotide polymorphism (SNP 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC, and of squamous cell carcinoma (SCC in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the -35 kb SNP (rs9264942 in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression -35 kb SNP genotype (CC reduced the likelihood of positive serology for multiple (≥2 β-HPV infections (OR = 0.49, 95% CI: 0.25-0.97, and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23-0.79. However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls.

TIA: algorithms for development of identity-linked SNP islands for analysis by massively parallel DNA sequencing.

Science.gov (United States)

Farris, M Heath; Scott, Andrew R; Texter, Pamela A; Bartlett, Marta; Coleman, Patricia; Masters, David

2018-04-11

Single nucleotide polymorphisms (SNPs) located within the human genome have been shown to have utility as markers of identity in the differentiation of DNA from individual contributors. Massively parallel DNA sequencing (MPS) technologies and human genome SNP databases allow for the design of suites of identity-linked target regions, amenable to sequencing in a multiplexed and massively parallel manner. Therefore, tools are needed for leveraging the genotypic information found within SNP databases for the discovery of genomic targets that can be evaluated on MPS platforms. The SNP island target identification algorithm (TIA) was developed as a user-tunable system to leverage SNP information within databases. Using data within the 1000 Genomes Project SNP database, human genome regions were identified that contain globally ubiquitous identity-linked SNPs and that were responsive to targeted resequencing on MPS platforms. Algorithmic filters were used to exclude target regions that did not conform to user-tunable SNP island target characteristics. To validate the accuracy of TIA for discovering these identity-linked SNP islands within the human genome, SNP island target regions were amplified from 70 contributor genomic DNA samples using the polymerase chain reaction. Multiplexed amplicons were sequenced using the Illumina MiSeq platform, and the resulting sequences were analyzed for SNP variations. 166 putative identity-linked SNPs were targeted in the identified genomic regions. Of the 309 SNPs that provided discerning power across individual SNP profiles, 74 previously undefined SNPs were identified during evaluation of targets from individual genomes. Overall, DNA samples of 70 individuals were uniquely identified using a subset of the suite of identity-linked SNP islands. TIA offers a tunable genome search tool for the discovery of targeted genomic regions that are scalable in the population frequency and numbers of SNPs contained within the SNP island regions

High-density carbon ablator ignition path with low-density gas-filled rugby hohlraum

International Nuclear Information System (INIS)

Amendt, Peter; Ho, Darwin D.; Jones, Ogden S.

2015-01-01

A recent low gas-fill density (0.6 mg/cc 4 He) cylindrical hohlraum experiment on the National Ignition Facility has shown high laser-coupling efficiency (>96%), reduced phenomenological laser drive corrections, and improved high-density carbon capsule implosion symmetry [Jones et al., Bull. Am. Phys. Soc. 59(15), 66 (2014)]. In this Letter, an ignition design using a large rugby-shaped hohlraum [Amendt et al., Phys. Plasmas 21, 112703 (2014)] for high energetics efficiency and symmetry control with the same low gas-fill density (0.6 mg/cc 4 He) is developed as a potentially robust platform for demonstrating thermonuclear burn. The companion high-density carbon capsule for this hohlraum design is driven by an adiabat-shaped [Betti et al., Phys. Plasmas 9, 2277 (2002)] 4-shock drive profile for robust high gain (>10) 1-D ignition performance and large margin to 2-D perturbation growth

High-density carbon ablator ignition path with low-density gas-filled rugby hohlraum

Science.gov (United States)

Amendt, Peter; Ho, Darwin D.; Jones, Ogden S.

2015-04-01

A recent low gas-fill density (0.6 mg/cc 4He) cylindrical hohlraum experiment on the National Ignition Facility has shown high laser-coupling efficiency (>96%), reduced phenomenological laser drive corrections, and improved high-density carbon capsule implosion symmetry [Jones et al., Bull. Am. Phys. Soc. 59(15), 66 (2014)]. In this Letter, an ignition design using a large rugby-shaped hohlraum [Amendt et al., Phys. Plasmas 21, 112703 (2014)] for high energetics efficiency and symmetry control with the same low gas-fill density (0.6 mg/cc 4He) is developed as a potentially robust platform for demonstrating thermonuclear burn. The companion high-density carbon capsule for this hohlraum design is driven by an adiabat-shaped [Betti et al., Phys. Plasmas 9, 2277 (2002)] 4-shock drive profile for robust high gain (>10) 1-D ignition performance and large margin to 2-D perturbation growth.

High-density carbon ablator ignition path with low-density gas-filled rugby hohlraum

Energy Technology Data Exchange (ETDEWEB)

Amendt, Peter; Ho, Darwin D.; Jones, Ogden S. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

2015-04-15

A recent low gas-fill density (0.6 mg/cc {sup 4}He) cylindrical hohlraum experiment on the National Ignition Facility has shown high laser-coupling efficiency (>96%), reduced phenomenological laser drive corrections, and improved high-density carbon capsule implosion symmetry [Jones et al., Bull. Am. Phys. Soc. 59(15), 66 (2014)]. In this Letter, an ignition design using a large rugby-shaped hohlraum [Amendt et al., Phys. Plasmas 21, 112703 (2014)] for high energetics efficiency and symmetry control with the same low gas-fill density (0.6 mg/cc {sup 4}He) is developed as a potentially robust platform for demonstrating thermonuclear burn. The companion high-density carbon capsule for this hohlraum design is driven by an adiabat-shaped [Betti et al., Phys. Plasmas 9, 2277 (2002)] 4-shock drive profile for robust high gain (>10) 1-D ignition performance and large margin to 2-D perturbation growth.

MDM2 promoter SNP344T>A (rs1196333 status does not affect cancer risk.

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Stian Knappskog

Full Text Available The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744 facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649, located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333 located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954 and patients suffering from ovarian (n = 1,927, breast (n = 1,271, endometrial (n = 895 or prostatic cancer (n = 641, we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively. In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk.

Development of Bi-based high critical current density superconducting tapes

International Nuclear Information System (INIS)

Swaminathan, G.

1995-01-01

In order to achieve the aim of developing suitable superconducting materials the main emphasis has to be made in the following areas viz., synthesizing powders, detailed study of sintering and phase conversion process in relation to the critical current density (J c ) on pellets and optimising of tape processing parameters. The bismuth system has been found to be more favourable for making wires and tapes because of its high transition temperature, good stability, does not require oxygen on cooling and is non-toxic. These have been the most convenient properties which made the BiSCO material the most popular one

Detection of High-Density Crowds in Aerial Images Using Texture Classification

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Oliver Meynberg

2016-06-01

Full Text Available Automatic crowd detection in aerial images is certainly a useful source of information to prevent crowd disasters in large complex scenarios of mass events. A number of publications employ regression-based methods for crowd counting and crowd density estimation. However, these methods work only when a correct manual count is available to serve as a reference. Therefore, it is the objective of this paper to detect high-density crowds in aerial images, where counting– or regression–based approaches would fail. We compare two texture–classification methodologies on a dataset of aerial image patches which are grouped into ranges of different crowd density. These methodologies are: (1 a Bag–of–words (BoW model with two alternative local features encoded as Improved Fisher Vectors and (2 features based on a Gabor filter bank. Our results show that a classifier using either BoW or Gabor features can detect crowded image regions with 97% classification accuracy. In our tests of four classes of different crowd-density ranges, BoW–based features have a 5%–12% better accuracy than Gabor.

