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Sample records for haplotype analysis resolves

  1. De novo assembly of a haplotype-resolved human genome.

    Science.gov (United States)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun

    2015-06-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

  2. De novo assembly of a haplotype-resolved human genome

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang

    2015-01-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-...

  3. iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

    Directory of Open Access Journals (Sweden)

    Lim Yun Ping

    2006-12-01

    Full Text Available Abstract Background The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. Results To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. Conclusion The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

  4. Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)

    International Nuclear Information System (INIS)

    Monos, D.S.; Radka, S.F.; Zmijewski, C.M.; Kamoun, M.

    1986-01-01

    Population studies indicate that HLA-DR4 is implicated in the susceptibility of IDD. However, biochemical characterization of the serologically defined DR4 haplotype from normal individuals revealed five DR4 and three DQW3 molecular forms. Hence, in this study, they investigated the heterogeneity of the DR4 haplotype, using B-lymphoblastoid cell lines (B-LCL) generated from patients with IDD and seropositive for DR4. Class II molecules, metabolically labeled with 35 S-methionine, were immunoprecipitated with monoclonal antibodies specific for DR(L243), DQ(N297), DQW3(IVD12) or DR and DQ(SG465) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The isoelectrofocusing (IEF) conditions employed in this study allow representation only of the DR4 haplotype from either DR3/4 or DR4/4 cell lines. The analysis of six different DR4 haplotypes from seven IDD patients, revealed the presence of two DR4 β and two DQW3 β chains. Three of the six DR4 β haplotypes analyzed shared the same DR4 β chain and three others shared a different one. Additionally five of the six haplotypes shared a different one. Additionally five of the six haplotypes shared the same DQW3 β chain and only one was carrying a different one. Different combinations of the two DR4 and two DQW3 β chains constitute three distinct patterns of DR4 haplotypes. These results suggest the prevalence of a DQW3 β chain in the small sample of IDD patients studied. Studies of a large number of patients should clarify whether IDD is associated with unique variants of DR4 or DQW3 β chains

  5. Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

    Science.gov (United States)

    Park, Joonhong; Kim, Myungshin; Jang, Woori; Chae, Hyojin; Kim, Yonggoo; Chung, Nack-Gyun; Lee, Jae-Wook; Cho, Bin; Jeong, Dae-Chul; Park, In Yang; Park, Mi Sun

    2015-05-01

    A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population. © 2015 John Wiley & Sons Ltd/University College London.

  6. Haplotype association analysis of human disease traits using genotype data of unrelated individuals

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Christensen, Kaare

    2005-01-01

    unphased multi-locus genotype data, ranging from the early approach by the simple gene-counting method to the recent work using the generalized linear model. However, these methods are either confined to case – control design or unable to yield unbiased point and interval estimates of haplotype effects....... Based on the popular logistic regression model, we present a new approach for haplotype association analysis of human disease traits. Using haplotype-based parameterization, our model infers the effects of specific haplotypes (point estimation) and constructs confidence interval for the risks...... on the well-known logistic regression model is a useful tool for haplotype association analysis of human disease traits....

  7. Analysis of Multiallelic CNVs by Emulsion Haplotype Fusion PCR.

    Science.gov (United States)

    Tyson, Jess; Armour, John A L

    2017-01-01

    Emulsion-fusion PCR recovers long-range sequence information by combining products in cis from individual genomic DNA molecules. Emulsion droplets act as very numerous small reaction chambers in which different PCR products from a single genomic DNA molecule are condensed into short joint products, to unite sequences in cis from widely separated genomic sites. These products can therefore provide information about the arrangement of sequences and variants at a larger scale than established long-read sequencing methods. The method has been useful in defining the phase of variants in haplotypes, the typing of inversions, and determining the configuration of sequence variants in multiallelic CNVs. In this description we outline the rationale for the application of emulsion-fusion PCR methods to the analysis of multiallelic CNVs, and give practical details for our own implementation of the method in that context.

  8. Genome-wide haplotype analysis of cis expression quantitative trait loci in monocytes.

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    Sophie Garnier

    Full Text Available In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ~2,1 × 10(9 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >10(4-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested for 412 probes for which SNPs (or proxies that defined the detected haplotypes were available in the Gutenberg Health Study composed of 1,374 individuals. At the Bonferroni correction level of 1.2 × 10(-4 (~0.05/412, 193 haplotypic signals replicated. 1000 G imputation was then conducted, and 105 haplotypic signals still remained more informative than imputed SNPs. In-depth analysis of these 105 cis eQTL revealed that at 76 loci genetic associations were compatible with additive effects of several SNPs, while for the 29 remaining regions data could be compatible with a more complex haplotypic pattern. As 24 of the 105 cis eQTL have previously been reported to be disease-associated loci, this work highlights the need for conducting haplotype-based and 1000 G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.

  9. Haplotype analysis and linkage disequilibrium for DGAT1

    OpenAIRE

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

    2010-01-01

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

  10. Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

    Science.gov (United States)

    Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

    2017-02-01

    Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

  11. Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level.

    Science.gov (United States)

    Huang, Da Wei; Raley, Castle; Jiang, Min Kang; Zheng, Xin; Liang, Dun; Rehman, M Tauseef; Highbarger, Helene C; Jiao, Xiaoli; Sherman, Brad; Ma, Liang; Chen, Xiaofeng; Skelly, Thomas; Troyer, Jennifer; Stephens, Robert; Imamichi, Tomozumi; Pau, Alice; Lempicki, Richard A; Tran, Bao; Nissley, Dwight; Lane, H Clifford; Dewar, Robin L

    2016-01-01

    Development of HIV-1 drug resistance mutations (HDRMs) is one of the major reasons for the clinical failure of antiretroviral therapy. Treatment success rates can be improved by applying personalized anti-HIV regimens based on a patient's HDRM profile. However, the sensitivity and specificity of the HDRM profile is limited by the methods used for detection. Sanger-based sequencing technology has traditionally been used for determining HDRM profiles at the single nucleotide variant (SNV) level, but with a sensitivity of only ≥ 20% in the HIV population of a patient. Next Generation Sequencing (NGS) technologies offer greater detection sensitivity (~ 1%) and larger scope (hundreds of samples per run). However, NGS technologies produce reads that are too short to enable the detection of the physical linkages of individual SNVs across the haplotype of each HIV strain present. In this article, we demonstrate that the single-molecule long reads generated using the Third Generation Sequencer (TGS), PacBio RS II, along with the appropriate bioinformatics analysis method, can resolve the HDRM profile at a more advanced quasispecies level. The case studies on patients' HIV samples showed that the quasispecies view produced using the PacBio method offered greater detection sensitivity and was more comprehensive for understanding HDRM situations, which is complement to both Sanger and NGS technologies. In conclusion, the PacBio method, providing a promising new quasispecies level of HDRM profiling, may effect an important change in the field of HIV drug resistance research.

  12. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

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    Sara Karami

    2009-09-01

    Full Text Available In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR, most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC etiology. RCC cases (N = 777 and controls (N = 1,035 were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02 and retinoid-X-receptor-alpha (RXRA (p-value = 0.10 were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991 across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57 haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523, increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

  13. Cluster analysis of European Y-chromosomal STR haplotypes using the discrete Laplace method

    DEFF Research Database (Denmark)

    Andersen, Mikkel Meyer; Eriksen, Poul Svante; Morling, Niels

    2014-01-01

    The European Y-chromosomal short tandem repeat (STR) haplotype distribution has previously been analysed in various ways. Here, we introduce a new way of analysing population substructure using a new method based on clustering within the discrete Laplace exponential family that models the probabi......The European Y-chromosomal short tandem repeat (STR) haplotype distribution has previously been analysed in various ways. Here, we introduce a new way of analysing population substructure using a new method based on clustering within the discrete Laplace exponential family that models...... the probability distribution of the Y-STR haplotypes. Creating a consistent statistical model of the haplotypes enables us to perform a wide range of analyses. Previously, haplotype frequency estimation using the discrete Laplace method has been validated. In this paper we investigate how the discrete Laplace...... method can be used for cluster analysis to further validate the discrete Laplace method. A very important practical fact is that the calculations can be performed on a normal computer. We identified two sub-clusters of the Eastern and Western European Y-STR haplotypes similar to results of previous...

  14. Analysis of Molecular Variance Inferred from Metric Distances among DNA Haplotypes: Application to Human Mitochondrial DNA Restriction Data

    OpenAIRE

    Excoffier, L.; Smouse, P. E.; Quattro, J. M.

    1992-01-01

    We present here a framework for the study of molecular variation within a single species. Information on DNA haplotype divergence is incorporated into an analysis of variance format, derived from a matrix of squared-distances among all pairs of haplotypes. This analysis of molecular variance (AMOVA) produces estimates of variance components and F-statistic analogs, designated here as φ-statistics, reflecting the correlation of haplotypic diversity at different levels of hierarchical subdivisi...

  15. Transient analysis for resolving safety issues

    International Nuclear Information System (INIS)

    Chao, J.; Layman, W.

    1987-01-01

    The Nuclear Safety Analysis Center (NSAC) has a Generic Safety Analysis Program to help resolve high priority generic safety issues. This paper describes several high priority safety issues considered at NSAC and how they were resolved by transient analysis using thermal hydraulics and neutronics codes. These issues are pressurized thermal shock (PTS), anticipated transients without scram (ATWS), steam generator tube rupture (SGTR), and reactivity transients in light of the Chernobyl accident

  16. SNP and haplotype analysis reveal IGF2 variants associated with growth traits in Chinese Qinchuan cattle.

    Science.gov (United States)

    Huang, Yong-Zhen; Zhan, Zhao-Yang; Li, Xin-Yi; Wu, Sheng-Ru; Sun, Yu-Jia; Xue, Jing; Lan, Xian-Yong; Lei, Chu-Zhao; Zhang, Chun-Lei; Jia, Yu-Tang; Chen, Hong

    2014-02-01

    Insulin-like growth factor 2 (IGF2) is a potent cell growth and differentiation factor and is implicated in mammals' growth and development. The objective of this study was to evaluate the effects of the mutations in the bovine IGF2 with growth traits in Chinese Qinchuan cattle. Four single nucleotide polymorphisms (SNPs) were detected of the bovine IGF2 by DNA pool sequencing and forced polymerase chain reaction-restriction fragment length polymorphism (forced PCR-RFLP) methods. We also investigated haplotype structure and linkage disequilibrium (LD) coefficients for four SNPs in 817 individuals representing two main cattle breeds from China. The result of haplotype analysis showed eight different haplotypes and 27 combined genotypes within the study population. The statistical analyses indicated that the four SNPs, combined genotypes and haplotypes are associated with the withers height, body length, chest breadth, chest depth and body weight in Qinchuan cattle population (P growth traits; the heterozygote diplotype was associated with higher growth traits compared to wild-type homozygote. Our results provide evidence that polymorphisms in the IGF2 gene are associated with growth traits, and may be used for marker-assisted selection in beef cattle breeding program.

  17. The analysis of APOL1 genetic variation and haplotype diversity provided by 1000 Genomes project.

    Science.gov (United States)

    Peng, Ting; Wang, Li; Li, Guisen

    2017-08-11

    The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3'UTR. Total 12 SNPs in URR and 24 SNPs in 3'UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3'UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P < 0.01), UTR-1 and UTR-5 presented much higher frequency in African population, while UTR-2, UTR-3 and UTR-4 were much lower. APOL1 coding region showed that two SNP of G1 with higher frequency are actually pull down the haplotype H-1 frequency when considering all populations pooled together, and the diversity among the four populations be widen by the G1 two mutation (P 1  = 3.33E-4 vs P 2  = 3.61E-30). The distributions of APOL1 gene variants and haplotypes were significantly different among the different populations, in either regulatory or coding regions. It could provide

  18. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan

    2009-11-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  19. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan; Chen, Yi-Hau; Luo, Sheng; Carroll, Raymond J.

    2009-01-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  20. Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs.

    Science.gov (United States)

    Mishima, Hiroyuki; Lidral, Andrew C; Ni, Jun

    2008-05-28

    Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies. Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4-15.9 times faster, while Unphased jobs performed 1.1-18.6 times faster compared to the accumulated computation duration. Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance.

  1. Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy.

    Science.gov (United States)

    Jaruzelska, J; Zietkiewicz, E; Batzer, M; Cole, D E; Moisan, J P; Scozzari, R; Tavaré, S; Labuda, D

    1999-07-01

    With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World.

  2. Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

    Science.gov (United States)

    Ma, Jennie Z; Beuten, Joke; Payne, Thomas J; Dupont, Randolph T; Elston, Robert C; Li, Ming D

    2005-06-15

    DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

  3. KIR And HLA Haplotype Analysis in a Family Lacking The KIR 2DL1-2DP1 Genes

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    Vojvodić Svetlana

    2015-06-01

    Full Text Available The killer cell immunoglobulin-like receptor (KIR gene cluster exhibits extensive allelic and haplotypic diversity that is observed as presence/absence of genes, resulting in expansion and contraction of KIR haplotypes and by allelic variation of individual KIR genes. We report a case of KIR pseudogene 2DP1 and 2DL1 gene absence in members of one family with the children suffering from acute myelogenous leukemia (AML. Killer cell immunoglo-bulin-like receptor low resolution genotyping was performed by the polymerase chain reaction (PCR-sequencespecific primers (SSP/sequence-specific oligonucleotide (SSO method and haplotype assignment was done by gene content analysis. Both parents and the maternal grandfather, shared the same Cen-B2 KIR haplotype, containing KIR 3DL3, -2DS2, -2DL2 and -3DP1 genes. The second haplotype in the KIR genotype of the mother and grandfather was Tel-A1 with KIR 2DL4 (normal and deleted variant, -3DL1, -22 bp deletion variant of the 2DS4 gene and -3DL2, while the second haplotype in the KIR genotype of the father was Tel-B1 with 2DL4 (normal variant, -3DS1, -2DL5, -2DS5, -2DS1 and 3DL2 genes. Haplotype analysis in all three offsprings revealed that the children inherited the Cen-B2 haplotype with the same gene content but two of the children inherited a deleted variant of the 2DL4 gene, while the third child inherited a normal one. The second haplotype of all three offspring contained KIR 2DL4, -2DL5, -2DS1, -2DS4 (del 22bp variant, -2DS5, -3DL1 and -3DL2 genes, which was the basis of the assumption that there is a hybrid haplotype and that the present 3DL1 gene is a variant of the 3DS1 gene. Due to consanguinity among the ancestors, the results of KIR segregation analysis showed the existence of a very rare KIR genotype in the offspring. The family who is the subject of this case is even more interesting because the father was 10/10 human leukocyte antigen (HLA-matched to his daughter, all members of the family have

  4. Spatially Resolved Analysis of Bragg Selectivity

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    Tina Sabel

    2015-11-01

    Full Text Available This paper targets an inherent control of optical shrinkage in photosensitive polymers, contributing by means of spatially resolved analysis of volume holographic phase gratings. Point by point scanning of the local material response to the Gaussian intensity distribution of the recording beams is accomplished. Derived information on the local grating period and grating slant is evaluated by mapping of optical shrinkage in the lateral plane as well as through the depth of the layer. The influence of recording intensity, exposure duration and the material viscosity on the Bragg selectivity is investigated.

  5. Hemoglobin Constant Spring among Southeast Asian Populations: Haplotypic Heterogeneities and Phylogenetic Analysis.

    Directory of Open Access Journals (Sweden)

    Wittaya Jomoui

    Full Text Available Hemoglobin Constant Spring (Hb CS is an abnormal Hb caused by a mutation at the termination codon of α2-globin gene found commonly among Southeast Asian and Chinese people. Association of Hb CS with α°-thalassemia leads to a thalassemia intermedia syndrome commonly encountered in the region. We report chromosome background and addressed genetic origins of Hb CS observed in a large cohort of Hb CS among Southeast Asian populations.A study was done on 102 Vietnamese (aged 15-49 year-old and 40 Laotian (aged 18-39 year-old subjects with Hb CS and results compared with 120 Hb CS genes in Thailand. Hematological parameters were recorded and Hb analysis was performed using capillary electrophoresis. Hb CS mutation and thalassemia genotypes were defined by DNA analysis. Six DNA polymorphisms within α-globin gene cluster including 5'Xba I, Bgl I, Inter-zeta HVR, AccI, RsaI and αPstI 3', were determined using PCR-RFLP assay.Nine different genotypes of Hb CS were observed. In contrast to the Thai Hb CS alleles which are mostly linked to haplotype (+-S + + -, most of the Vietnamese and the Laotian Hb CS genes were associated with haplotype (+-M + + -, both of which are different from that of the European Hb CS.Hb CS is commonly found in combination with other thalassemias among Southeast Asian populations. Accurate genotyping of the cases requires both hematologic and DNA analyses. At least two independent origins are associated with the Hb CS gene which could indirectly explain the high prevalence of this Hb variant in the region.

  6. Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

    International Nuclear Information System (INIS)

    Cox, David G; Kraft, Peter; Hankinson, Susan E; Hunter, David J

    2005-01-01

    Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02–1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear

  7. Deletion analysis of male sterility effects of t-haplotypes in the mouse.

    Science.gov (United States)

    Bennett, D; Artzt, K

    1990-01-01

    We present data on the effects of three chromosome 17 deletions on transmission ratio distortion (TRD) and sterility of several t-haplotypes. All three deletions have similar effects on male TRD: that is, Tdel/tcomplete genotypes all transmit their t-haplotype in very high proportion. However, each deletion has different effects on sterility of heterozygous males, with TOr/t being fertile, Thp/t less fertile, and TOrl/t still less fertile. These data suggest that wild-type genes on chromosomes homologous to t-haplotypes can be important regulators of both TRD and fertility in males, and that the wild-type genes concerned with TRD and fertility are at least to some extent different. The data also provide a rough map of the positions of these genes.

  8. Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1 and association with bipolar affective disorder in Taiwan

    Directory of Open Access Journals (Sweden)

    Lin Yi-Mei J

    2005-03-01

    Full Text Available Abstract Background Disturbances in serotonin neurotransmission are implicated in the etiology of many psychiatric disorders, including bipolar affective disorder (BPD. The tryptophan hydroxylase gene (TPH, which codes for the enzyme catalyzing the rate-limiting step in serotonin biosynthetic pathway, is one of the leading candidate genes for psychiatric and behavioral disorders. In a preliminary study, we found that TPH1 intron7 A218C polymorphism was associated with BPD. This study was designed to investigate sequence variants of the TPH1 gene in Taiwanese and to test whether the TPH1 gene is a susceptibility factor for the BPD. Methods Using a systematic approach, we have searched the exons and promoter region of the TPH1 gene for sequence variants in Taiwanese Han and have identified five variants, A-1067G, G-347T, T3804A, C27224T, and A27237G. These five variants plus another five taken from the literature and a public database were examined for an association in 108 BPD patients and 103 controls; no association was detected for any of the 10 variants. Results Haplotype constructions using these 10 SNPs showed that the 3 most common haplotypes in both patients and controls were identical. One of the fourth common haplotype in the patient group (i.e. GGGAGACCCA was unique and showed a trend of significance with the disease (P = 0.028. However, the significance was abolished after Bonferroni correction thus suggesting the association is weak. In addition, three haplotype-tagged SNPs (htSNPs were selected to represent all haplotypes with frequencies larger than 2% in the Taiwanese Han population. The defined TPH1 htSNPs significantly reduce the marker number for haplotype analysis thus provides useful information for future association studies in our population. Conclusion Results of this study did not support the role of TPH1 gene in BPD etiology. As the current studies found the TPH1 gene under investigation belongs to the peripheral

  9. Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

    Science.gov (United States)

    Le Hellard, Stephanie; Lee, Andrew J; Underwood, Sarah; Thomson, Pippa A; Morris, Stewart W; Torrance, Helen S; Anderson, Susan M; Adams, Richard R; Navarro, Pau; Christoforou, Andrea; Houlihan, Lorna M; Detera-Wadleigh, Sevilla; Owen, Michael J; Asherson, Philip; Muir, Walter J; Blackwood, Douglas H R; Wray, Naomi R; Porteous, David J; Evans, Kathryn L

    2007-03-15

    Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.

  10. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

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    Christopher G Bell

    2010-11-01

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  11. Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies.

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    Soma Ghosh

    Full Text Available 5-Fluorouracil (5FU, a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms. Prior studies implicated a VNTR (variable numbers of tandem repeats polymorphism in the 5'-untranslated region (5'-UTR of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T repeats and novel single nucleotide polymorphisms (SNPs flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt, polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing.

  12. Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation.

    Science.gov (United States)

    von Salomé, Jenny; Liu, Tao; Keihäs, Markku; Morak, Moni; Holinski-Feder, Elke; Berry, Ian R; Moilanen, Jukka S; Baert-Desurmont, Stéphanie; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-12-29

    Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

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

    Directory of Open Access Journals (Sweden)

    Wobus Ulrich

    2011-01-01

    Full Text Available Abstract Background The increasingly narrow genetic background characteristic of modern crop germplasm presents a challenge for the breeding of cultivars that require adaptation to the anticipated change in climate. Thus, high priority research aims at the identification of relevant allelic variation present both in the crop itself as well as in its progenitors. This study is based on the characterization of genetic variation in barley, with a view to enhancing its response to terminal drought stress. Results The expression patterns of drought regulated genes were monitored during plant ontogeny, mapped and the location of these genes was incorporated into a comprehensive barley SNP linkage map. Haplotypes within a set of 17 starch biosynthesis/degradation genes were defined, and a particularly high level of haplotype variation was uncovered in the genes encoding sucrose synthase (types I and II and starch synthase. The ability of a panel of 50 barley accessions to maintain grain starch content under terminal drought conditions was explored. Conclusion The linkage/expression map is an informative resource in the context of characterizing the response of barley to drought stress. The high level of haplotype variation among starch biosynthesis/degradation genes in the progenitors of cultivated barley shows that domestication and breeding have greatly eroded their allelic diversity in current elite cultivars. Prospective association analysis based on core drought-regulated genes may simplify the process of identifying favourable alleles, and help to understand the genetic basis of the response to terminal drought.

  14. High resolving power spectrometer for beam analysis

    International Nuclear Information System (INIS)

    Moshammer, H.W.; Spencer, J.E.

    1992-03-01

    We describe a system designed to analyze the high energy, closely spaced bunches from individual RF pulses. Neither a large solid angle nor momentum range is required so this allows characteristics that appear useful for other applications such as ion beam lithography. The spectrometer is a compact, double-focusing QBQ design whose symmetry allows the Quads to range between F or D with a correspondingly large range of magnifications, dispersion and resolving power. This flexibility insures the possibility of spatially separating all of the bunches along the focal plane with minimal transverse kicks and bending angle for differing input conditions. The symmetry of the system allows a simple geometric interpretationof the resolving power in terms of thin lenses and ray optics. We discuss the optics and the hardware that is proposed to measure emittance, energy, energy spread and bunch length for each bunch in an RF pulse train for small bunch separations. We also discuss how to use such measurements for feedback and feedforward control of these bunch characteristics as well as maintain their stability. 2 refs

  15. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Science.gov (United States)

    Palta, Priit; Kaplinski, Lauris; Nagirnaja, Liina; Veidenberg, Andres; Möls, Märt; Nelis, Mari; Esko, Tõnu; Metspalu, Andres; Laan, Maris; Remm, Maido

    2015-01-01

    DNA copy number variants (CNVs) that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i) phase normal and CNV-carrying haplotypes in the copy number variable regions, ii) resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii) infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  16. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Directory of Open Access Journals (Sweden)

    Priit Palta

    Full Text Available DNA copy number variants (CNVs that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i phase normal and CNV-carrying haplotypes in the copy number variable regions, ii resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  17. Major soybean maturity gene haplotypes revealed by SNPViz analysis of 72 sequenced soybean genomes.

    Directory of Open Access Journals (Sweden)

    Tiffany Langewisch

    Full Text Available In this Genomics Era, vast amounts of next-generation sequencing data have become publicly available for multiple genomes across hundreds of species. Analyses of these large-scale datasets can become cumbersome, especially when comparing nucleotide polymorphisms across many samples within a dataset and among different datasets or organisms. To facilitate the exploration of allelic variation and diversity, we have developed and deployed an in-house computer software to categorize and visualize these haplotypes. The SNPViz software enables users to analyze region-specific haplotypes from single nucleotide polymorphism (SNP datasets for different sequenced genomes. The examination of allelic variation and diversity of important soybean [Glycine max (L. Merr.] flowering time and maturity genes may provide additional insight into flowering time regulation and enhance researchers' ability to target soybean breeding for particular environments. For this study, we utilized two available soybean genomic datasets for a total of 72 soybean genotypes encompassing cultivars, landraces, and the wild species Glycine soja. The major soybean maturity genes E1, E2, E3, and E4 along with the Dt1 gene for plant growth architecture were analyzed in an effort to determine the number of major haplotypes for each gene, to evaluate the consistency of the haplotypes with characterized variant alleles, and to identify evidence of artificial selection. The results indicated classification of a small number of predominant haplogroups for each gene and important insights into possible allelic diversity for each gene within the context of known causative mutations. The software has both a stand-alone and web-based version and can be used to analyze other genes, examine additional soybean datasets, and view similar genome sequence and SNP datasets from other species.