Anti-Ferroelectric Ceramics for High Energy Density Capacitors

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Aditya Chauhan

2015-11-01

Full Text Available With an ever increasing dependence on electrical energy for powering modern equipment and electronics, research is focused on the development of efficient methods for the generation, storage and distribution of electrical power. In this regard, the development of suitable dielectric based solid-state capacitors will play a key role in revolutionizing modern day electronic and electrical devices. Among the popular dielectric materials, anti-ferroelectrics (AFE display evidence of being a strong contender for future ceramic capacitors. AFE materials possess low dielectric loss, low coercive field, low remnant polarization, high energy density, high material efficiency, and fast discharge rates; all of these characteristics makes AFE materials a lucrative research direction. However, despite the evident advantages, there have only been limited attempts to develop this area. This article attempts to provide a focus to this area by presenting a timely review on the topic, on the relevant scientific advancements that have been made with respect to utilization and development of anti-ferroelectric materials for electric energy storage applications. The article begins with a general introduction discussing the need for high energy density capacitors, the present solutions being used to address this problem, and a brief discussion of various advantages of anti-ferroelectric materials for high energy storage applications. This is followed by a general description of anti-ferroelectricity and important anti-ferroelectric materials. The remainder of the paper is divided into two subsections, the first of which presents various physical routes for enhancing the energy storage density while the latter section describes chemical routes for enhanced storage density. This is followed by conclusions and future prospects and challenges which need to be addressed in this particular field.

Graphene-based in-plane micro-supercapacitors with high power and energy densities.

Science.gov (United States)

Wu, Zhong-Shuai; Parvez, Khaled; Feng, Xinliang; Müllen, Klaus

2013-01-01

Micro-supercapacitors are important on-chip micro-power sources for miniaturized electronic devices. Although the performance of micro-supercapacitors has been significantly advanced by fabricating nanostructured materials, developing thin-film manufacture technologies and device architectures, their power or energy densities remain far from those of electrolytic capacitors or lithium thin-film batteries. Here we demonstrate graphene-based in-plane interdigital micro-supercapacitors on arbitrary substrates. The resulting micro-supercapacitors deliver an area capacitance of 80.7 μF cm⁻² and a stack capacitance of 17.9 F cm⁻³. Further, they show a power density of 495 W cm⁻³ that is higher than electrolytic capacitors, and an energy density of 2.5 mWh cm⁻³ that is comparable to lithium thin-film batteries, in association with superior cycling stability. Such microdevices allow for operations at ultrahigh rate up to 1,000 V s⁻¹, three orders of magnitude higher than that of conventional supercapacitors. Micro-supercapacitors with an in-plane geometry have great promise for numerous miniaturized or flexible electronic applications.

Graphene-based in-plane micro-supercapacitors with high power and energy densities

Science.gov (United States)

Wu, Zhong–Shuai; Parvez, Khaled; Feng, Xinliang; Müllen, Klaus

2013-01-01

Micro-supercapacitors are important on-chip micro-power sources for miniaturized electronic devices. Although the performance of micro-supercapacitors has been significantly advanced by fabricating nanostructured materials, developing thin-film manufacture technologies and device architectures, their power or energy densities remain far from those of electrolytic capacitors or lithium thin-film batteries. Here we demonstrate graphene-based in-plane interdigital micro-supercapacitors on arbitrary substrates. The resulting micro-supercapacitors deliver an area capacitance of 80.7 μF cm−2 and a stack capacitance of 17.9 F cm−3. Further, they show a power density of 495 W cm−3 that is higher than electrolytic capacitors, and an energy density of 2.5 mWh cm−3 that is comparable to lithium thin-film batteries, in association with superior cycling stability. Such microdevices allow for operations at ultrahigh rate up to 1,000 V s−1, three orders of magnitude higher than that of conventional supercapacitors. Micro-supercapacitors with an in-plane geometry have great promise for numerous miniaturized or flexible electronic applications. PMID:24042088

Experience from large scale use of the EuroGenomics custom SNP chip in cattle

DEFF Research Database (Denmark)

Boichard, Didier A; Boussaha, Mekki; Capitan, Aurélien

2018-01-01

This article presents the strategy to evaluate candidate mutations underlying QTL or responsible for genetic defects, based upon the design and large-scale use of the Eurogenomics custom SNP chip set up for bovine genomic selection. Some variants under study originated from mapping genetic defect...

Coupling amplified DNA from flow-sorted chromosomes to high-density SNP mapping in barley

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Bartoš Jan

2008-06-01

Full Text Available Abstract Background Flow cytometry facilitates sorting of single chromosomes and chromosome arms which can be used for targeted genome analysis. However, the recovery of microgram amounts of DNA needed for some assays requires sorting of millions of chromosomes which is laborious and time consuming. Yet, many genomic applications such as development of genetic maps or physical mapping do not require large DNA fragments. In such cases time-consuming de novo sorting can be minimized by utilizing whole-genome amplification. Results Here we report a protocol optimized in barley including amplification of DNA from only ten thousand chromosomes, which can be isolated in less than one hour. Flow-sorted chromosomes were treated with proteinase K and amplified using Phi29 multiple displacement amplification (MDA. Overnight amplification in a 20-microlitre reaction produced 3.7 – 5.7 micrograms DNA with a majority of products between 5 and 30 kb. To determine the purity of sorted fractions and potential amplification bias we used quantitative PCR for specific genes on each chromosome. To extend the analysis to a whole genome level we performed an oligonucleotide pool assay (OPA for interrogation of 1524 loci, of which 1153 loci had known genetic map positions. Analysis of unamplified genomic DNA of barley cv. Akcent using this OPA resulted in 1426 markers with present calls. Comparison with three replicates of amplified genomic DNA revealed >99% concordance. DNA samples from amplified chromosome 1H and a fraction containing chromosomes 2H – 7H were examined. In addition to loci with known map positions, 349 loci with unknown map positions were included. Based on this analysis 40 new loci were mapped to 1H. Conclusion The results indicate a significant potential of using this approach for physical mapping. Moreover, the study showed that multiple displacement amplification of flow-sorted chromosomes is highly efficient and representative which

High Density Interconnect Microstrip Patch Antenna for 5G Base Stations with Integrated Filtering Performance

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Marco Salucci

2018-04-01

Full Text Available The elementary radiator of a planar array for next generation millimeter-wave (mm-wave 5G base stations is described. The antenna is designed for high density interconnect (HDI manufacturing for yielding a compact, densely-interconnected, and highly-integrable stacked structure. The layout of the single element is determined by directly optimizing key radiation features of the whole planar arrangement according to specific application-driven requirements. In addition, thanks to the exploitation of a spline-shaped modelling of the radiator, suitable performance in terms of impedance matching, realized gain, half-power beamwidth (HPBW, polarization purity, and inter-element isolation are achieved within the 28-GHz pass-band. Moreover, integrated out-of-band filtering capabilities are obtained in selected and wide non-contiguous stop-bands without additional circuitry.

Electronic DC transformer with high power density

NARCIS (Netherlands)

Pavlovský, M.

2006-01-01

This thesis is concerned with the possibilities of increasing the power density of high-power dc-dc converters with galvanic isolation. Three cornerstones for reaching high power densities are identified as: size reduction of passive components, reduction of losses particularly in active components

Genetic search for an optimal power flow solution from a high density cluster

Energy Technology Data Exchange (ETDEWEB)

Amarnath, R.V. [Hi-Tech College of Engineering and Technology, Hyderabad (India); Ramana, N.V. [JNTU College of Engineering, Jagityala (India)

2008-07-01

This paper proposed a novel method to solve optimal power flow (OPF) problems. The method is based on a genetic algorithm (GA) search from a High Density Cluster (GAHDC). The algorithm of the proposed method includes 3 stages, notably (1) a suboptimal solution is obtained via a conventional analytical method, (2) a high density cluster, which consists of other suboptimal data points from the first stage, is formed using a density-based cluster algorithm, and (3) a genetic algorithm based search is carried out for the exact optimal solution from a low population sized, high density cluster. The final optimal solution thoroughly satisfies the well defined fitness function. A standard IEEE 30-bus test system was considered for the simulation study. Numerical results were presented and compared with the results of other approaches. It was concluded that although there is not much difference in numerical values, the proposed method has the advantage of minimal computational effort and reduced CPU time. As such, the method would be suitable for online applications such as the present Optimal Power Flow problem. 24 refs., 2 tabs., 4 figs.

Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

Science.gov (United States)

Kijas, James W.; Lenstra, Johannes A.; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R.; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

2012-01-01

Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. PMID:22346734

Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.

Directory of Open Access Journals (Sweden)

James W Kijas

2012-02-01

Full Text Available Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.

Effects of Single Nucleotide Polymorphism Marker Density on Haplotype Block Partition

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Sun Ah Kim

2016-12-01

Full Text Available Many researchers have found that one of the most important characteristics of the structure of linkage disequilibrium is that the human genome can be divided into non-overlapping block partitions in which only a small number of haplotypes are observed. The location and distribution of haplotype blocks can be seen as a population property influenced by population genetic events such as selection, mutation, recombination and population structure. In this study, we investigate the effects of the density of markers relative to the full set of all polymorphisms in the region on the results of haplotype partitioning for five popular haplotype block partition methods: three methods in Haploview (confidence interval, four gamete test, and solid spine, MIG++ implemented in PLINK 1.9 and S-MIG++. We used several experimental datasets obtained by sampling subsets of single nucleotide polymorphism (SNP markers of chromosome 22 region in the 1000 Genomes Project data and also the HapMap phase 3 data to compare the results of haplotype block partitions by five methods. With decreasing sampling ratio down to 20% of the original SNP markers, the total number of haplotype blocks decreases and the length of haplotype blocks increases for all algorithms. When we examined the marker-independence of the haplotype block locations constructed from the datasets of different density, the results using below 50% of the entire SNP markers were very different from the results using the entire SNP markers. We conclude that the haplotype block construction results should be used and interpreted carefully depending on the selection of markers and the purpose of the study.

StreamMap: Smooth Dynamic Visualization of High-Density Streaming Points.

Science.gov (United States)

Li, Chenhui; Baciu, George; Han, Yu

2018-03-01

Interactive visualization of streaming points for real-time scatterplots and linear blending of correlation patterns is increasingly becoming the dominant mode of visual analytics for both big data and streaming data from active sensors and broadcasting media. To better visualize and interact with inter-stream patterns, it is generally necessary to smooth out gaps or distortions in the streaming data. Previous approaches either animate the points directly or present a sampled static heat-map. We propose a new approach, called StreamMap, to smoothly blend high-density streaming points and create a visual flow that emphasizes the density pattern distributions. In essence, we present three new contributions for the visualization of high-density streaming points. The first contribution is a density-based method called super kernel density estimation that aggregates streaming points using an adaptive kernel to solve the overlapping problem. The second contribution is a robust density morphing algorithm that generates several smooth intermediate frames for a given pair of frames. The third contribution is a trend representation design that can help convey the flow directions of the streaming points. The experimental results on three datasets demonstrate the effectiveness of StreamMap when dynamic visualization and visual analysis of trend patterns on streaming points are required.

Spontaneous magnetization in high-density quark matter

DEFF Research Database (Denmark)

Tsue, Yasuhiko; da Providência, João; Providência, Constanca

2015-01-01

It is shown that spontaneous magnetization occurs due to the anomalous magnetic moments of quarks in high-density quark matter under the tensor-type four-point interaction. The spin polarized condensate for each flavor of quark appears at high baryon density, which leads to the spontaneous magnet...

High power density yeast catalyzed microbial fuel cells

Science.gov (United States)

Ganguli, Rahul

increase was shown to quickly saturate with cell mass attached on the electrode. Based on recent modelling data that suggested that the electrode currents might be limited by the poor electrical conductivity of the anode, the power density versus electrical conductivity of a yeast-immobilized anode was investigated. Introduction of high aspect ratio carbon fiber filaments to the immobilization matrix increased the electrical conductivity of the anode. Although a higher electrical conductivity clearly led to an increase in power densities, it was shown that the principal limitation to power density increase was coming from proton transfer limitations in the immobilized anode. Partial overcoming of the gradients lead a power density of ca. 250 microW cm-2, which is the highest reported for yeast powered MFCs. A yeast-catalyzed microbial fuel cell was investigated as a power source for low power sensors using raw tree sap. It was shown that yeast can efficiently utilize the sucrose present in the raw tree sap to produce electricity when excess salt is added to the medium. Therefore the salinity of a potential energy source is an important consideration when MFCs are being considered for energy harvesting from natural sources.

High Energy Density Sciences with High Power Lasers at SACLA

Science.gov (United States)

Kodama, Ryosuke

2013-10-01

One of the interesting topics on high energy density sciences with high power lasers is creation of extremely high pressures in material. The pressures of more than 0.1 TPa are the energy density corresponding to the chemical bonding energy, resulting in expectation of dramatic changes in the chemical reactions. At pressures of more than TPa, most of material would be melted on the shock Hugoniot curve. However, if the temperature is less than 1eV or lower than a melting point at pressures of more than TPa, novel solid states of matter must be created through a pressured phase transition. One of the interesting materials must be carbon. At pressures of more than TPa, the diamond structure changes to BC and cubic at more than 3TPa. To create such novel states of matter, several kinds of isentropic-like compression techniques are being developed with high power lasers. To explore the ``Tera-Pascal Science,'' now we have a new tool which is an x-ray free electron laser as well as high power lasers. The XFEL will clear the details of the HED states and also efficiently create hot dense matter. We have started a new project on high energy density sciences using an XFEL (SACLA) in Japan, which is a HERMES (High Energy density Revolution of Matter in Extreme States) project.

Flexible Semitransparent Energy Harvester with High Pressure Sensitivity and Power Density Based on Laterally Aligned PZT Single-Crystal Nanowires.

Science.gov (United States)

Zhao, Quan-Liang; He, Guang-Ping; Di, Jie-Jian; Song, Wei-Li; Hou, Zhi-Ling; Tan, Pei-Pei; Wang, Da-Wei; Cao, Mao-Sheng

2017-07-26

A flexible semitransparent energy harvester is assembled based on laterally aligned Pb(Zr 0.52 Ti 0.48 )O 3 (PZT) single-crystal nanowires (NWs). Such a harvester presents the highest open-circuit voltage and a stable area power density of up to 10 V and 0.27 μW/cm 2 , respectively. A high pressure sensitivity of 0.14 V/kPa is obtained in the dynamic pressure sensing, much larger than the values reported in other energy harvesters based on piezoelectric single-crystal NWs. Furthermore, theoretical and finite element analyses also confirm that the piezoelectric voltage constant g 33 of PZT NWs is competitive to the lead-based bulk single crystals and ceramics, and the enhanced pressure sensitivity and power density are substantially linked to the flexible structure with laterally aligned PZT NWs. The energy harvester in this work holds great potential in flexible and transparent sensing and self-powered systems.

High-density self-contained microfluidic KOALA kits for use by everyone.

Science.gov (United States)

Guckenberger, David J; Berthier, Erwin; Beebe, David J

2015-04-01

Cell-based assays are essential tools used by research labs in a wide range of fields, including cell biology, toxicology, and natural product discovery labs. However, in some situations, the need for cell-based assays does not justify the costs of maintaining cell culture facilities and retaining skilled staff. The kit-on-a-lid assay (KOALA) technology enables accessible low-cost and prepackageable microfluidic platforms that can be operated with minimal infrastructure or training. Here, we demonstrate and characterize high-density KOALA methods for high-throughput applications, achieving an assay density comparable to that of a 384-well plate and usability by hand with no liquid-handling equipment. We show the potential for high-content screening and complex assays such as quantitative immunochemistry assays requiring multiple steps and reagents. © 2014 Society for Laboratory Automation and Screening.

UGbS-Flex, a novel bioinformatics pipeline for imputation-free SNP discovery in polyploids without a reference genome: finger millet as a case study.