  18. [The haplomatch program for comparing Y-chromosome STR-haplotypes and its application to the analysis of the origin of Don Cossacks].

    Science.gov (United States)

    Chukhryaeva, M I; Ivanov, I O; Frolova, S A; Koshel, S M; Utevska, O M; Skhalyakho, R A; Agdzhoyan, A T; Bogunov, Yu V; Balanovska, E V; Balanovsky, O P

    2016-05-01

    STR haplotypes of the Y chromosome are widely used as effective genetic markers in studies of human populations and in forensic DNA analysis. The task often arises to compare the spectrum of haplotypes in individuals or entire populations. Performing this task manually is too laborious and thus unrealistic. We propose an algorithm for counting similarity between STR haplotypes. This algorithm is suitable for massive analyses of samples. It is implemented in the computer program Haplomatch, which makes it possible to find haplotypes that differ from the target haplotype by 0, 1, 2, 3, or more mutational steps. The program may operate in two modes: comparison of individuals and comparison of populations. Flexibility of the program (the possibility of using any external database), its usability (MS Excel spreadsheets are used), and the capability of being applied to other chromosomes and other species could make this software a new useful tool in population genetics and forensic and genealogical studies. The Haplomatch software is freely available on our website www.genofond.ru. The program is applied to studying the gene pool of Cossacks. Experimental analysis of Y-chromosomal diversity in a representative set (N = 131) of Upper Don Cossacks is performed. Analysis of the STR haplotypes detects genetic proximity of Cossacks to East Slavic populations (in particular, to Southern and Central Russians, as well as to Ukrainians), which confirms the hypothesis of the origin of the Cossacks mainly due to immigration from Russia and Ukraine. Also, a small genetic influence of Turkicspeaking Nogais is found, probably caused by their occurrence in the Don Voisko as part of the Tatar layer. No similarities between haplotype spectra of Cossacks and Caucasus populations are found. This case study demonstrates the effectiveness of the Haplomatch software in analyzing large sets of STR haplotypes.

  19. Haplotyping Problem, A Clustering Approach

    International Nuclear Information System (INIS)

    Eslahchi, Changiz; Sadeghi, Mehdi; Pezeshk, Hamid; Kargar, Mehdi; Poormohammadi, Hadi

    2007-01-01

    Construction of two haplotypes from a set of Single Nucleotide Polymorphism (SNP) fragments is called haplotype reconstruction problem. One of the most popular computational model for this problem is Minimum Error Correction (MEC). Since MEC is an NP-hard problem, here we propose a novel heuristic algorithm based on clustering analysis in data mining for haplotype reconstruction problem. Based on hamming distance and similarity between two fragments, our iterative algorithm produces two clusters of fragments; then, in each iteration, the algorithm assigns a fragment to one of the clusters. Our results suggest that the algorithm has less reconstruction error rate in comparison with other algorithms

  20. Association analysis of calpain 10 gene variants/haplotypes with gestational diabetes mellitus among Mexican women.

    Science.gov (United States)

    Castro-Martínez, Anna Gabriela; Sánchez-Corona, José; Vázquez-Vargas, Adriana Patricia; García-Zapién, Alejandra Guadalupe; López-Quintero, Andres; Villalpando-Velazco, Héctor Javier; Flores-Martínez, Silvia Esperanza

    2018-02-28

    Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays.  The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

  1. Analysis of 24 Y chromosomal STR haplotypes in a Chinese Han population sample from Henan Province, Central China.

    Science.gov (United States)

    Shi, Meisen; Liu, Yaju; Zhang, Juntao; Bai, Rufeng; Lv, Xiaojiao; Ma, Shuhua

    2015-07-01

    We analyzed haplotypes for 24 Y chromosomal STRs (Y-STRs), including 17 Yfiler loci (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DY438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4) and 7 additional STRs (DYS388, DYS444, DYS447, DYS449, DYS522 and DYS527a/b) in 1100 unrelated Chinese Han individuals from Henan Province using AGCU Y24 STR kit systems. The calculated average gene diversity (GD) values ranged from 0.4105 to 0.9647 for the DYS388 and DYS385a/b loci, respectively. The discriminatory capacity (DC) was 72.91% with 802 observed haplotypes using 17 Yfiler loci, by the addition of 7 Y-STRs to the Yfiler system, the DC was increased to 79.09% while showing 870 observed haplotypes. Among the additional 7 Y-STRs, DYS449, DYS527a/b, DYS444 and DYS522 were major contributors to enhancing discrimination. In the analysis of molecular variance, the Henan Han population clustered with Han origin populations and showed significant differences from other Non-Han populations. In the present study, we report 24 Y-STR population data in Henan Han population, and we emphasize the need for adding additional markers to the commonly used 17 Yfiler loci to achieve more improved discriminatory capacity in a population with low genetic diversity. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. Mapping Haplotype-haplotype Interactions with Adaptive LASSO

    Directory of Open Access Journals (Sweden)

    Li Ming

    2010-08-01

    Full Text Available Abstract Background The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA neonates data set, and significant interactions between different genomes are detected. Conclusions As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be

  3. Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation

    DEFF Research Database (Denmark)

    Andersen, A.D.H.; Lange, Marianne; Lillevang, S.T.

    2003-01-01

    The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA-4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations...... in the amino acid sequences except for one polymorphism in, the leader sequence of CTLA-4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G-insert and two repeat regions in intron 4......, consistent with the [T](n) and the [GT](n) regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of similar to3500 by of the upstream region of ICOS revealed an additional eight SNP of which two...

  4. Haplotype analysis of the HFE gene among populations of Northern Eurasia, in patients with metabolic disorders or stomach cancer, and in long-lived people.

    Science.gov (United States)

    Mikhailova, S V; Babenko, V N; Ivanoshchuk, D E; Gubina, M A; Maksimov, V N; Solovjova, I G; Voevoda, M I

    2016-06-17

    Previously, it was shown that the HFE gene (associated with human hereditary hemochromatosis) has several haplotypes of intronic polymorphisms. Some haplotype frequencies are race specific and hence can be used in phylogenetic analysis. We assumed that analysis of Caucasoid patients-living now in Western Siberia and having diseases associated with dietary habits and metabolic rate-will allow us to understand the processes of possible selection during settling of the northern part of Asia. Haplotype analysis of Northern Eurasian native and recently settled ethnic groups was performed on polymorphisms rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, rs1572982, rs2794719, rs807209, and rs2032451 of this gene. The CCA haplotype of the rs2071303, rs1800708, and rs1572982 was found to be associated with HLA-A2 (39 %) in Asian populations. Haplotype analysis for the rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, and rs1572982 was performed on Russian patients with some metabolic disorders or stomach cancer and among long-lived people. Decreased frequencies of the TTA haplotype (T in rs2071303, T in rs1800708, and A in rs1572982) were observed in the groups of patients with diseases associated with overweight (fatty liver disease, type 2 diabetes mellitus, or metabolic syndrome + arterial hypertension) as compared with the control sample. We detected significant differences in this haplotype's frequency between the patients with type 2 diabetes mellitus and Russian adolescents, elderly citizens, and long-lived people (χ(2) P value = 0.003, 0.010, and 0.015, respectively). No significant differences in frequencies of the alleles with mutations in coding regions of the HFE gene (C282Y, H63D, and S65C) were detected between the analyzed patients (with stomach cancer, metabolic syndrome, fatty liver disease, or type 2 diabetes mellitus) and the control Caucasoid sample. Monophyletic origin of H63D (rs1799945) was confirmed in Caucasoids and Northern

  5. Application of gene network analysis techniques identifies AXIN1/PDIA2 and endoglin haplotypes associated with bicuspid aortic valve.

    Directory of Open Access Journals (Sweden)

    Eric C Wooten

    2010-01-01

    Full Text Available Bicuspid Aortic Valve (BAV is a highly heritable congenital heart defect. The low frequency of BAV (1% of general population limits our ability to perform genome-wide association studies. We present the application of four a priori SNP selection techniques, reducing the multiple-testing penalty by restricting analysis to SNPs relevant to BAV in a genome-wide SNP dataset from a cohort of 68 BAV probands and 830 control subjects. Two knowledge-based approaches, CANDID and STRING, were used to systematically identify BAV genes, and their SNPs, from the published literature, microarray expression studies and a genome scan. We additionally tested Functionally Interpolating SNPs (fitSNPs present on the array; the fourth consisted of SNPs selected by Random Forests, a machine learning approach. These approaches reduced the multiple testing penalty by lowering the fraction of the genome probed to 0.19% of the total, while increasing the likelihood of studying SNPs within relevant BAV genes and pathways. Three loci were identified by CANDID, STRING, and fitSNPS. A haplotype within the AXIN1-PDIA2 locus (p-value of 2.926x10(-06 and a haplotype within the Endoglin gene (p-value of 5.881x10(-04 were found to be strongly associated with BAV. The Random Forests approach identified a SNP on chromosome 3 in association with BAV (p-value 5.061x10(-06. The results presented here support an important role for genetic variants in BAV and provide support for additional studies in well-powered cohorts. Further, these studies demonstrate that leveraging existing expression and genomic data in the context of GWAS studies can identify biologically relevant genes and pathways associated with a congenital heart defect.

  6. Meta-analysis reveals association between most common class II haplotype in full-heritage Native Americans and rheumatoid arthritis.

    Science.gov (United States)

    Williams, R C; Jacobsson, L T; Knowler, W C; del Puente, A; Kostyu, D; McAuley, J E; Bennett, P H; Pettitt, D J

    1995-01-01

    The association of RA with the alleles at the HLA system was tested among Pima and Tohono O'odham Indians (Pimans) of the Gila River Indian Community of Arizona. Serologic class I (HLA-A, -B, and -C) alleles were typed in 51 individuals with RA and in 302 without RA. Serologic class II (HLA-DR, DQ; DR52 DR53) alleles were typed in a subset of 47 with RA and 147 without RA. Molecular subtypes of DR3X6, DRB1*1402, and *1406 were determined in 29 individuals, 16 with RA and 13 without RA. Among the cases with RA, 46 of 47 had the serologic antigen HLA-DR3X6, as did 140 of 147 of those without the disease. However, this association was not statistically significant because of the high prevalence of the antigen in the controls. Data from Pimans were analyzed with similar results from the Tlingit and Yakima Indians. A meta-analysis employing the Mantel-Haenszel procedure, stratified by tribe, revealed a statistically significant association between the most common haplotype, DRB1*1402 DQA1*0501 DQB1*0301 DRB3*0101, and RA (summary odds ratio = 2.63, 95% confidence interval = 1.08, 6.46). There was also a statistically significant difference in the genotype distributions of one class I locus, HLA-C, between those with and without RA (chi 2 = 12.4, 5 df; p = 0.03). It is concluded that the association with the most common class II haplotype in full-heritage Native Americans might help explain their high prevalence of RA.

  7. Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David M. Howard

    2017-08-01

    Full Text Available Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002 were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS, the English Longitudinal Study of Ageing (ELSA, and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7, was the butyrylcholinesterase (BCHE gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

  8. A Back Migration from Asia to Sub-Saharan Africa Is Supported by High-Resolution Analysis of Human Y-Chromosome Haplotypes

    Science.gov (United States)

    Cruciani, Fulvio; Santolamazza, Piero; Shen, Peidong; Macaulay, Vincent; Moral, Pedro; Olckers, Antonel; Modiano, David; Holmes, Susan; Destro-Bisol, Giovanni; Coia, Valentina; Wallace, Douglas C.; Oefner, Peter J.; Torroni, Antonio; Cavalli-Sforza, L. Luca; Scozzari, Rosaria; Underhill, Peter A.

    2002-01-01

    The variation of 77 biallelic sites located in the nonrecombining portion of the Y chromosome was examined in 608 male subjects from 22 African populations. This survey revealed a total of 37 binary haplotypes, which were combined with microsatellite polymorphism data to evaluate internal diversities and to estimate coalescence ages of the binary haplotypes. The majority of binary haplotypes showed a nonuniform distribution across the continent. Analysis of molecular variance detected a high level of interpopulation diversity (ΦST=0.342), which appears to be partially related to the geography (ΦCT=0.230). In sub-Saharan Africa, the recent spread of a set of haplotypes partially erased pre-existing diversity, but a high level of population (ΦST=0.332) and geographic (ΦCT=0.179) structuring persists. Correspondence analysis shows that three main clusters of populations can be identified: northern, eastern, and sub-Saharan Africans. Among the latter, the Khoisan, the Pygmies, and the northern Cameroonians are clearly distinct from a tight cluster formed by the Niger-Congo–speaking populations from western, central western, and southern Africa. Phylogeographic analyses suggest that a large component of the present Khoisan gene pool is eastern African in origin and that Asia was the source of a back migration to sub-Saharan Africa. Haplogroup IX Y chromosomes appear to have been involved in such a migration, the traces of which can now be observed mostly in northern Cameroon. PMID:11910562

  9. Comparative sequence analysis of the potato cyst nematode resistance locus H1 reveals a major lack of co-linearity between three haplotypes in potato (Solanum tuberosum ssp.).

    Science.gov (United States)

    Finkers-Tomczak, Anna; Bakker, Erin; de Boer, Jan; van der Vossen, Edwin; Achenbach, Ute; Golas, Tomasz; Suryaningrat, Suwardi; Smant, Geert; Bakker, Jaap; Goverse, Aska

    2011-02-01

    The H1 locus confers resistance to the potato cyst nematode Globodera rostochiensis pathotypes 1 and 4. It is positioned at the distal end of chromosome V of the diploid Solanum tuberosum genotype SH83-92-488 (SH) on an introgression segment derived from S. tuberosum ssp. andigena. Markers from a high-resolution genetic map of the H1 locus (Bakker et al. in Theor Appl Genet 109:146-152, 2004) were used to screen a BAC library to construct a physical map covering a 341-kb region of the resistant haplotype coming from SH. For comparison, physical maps were also generated of the two haplotypes from the diploid susceptible genotype RH89-039-16 (S. tuberosum ssp. tuberosum/S. phureja), spanning syntenic regions of 700 and 319 kb. Gene predictions on the genomic segments resulted in the identification of a large cluster consisting of variable numbers of the CC-NB-LRR type of R genes for each haplotype. Furthermore, the regions were interspersed with numerous transposable elements and genes coding for an extensin-like protein and an amino acid transporter. Comparative analysis revealed a major lack of gene order conservation in the sequences of the three closely related haplotypes. Our data provide insight in the evolutionary mechanisms shaping the H1 locus and will facilitate the map-based cloning of the H1 resistance gene.

  10. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

    Science.gov (United States)

    Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

    2018-03-15

    Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

  11. Population haplotype analysis and evolutionary relations of the COL2A1 gene

    NARCIS (Netherlands)

    Meulenbelt, I.; Williams, G.J.; Koppele, J.M.T.E.; Giessen, G.C.D.E. van; Slagboom, P.E.

    1996-01-01

    We have determined the allele frequencies mad pairwise linkage disequilibria of restriction fragment length polymorphisms (RFLPs) distributed over the entire COL2A1 gene (spanning 23 · 6 kb) in a population of unrelated Dutch Caucasians. Pairwise linkage disequilibrium analysis of RFLP sites between

  12. Analysis of associations between major histocompatibility complex (BoLA) class I haplotypes and subclinical mastitis of dairy cows

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Jensen, N. E.; Østergård, H.

    1995-01-01

    The associations between BoLA class I haplotypes and subclinical mastitis were investigated using information on 333 cows from three different breeds and crossbreeds from 14 dairy herds in Denmark. Somatic cell count and bacteriological status were used as markers for subclinical mastitis....... Associations between BoLA class I haplotypes and IMI status were also determined. The association between BoLA class I haplotypes and subclinical mastitis was weak. The A10(W50), A11, A12(A30), A16, A19(A6), A21, A26, and A31(A30) alleles were associated with different markers of subclinical mastitis....... Susceptibility or resistance to the two bacteria categories was associated with different alleles. This study indicated that BoLA antigens may be involved in resistance to mastitis and that resistance may be specific for a particular pathogen....

  13. Local crystallography analysis for atomically resolved scanning tunneling microscopy images

    International Nuclear Information System (INIS)

    Lin, Wenzhi; Li, Qing; Belianinov, Alexei; Gai, Zheng; Baddorf, Arthur P; Pan, Minghu; Jesse, Stephen; Kalinin, Sergei V; Sales, Brian C; Sefat, Athena

    2013-01-01

    Scanning probe microscopy has emerged as a powerful and flexible tool for atomically resolved imaging of surface structures. However, due to the amount of information extracted, in many cases the interpretation of such data is limited to being qualitative and semi-quantitative in nature. At the same time, much can be learned from local atom parameters, such as distances and angles, that can be analyzed and interpreted as variations of local chemical bonding, or order parameter fields. Here, we demonstrate an iterative algorithm for indexing and determining atomic positions that allows the analysis of inhomogeneous surfaces. This approach is further illustrated by local crystallographic analysis of several real surfaces, including highly ordered pyrolytic graphite and an Fe-based superconductor FeTe 0.55 Se 0.45 . This study provides a new pathway to extract and quantify local properties for scanning probe microscopy images. (paper)

  14. Haplotype Analysis Discriminates Genetic Risk for DR3-Associated Endocrine Autoimmunity and Helps Define Extreme Risk for Addison’s Disease

    Science.gov (United States)

    Baker, Peter R.; Baschal, Erin E.; Fain, Pam R.; Triolo, Taylor M.; Nanduri, Priyaanka; Siebert, Janet C.; Armstrong, Taylor K.; Babu, Sunanda R.; Rewers, Marian J.; Gottlieb, Peter A.; Barker, Jennifer M.; Eisenbarth, George S.

    2010-01-01

    Context: Multiple autoimmune disorders (e.g. Addison’s disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. Objective: The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison’s disease (AD). Design, Setting, and Participants: Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34. Main Outcome Measures: AD and genotype were measured. Result: Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10−4) and 13% of general population controls (P = 3.00 × 10−19). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10−191). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10−5) and type 1 diabetes patients (73%, P = 1.93 × 10−3). Analysis of 1228 SNPs across the MHC for individuals with AD revealed a shorter conserved haplotype (3.8) with the loss of the extended conserved 3.8.1 haplotype approximately halfway between HLA-B and HLA-A. Conclusion: Extreme risk for AD, especially in multiplex families, is associated with haplotypic DR3 variants, in particular a portion (3.8) but not all of the conserved 3.8.1 haplotype. PMID:20631027

  15. Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent

    International Nuclear Information System (INIS)

    Cavallone, Luca; Arcand, Suzanna L; Maugard, Christine; Ghadirian, Parviz; Mes-Masson, Anne-Marie; Provencher, Diane; Tonin, Patricia N

    2008-01-01

    small sample size did not permit analysis of all possible haplotypes, we observed that BRCA2 mutation carriers harboring the Ins16minus-72Arg haplotype had a significantly younger mean age of diagnosis of breast cancer. These observations suggest that investigations in a larger French Canadian sample are warranted to further elucidate the effects of TP53 variants on age of diagnosis of breast cancer among BRCA1 and BRCA2 mutation carriers

  16. Haplotype Analysis of the Pre-harvest Sprouting Resistance Locus Phs-A1 Reveals a Causal Role of TaMKK3-A in Global Germplasm.

    Science.gov (United States)

    Shorinola, Oluwaseyi; Balcárková, Barbara; Hyles, Jessica; Tibbits, Josquin F G; Hayden, Matthew J; Holušova, Katarina; Valárik, Miroslav; Distelfeld, Assaf; Torada, Atsushi; Barrero, Jose M; Uauy, Cristobal

    2017-01-01

    Pre-harvest sprouting (PHS) is an important cause of quality loss in many cereal crops and is particularly prevalent and damaging in wheat. Resistance to PHS is therefore a valuable target trait in many breeding programs. The Phs-A1 locus on wheat chromosome arm 4AL has been consistently shown to account for a significant proportion of natural variation to PHS in diverse mapping populations. However, the deployment of sprouting resistance is confounded by the fact that different candidate genes, including the tandem duplicated Plasma Membrane 19 ( PM19 ) genes and the mitogen-activated protein kinase kinase 3 ( TaMKK3-A) gene, have been proposed to underlie Phs-A1 . To further define the Phs-A1 locus, we constructed a physical map across this interval in hexaploid and tetraploid wheat. We established close proximity of the proposed candidate genes which are located within a 1.2 Mb interval. Genetic characterization of diverse germplasm used in previous genetic mapping studies suggests that TaMKK3-A , and not PM19 , is the major gene underlying the Phs-A1 effect in European, North American, Australian and Asian germplasm. We identified the non-dormant TaMKK3-A allele at low frequencies within the A-genome diploid progenitor Triticum urartu genepool, and show an increase in the allele frequency in modern varieties. In United Kingdom varieties, the frequency of the dormant TaMKK3-A allele was significantly higher in bread-making quality varieties compared to feed and biscuit-making cultivars. Analysis of exome capture data from 58 diverse hexaploid wheat accessions identified fourteen haplotypes across the extended Phs-A1 locus and four haplotypes for TaMKK3-A . Analysis of these haplotypes in a collection of United Kingdom and Australian cultivars revealed distinct major dormant and non-dormant Phs-A1 haplotypes in each country, which were either rare or absent in the opposing germplasm set. The diagnostic markers and haplotype information reported in the study will

  17. Haplotype Analysis of the Pre-harvest Sprouting Resistance Locus Phs-A1 Reveals a Causal Role of TaMKK3-A in Global Germplasm

    Directory of Open Access Journals (Sweden)

    Oluwaseyi Shorinola

    2017-09-01

    Full Text Available Pre-harvest sprouting (PHS is an important cause of quality loss in many cereal crops and is particularly prevalent and damaging in wheat. Resistance to PHS is therefore a valuable target trait in many breeding programs. The Phs-A1 locus on wheat chromosome arm 4AL has been consistently shown to account for a significant proportion of natural variation to PHS in diverse mapping populations. However, the deployment of sprouting resistance is confounded by the fact that different candidate genes, including the tandem duplicated Plasma Membrane 19 (PM19 genes and the mitogen-activated protein kinase kinase 3 (TaMKK3-A gene, have been proposed to underlie Phs-A1. To further define the Phs-A1 locus, we constructed a physical map across this interval in hexaploid and tetraploid wheat. We established close proximity of the proposed candidate genes which are located within a 1.2 Mb interval. Genetic characterization of diverse germplasm used in previous genetic mapping studies suggests that TaMKK3-A, and not PM19, is the major gene underlying the Phs-A1 effect in European, North American, Australian and Asian germplasm. We identified the non-dormant TaMKK3-A allele at low frequencies within the A-genome diploid progenitor Triticum urartu genepool, and show an increase in the allele frequency in modern varieties. In United Kingdom varieties, the frequency of the dormant TaMKK3-A allele was significantly higher in bread-making quality varieties compared to feed and biscuit-making cultivars. Analysis of exome capture data from 58 diverse hexaploid wheat accessions identified fourteen haplotypes across the extended Phs-A1 locus and four haplotypes for TaMKK3-A. Analysis of these haplotypes in a collection of United Kingdom and Australian cultivars revealed distinct major dormant and non-dormant Phs-A1 haplotypes in each country, which were either rare or absent in the opposing germplasm set. The diagnostic markers and haplotype information reported in the

  18. Analysis of HLA-A, HLA-B, HLA-DRB1 allelic, genotypic, and haplotypic frequencies in colombian population

    OpenAIRE

    Yazmin Rocío Árias-Murillo; Miguel Ángel Castro-Jiménez; María Fernanda Ríos-Espinosa; Juan Javier López-Rivera; Sandra Johanna Echeverry-Coral; Oscar Martínez-Nieto

    2010-01-01

    Introduction: The high polymorphism of the HLA system allows its typification to be used as valuable tool in establishing association to various illnesses, immune and genetic profiles; it also provides a guide to identifying compatibility among donors and receptors of organs transplants. Objective: To establish HLA-A, HLA-B, and HLA.DRB1 allele, genotype and haplotype frequencies among patients treated at Clinica Colsanitas SA. Methods: 561 patients coming from different regions in Col...

  19. The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

  20. First John structure resolved: Exegetical analysis, Part 2

    Directory of Open Access Journals (Sweden)

    Ron J. Bigalke

    2013-11-01

    Full Text Available Numerous attempts have been suggested regarding the structure of First John. The only nearly unanimous agreement amongst commentators is concerning the prologue (1:1–4 and the conclusion (5:13–21. The lack of unanimity can be frustrating for the majority of those who seek to understand the macrostructure of the First Epistle of John. Consequentially, some commentators have opined that it is impossible to determine a notable structure of First John, and the epistle is thus regarded as a relatively imprecise series of various thoughts that were composed on the basis of mere association. Many exegetes have therefore proposed suggested outlines to aid the understanding of First John as opposed to providing genuine efforts to articulate a discernable structure of the epistle. The final part of this exegetical analysis seeks to demonstrate that exegetes need not succumb to such pessimism because there does appear to be a discernable structure to First John. Providing and stating resolve concerning the First John structure is fundamental for understanding the revealed contents of the epistle.