Science.gov (United States)

Qi, Peng; Gimode, Davis; Saha, Dipnarayan; Schröder, Stephan; Chakraborty, Debkanta; Wang, Xuewen; Dida, Mathews M; Malmberg, Russell L; Devos, Katrien M

2018-06-15

Research on orphan crops is often hindered by a lack of genomic resources. With the advent of affordable sequencing technologies, genotyping an entire genome or, for large-genome species, a representative fraction of the genome has become feasible for any crop. Nevertheless, most genotyping-by-sequencing (GBS) methods are geared towards obtaining large numbers of markers at low sequence depth, which excludes their application in heterozygous individuals. Furthermore, bioinformatics pipelines often lack the flexibility to deal with paired-end reads or to be applied in polyploid species. UGbS-Flex combines publicly available software with in-house python and perl scripts to efficiently call SNPs from genotyping-by-sequencing reads irrespective of the species' ploidy level, breeding system and availability of a reference genome. Noteworthy features of the UGbS-Flex pipeline are an ability to use paired-end reads as input, an effective approach to cluster reads across samples with enhanced outputs, and maximization of SNP calling. We demonstrate use of the pipeline for the identification of several thousand high-confidence SNPs with high representation across samples in an F 3 -derived F 2 population in the allotetraploid finger millet. Robust high-density genetic maps were constructed using the time-tested mapping program MAPMAKER which we upgraded to run efficiently and in a semi-automated manner in a Windows Command Prompt Environment. We exploited comparative GBS with one of the diploid ancestors of finger millet to assign linkage groups to subgenomes and demonstrate the presence of chromosomal rearrangements. The paper combines GBS protocol modifications, a novel flexible GBS analysis pipeline, UGbS-Flex, recommendations to maximize SNP identification, updated genetic mapping software, and the first high-density maps of finger millet. The modules used in the UGbS-Flex pipeline and for genetic mapping were applied to finger millet, an allotetraploid selfing species

The high density and high βpol disruption mechanism on TFTR

International Nuclear Information System (INIS)

Fredrickson, E.D.; Manickam, J.; McGuire, K.M.; Monticello, D.; Nagayama, Y.; Park, W.; Taylor, G.

1992-01-01

Studies of disruptions on TFTR have been extended to include high density disruptions as well as the high β pol disruptions. The data strongly suggests that the (m,n)=(1,1) mode plays an important role in both types of disruptions. Further, for the first time, it is unambiguously shown, using a fast electron cyclotron emission (ECE) instrument for the electron temperature profile measurements, that the (m,n)=(1,1) precursor to the high density disruptions has a 'cold bubble' structure. The precursor to the major disruption at high density resembles the 'vacuum bubble' model of disruptions first proposed by Kadomtsev and Pogutse. (author) 2 refs., 2 figs

Interactions Between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians

Directory of Open Access Journals (Sweden)

Sumiko Anno

2007-01-01

Full Text Available This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

SNP2Structure: A Public and Versatile Resource for Mapping and Three-Dimensional Modeling of Missense SNPs on Human Protein Structures

Directory of Open Access Journals (Sweden)

Difei Wang

2015-01-01

Full Text Available One of the long-standing challenges in biology is to understand how non-synonymous single nucleotide polymorphisms (nsSNPs change protein structure and further affect their function. While it is impractical to solve all the mutated protein structures experimentally, it is quite feasible to model the mutated structures in silico. Toward this goal, we built a publicly available structure database resource (SNP2Structure, https://apps.icbi.georgetown.edu/snp2structure focusing on missense mutations, msSNP. Compared with web portals with similar aims, SNP2Structure has the following major advantages. First, our portal offers direct comparison of two related 3D structures. Second, the protein models include all interacting molecules in the original PDB structures, so users are able to determine regions of potential interaction changes when a protein mutation occurs. Third, the mutated structures are available to download locally for further structural and functional analysis. Fourth, we used Jsmol package to display the protein structure that has no system compatibility issue. SNP2Structure provides reliable, high quality mapping of nsSNPs to 3D protein structures enabling researchers to explore the likely functional impact of human disease-causing mutations.

Electrode/Dielectric Strip For High-Energy-Density Capacitor

Science.gov (United States)

Yen, Shiao-Ping S.

1994-01-01

Improved unitary electrode/dielectric strip serves as winding in high-energy-density capacitor in pulsed power supply. Offers combination of qualities essential for high energy density: high permittivity of dielectric layers, thinness, and high resistance to breakdown of dielectric at high electric fields. Capacitors with strip material not impregnated with liquid.

Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic Map Construction in Cauliflower Using Specific-Locus Amplified Fragment Sequencing

Science.gov (United States)

Zhao, Zhenqing; Gu, Honghui; Sheng, Xiaoguang; Yu, Huifang; Wang, Jiansheng; Huang, Long; Wang, Dan

2016-01-01

Molecular markers and genetic maps play an important role in plant genomics and breeding studies. Cauliflower is an important and distinctive vegetable; however, very few molecular resources have been reported for this species. In this study, a novel, specific-locus amplified fragment (SLAF) sequencing strategy was employed for large-scale single nucleotide polymorphism (SNP) discovery and high-density genetic map construction in a double-haploid, segregating population of cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were obtained after processing and 6815 polymorphic SLAFs between the two parents were detected. The average sequencing depths reached 52.66-fold for the female parent and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were used to genotype the population and further filtered based on several criteria to construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF markers, including 2741 SNPs, constituted the linkage map with average data integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference genome. The markers and genetic map developed in this study could provide an important foundation not only for comparative genomics studies within Brassica oleracea species but also for quantitative trait loci identification and molecular breeding of cauliflower. PMID:27047515

Rapid identification of tomato Sw-5 resistance-breaking isolates of Tomato spotted wilt virus using high resolution melting and TaqMan SNP Genotyping assays as allelic discrimination techniques.

Directory of Open Access Journals (Sweden)

Valentina di Rienzo

Full Text Available In tomato, resistance to Tomato spotted wilt virus (TSWV is conferred by the dominant gene, designated Sw-5. Virulent Sw-5 resistance breaking (SRB mutants of TSWV have been reported on Sw-5 tomato cultivars. Two different PCR-based allelic discrimination techniques, namely Custom TaqMan™ SNP Genotyping and high-resolution melting (HRM assays, were developed and compared for their ability to distinguish between avirulent (Sw-5 non-infecting, SNI and SRB biotypes. TaqMan assays proved to be more sensitive (threshold of detection in a range of 50-70 TSWV RNA copies and more reliable than HRM, assigning 25 TSWV isolates to their correct genotype with an accuracy of 100%. Moreover, the TaqMan SNP assays were further improved developing a rapid and simple protocol that included crude leaf extraction for RNA template preparations. On the other hand, HRM assays showed higher levels of sensitivity than TaqMan when used to co-detect both biotypes in different artificial mixtures. These diagnostic assays contributed to gain preliminary information on the epidemiology of TSWV isolates in open field conditions. In fact, the presented data suggest that SRB isolates are present as stable populations established year round, persisting on both winter (globe artichoke and summer (tomato crops, in the same cultivated areas of Southern Italy.

A single nucleotide polymorphism (SNP) assay for population ...

African Journals Online (AJOL)

A single nucleotide polymorphism (SNP) assay for population stratification test ... phenotypes and unlinked candidate loci in case-control and cohort studies of ... Key words: Chinese, Japanese, population stratification, ancestry informative ...

Operation and control of high density tokamak reactors

International Nuclear Information System (INIS)

Attenberger, S.E.; McAlees, D.G.

1976-01-01

The incentive for high density operation of a tokamak reactor was discussed. It is found that high density permits ignition in a relatively small, moderately elongated plasma with a moderate magnetic field strength. Under these conditions, neutron wall loadings approximately 4 MW/m 2 must be tolerated. The sensitivity analysis with respect to impurity effects shows that impurity control will most likely be necessary to achieve the desired plasma conditions. The charge exchange sputtered impurities are found to have an important effect so that maintaining a low neutral density in the plasma is critical. If it is assumed that neutral beams will be used to heat the plasma to ignition, high energy injection is required (approximately 250 keV) when heating is accompished at full density. A scenario is outlined where the ignition temperature is established at low density and then the fueling rate is increased to attain ignition. This approach may permit beams with energies being developed for use in TFTR to be successfully used to heat a high density device of the type described here to ignition

High density high-TC ceramic superconductors by hot pressing

International Nuclear Information System (INIS)

Mak, S.; Chaklader, A.C.D.

1989-01-01

High density and high T C superconductor specimens, YBa 2 Cu 3 O x , have been produced by hot-pressing. The factors studied are the effect of hot pressing on the density, the oxygen stoichiometry, the crystal structure, and the critical temperature. Hot pressing followed by heat treatment increased the density of the specimen to 93%. The hot pressing itself did not significantly affect the oxygen content in the specimen, and although the crystal structure appeared to be orthorhombic, the specimens were not superconducting above liquid nitrogen temperature. The superconductivity was restored after head treatment in oxygen. The highest critical temperature (T C ) of the hot pressed pellets was 82K, which was slightly lower than the T C that could be obtained with the cold pressed/sintered pellets. (6 refs., 5 figs., tab.)

Snpdat: Easy and rapid annotation of results from de novo snp discovery projects for model and non-model organisms

Directory of Open Access Journals (Sweden)

Doran Anthony G

2013-02-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most abundant genetic variant found in vertebrates and invertebrates. SNP discovery has become a highly automated, robust and relatively inexpensive process allowing the identification of many thousands of mutations for model and non-model organisms. Annotating large numbers of SNPs can be a difficult and complex process. Many tools available are optimised for use with organisms densely sampled for SNPs, such as humans. There are currently few tools available that are species non-specific or support non-model organism data. Results Here we present SNPdat, a high throughput analysis tool that can provide a comprehensive annotation of both novel and known SNPs for any organism with a draft sequence and annotation. Using a dataset of 4,566 SNPs identified in cattle using high-throughput DNA sequencing we demonstrate the annotations performed and the statistics that can be generated by SNPdat. Conclusions SNPdat provides users with a simple tool for annotation of genomes that are either not supported by other tools or have a small number of annotated SNPs available. SNPdat can also be used to analyse datasets from organisms which are densely sampled for SNPs. As a command line tool it can easily be incorporated into existing SNP discovery pipelines and fills a niche for analyses involving non-model organisms that are not supported by many available SNP annotation tools. SNPdat will be of great interest to scientists involved in SNP discovery and analysis projects, particularly those with limited bioinformatics experience.

SNP detection from de novo transcriptome sequencing in the bivalve Macoma balthica: marker development for evolutionary studies.

Directory of Open Access Journals (Sweden)

Eric Pante

Full Text Available Hybrid zones are noteworthy systems for the study of environmental adaptation to fast-changing environments, as they constitute reservoirs of polymorphism and are key to the maintenance of biodiversity. They can move in relation to climate fluctuations, as temperature can affect both selection and migration, or remain trapped by environmental and physical barriers. There is therefore a very strong incentive to study the dynamics of hybrid zones subjected to climate variations. The infaunal bivalve Macoma balthica emerges as a noteworthy model species, as divergent lineages hybridize, and its native NE Atlantic range is currently contracting to the North. To investigate the dynamics and functioning of hybrid zones in M. balthica, we developed new molecular markers by sequencing the collective transcriptome of 30 individuals. Ten individuals were pooled for each of the three populations sampled at the margins of two hybrid zones. A single 454 run generated 277 Mb from which 17K SNPs were detected. SNP density averaged 1 polymorphic site every 14 to 19 bases, for mitochondrial and nuclear loci, respectively. An [Formula: see text] scan detected high genetic divergence among several hundred SNPs, some of them involved in energetic metabolism, cellular respiration and physiological stress. The high population differentiation, recorded for nuclear-encoded ATP synthase and NADH dehydrogenase as well as most mitochondrial loci, suggests cytonuclear genetic incompatibilities. Results from this study will help pave the way to a high-resolution study of hybrid zone dynamics in M. balthica, and the relative importance of endogenous and exogenous barriers to gene flow in this system.

High density thermite mixture for shaped charge ordnance disposal

Directory of Open Access Journals (Sweden)

Tamer Elshenawy

2017-10-01

Full Text Available The effect of thermite mixture based on aluminum and ferric oxides for ammunition neutralization has been studied and tested. Thermochemical calculations have been carried out for different percentage of Al using Chemical Equilibrium Code to expect the highest performance thermite mixture used for shaped charge ordnance disposal. Densities and enthalpy of different formulations have been calculated and demonstrated. The optimized thermite formulation has been prepared experimentally using cold iso-static pressing technique, which exhibited relatively high density and high burning rate thermite mixture. The produced green product compacted powder mixture was tested against small caliber shaped charge bomblet for neutralization. Theoretical and experimental results showed that the prepared thermite mixture containing 33% of aluminum as a fuel with ferric oxide can be successfully used for shaped charge ordnance disposal.

Occupation and mammographic density: A population-based study (DDM-Occup).

Science.gov (United States)

García-Pérez, Javier; Pollán, Marina; Pérez-Gómez, Beatriz; González-Sánchez, Mario; Cortés Barragán, Rosa Ana; Maqueda Blasco, Jerónimo; González-Galarzo, María Carmen; Alba, Miguel Ángel; van der Haar, Rudolf; Casas, Silvia; Vicente, Cándida; Medina, Pilar; Ederra, María; Santamariña, Carmen; Moreno, María Pilar; Casanova, Francisco; Pedraz-Pingarrón, Carmen; Moreo, Pilar; Ascunce, Nieves; García, Montse; Salas-Trejo, Dolores; Sánchez-Contador, Carmen; Llobet, Rafael; Lope, Virginia

2017-11-01

High mammographic density is one of the main risk factors for breast cancer. Although several occupations have been associated with breast cancer, there are no previous occupational studies exploring the association with mammographic density. Our objective was to identify occupations associated with high mammographic density in Spanish female workers. We conducted a population-based cross-sectional study of occupational determinants of high mammographic density in Spain, based on 1476 women, aged 45-68 years, recruited from seven screening centers within the Spanish Breast Cancer Screening Program network. Reproductive, family, personal, and occupational history data were collected. The latest occupation of each woman was collected and coded according to the 1994 National Classification of Occupations. Mammographic density was assessed from the cranio-caudal mammogram of the left breast using a semi-automated computer-assisted tool. Association between mammographic density and occupation was evaluated by using mixed linear regression models, using log-transformed percentage of mammographic density as dependent variable. Models were adjusted for age, body mass index, menopausal status, parity, smoking, alcohol intake, educational level, type of mammography, first-degree relative with breast cancer, and hormonal replacement therapy use. Screening center and professional reader were included as random effects terms. Mammographic density was higher, although non-statistically significant, among secondary school teachers (e β = 1.41; 95%CI = 0.98-2.03) and nurses (e β = 1.23; 95%CI = 0.96-1.59), whereas workers engaged in the care of people (e β = 0.81; 95%CI = 0.66-1.00) and housewives (e β = 0.87; 95%CI = 0.79-0.95) showed an inverse association with mammographic density. A positive trend for every 5 years working as secondary school teachers was also detected (p-value = 0.035). Nurses and secondary school teachers were the occupations with the highest

High Density Digital Data Storage System

Science.gov (United States)

Wright, Kenneth D., II; Gray, David L.; Rowland, Wayne D.