  1. Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR.

    Science.gov (United States)

    Tyson, Jess; Armour, John A L

    2012-12-11

    Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in) regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

  2. Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR

    Directory of Open Access Journals (Sweden)

    Tyson Jess

    2012-12-01

    Full Text Available Abstract Background Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. Results In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. Conclusion This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

  3. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  4. The analysis of time-resolved optically stimulated luminescence: I. Theoretical considerations

    International Nuclear Information System (INIS)

    Chithambo, M L

    2007-01-01

    This is the first of two linked papers on the analysis of time-resolved optically stimulated luminescence. This paper focusses on a theoretical basis of analytical methods and on methods for interpretation of time-resolved luminescence spectra and calculation of luminescence throughput. Using a comparative analysis of the principal features of time-resolved luminescence and relevant analogues from steady state optical stimulation, formulae for configuring a measurement system for optimum performance are presented. We also examine the possible use of stretched-exponential functions for analysis of time-resolved optically stimulated luminescence spectra

  5. SUPERORBITAL PHASE-RESOLVED ANALYSIS OF SMC X-1

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Chin-Ping; Chou, Yi; Yang, Ting-Chang; Su, Yi-Hao, E-mail: m929011@astro.ncu.edu.tw, E-mail: yichou@astro.ncu.edu.tw [Graduate Institute of Astronomy, National Central University, Jhongli 32001, Taiwan (China)

    2013-08-10

    The high-mass X-ray binary SMC X-1 is an eclipsing binary with an orbital period of 3.89 days. This system exhibits a superorbital modulation with a period varying between {approx}40 days and {approx}65 days. The instantaneous frequency and the corresponding phase of the superorbital modulation can be obtained by a recently developed time-frequency analysis technique, the Hilbert-Huang transform (HHT). We present a phase-resolved analysis of both the spectra and the orbital profiles with the superorbital phase derived from the HHT. The X-ray spectra observed by the Proportional Counter Array on board the Rossi X-ray Timing Explorer are fitted well by a blackbody plus a Comptonized component. The plasma optical depth, which is a good indicator of the distribution of material along the line of sight, is significantly anti-correlated with the flux detected at 2.5-25 keV. However, the relationship between the plasma optical depth and the equivalent width of the iron line is not monotonic. There is no significant correlation for fluxes higher than {approx}35 mCrab but clear positive correlation when the intensity is lower than {approx}20 mCrab. This indicates that the iron line production is dominated by different regions of this binary system in different superorbital phases. To study the dependence of the orbital profile on the superorbital phase, we obtained the eclipse profiles by folding the All Sky Monitor light curve with the orbital period for different superorbital states. A dip feature, similar to the pre-eclipse dip in Her X-1, lying at orbital phase {approx}0.6-0.85, was discovered during the superorbital transition state. This indicates that the accretion disk has a bulge that absorbs considerable X-ray emission in the stream-disk interaction region. The dip width is anti-correlated with the flux, and this relation can be interpreted by the precessing tilted accretion disk scenario.

  6. Time-resolved fluorescence analysis of the mobile flavin cofactor

    Indian Academy of Sciences (India)

    Conformational heterogeneity of the FAD cofactor in -hydroxybenzoate hydroxylase (PHBH) was investigated with time-resolved polarized flavin fluorescence. For binary enzyme/substrate (analogue) complexes of wild-type PHBH and Tyr222 mutants, crystallographic studies have revealed two distinct flavin conformations ...

  7. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females.

    Science.gov (United States)

    Rahikainen, Anna-Liina; Palo, Jukka U; Haukka, Jari; Sajantila, Antti

    2018-04-01

    Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed. Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance

  8. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mohamed N. Saad

    2016-01-01

    Full Text Available Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field.

  9. FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome.

    Science.gov (United States)

    Rajan-Babu, Indhu-Shree; Lian, Mulias; Cheah, Felicia S H; Chen, Min; Tan, Arnold S C; Prasath, Ethiraj B; Loh, Seong Feei; Chong, Samuel S

    2017-07-19

    Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all 'embryos'. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.

  10. Green turtles (Chelonia mydas foraging at Arvoredo Island in Southern Brazil: genetic characterization and mixed stock analysis through mtDNA control region haplotypes

    Directory of Open Access Journals (Sweden)

    Maíra Carneiro Proietti

    2009-01-01

    Full Text Available We analyzed mtDNA control region sequences of green turtles (Chelonia mydas from Arvoredo Island, a foraging ground in southern Brazil, and identified eight haplotypes. Of these, CM-A8 (64% and CM-A5 (22% were dominant, the remainder presenting low frequencies ( 0.05. Mixed Stock Analysis, incorporating eleven Atlantic and one Mediterranean rookery as possible sources of individuals, indicated Ascension and Aves islands as the main contributing stocks to the Arvoredo aggregation (68.01% and 22.96%, respectively. These results demonstrate the extensive relationships between Arvoredo Island and other Atlantic foraging and breeding areas. Such an understanding provides a framework for establishing adequate management and conservation strategies for this endangered species.

  11. Glow discharge optical emission spectroscopy for accurate and well resolved analysis of coatings and thin films

    KAUST Repository

    Wilke, Marcus; Teichert, Gerd; Gemma, Ryota; Pundt, Astrid; Kirchheim, Reiner; Romanus, Henry; Schaaf, Peter

    2011-01-01

    overview on new developments in instrument design for accurate and well resolved thin film analyses is presented. The article focuses on the analytical capabilities of glow discharge optical emission spectrometry in the analysis of metallic coatings

  12. Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

    Science.gov (United States)

    Vina, Marcelo A. Fernandez; Hollenbach, Jill A.; Lyke, Kirsten E.; Sztein, Marcelo B.; Maiers, Martin; Klitz, William; Cano, Pedro; Mack, Steven; Single, Richard; Brautbar, Chaim; Israel, Shosahna; Raimondi, Eduardo; Khoriaty, Evelyne; Inati, Adlette; Andreani, Marco; Testi, Manuela; Moraes, Maria Elisa; Thomson, Glenys; Stastny, Peter; Cao, Kai

    2012-01-01

    The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans. PMID:22312049

  13. Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations.

    Science.gov (United States)

    Jiang, Li; Peng, Jianxiong; Huang, Meisha; Liu, Jing; Wang, Ling; Ma, Quan; Zhao, Hui; Yang, Xin; Ji, Anquan; Li, Caixia

    2018-02-10

    Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.

  14. Multilevel component analysis of time-resolved metabolic fingerprinting data

    NARCIS (Netherlands)

    Jansen, J.J.; Hoefsloot, H.C.J.; Greef, J. van der; Timmerman, M.E.; Smilde, A.K.

    2005-01-01

    Genomics-based technologies in systems biology have gained a lot of popularity in recent years. These technologies generate large amounts of data. To obtain information from this data, multivariate data analysis methods are required. Many of the datasets generated in genomics are multilevel

  15. Haplotype analysis of the genes encoding glutamine synthetase plastic isoforms and their association with nitrogen-use- and yield-related traits in bread wheat.

    Science.gov (United States)

    Li, Xin-Peng; Zhao, Xue-Qiang; He, Xue; Zhao, Guang-Yao; Li, Bin; Liu, Dong-Cheng; Zhang, Ai-Min; Zhang, Xue-Yong; Tong, Yi-Ping; Li, Zhen-Sheng

    2011-01-01

    Glutamine synthetase (GS) plays a key role in the growth, nitrogen (N) use and yield potential of cereal crops. Investigating the haplotype variation of GS genes and its association with agronomic traits may provide useful information for improving wheat N-use efficiency and yield. We isolated the promoter and coding region sequences of the plastic glutamine synthetase isoform (GS2) genes located on chromosomes 2A, 2B and 2D in bread wheat. By analyzing nucleotide sequence variations of the coding region, two, six and two haplotypes were distinguished for TaGS2-A1 (a and b), TaGS2-B1 (a-f) and TaGS2-D1 (a and b), respectively. By analyzing the frequency data of different haplotypes and their association with N use and agronomic traits, four major and favorable TaGS2 haplotypes (A1b, B1a, B1b, D1a) were revealed. These favorable haplotypes may confer better seedling growth, better agronomic performance, and improved N uptake during vegetative growth or grain N concentration. Our data suggest that certain TaGS2 haplotypes may be valuable in breeding wheat varieties with improved agronomic performance and N-use efficiency. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  16. Using resolvent analysis for the design of separation control on a NACA 0012 airfoil

    Science.gov (United States)

    Yeh, Chi-An; Taira, Kunihiko

    2017-11-01

    A combined effort based on large-eddy simulation and resolvent analysis on the separated flow over a NACA 0012 airfoil is conducted to design active flow control for suppression of separation. This study considers the the airfoil at 6 deg. angle-of-attack and Reynolds number of 23000. The response mode obtained from the resolvent analysis about the baseline turbulent mean flow reveals modal structures that can be categorized into three families when sweeping through the resonant frequency: (1) von Karman wake structure for low frequency; (2) Kelvin-Helmholtz structure in the separation bubble for high frequency; (3) blended structure of (1) and (2) for the intermediate frequency. Leveraging the insights from resolvent analysis, unsteady thermal actuation is introduced to the flow near the leading-edge to examine the use of the frequencies from three families for separation control in LES. As indicated by the resolvent response modes, we find that the use of intermediate frequencies are most effective in suppressing the flow separation, since the shear layer over the separation bubble and the wake are both receptive to the perturbation at the these frequencies. The resolvent-analysis-based control strategy achieves 35% drag reduction and 9% lift increase with effective frequency. This work was supported by Office of Naval Research (N00014-15-R-FO13) and Army Research Office (W911NF-14-1-0224).

  17. The Pomatocalpa maculosum Complex (Orchidaceae Resolved by Multivariate Morphometric Analysis

    Directory of Open Access Journals (Sweden)

    Santi Watthana

    2006-03-01

    Full Text Available Principal components analysis (PCA was employed to analyse the morphological variation among 63 herbarium specimens tentatively identified as Pomatocalpa andamanicum (Hook.f. J. J. Sm., P. koordersii (Rolfe J. J. Sm., P. latifolium (Lindl. J. J. Sm., P. linearifolium Seidenf., P. maculosum (Lindl. J. J. Sm., P. marsupiale (Kraenzl. J. J. Sm., P. naevatum J. J. Sm., or P. siamense (Rolfe ex Downie Summerh. Thirty-seven quantitative and 5 binary characters were included in the analyses. Taxa were delimited according to the observed clustering of specimens in the PCA plots, diagnostic characters were identified, and the correct nomenclature was established through examination of type material. Four species could be recognized viz, P. diffusum Breda (syn. P. latifolium, P. fuscum (Lindl. J. J. Sm. (syn. P. latifolium, P. marsupiale (syn. P. koordersii and P. maculosum. For the latter species, two subspecies could be recognized, viz P. maculosum (Lindl. J. J. Sm. subsp. maculosum (syn. P. maculosum, P. naevatum p.p. and P. maculosum (Lindl. J. J. Sm. subsp. andamanicum (Hook.f. S. Watthana (syn. P. andamanicum, P. linearifolium, P. siamense, P. naevatum p.p.. An identification key and a taxonomic synopsis are provided.

  18. Association analysis of the dopamine D{sub 2} receptor gene in Tourette`s syndrome using the haplotype relative risk method

    Energy Technology Data Exchange (ETDEWEB)

    Noethen, M.M.; Cichon, S.; Propping, P. [Univ. of Bonn (Germany)] [and others

    1994-09-15

    Comings et al. have recently reported a highly significant association between Tourette`s syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D{sub 2} receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited by the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, sub-populations of probands classified according to tic severity, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands. 40 refs., 1 tab.

  19. Are molecular haplotypes worth the time and expense? A cost-effective method for applying molecular haplotypes.

    Directory of Open Access Journals (Sweden)

    Mark A Levenstien

    2006-08-01

    Full Text Available Because current molecular haplotyping methods are expensive and not amenable to automation, many researchers rely on statistical methods to infer haplotype pairs from multilocus genotypes, and subsequently treat these inferred haplotype pairs as observations. These procedures are prone to haplotype misclassification. We examine the effect of these misclassification errors on the false-positive rate and power for two association tests. These tests include the standard likelihood ratio test (LRTstd and a likelihood ratio test that employs a double-sampling approach to allow for the misclassification inherent in the haplotype inference procedure (LRTae. We aim to determine the cost-benefit relationship of increasing the proportion of individuals with molecular haplotype measurements in addition to genotypes to raise the power gain of the LRTae over the LRTstd. This analysis should provide a guideline for determining the minimum number of molecular haplotypes required for desired power. Our simulations under the null hypothesis of equal haplotype frequencies in cases and controls indicate that (1 for each statistic, permutation methods maintain the correct type I error; (2 specific multilocus genotypes that are misclassified as the incorrect haplotype pair are consistently misclassified throughout each entire dataset; and (3 our simulations under the alternative hypothesis showed a significant power gain for the LRTae over the LRTstd for a subset of the parameter settings. Permutation methods should be used exclusively to determine significance for each statistic. For fixed cost, the power gain of the LRTae over the LRTstd varied depending on the relative costs of genotyping, molecular haplotyping, and phenotyping. The LRTae showed the greatest benefit over the LRTstd when the cost of phenotyping was very high relative to the cost of genotyping. This situation is likely to occur in a replication study as opposed to a whole-genome association study.

  20. Transcriptome analysis reveals the same 17 S-locus F-box genes in two haplotypes of the self-incompatibility locus of Petunia inflata.

    Science.gov (United States)

    Williams, Justin S; Der, Joshua P; dePamphilis, Claude W; Kao, Teh-Hui

    2014-07-01

    Petunia possesses self-incompatibility, by which pistils reject self-pollen but accept non-self-pollen for fertilization. Self-/non-self-recognition between pollen and pistil is regulated by the pistil-specific S-RNase gene and by multiple pollen-specific S-locus F-box (SLF) genes. To date, 10 SLF genes have been identified by various methods, and seven have been shown to be involved in pollen specificity. For a given S-haplotype, each SLF interacts with a subset of its non-self S-RNases, and an as yet unknown number of SLFs are thought to collectively mediate ubiquitination and degradation of all non-self S-RNases to allow cross-compatible pollination. To identify a complete suite of SLF genes of P. inflata, we used a de novo RNA-seq approach to analyze the pollen transcriptomes of S2-haplotype and S3-haplotype, as well as the leaf transcriptome of the S3S3 genotype. We searched for genes that fit several criteria established from the properties of the known SLF genes and identified the same seven new SLF genes in S2-haplotype and S3-haplotype, suggesting that a total of 17 SLF genes constitute pollen specificity in each S-haplotype. This finding lays the foundation for understanding how multiple SLF genes evolved and the biochemical basis for differential interactions between SLF proteins and S-RNases. © 2014 American Society of Plant Biologists. All rights reserved.

  1. Finite-difference time-domain analysis of time-resolved terahertz spectroscopy experiments

    DEFF Research Database (Denmark)

    Larsen, Casper; Cooke, David G.; Jepsen, Peter Uhd

    2011-01-01

    In this paper we report on the numerical analysis of a time-resolved terahertz (THz) spectroscopy experiment using a modified finite-difference time-domain method. Using this method, we show that ultrafast carrier dynamics can be extracted with a time resolution smaller than the duration of the T...

  2. Energy and angle resolved ion scattering spectroscopy: new possibilities for surface analysis

    International Nuclear Information System (INIS)

    Hellings, G.J.A.

    1986-01-01

    In this thesis the design and development of a novel, very sensitive and high-resolving spectrometer for surface analysis is described. This spectrometer is designed for Energy and Angle Resolved Ion Scattering Spectroscopy (EARISS). There are only a few techniques that are sensitive enough to study the outermost atomic layer of surfaces. One of these techniques, Low-Energy Ion Scattering (LEIS), is discussed in chapter 2. Since LEIS is destructive, it is important to make a very efficient use of the scattered ions. This makes it attractive to simultaneously carry out energy and angle dependent measurements (EARISS). (Auth.)

  3. Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins.

    Science.gov (United States)

    Adato, A; Weil, D; Kalinski, H; Pel-Or, Y; Ayadi, H; Petit, C; Korostishevsky, M; Bonne-Tamir, B

    1997-10-01

    Usher syndrome types I (USH1A-USH1E) are a group of autosomal recessive diseases characterized by profound congenital hearing loss, vestibular areflexia, and progressive visual loss due to retinitis pigmentosa. The human myosin VIIA gene, located on 11q14, has been shown to be responsible for Usher syndrome type 1B (USH1B). Haplotypes were constructed in 28 USH1 families by use of the following polymorphic markers spanning the USH1B locus: D11S787, D11S527, D11S1789, D11S906, D11S4186, and OMP. Affected individuals and members of their families from 12 different ethnic origins were screened for the presence of mutations in all 49 exons of the myosin VIIA gene. In 15 families myosin VIIA mutations were detected, verifying their classification as USH1B. All these mutations are novel, including three missense mutations, one premature stop codon, two splicing mutations, one frameshift, and one deletion of >2 kb comprising exons 47 and 48, a part of exon 49, and the introns between them. Three mutations were shared by more than one family, consistent with haplotype similarities. Altogether, 16 USH1B haplotypes were observed in the 15 families; most haplotypes were population specific. Several exonic and intronic polymorphisms were also detected. None of the 20 known USH1B mutations reported so far in other world populations were identified in our families.

  4. Analysis of HLA class II haplotypes in the Cayapa indians of ecuador: A novel DRBI allele reveals evidence for convergent evolution and balancing selection at position 86

    Energy Technology Data Exchange (ETDEWEB)

    Titus-Trachtenberg, E.A.; Erlich, H. (Roche Molecular Systems, Alameda, CA (United States)); Rickards, O.; De Stefano, G.F. (Universita di Roma, Rome (Italy))

    1994-07-01

    PCR amplification, oligonucleotide probe typing, and sequencing were used to analyze the HLA class II loci (DRB1, DQA1, DAB1, and DPB1) of an isolated South Amerindian tribe. Here the authors report HLA class II variation, including the identification of a new DRB1 allele, several novel DR/DQ haplotypes, and an unusual distribution of DPB1 alleles, among the Cayapa Indians (N=100) of Ecuador. A general reduction of HLA class II allelic variation in the Cayapa is consistent with a population bottleneck during the colonization of the Americas. The new Cayapa DRB1 allele, DRB1[sup *]08042, which arose by a G[yields]T point mutation in the parental DRB1[sup *]0802, contains a novel Val codon (GTT) at position 86. The generation of DRB1[sup *]08042 (Val-86) from DRB1[sup *]0802 (Gly-86) in the Cayapa, by a different mechanism than the (GT[yields]TG) change in the creation of DRB1[sub *]08041 (Val-86) from DRB1[sup *]0802 in Africa, implicates selection in the convergent evolution of position 86 DR[beta] variants. The DRB1[sup *]08042 allele has not been found in >1,800 Amerindian haplotypes and thus presumably arose after the Cayapa separated from other South American Amerindians. Selection pressure for increased haplotype diversity can be inferred in the generation and maintenance of three new DRB1[sup *]08042 haplotypes and several novel DR/DQ haplotypes in this population. The DPB1 allelic distribution in the Cayapa is also extraordinary, with two alleles, DPB1[sup *]1401, a very rare allele in North American Amerindian populations, and DPB1[sup *]0402, the most common Amerindian DPB1 allele, constituting 89% of the Cayapa DPB1. These data are consistent with the postulated rapid rate of evolution as noted for the class I HLA-B locus of other South American Indians. 34 refs., 2 figs., 2 tabs.

  5. Laser induced breakdown spectroscopy of the uranium including calcium. Time resolved measurement spectroscopic analysis (Contract research)

    International Nuclear Information System (INIS)

    Akaoka, Katsuaki; Maruyama, Youichiro; Oba, Masaki; Miyabe, Masabumi; Otobe, Haruyoshi; Wakaida, Ikuo

    2010-05-01

    For the remote analysis of low DF TRU (Decontamination Factor Transuranic) fuel, Laser Breakdown Spectroscopy (LIBS) was applied to uranium oxide including a small amount of calcium oxide. The characteristics, such as spectrum intensity and plasma excitation temperature, were measured using time-resolved spectroscopy. As a result, in order to obtain the stable intensity of calcium spectrum for the uranium spectrum, it was found out that the optimum observation delay time of spectrum is 4 microseconds or more after laser irradiation. (author)

  6. The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat.

    Science.gov (United States)

    Hao, Chenyang; Wang, Yuquan; Chao, Shiaoman; Li, Tian; Liu, Hongxia; Wang, Lanfen; Zhang, Xueyong

    2017-01-30

    A Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.

  7. Designing and conducting in silico analysis for identifying of Echinococcus spp. with discrimination of novel haplotypes: an approach to better understanding of parasite taxonomic.

    Science.gov (United States)

    Spotin, Adel; Gholami, Shirzad; Nasab, Abbas Najafi; Fallah, Esmaeil; Oskouei, Mahmoud Mahami; Semnani, Vahid; Shariatzadeh, Seyyed Ali; Shahbazi, Abbas

    2015-04-01

    The definitive identification of Echinococcus species is currently carried out by sequencing and phylogenetic strategies. However, the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns is not broadly used as a result of heterogeneity traits of Echinococcus genome in different regions of the world. Therefore, designing and conducting a standardized pattern should indigenously be considered in under-studied areas. In this investigation, an in silico mapping was designed and developed for eight Echinococcus spp. on the basis of regional sequences in Iran and the world. The numbers of 60 Echinococcus isolates were collected from the liver and lungs of 15 human, 15 sheep, 15 cattle, and 15 camel cases in Semnan province, Central Iran. DNA samples were extracted and examined by polymerase chain reaction of ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1) and PCR-RFLP via Rsa1 endonuclease enzyme. Moreover, 15 amplicons of cytochrome oxidase 1 (Cox1) were directly sequenced in order to identify the strains/haplotypes. PCR-RFLP and phylogenetic analyses revealed firmly the presence of the G1 and G6 genotypes with heterogeneity (three novel haplotypes) of Cox1 gene although no other expected genotypes were found in the region. Finding shows that the identification of novel haplotypes along with discrimination of Echinococcus spp. through regional patterns can unambiguously illustrate the real taxonomic status of parasite in Central Iran.

  8. Approximation properties of haplotype tagging

    Directory of Open Access Journals (Sweden)

    Dreiseitl Stephan

    2006-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are locations at which the genomic sequences of population members differ. Since these differences are known to follow patterns, disease association studies are facilitated by identifying SNPs that allow the unique identification of such patterns. This process, known as haplotype tagging, is formulated as a combinatorial optimization problem and analyzed in terms of complexity and approximation properties. Results It is shown that the tagging problem is NP-hard but approximable within 1 + ln((n2 - n/2 for n haplotypes but not approximable within (1 - ε ln(n/2 for any ε > 0 unless NP ⊂ DTIME(nlog log n. A simple, very easily implementable algorithm that exhibits the above upper bound on solution quality is presented. This algorithm has running time O((2m - p + 1 ≤ O(m(n2 - n/2 where p ≤ min(n, m for n haplotypes of size m. As we show that the approximation bound is asymptotically tight, the algorithm presented is optimal with respect to this asymptotic bound. Conclusion The haplotype tagging problem is hard, but approachable with a fast, practical, and surprisingly simple algorithm that cannot be significantly improved upon on a single processor machine. Hence, significant improvement in computatational efforts expended can only be expected if the computational effort is distributed and done in parallel.

  9. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elie Aoun

    2008-04-01

    Full Text Available The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways that are initiated by different metabolic or environmental factors (etiologies and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis.The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93, but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85 was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67 or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56. Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I(2 = 80.95%.The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint.

  10. Quantitative analysis of pulmonary perfusion using time-resolved parallel 3D MRI - initial results

    International Nuclear Information System (INIS)

    Fink, C.; Buhmann, R.; Plathow, C.; Puderbach, M.; Kauczor, H.U.; Risse, F.; Ley, S.; Meyer, F.J.

    2004-01-01

    Purpose: to assess the use of time-resolved parallel 3D MRI for a quantitative analysis of pulmonary perfusion in patients with cardiopulmonary disease. Materials and methods: eight patients with pulmonary embolism or pulmonary hypertension were examined with a time-resolved 3D gradient echo pulse sequence with parallel imaging techniques (FLASH 3D, TE/TR: 0.8/1.9 ms; flip angle: 40 ; GRAPPA). A quantitative perfusion analysis based on indicator dilution theory was performed using a dedicated software. Results: patients with pulmonary embolism or chronic thromboembolic pulmonary hypertension revealed characteristic wedge-shaped perfusion defects at perfusion MRI. They were characterized by a decreased pulmonary blood flow (PBF) and pulmonary blood volume (PBV) and increased mean transit time (MTT). Patients with primary pulmonary hypertension or eisenmenger syndrome showed a more homogeneous perfusion pattern. The mean MTT of all patients was 3.3 - 4.7 s. The mean PBF and PBV showed a broader interindividual variation (PBF: 104-322 ml/100 ml/min; PBV: 8 - 21 ml/100 ml). Conclusion: time-resolved parallel 3D MRI allows at least a semi-quantitative assessment of lung perfusion. Future studies will have to assess the clinical value of this quantitative information for the diagnosis and management of cardiopulmonary disease. (orig.) [de

  11. Detecting structure of haplotypes and local ancestry

    Science.gov (United States)

    We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

  12. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus

    Energy Technology Data Exchange (ETDEWEB)

    Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States))

    1992-12-01

    Analysis of mutant PAH chromosomes has identified approximately 60 different single-base substitutions and deletions within the PAH locus. Nearly all of these molecular lesions are in strong linkage disequilibrium with specific RFLP haplotypes in different ethnic populations. Thus, haplotype analysis is not only useful for diagnostic purposes but is proving to be a valuable tool in population genetic studies of the origin and spread of phenylketonuria alleles in human populations. PCR-based methods have been developed to detect six of the eight polymorphic restriction sites used for determination of RFLP haplotypes at the PAH locus. A table of the proposed expanded haplotypes is given.

  13. Scanning photoelectron microscope for nanoscale three-dimensional spatial-resolved electron spectroscopy for chemical analysis.

    Science.gov (United States)

    Horiba, K; Nakamura, Y; Nagamura, N; Toyoda, S; Kumigashira, H; Oshima, M; Amemiya, K; Senba, Y; Ohashi, H

    2011-11-01

    In order to achieve nondestructive observation of the three-dimensional spatially resolved electronic structure of solids, we have developed a scanning photoelectron microscope system with the capability of depth profiling in electron spectroscopy for chemical analysis (ESCA). We call this system 3D nano-ESCA. For focusing the x-ray, a Fresnel zone plate with a diameter of 200 μm and an outermost zone width of 35 nm is used. In order to obtain the angular dependence of the photoelectron spectra for the depth-profile analysis without rotating the sample, we adopted a modified VG Scienta R3000 analyzer with an acceptance angle of 60° as a high-resolution angle-resolved electron spectrometer. The system has been installed at the University-of-Tokyo Materials Science Outstation beamline, BL07LSU, at SPring-8. From the results of the line-scan profiles of the poly-Si/high-k gate patterns, we achieved a total spatial resolution better than 70 nm. The capability of our system for pinpoint depth-profile analysis and high-resolution chemical state analysis is demonstrated. © 2011 American Institute of Physics

  14. Haplotype Analysis of the Pre-harvest Sprouting Resistance Locus Phs-A1 Reveals a Causal Role of TaMKK3-A in Global Germplasm

    Czech Academy of Sciences Publication Activity Database

    Shorinola, O.; Balcárková, Barbora; Hyles, J.; Tibbits, J. F. G.; Hayden, M. J.; Holušová, Kateřina; Valárik, Miroslav; Distelfeld, A.; Torada, A.; Barrero, R. A.; Uauy, C.

    2017-01-01

    Roč. 8, SEP 13 (2017), č. článku 1555. ISSN 1664-462X R&D Projects: GA MŠk(CZ) LO1204; GA ČR(CZ) GA14-07164S Institutional support: RVO:61389030 Keywords : triticum-aestivum l. * controlling seed dormancy * white-grained wheat * pcr-based markers * chromosome 4a * winter-wheat * major qtl * abscisic-acid * bread wheat * genes * dormancy * seed * pm19 * TaMKK3-A * pre-harvest sprouting * Triticum aestivum * haplotype Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 4.298, year: 2016

  15. Analysis of the 235U neutron cross sections in the resolved resonance range

    International Nuclear Information System (INIS)

    Leal, L.C.; de Saussure, G.; Perez, R.B.

    1989-01-01

    Using recent high-resolution measurements of the neutron transmission of 235 U and the spin-separated fission cross-section data of Moore et al., a multilevel analysis of the 235 U neutron cross sections was performed up to 300 eV. The Dyson Metha Δ 3 statistics were used to help locate small levels above 100 eV where resonances are not clearly resolved even in the best resolution measurements available. The statistical properties of the resonance parameters are discussed

  16. Analysis of the 235U neutron cross sections in the resolved resonance range

    International Nuclear Information System (INIS)

    Leal, L.C.; de Saussure, G.; Perez, R.B.

    1989-01-01

    Using recent high-resolution measurements of the neutron transmission of 235 U and the spin-separated fission cross-section data of Moore et al., a multilevel analysis of the 235 U neutron cross sections was performed up to 300 eV. The Dyson Metha Δ 3 statistics were used to help locate small levels above 100 eV where resonances are not clearly resolved even in the best resolution measurements available. The statistical properties of the resonance parameters are discussed. 13 refs., 8 figs., 1 tab

  17. Evaluation of a High Resolving Power Time-of-Flight Mass Spectrometer for Drug Analysis in Terms of Resolving Power and Acquisition Rate

    Science.gov (United States)

    Pelander, Anna; Decker, Petra; Baessmann, Carsten; Ojanperä, Ilkka

    2011-02-01

    Liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) is applied increasingly to various fields of small molecule analysis. The moderate resolving power (RP) of standard TOFMS instruments poses a risk of false negative results when complex biological matrices are to be analyzed. In this study, the performance of a high resolving power TOFMS instrument (maXis by Bruker Daltonik, Bremen, Germany) was evaluated for drug analysis. By flow injection analysis of critical drug mixtures, including a total of 17 compounds with nominal masses of 212-415 Da and with mass differences of 8.8-23.5 mDa, RP varied from 34,400 to 51,900 (FWHM). The effect of acquisition rate on RP, mass accuracy, and isotopic pattern fit was studied by applying 1, 2, 5, 10, and 20 Hz acquisition rates in a 16 min gradient elution LC separation. All three variables were independent of the acquisition rate, with an average mass accuracy and isotopic pattern fit factor (mSigma) of 0.33 ppm and 5.9, respectively. The average relative standard deviation of RP was 1.8%, showing high repeatability. The performance was tested further with authentic urine extracts containing a co-eluting compound pair with a nominal mass of 296 Da and an 11.2 mDa mass difference. The authentic sample components were readily resolved and correctly identified by the automated data analysis. The average RP, mass accuracy, and isotopic pattern fit were 36,600, 0.9 ppm, and 7.3 mSigma, respectively.

  18. Flammable Gas Refined Safety Analysis Tool Software Verification and Validation Report for Resolve Version 2.5

    International Nuclear Information System (INIS)

    BRATZEL, D.R.

    2000-01-01

    The purpose of this report is to document all software verification and validation activities, results, and findings related to the development of Resolve Version 2.5 for the analysis of flammable gas accidents in Hanford Site waste tanks

  19. Noninvasive detection of inhomogeneities in turbid media with time-resolved log-slope analysis

    International Nuclear Information System (INIS)

    Wan, S.K.; Guo Zhixiong; Kumar, Sunil; Aber, Janice; Garetz, B.A.

    2004-01-01

    Detecting foreign objects embedded in turbid media using noninvasive optical tomography techniques is of great importance in many practical applications, such as in biomedical imaging and diagnosis, safety inspection on aircrafts and submarines, and LIDAR techniques. In this paper we develop a novel optical tomography approach based on slope analysis of time-resolved back-scattered signals collected at the medium boundaries where the light source is an ultrafast, short-pulse laser. As the optical field induced by the laser-pulse propagates, the detected temporal signals are influenced by the optical properties of the medium traversed. The detected temporal signatures therefore contain information that can indicate the presence of an inhomogeneity as well as its size and location relative to the laser source and detection systems. The log-slope analysis of the time-resolved back-scattered intensity is shown to be an effective method for extracting the information contained in the signal. The technique is validated by experimental results and by Monte Carlo simulations

  20. A new mathematical modeling for pure parsimony haplotyping problem.

    Science.gov (United States)

    Feizabadi, R; Bagherian, M; Vaziri, H R; Salahi, M

    2016-11-01

    Pure parsimony haplotyping (PPH) problem is important in bioinformatics because rational haplotyping inference plays important roles in analysis of genetic data, mapping complex genetic diseases such as Alzheimer's disease, heart disorders and etc. Haplotypes and genotypes are m-length sequences. Although several integer programing models have already been presented for PPH problem, its NP-hardness characteristic resulted in ineffectiveness of those models facing the real instances especially instances with many heterozygous sites. In this paper, we assign a corresponding number to each haplotype and genotype and based on those numbers, we set a mixed integer programing model. Using numbers, instead of sequences, would lead to less complexity of the new model in comparison with previous models in a way that there are neither constraints nor variables corresponding to heterozygous nucleotide sites in it. Experimental results approve the efficiency of the new model in producing better solution in comparison to two state-of-the art haplotyping approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Spatially resolved spectroscopy analysis of the XMM-Newton large program on SN1006

    Science.gov (United States)

    Li, Jiang-Tao; Decourchelle, Anne; Miceli, Marco; Vink, Jacco; Bocchino, Fabrizio

    2016-04-01

    We perform analysis of the XMM-Newton large program on SN1006 based on our newly developed methods of spatially resolved spectroscopy analysis. We extract spectra from low and high resolution meshes. The former (3596 meshes) is used to roughly decompose the thermal and non-thermal components and characterize the spatial distributions of different parameters, such as temperature, abundances of different elements, ionization age, and electron density of the thermal component, as well as photon index and cutoff frequency of the non-thermal component. On the other hand, the low resolution meshes (583 meshes) focus on the interior region dominated by the thermal emission and have enough counts to well characterize the Si lines. We fit the spectra from the low resolution meshes with different models, in order to decompose the multiple plasma components at different thermal and ionization states and compare their spatial distributions. In this poster, we will present the initial results of this project.

  2. PHASE-RESOLVED TIMING ANALYSIS OF GRS 1915+105 IN ITS ρ STATE

    International Nuclear Information System (INIS)

    Yan, Shu-Ping; Wang, Na; Ding, Guo-Qiang; Qu, Jin-Lu

    2013-01-01

    We made a phase-resolved timing analysis of GRS 1915+105 in its ρ state and obtained detailed ρ cycle evolutions of the frequency, amplitude, and coherence of the low-frequency quasi-periodic oscillation (LFQPO). We combined our timing results with the spectral study by Neilsen et al. to perform an elaborate comparison analysis. Our analyses show that the LFQPO frequency does not scale with the inner disk radius, but it is related to the spectral index, indicating a possible correlation between the LFQPO and the corona. The LFQPO amplitude spectrum and other results are naturally explained by tying the LFQPO to the corona. The similarities of the spectra of variability parameters between the LFQPOs from ρ state and those from more steady states indicate that the LFQPOs of GRS 1915+105 in very different states seem to share the same origin.

  3. PHASE-RESOLVED TIMING ANALYSIS OF GRS 1915+105 IN ITS {rho} STATE

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Shu-Ping; Wang, Na; Ding, Guo-Qiang [Xinjiang Astronomical Observatory, Chinese Academy of Sciences, 150 Science 1-Street, Urumqi, Xinjiang 830011 (China); Qu, Jin-Lu, E-mail: yanshup@xao.ac.cn, E-mail: na.wang@xao.ac.cn [Key Laboratory for Particle Astrophysics, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Beijing 100049 (China)

    2013-04-10

    We made a phase-resolved timing analysis of GRS 1915+105 in its {rho} state and obtained detailed {rho} cycle evolutions of the frequency, amplitude, and coherence of the low-frequency quasi-periodic oscillation (LFQPO). We combined our timing results with the spectral study by Neilsen et al. to perform an elaborate comparison analysis. Our analyses show that the LFQPO frequency does not scale with the inner disk radius, but it is related to the spectral index, indicating a possible correlation between the LFQPO and the corona. The LFQPO amplitude spectrum and other results are naturally explained by tying the LFQPO to the corona. The similarities of the spectra of variability parameters between the LFQPOs from {rho} state and those from more steady states indicate that the LFQPOs of GRS 1915+105 in very different states seem to share the same origin.

  4. Introduction to theory and analysis of resolved (and unresolved) neutron resonances via SAMMY

    Energy Technology Data Exchange (ETDEWEB)

    Larson, N.M.

    1998-07-01

    Neutron cross-section data are important for two distinct purposes: first, they provide insight into the nature of matter, thus assisting in the understanding of fundamental physics; second, they are needed for practical applications (e.g., for calculating when and how a reactor will become critical, or how much shielding is needed for storage of nuclear materials, and for medical applications). Neutron cross section data in the resolved-resonance region are generally obtained by time-of-flight experiments, which must be carefully analyzed if they are to be properly understood and utilized. In this paper, important features of the analysis process are discussed, with emphasis on the particular technique used in the analysis code SAMMY. Other features of the code are also described; these include such topics as calculation of group cross sections (including covariance matrices), generation and fitting of integral quantities, and extensions into the unresolved-resonance region and higher-energy regions.

  5. Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case–control study

    International Nuclear Information System (INIS)

    Tamimi, Rulla M; Hankinson, Susan E; Spiegelman, Donna; Kraft, Peter; Colditz, Graham A; Hunter, David J

    2004-01-01

    The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast cancer compared with noncarriers of the mutations, although not all studies have confirmed this association. Haplotype analysis has been suggested as an efficient method for investigating the role of common variation in the ATM gene and breast cancer. Five biallelic haplotype tagging single nucleotide polymorphisms are estimated to capture 99% of the haplotype diversity in Caucasian populations. We conducted a nested case–control study of breast cancer within the Nurses' Health Study cohort to address the role of common ATM haplotypes and breast cancer. Cases and controls were genotyped for five haplotype tagging single nucleotide polymorphisms. Haplotypes were predicted for 1309 cases and 1761 controls for which genotype information was available. Six unique haplotypes were predicted in this study, five of which occur at a frequency of 5% or greater. The overall distribution of haplotypes was not significantly different between cases and controls (χ 2 = 3.43, five degrees of freedom, P = 0.63). There was no evidence that common haplotypes of ATM are associated with breast cancer risk. Extensive single nucleotide polymorphism detection using the entire genomic sequence of ATM will be necessary to rule out less common variation in ATM and sporadic breast cancer risk

  6. Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

    Science.gov (United States)

    Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

    2018-04-01

    Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

  7. Spatially resolved δ13C analysis using laser ablation isotope ratio mass spectrometry

    Science.gov (United States)

    Moran, J.; Riha, K. M.; Nims, M. K.; Linley, T. J.; Hess, N. J.; Nico, P. S.

    2014-12-01

    Inherent geochemical, organic matter, and microbial heterogeneity over small spatial scales can complicate studies of carbon dynamics through soils. Stable isotope analysis has a strong history of helping track substrate turnover, delineate rhizosphere activity zones, and identifying transitions in vegetation cover, but most traditional isotope approaches are limited in spatial resolution by a combination of physical separation techniques (manual dissection) and IRMS instrument sensitivity. We coupled laser ablation sampling with isotope measurement via IRMS to enable spatially resolved analysis over solid surfaces. Once a targeted sample region is ablated the resulting particulates are entrained in a helium carrier gas and passed through a combustion reactor where carbon is converted to CO2. Cyrotrapping of the resulting CO2 enables a reduction in carrier gas flow which improves overall measurement sensitivity versus traditional, high flow sample introduction. Currently we are performing sample analysis at 50 μm resolution, require 65 ng C per analysis, and achieve measurement precision consistent with other continuous flow techniques. We will discuss applications of the laser ablation IRMS (LA-IRMS) system to microbial communities and fish ecology studies to demonstrate the merits of this technique and how similar analytical approaches can be transitioned to soil systems. Preliminary efforts at analyzing soil samples will be used to highlight strengths and limitations of the LA-IRMS approach, paying particular attention to sample preparation requirements, spatial resolution, sample analysis time, and the types of questions most conducive to analysis via LA-IRMS.

  8. Spatially resolved element analysis of historical violin varnishes by use of muPIXE.

    Science.gov (United States)

    von Bohlen, Alex; Röhrs, Stefan; Salomon, Joseph

    2007-02-01

    External muPIXE has been used for characterisation of small samples of varnish from historical violins, and pieces of varnished wood from historical and modern stringed instruments. To obtain spatially resolved information about the distribution of elements across the varnish layers single-spot analysis, line-scans, and area-mapping were performed. Local resolution of approximately 20 mum was obtained from the 3 MeV, 1 nA proton micro-probe. Results from simultaneous multi-element determination of Na, Mg, Al, Si, P, S, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Br, Rb, Sr, Ag, Cd, Sn, Ba, and Pb in historical varnishes are presented. Semi-quantitative evaluation of line-scans recorded on diverse historical varnishes is reported. The applied method is discussed in detail and the results obtained are critically reviewed and compared with those in the literature.

  9. Data and Analysis from a Time-Resolved Tomographic Optical Beam Diagnostic

    International Nuclear Information System (INIS)

    Frayer, Daniel K.; Johnson, Douglas; Ekdahl, Carl

    2010-01-01

    An optical tomographic diagnostic instrument developed for the acquisition of high-speed time-resolved images has been fielded at the Dual-Axis Radiographic Hydrodynamic Test (DARHT) Facility at Los Alamos National Laboratory. The instrument was developed for the creation of time histories of electron-beam cross section through the collection of Cerenkov light. Four optical lines of sight optically collapse an image and relay projections via an optical fiber relay to recording instruments; a tomographic reconstruction algorithm creates the time history. Because the instrument may be operated in an adverse environment, it may be operated, adjusted, and calibrated remotely. The instrument was operated over the course of various activities during and after DARHT commissioning, and tomographic reconstructions reported verifiable beam characteristics. Results from the collected data and reconstructions and analysis of the data are discussed.

  10. Time-resolved analysis of nonlinear optical limiting for laser synthesized carbon nanoparticles

    Science.gov (United States)

    Chen, G. X.; Hong, M. H.

    2010-11-01

    Nonlinear optical limiting materials have attracted much research interest in recent years. Carbon nanoparticles suspended in liquids show a strong nonlinear optical limiting function. It is important to investigate the nonlinear optical limiting process of carbon nanoparticles for further improving their nonlinear optical limiting performance. In this study, carbon nanoparticles were prepared by laser ablation of a carbon target in tetrahydrofuran (THF). Optical limiting properties of the samples were studied with 532-nm laser light, which is in the most sensitive wavelength band for human eyes. The shape of the laser pulse plays an important role for initializing the nonlinear optical limiting effect. Time-resolved analysis of laser pulses discovered 3 fluence stages of optical limiting. Theoretical simulation indicates that the optical limiting is initialized by a near-field optical enhancement effect.

  11. Frequency-resolved interferometric measurement of local density fluctuations for turbulent combustion analysis

    International Nuclear Information System (INIS)

    Köberl, S; Giuliani, F; Woisetschläger, J; Fontaneto, F

    2010-01-01

    A validation of a novel interferometric measurement technique for the frequency-resolved detection of local density fluctuation in turbulent combustion analysis was performed in this work. Two laser vibrometer systems together with a signal analyser were used to obtain frequency spectra of density fluctuations across a methane-jet flame. Since laser vibrometry is based on interferometric techniques, the derived signals are path-integrals along the measurement beam. To obtain local frequency spectra of density fluctuations, long-time-averaged measurements from each of the two systems were performed using correlation functions and cross spectra. Results were compared to data recorded by standard interferometric techniques for validation purposes. Additionally, Raman scattering and laser Doppler velocimetry were used for flame characterization

  12. Analysis of junior high school students' difficulty in resolving rectangular conceptual problems

    Science.gov (United States)

    Utami, Aliksia Kristiana Dwi; Mardiyana, Pramudya, Ikrar

    2017-08-01

    Geometry is one part of the mathematics that must be learned in school and it has important effects on the development of creative thinking skills of learners, but in fact, there are some difficulties experienced by the students. This research focuses on analysis difficulty in resolving rectangular conceptual problems among junior high school students in every creative thinking skills level. This research used a descriptive method aimed to identify the difficulties and cause of the difficulties experienced by five students. The difficulties are associated with rectangular shapes and related problems. Data collection was done based on students' work through test, interview, and observations. The result revealed that student' difficulties in understanding the rectangular concept can be found at every creative thinking skills level. The difficulties are identifying the objects rectangular in the daily life except for a rectangle and square, analyzing the properties of rectangular shapes, and seeing the interrelationships between figures.

  13. A haplotype regression approach for genetic evaluation using sequences from the 1000 bull genomes Project

    International Nuclear Information System (INIS)

    Lakhssassi, K.; González-Recio, O.

    2017-01-01

    Haplotypes from sequencing data may improve the prediction accuracy in genomic evaluations as haplotypes are in stronger linkage disequilibrium with quantitative trait loci than markers from SNP chips. This study focuses first, on the creation of haplotypes in a population sample of 450 Holstein animals, with full-sequence data from the 1000 bull genomes project; and second, on incorporating them into the whole genome prediction model. In total, 38,319,258 SNPs (and indels) from Next Generation Sequencing were included in the analysis. After filtering variants with minor allele frequency (MAF< 0.025) 13,912,326 SNPs were available for the haplotypes extraction with findhap.f90. The number of SNPs in the haploblocks was on average 924 SNP (166,552 bp). Unique haplotypes were around 97% in all chromosomes and were ignored leaving 153,428 haplotypes. Estimated haplotypes had a large contribution to the total variance of genomic estimated breeding values for kilogram of protein, Global Type Index, Somatic Cell Score and Days Open (between 32 and 99.9%). Haploblocks containing haplotypes with large effects were selected by filtering for each trait, haplotypes whose effect was larger/lower than the mean plus/minus 3 times the standard deviation (SD) and 1 SD above the mean of the haplotypes effect distribution. Results showed that filtering by 3 SD would not be enough to capture a large proportion of genetic variance, whereas filtering by 1 SD could be useful but model convergence should be considered. Additionally, sequence haplotypes were able to capture additional genetic variance to the polygenic effect for traits undergoing lower selection intensity like fertility and health traits.

  14. A haplotype regression approach for genetic evaluation using sequences from the 1000 bull genomes Project

    Energy Technology Data Exchange (ETDEWEB)

    Lakhssassi, K.; González-Recio, O.

    2017-07-01

    Haplotypes from sequencing data may improve the prediction accuracy in genomic evaluations as haplotypes are in stronger linkage disequilibrium with quantitative trait loci than markers from SNP chips. This study focuses first, on the creation of haplotypes in a population sample of 450 Holstein animals, with full-sequence data from the 1000 bull genomes project; and second, on incorporating them into the whole genome prediction model. In total, 38,319,258 SNPs (and indels) from Next Generation Sequencing were included in the analysis. After filtering variants with minor allele frequency (MAF< 0.025) 13,912,326 SNPs were available for the haplotypes extraction with findhap.f90. The number of SNPs in the haploblocks was on average 924 SNP (166,552 bp). Unique haplotypes were around 97% in all chromosomes and were ignored leaving 153,428 haplotypes. Estimated haplotypes had a large contribution to the total variance of genomic estimated breeding values for kilogram of protein, Global Type Index, Somatic Cell Score and Days Open (between 32 and 99.9%). Haploblocks containing haplotypes with large effects were selected by filtering for each trait, haplotypes whose effect was larger/lower than the mean plus/minus 3 times the standard deviation (SD) and 1 SD above the mean of the haplotypes effect distribution. Results showed that filtering by 3 SD would not be enough to capture a large proportion of genetic variance, whereas filtering by 1 SD could be useful but model convergence should be considered. Additionally, sequence haplotypes were able to capture additional genetic variance to the polygenic effect for traits undergoing lower selection intensity like fertility and health traits.

  15. Glow discharge optical emission spectroscopy for accurate and well resolved analysis of coatings and thin films

    KAUST Repository

    Wilke, Marcus

    2011-12-01

    In the last years, glow discharge optical emission spectrometry (GDOES) gained more and more acceptance in the analysis of functional coatings. GDOES thereby represents an interesting alternative to common depth profiling techniques like AES and SIMS, based on its unique combination of high erosion rates and erosion depths, sensitivity, analysis of nonconductive layers and easy quantification even for light elements such as C, N, O and H. Starting with the fundamentals of GDOES, a short overview on new developments in instrument design for accurate and well resolved thin film analyses is presented. The article focuses on the analytical capabilities of glow discharge optical emission spectrometry in the analysis of metallic coatings and thin films. Results illustrating the high depth resolution, confirmation of stoichiometry, the detection of light elements in coatings as well as contamination on the surface or interfaces will be demonstrated by measurements of: a multilayer system Cr/Ti on silicon, interface contamination on silicon during deposition of aluminum, Al2O3-nanoparticle containing conversion coatings on zinc for corrosion resistance, Ti3SiC2 MAX-phase coatings by pulsed laser deposition and hydrogen detection in a V/Fe multilayer system. The selected examples illustrate that GDOES can be successfully adopted as an analytical tool in the development of new materials and coatings. A discussion of the results as well as of the limitations of GDOES is presented. © 2011 Elsevier B.V.