1991-01-01

The High Density Digital Data Storage System was designed to provide a cost effective means for storing real-time data from the field-deployable digital acoustic measurement system. However, the high density data storage system is a standalone system that could provide a storage solution for many other real time data acquisition applications. The storage system has inputs for up to 20 channels of 16-bit digital data. The high density tape recorders presently being used in the storage system are capable of storing over 5 gigabytes of data at overall transfer rates of 500 kilobytes per second. However, through the use of data compression techniques the system storage capacity and transfer rate can be doubled. Two tape recorders have been incorporated into the storage system to produce a backup tape of data in real-time. An analog output is provided for each data channel as a means of monitoring the data as it is being recorded.

Tri-allelic SNP markers enable analysis of mixed and degraded DNA samples.

Science.gov (United States)

Westen, Antoinette A; Matai, Anuska S; Laros, Jeroen F J; Meiland, Hugo C; Jasper, Mandy; de Leeuw, Wiljo J F; de Knijff, Peter; Sijen, Titia

2009-09-01

For the analysis of degraded DNA in disaster victim identification (DVI) and criminal investigations, single nucleotide polymorphisms (SNPs) have been recognized as promising markers mainly because they can be analyzed in short sized amplicons. Most SNPs are bi-allelic and are thereby ineffective to detect mixtures, which may lead to incorrect genotyping. We developed an algorithm to find non-binary (i.e. tri-allelic or tetra-allelic) SNPs in the NCBI dbSNP database. We selected 31 potential tri-allelic SNPs with a minor allele frequency of at least 10%. The tri-allelic nature was confirmed for 15 SNPs residing on 14 different chromosomes. Multiplex SNaPshot assays were developed, and the allele frequencies of 16 SNPs were determined among 153 Dutch and 111 Netherlands Antilles reference samples. Using these multiplex SNP assays, the presence of a mixture of two DNA samples in a ratio up to 1:8 could be recognized reliably. Furthermore, we compared the genotyping efficiency of the tri-allelic SNP markers and short tandem repeat (STR) markers by analyzing artificially degraded DNA and DNA from 30 approximately 500-year-old bone and molar samples. In both types of degraded DNA samples, the larger sized STR amplicons failed to amplify whereas the tri-allelic SNP markers still provided valuable information. In conclusion, tri-allelic SNP markers are suited for the analysis of degraded DNA and enable the detection of a second DNA source in a sample.

Low- and high-density nuclear equation of state and the hyperon puzzle

Energy Technology Data Exchange (ETDEWEB)

Colucci, Giuseppe; Sedrakian, Armen [Frankfurt Univ. (Germany). Inst. fuer Theoretische Physik

2013-07-01

The measurements of the unusually high mass of the millisecond pulsar PSR J1614-2230 (1.97 ± 0.04 M {sub CircleDot}) imposes a strong constraint on the nuclear Equation of State (EoS), in particular for what concerns the finite density behaviour of nuclear and neutron matter. In my talk I first discuss a model for the low-density part of the EoS, based on chiral one-pion exchange. I consider a self-consistent approach at finite temperature and density and show that even in a fully-relativistic theory the one-pion exchange contribution is dominated by a contact interaction. Then, a relativistic mean-field approach is used to discuss the high-density part of the EoS, including the presence of hyperons. In the latter, a density dependent parametrization is used and a parameter study on the hyperon-scalar meson coupling is performed.

High-density-plasma diagnostics in magnetic-confinement fusion

International Nuclear Information System (INIS)

Jahoda, F.C.

1982-01-01

The lectures will begin by defining high density in the context of magnetic confinement fusion research and listing some alternative reactor concepts, ranging from n/sub e/ approx. 2 x 10 14 cm -3 to several orders of magnitude greater, that offer potential advantages over the main-line, n/sub e/ approx. 1 x 10 14 cm -3 , Tokamak reactor designs. The high density scalings of several major diagnostic techniques, some favorable and some disadvantageous, will be discussed. Special emphasis will be given to interferometric methods, both electronic and photographic, for which integral n/sub e/dl measurements and associated techniques are accessible with low wavelength lasers. Reactor relevant experience from higher density, smaller dimension devices exists. High density implies high β, which implies economies of scale. The specialized features of high β diagnostics will be discussed

Novel Quantitative Real-Time LCR for the Sensitive Detection of SNP Frequencies in Pooled DNA: Method Development, Evaluation and Application

Science.gov (United States)

Psifidi, Androniki; Dovas, Chrysostomos; Banos, Georgios

2011-01-01

Background Single nucleotide polymorphisms (SNP) have proven to be powerful genetic markers for genetic applications in medicine, life science and agriculture. A variety of methods exist for SNP detection but few can quantify SNP frequencies when the mutated DNA molecules correspond to a small fraction of the wild-type DNA. Furthermore, there is no generally accepted gold standard for SNP quantification, and, in general, currently applied methods give inconsistent results in selected cohorts. In the present study we sought to develop a novel method for accurate detection and quantification of SNP in DNA pooled samples. Methods The development and evaluation of a novel Ligase Chain Reaction (LCR) protocol that uses a DNA-specific fluorescent dye to allow quantitative real-time analysis is described. Different reaction components and thermocycling parameters affecting the efficiency and specificity of LCR were examined. Several protocols, including gap-LCR modifications, were evaluated using plasmid standard and genomic DNA pools. A protocol of choice was identified and applied for the quantification of a polymorphism at codon 136 of the ovine PRNP gene that is associated with susceptibility to a transmissible spongiform encephalopathy in sheep. Conclusions The real-time LCR protocol developed in the present study showed high sensitivity, accuracy, reproducibility and a wide dynamic range of SNP quantification in different DNA pools. The limits of detection and quantification of SNP frequencies were 0.085% and 0.35%, respectively. Significance The proposed real-time LCR protocol is applicable when sensitive detection and accurate quantification of low copy number mutations in DNA pools is needed. Examples include oncogenes and tumour suppressor genes, infectious diseases, pathogenic bacteria, fungal species, viral mutants, drug resistance resulting from point mutations, and genetically modified organisms in food. PMID:21283808

Evaluation of the OvineSNP50 chip for use in four South African ...

African Journals Online (AJOL)

Relatively rapid and cost-effective genotyping using the OvineSNP50 chip holds great promise for the South African sheep industry and research partners. However, SNP ascertainment bias may influence inferences from the genotyping results of South African sheep breeds. Therefore, samples from Dorper, Namaqua ...

Synthesis of high density aviation fuel with cyclopentanol derived from lignocellulose

Science.gov (United States)

Sheng, Xueru; Li, Ning; Li, Guangyi; Wang, Wentao; Yang, Jinfan; Cong, Yu; Wang, Aiqin; Wang, Xiaodong; Zhang, Tao

2015-03-01

For the first time, renewable high density aviation fuels were synthesized at high overall yield (95.6%) by the Guerbet reaction of cyclopentanol which can be derived from lignocellulose, followed by the hydrodeoxygenation (HDO). The solvent-free Guerbet reaction of cyclopentanol was carried out under the co-catalysis of solid bases and Raney metals. Among the investigated catalyst systems, the combinations of magnesium-aluminium hydrotalcite (MgAl-HT) and Raney Ni (or Raney Co) exhibited the best performances. Over them, high carbon yield (96.7%) of C10 and C15 oxygenates was achieved. The Guerbet reaction products were further hydrodeoxygenated to bi(cyclopentane) and tri(cyclopentane) over a series of Ni catalysts. These alkanes have high densities (0.86 g mL-1 and 0.91 g mL-1) and can be used as high density aviation fuels or additives to bio-jet fuel. Among the investigated HDO catalysts, the 35 wt.% Ni-SiO2-DP prepared by deposition-precipitation method exhibited the highest activity.

Novel approach for deriving genome wide SNP analysis data from archived blood spots

Science.gov (United States)

2012-01-01

Background The ability to transport and store DNA at room temperature in low volumes has the advantage of optimising cost, time and storage space. Blood spots on adapted filter papers are popular for this, with FTA (Flinders Technology Associates) Whatman™TM technology being one of the most recent. Plant material, plasmids, viral particles, bacteria and animal blood have been stored and transported successfully using this technology, however the method of porcine DNA extraction from FTA Whatman™TM cards is a relatively new approach, allowing nucleic acids to be ready for downstream applications such as PCR, whole genome amplification, sequencing and subsequent application to single nucleotide polymorphism microarrays has hitherto been under-explored. Findings DNA was extracted from FTA Whatman™TM cards (following adaptations of the manufacturer’s instructions), whole genome amplified and subsequently analysed to validate the integrity of the DNA for downstream SNP analysis. DNA was successfully extracted from 288/288 samples and amplified by WGA. Allele dropout post WGA, was observed in less than 2% of samples and there was no clear evidence of amplification bias nor contamination. Acceptable call rates on porcine SNP chips were also achieved using DNA extracted and amplified in this way. Conclusions DNA extracted from FTA Whatman cards is of a high enough quality and quantity following whole genomic amplification to perform meaningful SNP chip studies. PMID:22974252

QualitySNP: a pipeline for detecting single nucleotide polymorphisms and insertions/deletions in EST data from diploid and polyploid species

Directory of Open Access Journals (Sweden)

Voorrips Roeland E

2006-10-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are important tools in studying complex genetic traits and genome evolution. Computational strategies for SNP discovery make use of the large number of sequences present in public databases (in most cases as expressed sequence tags (ESTs and are considered to be faster and more cost-effective than experimental procedures. A major challenge in computational SNP discovery is distinguishing allelic variation from sequence variation between paralogous sequences, in addition to recognizing sequencing errors. For the majority of the public EST sequences, trace or quality files are lacking which makes detection of reliable SNPs even more difficult because it has to rely on sequence comparisons only. Results We have developed a new algorithm to detect reliable SNPs and insertions/deletions (indels in EST data, both with and without quality files. Implemented in a pipeline called QualitySNP, it uses three filters for the identification of reliable SNPs. Filter 1 screens for all potential SNPs and identifies variation between or within genotypes. Filter 2 is the core filter that uses a haplotype-based strategy to detect reliable SNPs. Clusters with potential paralogs as well as false SNPs caused by sequencing errors are identified. Filter 3 screens SNPs by calculating a confidence score, based upon sequence redundancy and quality. Non-synonymous SNPs are subsequently identified by detecting open reading frames of consensus sequences (contigs with SNPs. The pipeline includes a data storage and retrieval system for haplotypes, SNPs and alignments. QualitySNP's versatility is demonstrated by the identification of SNPs in EST datasets from potato, chicken and humans. Conclusion QualitySNP is an efficient tool for SNP detection, storage and retrieval in diploid as well as polyploid species. It is available for running on Linux or UNIX systems. The program, test data, and user manual are available at

SNP marker detection and genotyping in tilapia

NARCIS (Netherlands)

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

2012-01-01

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

Attractor comparisons based on density

International Nuclear Information System (INIS)

Carroll, T. L.

2015-01-01

Recognizing a chaotic attractor can be seen as a problem in pattern recognition. Some feature vector must be extracted from the attractor and used to compare to other attractors. The field of machine learning has many methods for extracting feature vectors, including clustering methods, decision trees, support vector machines, and many others. In this work, feature vectors are created by representing the attractor as a density in phase space and creating polynomials based on this density. Density is useful in itself because it is a one dimensional function of phase space position, but representing an attractor as a density is also a way to reduce the size of a large data set before analyzing it with graph theory methods, which can be computationally intensive. The density computation in this paper is also fast to execute. In this paper, as a demonstration of the usefulness of density, the density is used directly to construct phase space polynomials for comparing attractors. Comparisons between attractors could be useful for tracking changes in an experiment when the underlying equations are too complicated for vector field modeling

Probing topological relations between high-density and low-density regions of 2MASS with hexagon cells

Energy Technology Data Exchange (ETDEWEB)

Wu, Yongfeng [American Physical Society, San Diego, CA (United States); Xiao, Weike, E-mail: yongfeng.wu@maine.edu [Department of Astronautics Engineering, Harbin Institute of Technology, P.O. Box 345, Heilongjiang Province 150001 (China)

2014-02-01

We introduced a new two-dimensional (2D) hexagon technique for probing the topological structure of the universe in which we mapped regions of the sky with high and low galaxy densities onto a 2D lattice of hexagonal unit cells. We defined filled cells as corresponding to high-density regions and empty cells as corresponding to low-density regions. The numbers of filled cells and empty cells were kept the same by controlling the size of the cells. By analyzing the six sides of each hexagon, we could obtain and compare the statistical topological properties of high-density and low-density regions of the universe in order to have a better understanding of the evolution of the universe. We applied this hexagonal method to Two Micron All Sky Survey data and discovered significant topological differences between the high-density and low-density regions. Both regions had significant (>5σ) topological shifts from both the binomial distribution and the random distribution.

Population structure and genetic diversity characterization of a sunflower association mapping population using SSR and SNP markers.

Science.gov (United States)

Filippi, Carla V; Aguirre, Natalia; Rivas, Juan G; Zubrzycki, Jeremias; Puebla, Andrea; Cordes, Diego; Moreno, Maria V; Fusari, Corina M; Alvarez, Daniel; Heinz, Ruth A; Hopp, Horacio E; Paniego, Norma B; Lia, Veronica V

2015-02-13

Argentina has a long tradition of sunflower breeding, and its germplasm is a valuable genetic resource worldwide. However, knowledge of the genetic constitution and variability levels of the Argentinean germplasm is still scarce, rendering the global map of cultivated sunflower diversity incomplete. In this study, 42 microsatellite loci and 384 single nucleotide polymorphisms (SNPs) were used to characterize the first association mapping population used for quantitative trait loci mapping in sunflower, along with a selection of allied open-pollinated and composite populations from the germplasm bank of the National Institute of Agricultural Technology of Argentina. The ability of different kinds of markers to assess genetic diversity and population structure was also evaluated. The analysis of polymorphism in the set of sunflower accessions studied here showed that both the microsatellites and SNP markers were informative for germplasm characterization, although to different extents. In general, the estimates of genetic variability were moderate. The average genetic diversity, as quantified by the expected heterozygosity, was 0.52 for SSR loci and 0.29 for SNPs. Within SSR markers, those derived from non-coding regions were able to capture higher levels of diversity than EST-SSR. A significant correlation was found between SSR and SNP- based genetic distances among accessions. Bayesian and multivariate methods were used to infer population structure. Evidence for the existence of three different genetic groups was found consistently across data sets (i.e., SSR, SNP and SSR + SNP), with the maintainer/restorer status being the most prevalent characteristic associated with group delimitation. The present study constitutes the first report comparing the performance of SSR and SNP markers for population genetics analysis in cultivated sunflower. We show that the SSR and SNP panels examined here, either used separately or in conjunction, allowed consistent

Towards high-density matter with relativistic heavy-ion collisions

International Nuclear Information System (INIS)

Nagamiya, Shoji.

1990-04-01

Recent progress in nucleus-nucleus collisions at BNL and CERN suggests a hint that the formation of high-density nuclear matter could be possible with relativistic heavy-ion beams. What is the maximum density that can be achieved by heavy-ion collisions? Are there data which show evidence or hints on the formation of high density matter? Why is the research of high-density interesting? How about the future possibilities on this subject? These points are discussed. (author)

New aspects of high energy density plasma

International Nuclear Information System (INIS)

Hotta, Eiki

2005-10-01

The papers presented at the symposium on 'New aspects of high energy density plasma' held at National Institute for Fusion Science are collected in this proceedings. The papers reflect the present status and recent progress in the experiments and theoretical works on high energy density plasma produced by pulsed power technology. The 13 of the presented papers are indexed individually. (J.P.N.)