  16. Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype.

    Science.gov (United States)

    Bandeira, Izabel C J; Rocha, Lillianne B S; Barbosa, Maritza C; Elias, Darcielle B D; Querioz, José A N; Freitas, Max Vitor Carioca; Gonçalves, Romélia P

    2014-02-01

    The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0±0.6)mg/kg/day for 6-60 (18±3.4)months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with

  17. Estimating haplotype effects for survival data

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, Torben; Silver, J

    2010-01-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplo...

  18. Haplotype-Based Genotyping in Polyploids

    Directory of Open Access Journals (Sweden)

    Josh P. Clevenger

    2018-04-01

    Full Text Available Accurate identification of polymorphisms from sequence data is crucial to unlocking the potential of high throughput sequencing for genomics. Single nucleotide polymorphisms (SNPs are difficult to accurately identify in polyploid crops due to the duplicative nature of polyploid genomes leading to low confidence in the true alignment of short reads. Implementing a haplotype-based method in contrasting subgenome-specific sequences leads to higher accuracy of SNP identification in polyploids. To test this method, a large-scale 48K SNP array (Axiom Arachis2 was developed for Arachis hypogaea (peanut, an allotetraploid, in which 1,674 haplotype-based SNPs were included. Results of the array show that 74% of the haplotype-based SNP markers could be validated, which is considerably higher than previous methods used for peanut. The haplotype method has been implemented in a standalone program, HAPLOSWEEP, which takes as input bam files and a vcf file and identifies haplotype-based markers. Haplotype discovery can be made within single reads or span paired reads, and can leverage long read technology by targeting any length of haplotype. Haplotype-based genotyping is applicable in all allopolyploid genomes and provides confidence in marker identification and in silico-based genotyping for polyploid genomics.

  19. A new framework for the analysis of continental-scale convection-resolving climate simulations

    Science.gov (United States)

    Leutwyler, D.; Charpilloz, C.; Arteaga, A.; Ban, N.; Di Girolamo, S.; Fuhrer, O.; Hoefler, T.; Schulthess, T. C.; Christoph, S.

    2017-12-01

    High-resolution climate simulations at horizontal resolution of O(1-4 km) allow explicit treatment of deep convection (thunderstorms and rain showers). Explicitly treating convection by the governing equations reduces uncertainties associated with parametrization schemes and allows a model formulation closer to physical first principles [1,2]. But kilometer-scale climate simulations with long integration periods and large computational domains are expensive and data storage becomes unbearably voluminous. Hence new approaches to perform analysis are required. In the crCLIM project we propose a new climate modeling framework that allows scientists to conduct analysis at high spatial and temporal resolution. We tackle the computational cost by using the largest available supercomputers such as hybrid CPU-GPU architectures. For this the COSMO model has been adapted to run on such architectures [2]. We then alleviate the I/O-bottleneck by employing a simulation data-virtualizer (SDaVi) that allows to trade-off storage (space) for computational effort (time). This is achieved by caching the simulation outputs and efficiently launching re-simulations in case of cache misses. All this is done transparently from the analysis applications [3]. For the re-runs this approach requires a bit-reproducible version of COSMO. That is to say a model that produces identical results on different architectures to ensure coherent recomputation of the requested data [4]. In this contribution we present a version of SDaVi, a first performance model, and a strategy to obtain bit-reproducibility across hardware architectures.[1] N. Ban, J. Schmidli, C. Schär. Evaluation of the convection-resolving regional climate modeling approach in decade-long simulations. J. Geophys. Res. Atmos., 7889-7907, 2014.[2] D. Leutwyler, O. Fuhrer, X. Lapillonne, D. Lüthi, C. Schär. Towards European-scale convection-resolving climate simulations with GPUs: a study with COSMO 4.19. Geosci. Model Dev, 3393

  20. Organelle DNA haplotypes reflect crop-use characteristics and geographic origins of Cannabis sativa.

    Science.gov (United States)

    Gilmore, Simon; Peakall, Rod; Robertson, James

    2007-10-25

    Comparative sequencing of cannabis individuals across 12 chloroplast and mitochondrial DNA loci revealed 7 polymorphic sites, including 5 length variable regions and 2 single nucleotide polymorphisms. Simple PCR assays were developed to assay these polymorphisms, and organelle DNA haplotypes were obtained for 188 cannabis individuals from 76 separate populations, including drug-type, fibre-type and wild populations. The haplotype data were analysed using parsimony, UPGMA and neighbour joining methods. Three haplotype groups were recovered by each analysis method, and these groups are suggestive of the crop-use characteristics and geographical origin of the populations, although not strictly diagnostic. We discuss the relationship between our haplotype data and taxonomic opinions of cannabis, and the implications of organelle DNA haplotyping to forensic investigations of cannabis.

  1. The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

    Science.gov (United States)

    Nadeau, J H; Phillips, S J

    1987-11-01

    Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

  2. Structure analysis of bubble driven flow by time-resolved PIV and POD techniques

    International Nuclear Information System (INIS)

    Kim, Hyun Dong; Yi, Seung Jae; Kim, Jong Wook; Kim, Kyung Chun

    2010-01-01

    In this paper, the recirculation flow motion and turbulence characteristics of liquid flow driven by air bubble stream in a rectangular water tank are studied. The time-resolved Particle Image Velocimetry (PIV) technique is adopted for the quantitative visualization and analysis. 532nm Diode CW laser is used for illumination and orange fluorescent (λex = 540nm, λem = 584nm) particle images are acquired by a 1280X1024 high-speed camera. To obtain clean particle images, 545nm long pass optical filter and an image intensifier are employed and the flow rate of compressed air is 3/min at 0.5MPa. The recirculation and mixing flow field is further investigated by timeresolved Proper Orthogonal Decomposition (POD) analysis technique. It is observed that the large scale recirculation resulting from the interaction between rising bubble stream and side wall is the most dominant flow structure and there are small scale vortical structures moving along with the large scale recirculation flow. It is also verified that the sum of 20 modes of velocity field has about 67.4% of total turbulent energy

  3. Major issues in threat analysis and resolving such problems: an addendum to the GAP analysis

    Directory of Open Access Journals (Sweden)

    T.D. Surasinghe

    2012-04-01

    Full Text Available Identification of regions that warrant conservation attention is a top priority among global environmental concerns. Conventionally, this objective was achieved via recognizing natural landscapes based on the number of IUCN Red Listed species, percentage of endemism and species diversity. A recent innovation in conservation biology is the use of GIS-based threat analysis models to identify key areas of conservation importance. Compared with GAP Analysis, which only identifies biodiversity-rich unprotected lands, threat analysis serves as a rigorous tool in conservation planning which specifically recognizes threats and habitat suitability to different taxa based on a spatially-explicit analysis. Threat analysis is a highly flexible process which involves building up a model with multiple independent (without autocorrelations variables that both positively and negatively affect distribution and population persistence of a concerned species. Parameters include rate of land-use change, population density, population growth rate, land management regimes, protection status, habitat suitability and land stewardship. Threat analysis models can be used to understand the current status of a particular species (or a community and can be used to project future trends about the species under consideration. This publication provides an overview of uses of GIS-based threat analyses in conservation biology and provides insights on the limitations of these models and the directions that should be taken in future.

  4. Timing the formation and assembly of early-type galaxies via spatially resolved stellar populations analysis

    Science.gov (United States)

    Martín-Navarro, Ignacio; Vazdekis, Alexandre; Falcón-Barroso, Jesús; La Barbera, Francesco; Yıldırım, Akın; van de Ven, Glenn

    2018-04-01

    To investigate star formation and assembly processes of massive galaxies, we present here a spatially resolved stellar population analysis of a sample of 45 elliptical galaxies (Es) selected from the Calar Alto Legacy Integral Field Area survey. We find rather flat age and [Mg/Fe] radial gradients, weakly dependent on the effective velocity dispersion of the galaxy within half-light radius. However, our analysis shows that metallicity gradients become steeper with increasing galaxy velocity dispersion. In addition, we have homogeneously compared the stellar population gradients of our sample of Es to a sample of nearby relic galaxies, i.e. local remnants of the high-z population of red nuggets. This comparison indicates that, first, the cores of present-day massive galaxies were likely formed in gas-rich, rapid star formation events at high redshift (z ≳ 2). This led to radial metallicity variations steeper than observed in the local Universe, and positive [Mg/Fe] gradients. Secondly, our analysis also suggests that a later sequence of minor dry mergers, populating the outskirts of early-type galaxies (ETGs), flattened the pristine [Mg/Fe] and metallicity gradients. Finally, we find a tight age-[Mg/Fe] relation, supporting that the duration of the star formation is the main driver of the [Mg/Fe] enhancement in massive ETGs. However, the star formation time-scale alone is not able to fully explain our [Mg/Fe] measurements. Interestingly, our results match the expected effect that a variable stellar initial mass function would have on the [Mg/Fe] ratio.

  5. Free digital image analysis software helps to resolve equivocal scores in HER2 immunohistochemistry.

    Science.gov (United States)

    Helin, Henrik O; Tuominen, Vilppu J; Ylinen, Onni; Helin, Heikki J; Isola, Jorma

    2016-02-01

    Evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) is subject to interobserver variation and lack of reproducibility. Digital image analysis (DIA) has been shown to improve the consistency and accuracy of the evaluation and its use is encouraged in current testing guidelines. We studied whether digital image analysis using a free software application (ImmunoMembrane) can assist in interpreting HER2 IHC in equivocal 2+ cases. We also compared digital photomicrographs with whole-slide images (WSI) as material for ImmunoMembrane DIA. We stained 750 surgical resection specimens of invasive breast cancers immunohistochemically for HER2 and analysed staining with ImmunoMembrane. The ImmunoMembrane DIA scores were compared with the originally responsible pathologists' visual scores, a researcher's visual scores and in situ hybridisation (ISH) results. The originally responsible pathologists reported 9.1 % positive 3+ IHC scores, for the researcher this was 8.4 % and for ImmunoMembrane 9.5 %. Equivocal 2+ scores were 34 % for the pathologists, 43.7 % for the researcher and 10.1 % for ImmunoMembrane. Negative 0/1+ scores were 57.6 % for the pathologists, 46.8 % for the researcher and 80.8 % for ImmunoMembrane. There were six false positive cases, which were classified as 3+ by ImmunoMembrane and negative by ISH. Six cases were false negative defined as 0/1+ by IHC and positive by ISH. ImmunoMembrane DIA using digital photomicrographs and WSI showed almost perfect agreement. In conclusion, digital image analysis by ImmunoMembrane can help to resolve a majority of equivocal 2+ cases in HER2 IHC, which reduces the need for ISH testing.

  6. Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

    Science.gov (United States)

    Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

    2014-03-01

    The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P alkylating agents.

  7. Using Separable Nonnegative Matrix Factorization Techniques for the Analysis of Time-Resolved Raman Spectra

    Science.gov (United States)

    Luce, R.; Hildebrandt, P.; Kuhlmann, U.; Liesen, J.

    2016-09-01

    The key challenge of time-resolved Raman spectroscopy is the identification of the constituent species and the analysis of the kinetics of the underlying reaction network. In this work we present an integral approach that allows for determining both the component spectra and the rate constants simultaneously from a series of vibrational spectra. It is based on an algorithm for non-negative matrix factorization which is applied to the experimental data set following a few pre-processing steps. As a prerequisite for physically unambiguous solutions, each component spectrum must include one vibrational band that does not significantly interfere with vibrational bands of other species. The approach is applied to synthetic "experimental" spectra derived from model systems comprising a set of species with component spectra differing with respect to their degree of spectral interferences and signal-to-noise ratios. In each case, the species involved are connected via monomolecular reaction pathways. The potential and limitations of the approach for recovering the respective rate constants and component spectra are discussed.

  8. Analysis of detection limit to time-resolved coherent anti-Stokes Raman scattering nanoscopy

    International Nuclear Information System (INIS)

    Liu Wei; Liu Shuang-Long; Chen Dan-Ni; Niu Han-Ben

    2014-01-01

    In the implementation of CARS nanoscopy, signal strength decreases with focal volume size decreasing. A crucial problem that remains to be solved is whether the reduced signal generated in the suppressed focal volume can be detected. Here reported is a theoretical analysis of detection limit (DL) to time-resolved CARS (T-CARS) nanoscopy based on our proposed additional probe-beam-induced phonon depletion (APIPD) method for the low concentration samples. In order to acquire a detailed shot-noise limited signal-to-noise (SNR) and the involved parameters to evaluate DL, the T-CARS process is described with full quantum theory to estimate the extreme power density levels of the pump and Stokes beams determined by saturation behavior of coherent phonons, which are both actually on the order of ∼ 10 9 W/cm 2 . When the pump and Stokes intensities reach such values and the total intensity of the excitation beams arrives at a maximum tolerable by most biological samples in a certain suppressed focal volume (40-nm suppressed focal scale in APIPD method), the DL correspondingly varies with exposure time, for example, DL values are 10 3 and 10 2 when exposure times are 20 ms and 200 ms respectively. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  9. Analysis and design of lean direct injection fuel nozzles by eddy resolved turbulence simulation

    Science.gov (United States)

    Ryon, Jason Allen

    Combustion systems in gas turbine engines are subjected to particular scrutiny in regards to the emissions which they produce. Of special interest are the emissions of Oxides of Nitrogen (NOx), which have a direct impact on air quality as well as health aspects. There is a need in the industry for elegant designs for these combustion systems which reduce the formation of NOx. The present study includes an in depth analysis of a state-of-the art prefilming airblast injector which is designed for achieving low NOx. The design has been studied through the use of turbulence resolving simulation to differentiate what is important for the design of this system. The OpenFOAM CFD software, with a Delayed Detached Eddy Simulation (DDES) model recently developed at Iowa State University, is shown to provide a suitable design tool which has been used to accurately predict a variety of parameters important to this combustion system. Of particular interest are the mixing characteristics of the atomizer, which have been studied through a series of CFD simulations including single-phase, multi-species, and multi-phase simulations. Turbulence simulations are validated by comparison to United Technologies Aerospace Systems (UTAS) data with air only. It is shown how DDES is able to capture the downstream mixing of air streams. Finally, a novel atomizer has been designed with these methods which is intended to promote thorough mixing. The CFD mixing characteristics are described and compared to the existing injector.

  10. Factor IX gene haplotypes in Amerindians.

    Science.gov (United States)

    Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

    1997-02-01

    We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

  11. Polymorphism at Expressed DQ and DR Loci in Five Common Equine MHC Haplotypes

    Science.gov (United States)

    Miller, Donald; Tallmadge, Rebecca L.; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A.; Antczak, Douglas F.

    2016-01-01

    The polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common Equine Leukocyte Antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine Bacterial Artificial Chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next Generation Sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse. PMID:27889800

  12. Statistical analysis of time-resolved emission from ensembles of semiconductor quantum dots: interpretations of exponantial decay models

    NARCIS (Netherlands)

    van Driel, A.F.; Nikolaev, I.; Vergeer, P.; Lodahl, P.; Vanmaekelbergh, D.; Vos, Willem L.

    2007-01-01

    We present a statistical analysis of time-resolved spontaneous emission decay curves from ensembles of emitters, such as semiconductor quantum dots, with the aim of interpreting ubiquitous non-single-exponential decay. Contrary to what is widely assumed, the density of excited emitters and the

  13. Metabolic profiling based on two-dimensional J-resolved 1H NMR data and parallel factor analysis

    DEFF Research Database (Denmark)

    Yilmaz, Ali; Nyberg, Nils T; Jaroszewski, Jerzy W.

    2011-01-01

    the intensity variances along the chemical shift axis are taken into account. Here, we describe the use of parallel factor analysis (PARAFAC) as a tool to preprocess a set of two-dimensional J-resolved spectra with the aim of keeping the J-coupling information intact. PARAFAC is a mathematical decomposition......-model was done automatically by evaluating amount of explained variance and core consistency values. Score plots showing the distribution of objects in relation to each other, and loading plots in the form of two-dimensional pseudo-spectra with the same appearance as the original J-resolved spectra...

  14. Y-chromosome STR haplotypes in Somalis

    DEFF Research Database (Denmark)

    Hallenberg, Charlotte; Simonsen, Bo; Sanchez Sanchez, Juan Jose

    2005-01-01

    A total of 201 males from Somalia were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y kit (Promega). A total of 96 different haplotypes were observed and the haplotype diversity was 0.9715. The ......A total of 201 males from Somalia were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y kit (Promega). A total of 96 different haplotypes were observed and the haplotype diversity was 0...

  15. Two families from New England with usher syndrome type IC with distinct haplotypes.

    Science.gov (United States)

    DeAngelis, M M; McGee, T L; Keats, B J; Slim, R; Berson, E L; Dryja, T P

    2001-03-01

    To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction. We compared the haplotype of our patients who were homozygous in the USH1C region with the haplotypes found in previously reported USH1C Acadian families who reside in southwestern Louisiana and from a single family residing in Lebanon. Of 46 unrelated cases of Usher syndrome type I residing in New England, two were homozygous at genetic markers in the USH1C region. Of these, one carried the Acadian USH1C haplotype and had Acadian ancestors (that is, from Nova Scotia) who did not participate in the 1755 migration of Acadians to Louisiana. The second family had a haplotype that proved to be the same as that of a family with USH1C residing in Lebanon. Each of the two families had haplotypes distinct from the other. This is the first report that some patients residing in New England have Usher syndrome type IC. Patients with Usher syndrome type IC can have the Acadian haplotype or the Lebanese haplotype compatible with the idea that at least two independently arising pathogenic mutations have occurred in the yet-to-be identified USH1C gene.

  16. Time-resolved chromatographic analysis and mechanisms in adsorption and catalysis.

    Science.gov (United States)

    Roubani-Kalantzopoulou, Fani

    2009-03-06

    The main object of this review is the study of fundamentals of adsorption and heterogeneous catalysis, a benefit for the understanding of adsorptive and catalytic properties. This work aims to define and record, with the utmost accuracy, the phenomena and the possible reactions. A new methodology for the study of the adsorption is presented, which is a version of the well-known inverse gas chromatography. This reversed-flow inverse gas chromatography (RF-IGC) is technically very simple, and it is combined with a mathematical analysis that gives the possibility for the estimation of various physicochemical parameters related to adsorbent or catalyst characterization, under conditions compatible with the operation of real adsorbents and catalysts. On this base, this methodology has been successfully applied to the study of the impact of air pollutants, volatile organic and/or inorganic, on many solids such as marbles, ceramics, oxide-pigments of works of art, building materials, authentic statues of the Greek Archaeological Museums. Moreover, this methodology proved to be a powerful tool for studying the topography of active sites of heterogeneous surfaces in the nano-scale domain. Thus, some very important local quantities for the surface chemistry have been determined experimentally for many solids including thin films. These physicochemical local quantities (among which adsorption energy and entropy, surface diffusion coefficient, probability density function) have been determined from the experimental pairs of height of extra chromatographic peaks and time by a nonlinear least-squares method, through personal computer programs written in GW BASIC and lately in FORTRAN. Through the time-resolved analysis the surface characterization of the examined materials took place. In addition, the kinetic constants responsible for adsorption/desorption and surface chemical reactions have also been calculated. Thus, important answers have been provided to the following

  17. Development of a software system for spatial resolved trace analysis of high performance materials with SIMS

    International Nuclear Information System (INIS)

    Brunner, Ch. H.

    1997-09-01

    The following work is separated into two distinctly different parts. The first one is dealing with the SIMSScan software project, an application system for secondary ion mass spectrometry. This application system primarily lays down the foundation, for the research activity introduced in the second part of this work. SIMSScan is an application system designed to provide data acquisition routines for different requirements in the field of secondary ion mass spectroscopy. The whole application package is divided into three major sections, each one dealing with specific measurement tasks. Various supporting clients and wizards, providing extended functionality to the main application, build the core of the software. The MassScan as well as the DepthScan module incorporate the SIMS in the direct imaging or stigmatic mode and are featuring the capabilities for mass spectra recording or depth profile analysis. In combination with an image recording facility the DepthScan module features the capability of spatial resolved material analysis - 3D SIMS. The RasterScan module incorporates the SIMS in scanning mode and supports an fiber optical link for optimized data transfer. The primary goal of this work is to introduce the basic ideas behind the implementation of the main application modules and the supporting clients. Furthermore, it is the intention to lay down the foundation for further developments. At the beginning a short introduction into the paradigm of object oriented programming as well as Windows TM programming is given. Besides explaining the basic ideas behind the Doc/View application architecture the focus is mainly shifted to the routines controlling the SIMS hardware and the basic concepts of multithreaded programming. The elementary structures of the view and document objects is discussed in detail only for the MassScan module, because the ideas behind data abstraction and encapsulation are quite similar. The second part introduces the research activities

  18. RFLP's for the human pepsinogen A haplotypes (PGA)

    Energy Technology Data Exchange (ETDEWEB)

    Taggart, R T; Boudi, F B; Bell, G I

    1988-10-11

    PGA 101 is a 1340 bp cDNA clone containing exons 1-9 of the predicted human pepsinogen A coding sequence. Two distinct polymorphisms are detected with EcoRI and Bg1 II. Analysis with these enzymes provides for discrimination of the PGA haplotypes A, B, and C containing three, two and one PGA genes respectively. The PGA complex is located at 11q13. Mendelian inheritance was demonstrated in 20 families.

  19. Quantitative analysis of time-resolved infrared stimulated luminescence in feldspars

    DEFF Research Database (Denmark)

    Pagonis, Vasilis; Ankjærgaard, Christina; Jain, Mayank

    2016-01-01

    Time-resolved infrared-stimulated luminescence (TR-IRSL) from feldspar samples is of importance in the field of luminescence dating, since it provides information on the luminescence mechanism in these materials. In this paper we present new analytical equations which can be used to analyze TR-IR...

  20. A priori analysis of differential diffusion for model development for scale-resolving simulations

    Science.gov (United States)

    Hunger, Franziska; Dietzsch, Felix; Gauding, Michael; Hasse, Christian

    2018-01-01

    The present study analyzes differential diffusion and the mechanisms responsible for it with regard to the turbulent/nonturbulent interface (TNTI) with special focus on model development for scale-resolving simulations. In order to analyze differences between resolved and subfilter phenomena, direct numerical simulation (DNS) data are compared with explicitly filtered data. The DNS database stems from a temporally evolving turbulent plane jet transporting two passive scalars with Schmidt numbers of unity and 0.25 presented by Hunger et al. [F. Hunger et al., J. Fluid Mech. 802, R5 (2016), 10.1017/jfm.2016.471]. The objective of this research is twofold: (i) to compare the position of the turbulent-nonturbulent interface between the original DNS data and the filtered data and (ii) to analyze differential diffusion and the impact of the TNTI with regard to scale resolution in the filtered DNS data. For the latter, differential diffusion quantities are studied, clearly showing the decrease of differential diffusion at the resolved scales with increasing filter width. A transport equation for the scalar differences is evaluated. Finally, the existence of large scalar gradients, gradient alignment, and the diffusive fluxes being the physical mechanisms responsible for the separation of the two scalars are compared between the resolved and subfilter scales.

  1. Sensitivity Analysis and Requirements for Temporally and Spatially Resolved Thermometry Using Neutron Resonance Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Juan Carlos [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barnes, Cris William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mocko, Michael Jeffrey [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zavorka, Lukas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-01-31

    This report is intended to examine the use of neutron resonance spectroscopy (NRS) to make time- dependent and spatially-resolved temperature measurements of materials in extreme conditions. Specifically, the sensitivities of the temperature estimate on neutron-beam and diagnostic parameters is examined. Based on that examination, requirements are set on a pulsed neutron-source and diagnostics to make a meaningful measurement.

  2. Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia

    Science.gov (United States)

    Mórocz, István Akos; Janoos, Firdaus; van Gelderen, Peter; Manor, David; Karni, Avi; Breznitz, Zvia; von Aster, Michael; Kushnir, Tammar; Shalev, Ruth

    2012-01-01

    The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders. PMID:22368322

  3. The performance of phylogenetic algorithms in estimating haplotype genealogies with migration.

    Science.gov (United States)

    Salzburger, Walter; Ewing, Greg B; Von Haeseler, Arndt

    2011-05-01

    Genealogies estimated from haplotypic genetic data play a prominent role in various biological disciplines in general and in phylogenetics, population genetics and phylogeography in particular. Several software packages have specifically been developed for the purpose of reconstructing genealogies from closely related, and hence, highly similar haplotype sequence data. Here, we use simulated data sets to test the performance of traditional phylogenetic algorithms, neighbour-joining, maximum parsimony and maximum likelihood in estimating genealogies from nonrecombining haplotypic genetic data. We demonstrate that these methods are suitable for constructing genealogies from sets of closely related DNA sequences with or without migration. As genealogies based on phylogenetic reconstructions are fully resolved, but not necessarily bifurcating, and without reticulations, these approaches outperform widespread 'network' constructing methods. In our simulations of coalescent scenarios involving panmictic, symmetric and asymmetric migration, we found that phylogenetic reconstruction methods performed well, while the statistical parsimony approach as implemented in TCS performed poorly. Overall, parsimony as implemented in the PHYLIP package performed slightly better than other methods. We further point out that we are not making the case that widespread 'network' constructing methods are bad, but that traditional phylogenetic tree finding methods are applicable to haplotypic data and exhibit reasonable performance with respect to accuracy and robustness. We also discuss some of the problems of converting a tree to a haplotype genealogy, in particular that it is nonunique. © 2011 Blackwell Publishing Ltd.