Ambipolar zinc-polyiodide electrolyte for a high-energy density aqueous redox flow battery.

Science.gov (United States)

Li, Bin; Nie, Zimin; Vijayakumar, M; Li, Guosheng; Liu, Jun; Sprenkle, Vincent; Wang, Wei

2015-02-24

Redox flow batteries are receiving wide attention for electrochemical energy storage due to their unique architecture and advantages, but progress has so far been limited by their low energy density (~25 Wh l(-1)). Here we report a high-energy density aqueous zinc-polyiodide flow battery. Using the highly soluble iodide/triiodide redox couple, a discharge energy density of 167 Wh l(-1) is demonstrated with a near-neutral 5.0 M ZnI2 electrolyte. Nuclear magnetic resonance study and density functional theory-based simulation along with flow test data indicate that the addition of an alcohol (ethanol) induces ligand formation between oxygen on the hydroxyl group and the zinc ions, which expands the stable electrolyte temperature window to from -20 to 50 °C, while ameliorating the zinc dendrite. With the high-energy density and its benign nature free from strong acids and corrosive components, zinc-polyiodide flow battery is a promising candidate for various energy storage applications.

Differentiation of drug and non-drug Cannabis using a single nucleotide polymorphism (SNP) assay.

Science.gov (United States)

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. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Casein SNP in Norwegian goats: additive and dominance effects on milk composition and quality

Science.gov (United States)

2011-01-01

Background The four casein proteins in goat milk are encoded by four closely linked casein loci (CSN1S1, CSN2, CSN1S2 and CSN3) within 250 kb on caprine chromosome 6. A deletion in exon 12 of CSN1S1, so far reported only in Norwegian goats, has been found at high frequency (0.73). Such a high frequency is difficult to explain because the national breeding goal selects against the variant's effect. Methods In this study, 575 goats were genotyped for 38 Single Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk production records of these goats were obtained from the Norwegian Dairy Goat Control. Test-day mixed models with additive and dominance fixed effects of single SNP were fitted in a model including polygenic effects. Results Significant additive effects of single SNP within CSN1S1 and CSN3 were found for fat % and protein %, milk yield and milk taste. The allele with the deletion showed additive and dominance effects on protein % and fat %, and overdominance effects on milk quantity (kg) and lactose %. At its current frequency, the observed dominance (overdominance) effects of the deletion allele reduced its substitution effect (and additive genetic variance available for selection) in the population substantially. Conclusions The selection pressure of conventional breeding on the allele with the deletion is limited due to the observed dominance (overdominance) effects. Inclusion of molecular information in the national breeding scheme will reduce the frequency of this deletion in the population. PMID:21864407

High current density ion source

International Nuclear Information System (INIS)

King, H.J.

1977-01-01

A high-current-density ion source with high total current is achieved by individually directing the beamlets from an electron bombardment ion source through screen and accelerator electrodes. The openings in these screen and accelerator electrodes are oriented and positioned to direct the individual beamlets substantially toward a focus point. 3 figures, 1 table

A fast density-based clustering algorithm for real-time Internet of Things stream.

Science.gov (United States)

Amini, Amineh; Saboohi, Hadi; Wah, Teh Ying; Herawan, Tutut

2014-01-01

Data streams are continuously generated over time from Internet of Things (IoT) devices. The faster all of this data is analyzed, its hidden trends and patterns discovered, and new strategies created, the faster action can be taken, creating greater value for organizations. Density-based method is a prominent class in clustering data streams. It has the ability to detect arbitrary shape clusters, to handle outlier, and it does not need the number of clusters in advance. Therefore, density-based clustering algorithm is a proper choice for clustering IoT streams. Recently, several density-based algorithms have been proposed for clustering data streams. However, density-based clustering in limited time is still a challenging issue. In this paper, we propose a density-based clustering algorithm for IoT streams. The method has fast processing time to be applicable in real-time application of IoT devices. Experimental results show that the proposed approach obtains high quality results with low computation time on real and synthetic datasets.

SNIT: SNP identification for strain typing

Directory of Open Access Journals (Sweden)

Reifman Jaques

2011-09-01

Full Text Available Abstract 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

Plasma Photonic Devices for High Energy Density Science

International Nuclear Information System (INIS)

Kodama, R.

2005-01-01

High power laser technologies are opening a variety of attractive fields of science and technology using high energy density plasmas such as plasma physics, laboratory astrophysics, material science, nuclear science including medical applications and laser fusion. The critical issues in the applications are attributed to the control of intense light and enormous density of charged particles including efficient generation of the particles such as MeV electrons and protons with a current density of TA/cm2. Now these application possibilities are limited only by the laser technology. These applications have been limited in the control of the high power laser technologies and their optics. However, if we have another device consisted of the 4th material, i.e. plasma, we will obtain a higher energy density condition and explore the application possibilities, which could be called high energy plasma device. One of the most attractive devices has been demonstrated in the fast ignition scheme of the laser fusion, which is cone-guiding of ultra-intense laser light in to high density regions1. This is one of the applications of the plasma device to control the ultra-intense laser light. The other role of the devices consisted of transient plasmas is control of enormous energy-density particles in a fashion analogous to light control with a conventional optical device. A plasma fibre (5?m/1mm), as one example of the devices, has guided and deflected the high-density MeV electrons generated by ultra-intense laser light 2. The electrons have been well collimated with either a lens-like plasma device or a fibre-like plasma, resulting in isochoric heating and creation of ultra-high pressures such as Giga bar with an order of 100J. Plasmas would be uniquely a device to easily control the higher energy density particles like a conventional optical device as well as the ultra-intense laser light, which could be called plasma photonic device. (Author)

Integrating milk metabolite profile information for the prediction of traditional milk traits based on SNP information for Holstein cows.

Directory of Open Access Journals (Sweden)

Nina Melzer

Full Text Available In this study the benefit of metabolome level analysis for the prediction of genetic value of three traditional milk traits was investigated. Our proposed approach consists of three steps: First, milk metabolite profiles are used to predict three traditional milk traits of 1,305 Holstein cows. Two regression methods, both enabling variable selection, are applied to identify important milk metabolites in this step. Second, the prediction of these important milk metabolite from single nucleotide polymorphisms (SNPs enables the detection of SNPs with significant genetic effects. Finally, these SNPs are used to predict milk traits. The observed precision of predicted genetic values was compared to the results observed for the classical genotype-phenotype prediction using all SNPs or a reduced SNP subset (reduced classical approach. To enable a comparison between SNP subsets, a special invariable evaluation design was implemented. SNPs close to or within known quantitative trait loci (QTL were determined. This enabled us to determine if detected important SNP subsets were enriched in these regions. The results show that our approach can lead to genetic value prediction, but requires less than 1% of the total amount of (40,317 SNPs., significantly more important SNPs in known QTL regions were detected using our approach compared to the reduced classical approach. Concluding, our approach allows a deeper insight into the associations between the different levels of the genotype-phenotype map (genotype-metabolome, metabolome-phenotype, genotype-phenotype.

The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

Energy Technology Data Exchange (ETDEWEB)

Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Huang, Shu-Pin [Department of Urology, Kaohsiung Medical University Hospital, College of Medicine Kaohsiung Medical University, Kaohsiung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2011-12-15

Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG + GG genotype, in conjunction with high urinary total arsenic ({>=} 14.02 {mu}g/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg{sup 72}Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. -- Highlights: Black-Right-Pointing-Pointer Subjects with p53 Pro/Pro or MDM2 GG genotype significantly increased RCC risk. Black-Right-Pointing-Pointer A significant multiplicative joint effect of p53 and p21 on RCC risk. Black-Right-Pointing-Pointer RCC patients with p53 Arg/Arg genotype had efficient arsenic methylation capacity. Black-Right-Pointing-Pointer Joint effect of p53 or MDM2 genotype and high urinary total arsenic on RCC risk.