  4. β-globin haplotypes in normal and hemoglobinopathic individuals from Reconcavo Baiano, State of Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Wellington dos Santos Silva

    2010-01-01

    Full Text Available Five restriction site polymorphisms in the β-globin gene cluster (HincII-5'ε, HindIII-Gγ, HindIII-ªγ, HincII-'ψβ1 and HincII-3''ψβ1 were analyzed in three populations (n = 114 from Reconcavo Baiano, State of Bahia, Brazil. The groups included two urban populations from the towns of Cachoeira and Maragojipe and one rural Afro-descendant population, known as the "quilombo community", from Cachoeira municipality. The number of haplotypes found in the populations ranged from 10 to 13, which indicated higher diversity than in the parental populations. The haplotypes 2 (+----,3(----+,4(-+--+and6(-++-+onthe βA chromosomes were the most common, and two haplotypes, 9 (-++++and 14 (++--+, were found exclusively in the Maragojipe population. The other haplotypes (1, 5, 9, 11, 12, 13, 14 and 16 had lower frequencies. Restriction site analysis and the derived haplotypes indicated homogeneity among the populations. Thirty-two individuals with hemoglobinopathies (17 sickle cell disease, 12 HbSC disease and 3 HbCC disease were also analyzed. The haplotype frequencies of these patients differed significantly from those of the general population. In the sickle cell disease subgroup, the predominant haplotypes were BEN (Benin and CAR (Central African Republic, with frequencies of 52.9% and 32.4%, respectively. The high frequency of the BEN haplotype agreed with the historical origin of the afro-descendant population in the state of Bahia. However, this frequency differed from that of Salvador, the state capital, where the CAR and BEN haplotypes have similar frequencies, probably as a consequence of domestic slave trade and subsequent internal migrations to other regions of Brazil.

  5. Time-Resolved Fluorescent Immunochromatography of Aflatoxin B1 in Soybean Sauce: A Rapid and Sensitive Quantitative Analysis.

    Science.gov (United States)

    Wang, Du; Zhang, Zhaowei; Li, Peiwu; Zhang, Qi; Zhang, Wen

    2016-07-14

    Rapid and quantitative sensing of aflatoxin B1 with high sensitivity and specificity has drawn increased attention of studies investigating soybean sauce. A sensitive and rapid quantitative immunochromatographic sensing method was developed for the detection of aflatoxin B1 based on time-resolved fluorescence. It combines the advantages of time-resolved fluorescent sensing and immunochromatography. The dynamic range of a competitive and portable immunoassay was 0.3-10.0 µg·kg(-1), with a limit of detection (LOD) of 0.1 µg·kg(-1) and recoveries of 87.2%-114.3%, within 10 min. The results showed good correlation (R² > 0.99) between time-resolved fluorescent immunochromatographic strip test and high performance liquid chromatography (HPLC). Soybean sauce samples analyzed using time-resolved fluorescent immunochromatographic strip test revealed that 64.2% of samples contained aflatoxin B1 at levels ranging from 0.31 to 12.5 µg·kg(-1). The strip test is a rapid, sensitive, quantitative, and cost-effective on-site screening technique in food safety analysis.

  6. Analysis and implementation of a space resolving spherical crystal spectrometer for x-ray Thomson scattering experiments.

    Science.gov (United States)

    Harding, E C; Ao, T; Bailey, J E; Loisel, G; Sinars, D B; Geissel, M; Rochau, G A; Smith, I C

    2015-04-01

    The application of a space-resolving spectrometer to X-ray Thomson Scattering (XRTS) experiments has the potential to advance the study of warm dense matter. This has motivated the design of a spherical crystal spectrometer, which is a doubly focusing geometry with an overall high sensitivity and the capability of providing high-resolution, space-resolved spectra. A detailed analysis of the image fluence and crystal throughput in this geometry is carried out and analytical estimates of these quantities are presented. This analysis informed the design of a new spectrometer intended for future XRTS experiments on the Z-machine. The new spectrometer collects 6 keV x-rays with a spherically bent Ge (422) crystal and focuses the collected x-rays onto the Rowland circle. The spectrometer was built and then tested with a foam target. The resulting high-quality spectra prove that a spherical spectrometer is a viable diagnostic for XRTS experiments.

  7. Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

    Science.gov (United States)

    Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

    2017-06-26

    Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

  8. A unified framework for haplotype inference in nuclear families.

    Science.gov (United States)

    Iliadis, Alexandros; Anastassiou, Dimitris; Wang, Xiaodong

    2012-07-01

    Many large genome-wide association studies include nuclear families with more than one child (trio families), allowing for analysis of differences between siblings (sib pair analysis). Statistical power can be increased when haplotypes are used instead of genotypes. Currently, haplotype inference in families with more than one child can be performed either using the familial information or statistical information derived from the population samples but not both. Building on our recently proposed tree-based deterministic framework (TDS) for trio families, we augment its applicability to general nuclear families. We impose a minimum recombinant approach locally and independently on each multiple children family, while resorting to the population-derived information to solve the remaining ambiguities. Thus our framework incorporates all available information (familial and population) in a given study. We demonstrate that using all the constraints in our approach we can have gains in the accuracy as opposed to breaking the multiple children families to separate trios and resorting to a trio inference algorithm or phasing each family in isolation. We believe that our proposed framework could be the method of choice for haplotype inference in studies that include nuclear families with multiple children. Our software (tds2.0) is downloadable from www.ee.columbia.edu/∼anastas/tds. © 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London.

  9. A review of the analysis of complex time-resolved fluorescence anisotropy data

    International Nuclear Information System (INIS)

    Smith, Trevor A; Ghiggino, Kenneth P

    2015-01-01

    Time-resolved fluorescence anisotropy measurements (TRAMs) are widely used to probe the dynamics of the various processes that can lead to the depolarisation of emission following photoselection by polarised excitation. The most commonly investigated of these emission depolarising phenomena is molecular rotational motion, but TRAMs are very useful for determining the kinetics of a host of other processes. In this paper we review several examples for which we have observed in our laboratories initially unexpectedly complex temporal behaviour of the time-resolved fluorescence anisotropy signal from relatively ‘simple’ chemical systems. In certain circumstances the anisotropy (i) decays on timescales when superficially it might be thought it should remain constant, (ii) shows marked ‘dip and rise’ behaviour in its intensity, or (iii) can change sign as the anisotropy evolves in time. Fundamentally simple processes, including molecular rotational motion, energy migration and excited state photophysics, can cause such behaviour. (topical review)

  10. Quantitative analysis of time-resolved infrared stimulated luminescence in feldspars

    DEFF Research Database (Denmark)

    Pagonis, Vasilis; Ankjærgaard, Christina; Jain, Mayank

    2016-01-01

    Time-resolved infrared-stimulated luminescence (TR-IRSL) from feldspar samples is of importance in the field of luminescence dating, since it provides information on the luminescence mechanism in these materials. In this paper we present new analytical equations which can be used to analyze TR-IR....... The equations are applied to experimental TR-IRSL data of natural feldspars, and good agreement is found between experimental and modeling results....

  11. Time resolved analysis of water drainage in porous asphalt concrete using neutron radiography.

    Science.gov (United States)

    Poulikakos, L D; Sedighi Gilani, M; Derome, D; Jerjen, I; Vontobel, P

    2013-07-01

    Porous asphalt as a road surface layer controls aquaplaning as rain water can drain through its highly porous structure. The process of water drainage through this permeable layer is studied using neutron radiography. Time-resolved water configuration and distribution within the porous structure are reported. It is shown that radiography depicts the process of liquid water transport within the complex geometry of porous asphalt, capturing water films, filled dead end pores and water islands. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Endothelial Nitric Oxide Synthase Haplotypes Are Associated with Preeclampsia in Maya Mestizo Women

    Science.gov (United States)

    Díaz-Olguín, Lizbeth; Coral-Vázquez, Ramón Mauricio; Canto-Cetina, Thelma; Canizales-Quinteros, Samuel; Ramírez Regalado, Belem; Fernández, Genny; Canto, Patricia

    2011-01-01

    Preeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms in eNOS or their haplotypes are associated with preeclampsia in Maya mestizo women. A case-control study was performed where 127 preeclamptic patients and 263 controls were included. Genotyped and haplotypes for the -768T→C, intron 4 variants, Glu298Asp of eNOS were determined by PCR and real-time PCR allelic discrimination. Logistic regression analysis with adjustment for age and body mass index (BMI) was used to test for associations between genotype and preeclampsia under recessive, codominant and dominant models. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. Women homozygous for the Asp298 allele showed an association of preeclampsia. In addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298 haplotype was significantly more frequent in preeclamptic patients than in controls (0.143 vs. 0.041, respectively; OR = 3.01; 95% CI = 1.74–5.23; P = 2.9 × 10−4). Despite the Asp298 genotype in a recessive model associated with the presence of preeclampsia in Maya mestizo women, we believe that in this population the -786C-4b-Asp298 haplotype is a better genetic marker. PMID:21897002

  13. Haplotype-based stratification of Huntington's disease.

    Science.gov (United States)

    Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2017-11-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

  14. Estimating haplotype effects for survival data.

    Science.gov (United States)

    Scheike, Thomas H; Martinussen, Torben; Silver, Jeremy D

    2010-09-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplotype effects for survival data. These estimating equations are simple to implement and avoid the use of the EM algorithm, which may be slow in the context of the semiparametric Cox model with incomplete covariate information. These estimating equations also lead to easily computable, direct estimators of standard errors, and thus overcome some of the difficulty in obtaining variance estimators based on the EM algorithm in this setting. We also develop an easily implemented goodness-of-fit procedure for Cox's regression model including haplotype effects. Finally, we apply the procedures presented in this article to investigate possible haplotype effects of the PAF-receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm. © 2009, The International Biometric Society.

  15. Mitochondrial Haplotype Diversity in Zambian Lions: Bridging a Gap in the Biogeography of an Iconic Species.

    Science.gov (United States)

    Curry, Caitlin J; White, Paula A; Derr, James N

    2015-01-01

    Analysis of DNA sequence diversity at the 12S to 16S mitochondrial genes of 165 African lions (Panthera leo) from five main areas in Zambia has uncovered haplotypes which link Southern Africa with East Africa. Phylogenetic analysis suggests Zambia may serve as a bridge connecting the lion populations in southern Africa to eastern Africa, supporting earlier hypotheses that eastern-southern Africa may represent the evolutionary cradle for the species. Overall gene diversity throughout the Zambian lion population was 0.7319 +/- 0.0174 with eight haplotypes found; three haplotypes previously described and the remaining five novel. The addition of these five novel haplotypes, so far only found within Zambia, nearly doubles the number of haplotypes previously reported for any given geographic location of wild lions. However, based on an AMOVA analysis of these haplotypes, there is little to no matrilineal gene flow (Fst = 0.47) when the eastern and western regions of Zambia are considered as two regional sub-populations. Crossover haplotypes (H9, H11, and Z1) appear in both populations as rare in one but common in the other. This pattern is a possible result of the lion mating system in which predominately males disperse, as all individuals with crossover haplotypes were male. The determination and characterization of lion sub-populations, such as done in this study for Zambia, represent a higher-resolution of knowledge regarding both the genetic health and connectivity of lion populations, which can serve to inform conservation and management of this iconic species.

  16. Mitochondrial Haplotype Diversity in Zambian Lions: Bridging a Gap in the Biogeography of an Iconic Species.

    Directory of Open Access Journals (Sweden)

    Caitlin J Curry

    Full Text Available Analysis of DNA sequence diversity at the 12S to 16S mitochondrial genes of 165 African lions (Panthera leo from five main areas in Zambia has uncovered haplotypes which link Southern Africa with East Africa. Phylogenetic analysis suggests Zambia may serve as a bridge connecting the lion populations in southern Africa to eastern Africa, supporting earlier hypotheses that eastern-southern Africa may represent the evolutionary cradle for the species. Overall gene diversity throughout the Zambian lion population was 0.7319 +/- 0.0174 with eight haplotypes found; three haplotypes previously described and the remaining five novel. The addition of these five novel haplotypes, so far only found within Zambia, nearly doubles the number of haplotypes previously reported for any given geographic location of wild lions. However, based on an AMOVA analysis of these haplotypes, there is little to no matrilineal gene flow (Fst = 0.47 when the eastern and western regions of Zambia are considered as two regional sub-populations. Crossover haplotypes (H9, H11, and Z1 appear in both populations as rare in one but common in the other. This pattern is a possible result of the lion mating system in which predominately males disperse, as all individuals with crossover haplotypes were male. The determination and characterization of lion sub-populations, such as done in this study for Zambia, represent a higher-resolution of knowledge regarding both the genetic health and connectivity of lion populations, which can serve to inform conservation and management of this iconic species.

  17. Extended HLA-D region haplotype associated with celiac disease

    International Nuclear Information System (INIS)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II β-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this β-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP β-chain. This celiac disease-associated HLA-DP β-chain gene was flanked by HLA-DP α-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DPα-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP α- and β-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion

  18. Extended HLA-D region haplotype associated with celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  19. Association between β2-adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS.

    Science.gov (United States)

    Tellechea, Mariana L; Muzzio, Damián O; Iglesias Molli, Andrea E; Belli, Susana H; Graffigna, Mabel N; Levalle, Oscar A; Frechtel, Gustavo D; Cerrone, Gloria E

    2013-04-01

    The aim of this study was to explore β2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. Genetic polymorphism analysis. Cross-sectional case-control association study. Medical University Hospital and research laboratory. One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. Haplotype I (CCGG) has a protective role for IR and MS in PCOS. © 2012 Blackwell Publishing Ltd.

  20. Resolve. Version 2.5: Flammable Gas Accident Analysis Tool Acceptance Test Plan and Test Results

    International Nuclear Information System (INIS)

    LAVENDER, J.C.

    2000-01-01

    RESOLVE. Version 2 .5 is designed to quantify the risk and uncertainty of combustion accidents in double-shell tanks (DSTs) and single-shell tanks (SSTs). The purpose of the acceptance testing is to ensure that all of the options and features of the computer code run; to verify that the calculated results are consistent with each other; and to evaluate the effects of the changes to the parameter values on the frequency and consequence trends associated with flammable gas deflagrations or detonations

  1. Direct analysis of Holliday junction resolving enzyme in a DNA origami nanostructure.

    Science.gov (United States)

    Suzuki, Yuki; Endo, Masayuki; Cañas, Cristina; Ayora, Silvia; Alonso, Juan C; Sugiyama, Hiroshi; Takeyasu, Kunio

    2014-06-01

    Holliday junction (HJ) resolution is a fundamental step for completion of homologous recombination. HJ resolving enzymes (resolvases) distort the junction structure upon binding and prior cleavage, raising the possibility that the reactivity of the enzyme can be affected by a particular geometry and topology at the junction. Here, we employed a DNA origami nano-scaffold in which each arm of a HJ was tethered through the base-pair hybridization, allowing us to make the junction core either flexible or inflexible by adjusting the length of the DNA arms. Both flexible and inflexible junctions bound to Bacillus subtilis RecU HJ resolvase, while only the flexible junction was efficiently resolved into two duplexes by this enzyme. This result indicates the importance of the structural malleability of the junction core for the reaction to proceed. Moreover, cleavage preferences of RecU-mediated reaction were addressed by analyzing morphology of the reaction products. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Time-resolved ultraviolet laser-induced breakdown spectroscopy for organic material analysis

    Energy Technology Data Exchange (ETDEWEB)

    Baudelet, Matthieu; Boueri, Myriam [Laboratoire de Spectrometrie Ionique et Moleculaire, Universite Claude Bernard Lyon 1, UMR CNRS 5579, 43, Bd. du 11 Novembre 1918, F-69622 Villeurbanne Cedex (France); Yu Jin [Laboratoire de Spectrometrie Ionique et Moleculaire, Universite Claude Bernard Lyon 1, UMR CNRS 5579, 43, Bd. du 11 Novembre 1918, F-69622 Villeurbanne Cedex (France)], E-mail: jin.yu@lasim.univ-lyon1.fr; Mao, Samuel S; Piscitelli, Vincent; Xianglei, Mao; Russo, Richard E [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2007-12-15

    Ultraviolet pulses (266 nm) delivered by a quadrupled Nd:YAG laser were used to analyze organic samples with laser-induced breakdown spectroscopy (LIBS). We present characteristics of the spectra obtained from organic samples with special attentions on the emissions of organic elements, O and N, and molecular bonds CN. The choice of these atomic or molecular species is justified on one hand, by the importance of these species to specify organic or biological materials; and on the other hand by the possible interferences with ambient air when laser ablation takes place in the atmosphere. Time-resolved LIBS was used to determine the time-evolution of line intensity emitted from these species. We demonstrate different kinetic behaviors corresponding to different origins of emitters: native atomic or molecular species directly vaporized from the sample or those generated through dissociation or recombination due to interaction between laser-induced plasma and air molecules. Our results show the ability of time-resolved UV-LIBS for detection and identification of native atomic or molecular species from an organic sample.

  3. [Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

    Science.gov (United States)

    Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

    2016-05-01

    Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

  4. Spatially resolved chemical analysis of cicada wings using laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS).

    Science.gov (United States)

    Román, Jessica K; Walsh, Callee M; Oh, Junho; Dana, Catherine E; Hong, Sungmin; Jo, Kyoo D; Alleyne, Marianne; Miljkovic, Nenad; Cropek, Donald M

    2018-03-01

    Laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS) is an emerging bioanalytical tool for direct imaging and analysis of biological tissues. Performing ionization in an ambient environment, this technique requires little sample preparation and no additional matrix, and can be performed on natural, uneven surfaces. When combined with optical microscopy, the investigation of biological samples by LAESI allows for spatially resolved compositional analysis. We demonstrate here the applicability of LAESI-IMS for the chemical analysis of thin, desiccated biological samples, specifically Neotibicen pruinosus cicada wings. Positive-ion LAESI-IMS accurate ion-map data was acquired from several wing cells and superimposed onto optical images allowing for compositional comparisons across areas of the wing. Various putative chemical identifications were made indicating the presence of hydrocarbons, lipids/esters, amines/amides, and sulfonated/phosphorylated compounds. With the spatial resolution capability, surprising chemical distribution patterns were observed across the cicada wing, which may assist in correlating trends in surface properties with chemical distribution. Observed ions were either (1) equally dispersed across the wing, (2) more concentrated closer to the body of the insect (proximal end), or (3) more concentrated toward the tip of the wing (distal end). These findings demonstrate LAESI-IMS as a tool for the acquisition of spatially resolved chemical information from fragile, dried insect wings. This LAESI-IMS technique has important implications for the study of functional biomaterials, where understanding the correlation between chemical composition, physical structure, and biological function is critical. Graphical abstract Positive-ion laser-ablation electrospray ionization mass spectrometry coupled with optical imaging provides a powerful tool for the spatially resolved chemical analysis of cicada wings.

  5. Unique haplotypes of cacao trees as revealed by trnH-psbA chloroplast DNA

    Directory of Open Access Journals (Sweden)

    Nidia Gutiérrez-López

    2016-04-01

    Full Text Available Cacao trees have been cultivated in Mesoamerica for at least 4,000 years. In this study, we analyzed sequence variation in the chloroplast DNA trnH-psbA intergenic spacer from 28 cacao trees from different farms in the Soconusco region in southern Mexico. Genetic relationships were established by two analysis approaches based on geographic origin (five populations and genetic origin (based on a previous study. We identified six polymorphic sites, including five insertion/deletion (indels types and one transversion. The overall nucleotide diversity was low for both approaches (geographic = 0.0032 and genetic = 0.0038. Conversely, we obtained moderate to high haplotype diversity (0.66 and 0.80 with 10 and 12 haplotypes, respectively. The common haplotype (H1 for both networks included cacao trees from all geographic locations (geographic approach and four genetic groups (genetic approach. This common haplotype (ancient derived a set of intermediate haplotypes and singletons interconnected by one or two mutational steps, which suggested directional selection and event purification from the expansion of narrow populations. Cacao trees from Soconusco region were grouped into one cluster without any evidence of subclustering based on AMOVA (FST = 0 and SAMOVA (FST = 0.04393 results. One population (Mazatán showed a high haplotype frequency; thus, this population could be considered an important reservoir of genetic material. The indels located in the trnH-psbA intergenic spacer of cacao trees could be useful as markers for the development of DNA barcoding.

  6. VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

    Energy Technology Data Exchange (ETDEWEB)

    Martinson, J.J.; Clegg, J.B.; Boyce, A.J. [Univ. of Oxford (United Kingdom)

    1994-09-01

    The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.

  7. Depth profile analysis of polymerized fluorine compound on photo-resist film with angle-resolved XPS

    International Nuclear Information System (INIS)

    Iijima, Yoshitoki; Kubota, Toshio; Oinaka, Syuhei

    2013-01-01

    Angle-resolved XPS (ARXPS) is an observation technique which is very effective in chemical depth analysis method less than photoelectron detected depth. For the analysis of depth profile, several analysis methods have been proposed to calculate the depth profile using the ARXPS method. The present report is the measurements of depth profile of the fluorine in a fluorine-containing photo-resist film using the ARXPS method and the depth profile of concentration have been successfully determined using the ARCtick 1.0 software. It has been observed that thickness of the fluorocarbon enriched surface layer of the photo-resist was 2.7 nm, and so that the convert of the ARXPS data from the angle profile to the depth profile was proved to be useful analysis method for the ultrathin layer depth. (author)

  8. Analysis of electronic models for solar cells including energy resolved defect densities

    Energy Technology Data Exchange (ETDEWEB)

    Glitzky, Annegret

    2010-07-01

    We introduce an electronic model for solar cells including energy resolved defect densities. The resulting drift-diffusion model corresponds to a generalized van Roosbroeck system with additional source terms coupled with ODEs containing space and energy as parameters for all defect densities. The system has to be considered in heterostructures and with mixed boundary conditions from device simulation. We give a weak formulation of the problem. If the boundary data and the sources are compatible with thermodynamic equilibrium the free energy along solutions decays monotonously. In other cases it may be increasing, but we estimate its growth. We establish boundedness and uniqueness results and prove the existence of a weak solution. This is done by considering a regularized problem, showing its solvability and the boundedness of its solutions independent of the regularization level. (orig.)

  9. Grain-resolved analysis of localized deformation in nickel-titanium wire under tensile load.

    Science.gov (United States)

    Sedmák, P; Pilch, J; Heller, L; Kopeček, J; Wright, J; Sedlák, P; Frost, M; Šittner, P

    2016-08-05

    The stress-induced martensitic transformation in tensioned nickel-titanium shape-memory alloys proceeds by propagation of macroscopic fronts of localized deformation. We used three-dimensional synchrotron x-ray diffraction to image at micrometer-scale resolution the grain-resolved elastic strains and stresses in austenite around one such front in a prestrained nickel-titanium wire. We found that the local stresses in austenite grains are modified ahead of the nose cone-shaped buried interface where the martensitic transformation begins. Elevated shear stresses at the cone interface explain why the martensitic transformation proceeds in a localized manner. We established the crossover from stresses in individual grains to a continuum macroscopic internal stress field in the wire and rationalized the experimentally observed internal stress field and the topology of the macroscopic front by means of finite element simulations of the localized deformation. Copyright © 2016, American Association for the Advancement of Science.

  10. Quantitative analysis of time-resolved infrared stimulated luminescence in feldspars

    Energy Technology Data Exchange (ETDEWEB)

    Pagonis, Vasilis, E-mail: vpagonis@mcdaniel.edu [McDaniel College, Physics Department, Westminster, MD 21157 (United States); Ankjærgaard, Christina [Soil Geography and Landscape Group & Netherlands Centre for Luminescence dating, Wageningen University, PO Box 47, 6700 AA Wageningen (Netherlands); Jain, Mayank [Center for Nuclear Technologies, Technical University of Denmark, DTU Risø Campus, Roskilde (Denmark); Chithambo, Makaiko L. [Department of Physics and Electronics, Rhodes University, PO BOX 94, Grahamstown 6140 (South Africa)

    2016-09-15

    Time-resolved infrared-stimulated luminescence (TR-IRSL) from feldspar samples is of importance in the field of luminescence dating, since it provides information on the luminescence mechanism in these materials. In this paper we present new analytical equations which can be used to analyze TR-IRSL signals, both during and after short infrared stimulation pulses. The equations are developed using a recently proposed kinetic model, which describes localized electronic recombination via tunneling between trapped electrons and recombination centers in luminescent materials. Recombination is assumed to take place from the excited state of the trapped electron to the nearest-neighbor center within a random distribution of luminescence recombination centers. Different possibilities are examined within the model, depending on the relative importance of electron de-excitation and recombination. The equations are applied to experimental TR-IRSL data of natural feldspars, and good agreement is found between experimental and modeling results.

  11. MCP1 haplotypes associated with protection from pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Owusu-Dabo Ellis

    2011-04-01

    Full Text Available Abstract Background The monocyte chemoattractant protein 1 (MCP-1 is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. Results A 14 base-pair deletion in the first MCP1 intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected = 0.00098. Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal = 0.00002; adjusted Pglobal = 0.0028. In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006. The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB. Conclusions In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the MCP1 -362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91. Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the

  12. Association mapping and haplotype analysis of a 3.1-Mb genomic region involved in Fusarium head blight resistance on wheat chromosome 3BS.

    Directory of Open Access Journals (Sweden)

    Chenyang Hao

    Full Text Available A previous study provided an in-depth understanding of molecular population genetics of European and Asian wheat gene pools using a sequenced 3.1-Mb contig (ctg954 on chromosome 3BS. This region is believed to carry the Fhb1 gene for response to Fusarium head blight. In this study, 266 wheat accessions were evaluated in three environments for Type II FHB response based on the single floret inoculation method. Hierarchical clustering (UPGMA based on a Manhattan dissimilarity matrix divided the accessions into eight groups according to five FHB-related traits which have a high correlation between them; Group VIII comprised six accessions with FHB response levels similar to variety Sumai 3. Based on the compressed mixed linear model (MLM, association analysis between five FHB-related traits and 42 molecular markers along the 3.1-Mb region revealed 12 significant association signals at a threshold of P0.1 and P0.05 within each HapB at r(2>0.1 and P<0.001 showed significant differences between the Hap carried by FHB resistant resources, such as Sumai 3 and Wangshuibai, and susceptible genotypes in HapB3 and HapB6. These results suggest that Fhb1 is located within HapB6, with the possibility that another gene is located at or near HapB3. SSR markers and Haps detected in this study will be helpful in further understanding the genetic basis of FHB resistance, and provide useful information for marker-assisted selection of Fhb1 in wheat breeding.

  13. The effect of genealogy-based haplotypes on genomic prediction

    DEFF Research Database (Denmark)

    Edriss, Vahid; Fernando, Rohan L.; Su, Guosheng

    2013-01-01

    on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. Methods A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using...... local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (pi) of the haplotype covariates had zero effect......, i.e. a Bayesian mixture method. Results About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some...

  14. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population.

    Science.gov (United States)

    Fukushima-Uesaka, Hiromi; Saito, Yoshiro; Watanabe, Hidemi; Shiseki, Kisho; Saeki, Mayumi; Nakamura, Takahiro; Kurose, Kouichi; Sai, Kimie; Komamura, Kazuo; Ueno, Kazuyuki; Kamakura, Shiro; Kitakaze, Masafumi; Hanai, Sotaro; Nakajima, Toshiharu; Matsumoto, Kenji; Saito, Hirohisa; Goto, Yu-ichi; Kimura, Hideo; Katoh, Masaaki; Sugai, Kenji; Minami, Narihiro; Shirao, Kuniaki; Tamura, Tomohide; Yamamoto, Noboru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Kitamura, Yutaka; Kamatani, Naoyuki; Ozawa, Shogo; Sawada, Jun-ichi

    2004-01-01

    In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A4 in a Japanese population, the distal enhancer and proximal promoter regions, all exons, and the surrounding introns were sequenced from genomic DNA of 416 Japanese subjects. We found 24 SNPs, including 17 novel ones: two in the distal enhancer, four in the proximal promoter, one in the 5'-untranslated region (UTR), seven in the introns, and three in the 3'-UTR. The most common SNP was c.1026+12G>A (IVS10+12G>A), with a 0.249 frequency. Four non-synonymous SNPs, c.554C>G (p.T185S, CYP3A4(*)16), c.830_831insA (p.E277fsX8, (*)6), c.878T>C (p.L293P, (*)18), and c.1088 C>T (p.T363M, (*)11) were found with frequencies of 0.014, 0.001, 0.028, and 0.002, respectively. No SNP was found in the known nuclear transcriptional factor-binding sites in the enhancer and promoter regions. Using these 24 SNPs, 16 haplotypes were unambiguously identified, and nine haplotypes were inferred by aid of an expectation-maximization-based program. In addition, using data from 186 subjects enabled a close linkage to be found between CYP3A4 and CYP3A5 SNPs, especially among the SNPs at c.1026+12 in CYP3A4 and c.219-237 (IVS3-237, a key SNP site for CYP3A5(*)3), c.865+77 (IVS9+77) and c.1523 in CYP3A5. This result suggested that CYP3A4 and CYP3A5 are within the same gene block. Haplotype analysis between CYP3A4 and CYP3A5 revealed several major haplotype combinations in the CYP3A4-CYP3A5 block. Our findings provide fundamental and useful information for genotyping CYP3A4 (and CYP3A5) in the Japanese, and probably Asian populations. Copyright 2003 Wiley-Liss, Inc.

  15. Network theory inspired analysis of time-resolved expression data reveals key players guiding P. patens stem cell development.

    Science.gov (United States)

    Busch, Hauke; Boerries, Melanie; Bao, Jie; Hanke, Sebastian T; Hiss, Manuel; Tiko, Theodhor; Rensing, Stefan A

    2013-01-01

    Transcription factors (TFs) often trigger developmental decisions, yet, their transcripts are often only moderately regulated and thus not easily detected by conventional statistics on expression data. Here we present a method that allows to determine such genes based on trajectory analysis of time-resolved transcriptome data. As a proof of principle, we have analysed apical stem cells of filamentous moss (P. patens) protonemata that develop from leaflets upon their detachment from the plant. By our novel correlation analysis of the post detachment transcriptome kinetics we predict five out of 1,058 TFs to be involved in the signaling leading to the establishment of pluripotency. Among the predicted regulators is the basic helix loop helix TF PpRSL1, which we show to be involved in the establishment of apical stem cells in P. patens. Our methodology is expected to aid analysis of key players of developmental decisions in complex plant and animal systems.

  16. Monthly and spatially resolved black carbon emission inventory of India: uncertainty analysis

    Directory of Open Access Journals (Sweden)

    U. Paliwal

    2016-10-01

    Full Text Available Black carbon (BC emissions from India for the year 2011 are estimated to be 901.11 ± 151.56 Gg yr−1 based on a new ground-up, GIS-based inventory. The grid-based, spatially resolved emission inventory includes, in addition to conventional sources, emissions from kerosene lamps, forest fires, diesel-powered irrigation pumps and electricity generators at mobile towers. The emissions have been estimated at district level and were spatially distributed onto grids at a resolution of 40 × 40 km2. The uncertainty in emissions has been estimated using a Monte Carlo simulation by considering the variability in activity data and emission factors. Monthly variation of BC emissions has also been estimated to account for the seasonal variability. To the total BC emissions, domestic fuels contributed most significantly (47 %, followed by industry (22 %, transport (17 %, open burning (12 % and others (2 %. The spatial and seasonal resolution of the inventory will be useful for modeling BC transport in the atmosphere for air quality, global warming and other process-level studies that require greater temporal resolution than traditional inventories.

  17. Geometrical Patterning of Super-Hydrophobic Biosensing Transistors Enables Space and Time Resolved Analysis of Biological Mixtures

    KAUST Repository

    Gentile, Francesco

    2016-01-12

    PEDOT:PSS is a conductive polymer that can be integrated into last generation Organic Electrochemical Transistor (OECT) devices for biological inspection, identification and analysis. While a variety of reports in literature demonstrated the chemical and biological sensitivity of these devices, still their ability in resolving complex mixtures remains controversial. Similar OECT devices display good time dynamics behavior but lack spatial resolution. In this work, we integrated PEDOT:PSS with patterns of super-hydrophobic pillars in which a finite number of those pillars is independently controlled for site-selective measurement of a solution. We obtained a multifunctional, hierarchical OECT device that bridges the micro- to the nano-scales for specific, combined time and space resolved analysis of the sample. Due to super-hydrophobic surface properties, the biological species in the drop are driven by convection, diffusion, and the externally applied electric field: the balance/unbalance between these forces will cause the molecules to be transported differently within its volume depending on particle size thus realizing a size-selective separation. Within this framework, the separation and identification of two different molecules, namely Cetyl Trimethyl Ammonium Bromid (CTAB) and adrenaline, in a biological mixture have been demonstrated, showing that geometrical control at the micro-nano scale impart unprecedented selectivity to the devices.

  18. Geometrical Patterning of Super-Hydrophobic Biosensing Transistors Enables Space and Time Resolved Analysis of Biological Mixtures

    KAUST Repository

    Gentile, Francesco; Ferrara, Lorenzo; Villani, Marco; Bettelli, Manuele; Iannotta, Salvatore; Zappettini, Andrea; Cesarelli, Mario; Di Fabrizio, Enzo M.; Coppedè , Nicola

    2016-01-01

    PEDOT:PSS is a conductive polymer that can be integrated into last generation Organic Electrochemical Transistor (OECT) devices for biological inspection, identification and analysis. While a variety of reports in literature demonstrated the chemical and biological sensitivity of these devices, still their ability in resolving complex mixtures remains controversial. Similar OECT devices display good time dynamics behavior but lack spatial resolution. In this work, we integrated PEDOT:PSS with patterns of super-hydrophobic pillars in which a finite number of those pillars is independently controlled for site-selective measurement of a solution. We obtained a multifunctional, hierarchical OECT device that bridges the micro- to the nano-scales for specific, combined time and space resolved analysis of the sample. Due to super-hydrophobic surface properties, the biological species in the drop are driven by convection, diffusion, and the externally applied electric field: the balance/unbalance between these forces will cause the molecules to be transported differently within its volume depending on particle size thus realizing a size-selective separation. Within this framework, the separation and identification of two different molecules, namely Cetyl Trimethyl Ammonium Bromid (CTAB) and adrenaline, in a biological mixture have been demonstrated, showing that geometrical control at the micro-nano scale impart unprecedented selectivity to the devices.

  19. A haplotype specific to North European wheat (Triticum aestivum L.)

    Czech Academy of Sciences Publication Activity Database

    Tsombalova, J.; Karafiátová, Miroslava; Vrána, Jan; Kubaláková, Marie; Peusa, H.; Jakobson, I.; Jarve, M.; Valárik, Miroslav; Doležel, Jaroslav; Jarve, K.

    2017-01-01

    Roč. 64, č. 4 (2017), s. 653-664 ISSN 0925-9864 R&D Projects: GA MŠk(CZ) LO1204; GA ČR(CZ) GA14-07164S Institutional support: RVO:61389030 Keywords : bread wheat * genetic diversity * polyploid wheat * introgression lines * molecular analysis * tetraploid wheat * hexaploid wheat * powdery mildew * spelta l. * map * Common wheat * Triticum aestivum L * Spelt * Triticum spelta L * Chromosome 4A * Zero alleles * Haplotype * Linkage disequilibrium Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 1.294, year: 2016

  20. A Haplotype Information Theory Method Reveals Genes of Evolutionary Interest in European vs. Asian Pigs.

    Science.gov (United States)

    Hudson, Nicholas J; Naval-Sánchez, Marina; Porto-Neto, Laercio; Pérez-Enciso, Miguel; Reverter, Antonio

    2018-06-05

    Asian and European wild boars were independently domesticated ca. 10,000 years ago. Since the 17th century, Chinese breeds have been imported to Europe to improve the genetics of European animals by introgression of favourable alleles, resulting in a complex mosaic of haplotypes. To interrogate the structure of these haplotypes further, we have run a new haplotype segregation analysis based on information theory, namely compression efficiency (CE). We applied the approach to sequence data from individuals from each phylogeographic region (n = 23 from Asia and Europe) including a number of major pig breeds. Our genome-wide CE is able to discriminate the breeds in a manner reflecting phylogeography. Furthermore, 24,956 non-overlapping sliding windows (each comprising 1,000 consecutive SNP) were quantified for extent of haplotype sharing within and between Asia and Europe. The genome-wide distribution of extent of haplotype sharing was quite different between groups. Unlike European pigs, Asian pigs haplotype sharing approximates a normal distribution. In line with this, we found the European breeds possessed a number of genomic windows of dramatically higher haplotype sharing than the Asian breeds. Our CE analysis of sliding windows capture some of the genomic regions reported to contain signatures of selection in domestic pigs. Prominent among these regions, we highlight the role of a gene encoding the mitochondrial enzyme LACTB which has been associated with obesity, and the gene encoding MYOG a fundamental transcriptional regulator of myogenesis. The origin of these regions likely reflects either a population bottleneck in European animals, or selective targets on commercial phenotypes reducing allelic diversity in particular genes and/or regulatory regions.

  1. Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus.

    Directory of Open Access Journals (Sweden)

    Chul-Woo Pyo

    Full Text Available The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.

  2. A comprehensive literature review of haplotyping software and methods for use with unrelated individuals

    Directory of Open Access Journals (Sweden)

    Salem Rany M

    2005-03-01

    Full Text Available Abstract Interest in the assignment and frequency analysis of haplotypes in samples of unrelated individuals has increased immeasurably as a result of the emphasis placed on haplotype analyses by, for example, the International HapMap Project and related initiatives. Although there are many available computer programs for haplotype analysis applicable to samples of unrelated individuals, many of these programs have limitations and/or very specific uses. In this paper, the key features of available haplotype analysis software for use with unrelated individuals, as well as pooled DNA samples from unrelated individuals, are summarised. Programs for haplotype analysis were identified through keyword searches on PUBMED and various internet search engines, a review of citations from retrieved papers and personal communications, up to June 2004. Priority was given to functioning computer programs, rather than theoretical models and methods. The available software was considered in light of a number of factors: the algorithm(s used, algorithm accuracy, assumptions, the accommodation of genotyping error, implementation of hypothesis testing, handling of missing data, software characteristics and web-based implementations. Review papers comparing specific methods and programs are also summarised. Forty-six haplotyping programs were identified and reviewed. The programs were divided into two groups: those designed for individual genotype data (a total of 43 programs and those designed for use with pooled DNA samples (a total of three programs. The accuracy of programs using various criteria are assessed and the programs are categorised and discussed in light of: algorithm and method, accuracy, assumptions, genotyping error, hypothesis testing, missing data, software characteristics and web implementation. Many available programs have limitations (eg some cannot accommodate missing data and/or are designed with specific tasks in mind (eg estimating

  3. Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

    Science.gov (United States)

    Huang, Chien-Lin; Hsu, Nien-Sheng

    2016-04-01

    This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

  4. Space-resolved analysis of trace elements in fresh vegetables using ultraviolet nanosecond laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Juve, Vincent; Portelli, Richard; Boueri, Myriam; Baudelet, Matthieu; Yu Jin

    2008-01-01

    Laser-induced breakdown spectroscopy (LIBS) has been applied to analyze trace elements contained in fresh vegetables. A quadrupled Nd:YAG laser is used in the experiments for ablation. Analyzed samples come from local markets and represent frequently consumed vegetables. For a typical root vegetable, such as potato, spectral analysis of the plasma emission reveals more than 400 lines emitted by 27 elements and 2 molecules, C 2 and CN. Among these species, one can find trace as well as ultra-trace elements. A space-resolved analysis of several trace elements with strong emissions is then applied to typical root, stem and fruit vegetables. The results from this study demonstrate the potential of an interesting tool for botanical and agricultural studies as well for food quality/safety and environment pollution assessment and control

  5. Time-resolved x-ray diffraction analysis of the experimental dehydration of serpentine at high pressure

    International Nuclear Information System (INIS)

    Inoue, Toru; Yoshimi, Isamu; Yamada, Akihiro; Kikegawa, Takumi

    2009-01-01

    Time-resolved, in situ X-ray diffraction analysis was used to determine the dehydration rate and kinetics of serpentine during experimental dehydration at high pressures. The capsule used comprises a diamond sleeve fitted with Au or Pt lids in order to provide high-quality, time-resolved X-ray diffraction data. Antigorite quickly dehydrated to enstatite + forsterite + fluid within 2 h at 650degC below ∼6 GPa. Avrami modeling of the results and SEM observations of the partially dehydrated sample revealed that the nucleation rate was quite high for enstatite but low for forsterite, showing incubation periods of ∼10 min before appearing. The crystallization of these minerals is controlled largely by the composition of the fluid generated from serpentine dehydration. The dehydration boundary determined below 6 GPa in the present study is consistent with the results of previous phase equilibrium studies. This study indicates that serpentine in a subducting slab dehydrates rapidly below 6 GPa when the slab intersects the dehydration boundary conditions. (author)

  6. Usefulness of component resolved analysis of cat allergy in routine clinical practice.

    Science.gov (United States)

    Eder, Katharina; Becker, Sven; San Nicoló, Marion; Berghaus, Alexander; Gröger, Moritz

    2016-01-01

    Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future

  7. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

    Science.gov (United States)

    Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

    2012-01-01

    Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

  8. Asteroid (21) Lutetia: Disk-resolved photometric analysis of Baetica region

    Science.gov (United States)

    Hasselmann, P. H.; Barucci, M. A.; Fornasier, S.; Leyrat, C.; Carvano, J. M.; Lazzaro, D.; Sierks, H.

    2016-03-01

    (21) Lutetia has been visited by Rosetta mission on July 2010 and observed with a phase angle ranging from 0.15° to 156.8°. The Baetica region, located at the north pole has been extensively observed by OSIRIS cameras system. Baetica encompass a region called North Pole Crater Cluster (NPCC), shows a cluster of superposed craters which presents signs of variegation at the small phase angle images. For studying the location, we used 187 images distributed throughout 14 filter recorded by the NAC (Narrow Angle Camera) and WAC (Wide Angle Camera) of the OSIRIS system on-board Rosetta taken during the fly-by. Then, we photometrically modeled the region using Minnaert disk-function and Akimov phase function to obtain a resolved spectral slope map at phase angles of 5 ° and 20 ° . We observed a dichotomy between Gallicum and Danuvius-Sarnus Labes in the NPCC, but no significant phase reddening (- 0.04 ± 0.045 % μm-1deg-1). In the next step, we applied the Hapke (Hapke, B. [2008]. Icarus 195, 918-926; Hapke, B. [2012]. Theory of Reflectance and Emittance Spectroscopy, second ed. Cambridge University Press) model for the NAC F82+F22 (649.2 nm), WAC F13 (375 nm) and WAC F17 (631.6 nm) and we obtained normal albedo maps and Hapke parameter maps for NAC F82+F22. On Baetica, at 649.2 nm, the geometric albedo is 0.205 ± 0.005 , the average single-scattering albedo is 0.181 ± 0.005 , the average asymmetric factor is - 0.342 ± 0.003 , the average shadow-hiding opposition effect amplitude and width are 0.824 ± 0.002 and 0.040 ± 0.0007 , the average roughness slope is 11.45 ° ± 3 ° and the average porosity is 0.85 ± 0.002 . We are unable to confirm the presence of coherent-backscattering mechanism. In the NPCC, the normal albedo variegation among the craters walls reach 8% brighter for Gallicum Labes and 2% fainter for Danuvius Labes. The Hapke parameter maps also show a dichotomy at the opposition effect coefficients, single-scattering albedo and asymmetric factor

  9. Deriving Quantitative Crystallographic Information from the Wavelength-Resolved Neutron Transmission Analysis Performed in Imaging Mode

    Directory of Open Access Journals (Sweden)

    Hirotaka Sato

    2017-12-01

    Full Text Available Current status of Bragg-edge/dip neutron transmission analysis/imaging methods is presented. The method can visualize real-space distributions of bulk crystallographic information in a crystalline material over a large area (~10 cm with high spatial resolution (~100 μm. Furthermore, by using suitable spectrum analysis methods for wavelength-dependent neutron transmission data, quantitative visualization of the crystallographic information can be achieved. For example, crystallographic texture imaging, crystallite size imaging and crystalline phase imaging with texture/extinction corrections are carried out by the Rietveld-type (wide wavelength bandwidth profile fitting analysis code, RITS (Rietveld Imaging of Transmission Spectra. By using the single Bragg-edge analysis mode of RITS, evaluations of crystal lattice plane spacing (d-spacing relating to macro-strain and d-spacing distribution’s FWHM (full width at half maximum relating to micro-strain can be achieved. Macro-strain tomography is performed by a new conceptual CT (computed tomography image reconstruction algorithm, the tensor CT method. Crystalline grains and their orientations are visualized by a fast determination method of grain orientation for Bragg-dip neutron transmission spectrum. In this paper, these imaging examples with the spectrum analysis methods and the reliabilities evaluated by optical/electron microscope and X-ray/neutron diffraction, are presented. In addition, the status at compact accelerator driven pulsed neutron sources is also presented.

  10. [Construction of haplotype and haplotype block based on tag single nucleotide polymorphisms and their applications in association studies].

    Science.gov (United States)

    Gu, Ming-liang; Chu, Jia-you

    2007-12-01

    Human genome has structures of haplotype and haplotype block which provide valuable information on human evolutionary history and may lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to complex diseases. Haplotype block can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of ptag SNPsq can be used to distinguish a large fraction of the haplotypes. These tag SNPs can be potentially useful for construction of haplotype and haplotype block, and association studies in complex diseases. There are two general classes of methods to construct haplotype and haplotype blocks based on genotypes on large pedigrees and statistical algorithms respectively. The author evaluate several construction methods to assess the power of different association tests with a variety of disease models and block-partitioning criteria. The advantages, limitations and applications of each method and the application in the association studies are discussed equitably. With the completion of the HapMap and development of statistical algorithms for addressing haplotype reconstruction, ideas of construction of haplotype based on combination of mathematics, physics, and computer science etc will have profound impacts on population genetics, location and cloning for susceptible genes in complex diseases, and related domain with life science etc.

  11. Research Update: Spatially resolved mapping of electronic structure on atomic level by multivariate statistical analysis

    International Nuclear Information System (INIS)

    Belianinov, Alex; Ganesh, Panchapakesan; Lin, Wenzhi; Jesse, Stephen; Pan, Minghu; Kalinin, Sergei V.; Sales, Brian C.; Sefat, Athena S.

    2014-01-01

    Atomic level spatial variability of electronic structure in Fe-based superconductor FeTe 0.55 Se 0.45 (T c = 15 K) is explored using current-imaging tunneling-spectroscopy. Multivariate statistical analysis of the data differentiates regions of dissimilar electronic behavior that can be identified with the segregation of chalcogen atoms, as well as boundaries between terminations and near neighbor interactions. Subsequent clustering analysis allows identification of the spatial localization of these dissimilar regions. Similar statistical analysis of modeled calculated density of states of chemically inhomogeneous FeTe 1−x Se x structures further confirms that the two types of chalcogens, i.e., Te and Se, can be identified by their electronic signature and differentiated by their local chemical environment. This approach allows detailed chemical discrimination of the scanning tunneling microscopy data including separation of atomic identities, proximity, and local configuration effects and can be universally applicable to chemically and electronically inhomogeneous surfaces

  12. Mixture analysis by long-range J-resolved 2D NMR

    International Nuclear Information System (INIS)

    Ha, S.T.K.; Lee, R.W.K.; Wilkins, C.L.

    1987-01-01

    In most spectroscopic qualitative analyses chromatographic separations are done before identification. Unfortunately, this general approach has suffered from a number of shortcomings. Off-line chromatographic separation followed by spectroscopic analysis is time consuming and inefficient and on-line analysis suffers from mismatch of the material flow requirements between chromatographic columns and spectroscopic instruments. An alternative mixture identification procedure solely based upon use of edited 13 C NMR spectra and a 13 C NMR chemical shift data base is reported. This approach has been demonstrated in the analyses of several mixtures, including a mixture of amino acids and some isomers. In all cases, identifications of components of these mixtures are successful

  13. PyLDM - An open source package for lifetime density analysis of time-resolved spectroscopic data.

    Directory of Open Access Journals (Sweden)

    Gabriel F Dorlhiac

    2017-05-01

    Full Text Available Ultrafast spectroscopy offers temporal resolution for probing processes in the femto- and picosecond regimes. This has allowed for investigation of energy and charge transfer in numerous photoactive compounds and complexes. However, analysis of the resultant data can be complicated, particularly in more complex biological systems, such as photosystems. Historically, the dual approach of global analysis and target modelling has been used to elucidate kinetic descriptions of the system, and the identity of transient species respectively. With regards to the former, the technique of lifetime density analysis (LDA offers an appealing alternative. While global analysis approximates the data to the sum of a small number of exponential decays, typically on the order of 2-4, LDA uses a semi-continuous distribution of 100 lifetimes. This allows for the elucidation of lifetime distributions, which may be expected from investigation of complex systems with many chromophores, as opposed to averages. Furthermore, the inherent assumption of linear combinations of decays in global analysis means the technique is unable to describe dynamic motion, a process which is resolvable with LDA. The technique was introduced to the field of photosynthesis over a decade ago by the Holzwarth group. The analysis has been demonstrated to be an important tool to evaluate complex dynamics such as photosynthetic energy transfer, and complements traditional global and target analysis techniques. Although theory has been well described, no open source code has so far been available to perform lifetime density analysis. Therefore, we introduce a python (2.7 based package, PyLDM, to address this need. We furthermore provide a direct comparison of the capabilities of LDA with those of the more familiar global analysis, as well as providing a number of statistical techniques for dealing with the regularization of noisy data.

  14. RAPID COMMUNICATION Time-resolved measurements with a vortex flowmeter in a pulsating turbulent flow using wavelet analysis

    Science.gov (United States)

    Laurantzon, F.; Örlü, R.; Segalini, A.; Alfredsson, P. H.

    2010-12-01

    Vortex flowmeters are commonly employed in technical applications and are obtainable in a variety of commercially available types. However their robustness and accuracy can easily be impaired by environmental conditions, such as inflow disturbances and/or pulsating conditions. Various post-processing techniques of the vortex signal have been used, but all of these methods are so far targeted on obtaining an improved estimate of the time-averaged bulk velocity. Here, on the other hand, we propose, based on wavelet analysis, a straightforward way to utilize the signal from a vortex shedder to extract the time-resolved and thereby the phase-averaged velocity under pulsatile flow conditions. The method was verified with hot-wire and laser Doppler velocimetry measurements.

  15. Statistical analysis of time-resolved emission from ensembles of semiconductor quantum dots: Interpretation of exponential decay models

    DEFF Research Database (Denmark)

    Van Driel, A.F.; Nikolaev, I.S.; Vergeer, P.

    2007-01-01

    We present a statistical analysis of time-resolved spontaneous emission decay curves from ensembles of emitters, such as semiconductor quantum dots, with the aim of interpreting ubiquitous non-single-exponential decay. Contrary to what is widely assumed, the density of excited emitters...... and the intensity in an emission decay curve are not proportional, but the density is a time integral of the intensity. The integral relation is crucial to correctly interpret non-single-exponential decay. We derive the proper normalization for both a discrete and a continuous distribution of rates, where every...... decay component is multiplied by its radiative decay rate. A central result of our paper is the derivation of the emission decay curve when both radiative and nonradiative decays are independently distributed. In this case, the well-known emission quantum efficiency can no longer be expressed...

  16. Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

    Science.gov (United States)

    Yamaguchi-Kabata, Yumi; Tsunoda, Tatsuhiko; Kumasaka, Natsuhiko; Takahashi, Atsushi; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

    2012-05-01

    Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clusters requires further genome-wide analyses based on a dense SNP set and comparison of haplotype frequencies. In the present study, we determined haplotypes for the Hondo cluster of the Japanese population by detecting SNP homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the haplotype frequencies. Haplotypes for the Ryukyu cluster were inferred by a statistical approach using the genotype data from 504 individuals. We then compared the haplotype frequencies between the Hondo and Ryukyu clusters. In most genomic regions, the haplotype frequencies in the Hondo and Ryukyu clusters were very similar. However, in addition to the human leukocyte antigen region on chromosome 6, other genomic regions (chromosomes 3, 4, 5, 7, 10 and 12) showed dissimilarities in haplotype frequency. These regions were enriched for genes involved in the immune system, cell-cell adhesion and the intracellular signaling cascade. These differentiated genomic regions between the Hondo and Ryukyu clusters are of interest because they (1) should be examined carefully in association studies and (2) likely contain genes responsible for morphological or physiological differences between the two groups.

  17. Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants

    Science.gov (United States)

    2014-01-01

    Background Following transmission, HIV-1 evolves into a diverse population, and next generation sequencing enables us to detect variants occurring at low frequencies. Studying viral evolution at the level of whole genomes was hitherto not possible because next generation sequencing delivers relatively short reads. Results We here provide a proof of principle that whole HIV-1 genomes can be reliably reconstructed from short reads, and use this to study the selection of immune escape mutations at the level of whole genome haplotypes. Using realistically simulated HIV-1 populations, we demonstrate that reconstruction of complete genome haplotypes is feasible with high fidelity. We do not reconstruct all genetically distinct genomes, but each reconstructed haplotype represents one or more of the quasispecies in the HIV-1 population. We then reconstruct 30 whole genome haplotypes from published short sequence reads sampled longitudinally from a single HIV-1 infected patient. We confirm the reliability of the reconstruction by validating our predicted haplotype genes with single genome amplification sequences, and by comparing haplotype frequencies with observed epitope escape frequencies. Conclusions Phylogenetic analysis shows that the HIV-1 population undergoes selection driven evolution, with successive replacement of the viral population by novel dominant strains. We demonstrate that immune escape mutants evolve in a dependent manner with various mutations hitchhiking along with others. As a consequence of this clonal interference, selection coefficients have to be estimated for complete haplotypes and not for individual immune escapes. PMID:24996694

  18. Mitochondrial control region haplotypes of the South American sea lion Otaria flavescens (Shaw, 1800).

    Science.gov (United States)

    Artico, L O; Bianchini, A; Grubel, K S; Monteiro, D S; Estima, S C; Oliveira, L R de; Bonatto, S L; Marins, L F

    2010-09-01

    The South American sea lion, Otaria flavescens, is widely distributed along the Pacific and Atlantic coasts of South America. However, along the Brazilian coast, there are only two nonbreeding sites for the species (Refúgio de Vida Silvestre da Ilha dos Lobos and Refúgio de Vida Silvestre do Molhe Leste da Barra do Rio Grande), both in Southern Brazil. In this region, the species is continuously under the effect of anthropic activities, mainly those related to environmental contamination with organic and inorganic chemicals and fishery interactions. This paper reports, for the first time, the genetic diversity of O. flavescens found along the Southern Brazilian coast. A 287-bp fragment of the mitochondrial DNA control region (D-loop) was analyzed. Seven novel haplotypes were found in 56 individuals (OFA1-OFA7), with OFA1 being the most frequent (47.54%). Nucleotide diversity was moderate (π = 0.62%) and haplotype diversity was relatively low (67%). Furthermore, the median joining network analysis indicated that Brazilian haplotypes formed a reciprocal monophyletic clade when compared to the haplotypes from the Peruvian population on the Pacific coast. These two populations do not share haplotypes and may have become isolated some time back. Further genetic studies covering the entire species distribution are necessary to better understand the biological implications of the results reported here for the management and conservation of South American sea lions.

  19. Mitochondrial control region haplotypes of the South American sea lion Otaria flavescens (Shaw, 1800

    Directory of Open Access Journals (Sweden)

    L.O. Artico

    2010-09-01

    Full Text Available The South American sea lion, Otaria flavescens, is widely distributed along the Pacific and Atlantic coasts of South America. However, along the Brazilian coast, there are only two nonbreeding sites for the species (Refúgio de Vida Silvestre da Ilha dos Lobos and Refúgio de Vida Silvestre do Molhe Leste da Barra do Rio Grande, both in Southern Brazil. In this region, the species is continuously under the effect of anthropic activities, mainly those related to environmental contamination with organic and inorganic chemicals and fishery interactions. This paper reports, for the first time, the genetic diversity of O. flavescens found along the Southern Brazilian coast. A 287-bp fragment of the mitochondrial DNA control region (D-loop was analyzed. Seven novel haplotypes were found in 56 individuals (OFA1-OFA7, with OFA1 being the most frequent (47.54%. Nucleotide diversity was moderate (π = 0.62% and haplotype diversity was relatively low (67%. Furthermore, the median joining network analysis indicated that Brazilian haplotypes formed a reciprocal monophyletic clade when compared to the haplotypes from the Peruvian population on the Pacific coast. These two populations do not share haplotypes and may have become isolated some time back. Further genetic studies covering the entire species distribution are necessary to better understand the biological implications of the results reported here for the management and conservation of South American sea lions.

  20. Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

    Science.gov (United States)

    Ferguson, Christopher J; Ceranoglu, T Atilla

    2014-03-01

    Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

  1. Method for spectrochemical analysis using time-resolved laser-induced breakdown. [Patent application

    Energy Technology Data Exchange (ETDEWEB)

    Loree, T.R.; Radziemski, L.J.

    1982-01-26

    A method for real-time elemental analysis using laser-induced breakdown of the material under investigation and spectroscopic analysis of the light emitted from the plasma consequently formed is described. By delaying the observation of the emitted radiation, the unwanted background continuum and line spectra from excited ionic species can be rendered unimportant relative to the excited atomic line spectra, thereby producing sharp, well-defined characteristic identifying atomic spectral features. These features provide the indicia for detailed elemental analyses of substances. The method is quite general in that it applies to gases, surfaces, and particulates entrained in gases. It requires no electrodes and can excite atomic species like fluorine and chlorine which are difficult to observe by more conventional analytical procedures.

  2. Conformational Analysis of DNA Repair Intermediates by Time-Resolved Fluorescence Spectroscopy

    OpenAIRE

    Lin, Su; Horning, David P.; Szostak, Jack W.; Chaput, John C.

    2009-01-01

    DNA repair enzymes are essential for maintaining the integrity of the DNA sequence. Unfortunately, very little is known about how these enzymes recognize damaged regions along the helix. Structural analysis of cellular repair enzymes bound to DNA reveals that these enzymes are able to recognize DNA in a variety of conformations. However, the prevalence of these deformations in the absence of enzymes remains unclear, as small populations of DNA conformations are often difficult to detect by NM...

  3. Strain analysis of trabecular bone using time-resolved X-ray microtomography

    Czech Academy of Sciences Publication Activity Database

    Jiroušek, Ondřej; Zlámal, Petr; Kytýř, Daniel; Kroupa, M.

    2011-01-01

    Roč. 633, Suppl. 1 (2011), s. 148-151 ISSN 0168-9002. [International Workshop on Radiation Imaging Detectors /11./. Praha, 28.06.2009-02.07.2009] R&D Projects: GA ČR(CZ) GP103/07/P483 Institutional research plan: CEZ:AV0Z20710524 Keywords : trabecular bone * X-ray microtomography * strain analysis * intrinsic material properties Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 1.207, year: 2011

  4. A method for in-situ spatially-resolved analysis of actinides in geomedia

    International Nuclear Information System (INIS)

    Clark, S.B.; Payne, R.F.

    2005-01-01

    It is well documented that U and Pu contamination in soils and sediments is not homogeneously distributed among all environmental surfaces, yet the composition of soil/sediment grains is quite variable and the chemistry controlling the partitioning to specific grains is not well understood. Fission track analysis (FTA) is a technique that directly detects nuclides with high fission cross sections, such as 235 U and 239 Pu, in many matrices including environmental materials. The fission track detector can be used to record the spatial distribution of contamination within the geomedia matrix. One limitation to FTA is that it cannot differentiate between 235 U and 239 Pu, nor does it provide any information about the composition of the grains to which the U or Pu is sorbed. In this work, we have developed an epoxy sample preparation technique that allows location of soil/sediment grains via FTA, and the irradiated sample can subsequently be coupled to laser ablation mass spectrometry (LAMS) with no additional sample preparation. This technique successfully allows grains containing 235 U and/or 239 Pu to be located and further analyzed. LAMS data provides Pu and U isotopic information and stable element analysis of the grains, thus providing the ability to study the nature of the interactions between the Pu and U with the environmental matrix.

  5. Trajectory resolved analysis of LEIS energy spectra: Neutralization and surface structure

    International Nuclear Information System (INIS)

    Beikler, Robert; Taglauer, Edmund

    2001-01-01

    For a quantitative evaluation of low-energy ion scattering (LEIS) data with respect to surface composition and structure a detailed analysis of the energy spectra is required. This includes the identification of multiple scattering processes and the determination of ion survival probabilities. We analyzed scattered ion energy spectra by using the computer code MARLOWE for which we developed a new analysis routine that allows to record energy distributions in dependence of the number of projectile-target atom collisions, in dependence of the distance of closest approach, or in dependence of the scattering crystalline layer. This procedure also permits the determination of ion survival probabilities by applying simple collision-dependent neutralization models. Experimental energy spectra for various projectile (He + , Ne + , Na + ) and target (transition metals, oxides) combinations are well reproduced and quantitative results for ion survival probabilities are obtained. These are largely in agreement with results obtained for bimetallic crystal surfaces obtained in a different way. Such MARLOWE calculations are also useful for the identification of structure relevant processes. This is shown exemplarily for the reconstructed Au(1 1 0) surface including a possibility to determine the (1x2)→(1x1) transition temperature

  6. Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ

    Directory of Open Access Journals (Sweden)

    Qing-Ming An

    2015-11-01

    Full Text Available The adiponectin gene (ADIPOQ plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5 of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A1-D1, A2-D2 were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A3-C3 and three SNPs were observed. Two patterns (A4-B4, A5-B5 and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg. In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A1, A2 and A3 were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A1-A3, A1-C3, B1-A3 and B1-C3 were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits.

  7. Atomic-layer-resolved analysis of surface magnetism by diffraction spectroscopy

    International Nuclear Information System (INIS)

    Matsui, Fumihiko; Matsushita, Tomohiro; Daimon, Hiroshi

    2010-01-01

    X-ray absorption near edge structure (XANES) and X-ray magnetic circular dichroism (XMCD) measurements by Auger-electron-yield detection are powerful analysis tools for the electronic and magnetic structures of surfaces, but all the information from atoms within the electron mean-free-path range is summed into the obtained spectrum. In order to investigate the electronic and magnetic structures of each atomic layer at subsurface, we have proposed a new method, diffraction spectroscopy, which is the combination of X-ray absorption spectroscopy and Auger electron diffraction (AED). From a series of measured thickness dependent AED patterns, we deduced a set of atomic-layer-specific AED patterns arithmetically. Based on these AED patterns, we succeeded in disentangling obtained XANES and XMCD spectra into those from different atomic layers.

  8. Time-resolved functional analysis of acute impairment of frataxin expression in an inducible cell model of Friedreich ataxia

    Directory of Open Access Journals (Sweden)

    Dörte Poburski

    2016-05-01

    Full Text Available Friedreich ataxia is a neurodegenerative disease caused by a GAA triplet repeat expansion in the first intron of the frataxin gene, which results in reduced expression levels of the corresponding protein. Despite numerous animal and cellular models, therapeutic options that mechanistically address impaired frataxin expression are lacking. Here, we have developed a new mammalian cell model employing the Cre/loxP recombination system to induce a homozygous or heterozygous frataxin knockout in mouse embryonic fibroblasts. Induction of Cre-mediated disruption by tamoxifen was successfully tested on RNA and protein levels. After loss of frataxin protein, cell division, aconitase activity and oxygen consumption rates were found to be decreased, while ROS production was increased in the homozygous state. By contrast, in the heterozygous state no such changes were observed. A time-resolved analysis revealed the loss of aconitase activity as an initial event after induction of complete frataxin deficiency, followed by secondarily elevated ROS production and a late increase in iron content. Initial impairments of oxygen consumption and ATP production were found to be compensated in the late state and seemed to play a minor role in Friedreich ataxia pathophysiology. In conclusion and as predicted from its proposed role in iron sulfur cluster (ISC biosynthesis, disruption of frataxin primarily causes impaired function of ISC-containing enzymes, whereas other consequences, including elevated ROS production and iron accumulation, appear secondary. These parameters and the robustness of the newly established system may additionally be used for a time-resolved study of pharmacological candidates in a HTS manner.

  9. Identifiability analysis of rotational diffusion tensor and electronic transition moments measured in time-resolved fluorescence depolarization experiment

    International Nuclear Information System (INIS)

    Szubiakowski, Jacek P.

    2014-01-01

    The subject of this paper is studies of the deterministic identifiability of molecular parameters, such as rotational diffusion tensor components and orientation of electronic transition moments, resulting from the time-resolved fluorescence anisotropy experiment. In the most general case considered, a pair of perpendicularly polarized emissions enables the unique determination of all the rotational diffusion tensor's principal components. The influence of the tensor's symmetry and the associated degeneration of its eigenvalues on the identifiability of the electronic transitions moments is systematically investigated. The analysis reveals that independently of the rotational diffusion tensor's symmetry, the transition moments involved in photoselection and emission processes cannot be uniquely identified without a priori information about their mutual orientation or their orientation with respect to the principal axes of the tensor. Moreover, it is shown that increasing the symmetry of the rotational diffusion tensor deteriorates the degree of the transition moments identifiability. To obtain these results analytically, a novel approach to solve bilinear system of equations for Markov parameters is applied. The effect of the additional information, obtained from fluorescence measurements for different molecular mobilities, to improve the identifiability at various levels of analysis is shown. The effectiveness and reliability of the target analysis method for experimental determination of the molecular parameters is also discussed

  10. Distribution pattern of Plasmodium falciparum chloroquine transporter (pfcrt) gene haplotypes in Sri Lanka 1996-2006

    DEFF Research Database (Denmark)

    Zhang, Jenny J; Senaratne, Tharanga N; Daniels, Rachel

    2011-01-01

    Abstract. Widespread antimalarial resistance has been a barrier to malaria elimination efforts in Sri Lanka. Analysis of genetic markers in historic parasites may uncover trends in the spread of resistance. We examined the frequency of Plasmodium falciparum chloroquine transporter (pfcrt; codons 72......-76) haplotypes in Sri Lanka in 1996-1998 and 2004-2006 using a high-resolution melting assay. Among 59 samples from 1996 to 1998, we detected the SVMNT (86%), CVMNK (10%), and CVIET (2%) haplotypes, with a positive trend in SVMNT and a negative trend in CVMNK frequency (P = 0.004) over time. Among 24 samples...

  11. Genomic sequence of 'Candidatus Liberibacter solanacearum' haplotype C and its comparison with haplotype A and B genomes.

    Directory of Open Access Journals (Sweden)

    Jinhui Wang

    Full Text Available Haplotypes A and B of 'Candidatus Liberibacter solanacearum' (CLso are associated with diseases of solanaceous plants, especially Zebra chip disease of potato, and haplotypes C, D and E are associated with symptoms on apiaceous plants. To date, one complete genome of haplotype B and two high quality draft genomes of haplotype A have been obtained for these unculturable bacteria using metagenomics from the psyllid vector Bactericera cockerelli. Here, we present the first genomic sequences obtained for the carrot-associated CLso. These two genomic sequences of haplotype C, FIN114 (1.24 Mbp and FIN111 (1.20 Mbp, were obtained from carrot psyllids (Trioza apicalis harboring CLso. Genomic comparisons between the haplotypes A, B and C revealed that the genome organization differs between these haplotypes, due to large inversions and other recombinations. Comparison of protein-coding genes indicated that the core genome of CLso consists of 885 ortholog groups, with the pan-genome consisting of 1327 ortholog groups. Twenty-seven ortholog groups are unique to CLso haplotype C, whilst 11 ortholog groups shared by the haplotypes A and B, are not found in the haplotype C. Some of these ortholog groups that are not part of the core genome may encode functions related to interactions with the different host plant and psyllid species.

  12. Large-scale phylogenomic analysis resolves a backbone phylogeny in ferns

    Science.gov (United States)

    Shen, Hui; Jin, Dongmei; Shu, Jiang-Ping; Zhou, Xi-Le; Lei, Ming; Wei, Ran; Shang, Hui; Wei, Hong-Jin; Zhang, Rui; Liu, Li; Gu, Yu-Feng; Zhang, Xian-Chun; Yan, Yue-Hong

    2018-01-01

    Abstract Background Ferns, originated about 360 million years ago, are the sister group of seed plants. Despite the remarkable progress in our understanding of fern phylogeny, with conflicting molecular evidence and different morphological interpretations, relationships among major fern lineages remain controversial. Results With the aim to obtain a robust fern phylogeny, we carried out a large-scale phylogenomic analysis using high-quality transcriptome sequencing data, which covered 69 fern species from 38 families and 11 orders. Both coalescent-based and concatenation-based methods were applied to both nucleotide and amino acid sequences in species tree estimation. The resulting topologies are largely congruent with each other, except for the placement of Angiopteris fokiensis, Cheiropleuria bicuspis, Diplaziopsis brunoniana, Matteuccia struthiopteris, Elaphoglossum mcclurei, and Tectaria subpedata. Conclusions Our result confirmed that Equisetales is sister to the rest of ferns, and Dennstaedtiaceae is sister to eupolypods. Moreover, our result strongly supported some relationships different from the current view of fern phylogeny, including that Marattiaceae may be sister to the monophyletic clade of Psilotaceae and Ophioglossaceae; that Gleicheniaceae and Hymenophyllaceae form a monophyletic clade sister to Dipteridaceae; and that Aspleniaceae is sister to the rest of the groups in eupolypods II. These results were interpreted with morphological traits, especially sporangia characters, and a new evolutionary route of sporangial annulus in ferns was suggested. This backbone phylogeny in ferns sets a foundation for further studies in biology and evolution in ferns, and therefore in plants. PMID:29186447

  13. Large-scale phylogenomic analysis resolves a backbone phylogeny in ferns.

    Science.gov (United States)

    Shen, Hui; Jin, Dongmei; Shu, Jiang-Ping; Zhou, Xi-Le; Lei, Ming; Wei, Ran; Shang, Hui; Wei, Hong-Jin; Zhang, Rui; Liu, Li; Gu, Yu-Feng; Zhang, Xian-Chun; Yan, Yue-Hong

    2018-02-01

    Ferns, originated about 360 million years ago, are the sister group of seed plants. Despite the remarkable progress in our understanding of fern phylogeny, with conflicting molecular evidence and different morphological interpretations, relationships among major fern lineages remain controversial. With the aim to obtain a robust fern phylogeny, we carried out a large-scale phylogenomic analysis using high-quality transcriptome sequencing data, which covered 69 fern species from 38 families and 11 orders. Both coalescent-based and concatenation-based methods were applied to both nucleotide and amino acid sequences in species tree estimation. The resulting topologies are largely congruent with each other, except for the placement of Angiopteris fokiensis, Cheiropleuria bicuspis, Diplaziopsis brunoniana, Matteuccia struthiopteris, Elaphoglossum mcclurei, and Tectaria subpedata. Our result confirmed that Equisetales is sister to the rest of ferns, and Dennstaedtiaceae is sister to eupolypods. Moreover, our result strongly supported some relationships different from the current view of fern phylogeny, including that Marattiaceae may be sister to the monophyletic clade of Psilotaceae and Ophioglossaceae; that Gleicheniaceae and Hymenophyllaceae form a monophyletic clade sister to Dipteridaceae; and that Aspleniaceae is sister to the rest of the groups in eupolypods II. These results were interpreted with morphological traits, especially sporangia characters, and a new evolutionary route of sporangial annulus in ferns was suggested. This backbone phylogeny in ferns sets a foundation for further studies in biology and evolution in ferns, and therefore in plants. © The Authors 2017. Published by Oxford University Press.

  14. Time-resolved transcriptome analysis of Bacillus subtilis responding to valine, glutamate, and glutamine.

    Directory of Open Access Journals (Sweden)

    Bang-Ce Ye

    Full Text Available Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector.

  15. Compound-specific isotope analysis resolves the dietary origin of docosahexaenoic acid in the mouse brain.

    Science.gov (United States)

    Lacombe, R J Scott; Giuliano, Vanessa; Colombo, Stefanie M; Arts, Michael T; Bazinet, Richard P

    2017-10-01

    DHA (22:6n-3) may be derived from two dietary sources, preformed dietary DHA or through synthesis from α-linolenic acid (ALA; 18:3n-3). However, conventional methods cannot distinguish between DHA derived from either source without the use of costly labeled tracers. In the present study, we demonstrate the proof-of-concept that compound-specific isotope analysis (CSIA) by GC-isotope ratio mass spectrometry (IRMS) can differentiate between sources of brain DHA based on differences in natural 13 C enrichment. Mice were fed diets containing either purified ALA or DHA as the sole n-3 PUFA. Extracted lipids were analyzed by CSIA for natural abundance 13 C enrichment. Brain DHA from DHA-fed mice was significantly more enriched (-23.32‰ to -21.92‰) compared with mice on the ALA diet (-28.25‰ to -27.49‰). The measured 13 C enrichment of brain DHA closely resembled the dietary n-3 PUFA source, -21.86‰ and -28.22‰ for DHA and ALA, respectively. The dietary effect on DHA 13 C enrichment was similar in liver and blood fractions. Our results demonstrate the effectiveness of CSIA, at natural 13 C enrichment, to differentiate between the incorporation of preformed or synthesized DHA into the brain and other tissues without the need for tracers. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  16. Plasmonic-based instrument response function for time-resolved fluorescence: toward proper lifetime analysis

    Energy Technology Data Exchange (ETDEWEB)

    Szlazak, Radoslaw; Tutaj, Krzysztof; Grudzinski, Wojciech; Gruszecki, Wieslaw I.; Luchowski, Rafal, E-mail: rafal.luchowski@umcs.pl [Maria Curie-Sklodowska University, Department of Biophysics, Institute of Physics (Poland)

    2013-06-15

    In this report, we investigated the so-called plasmonic platforms prepared to target ultra-short fluorescence and accurate instrumental response function in a time-domain spectroscopy and microscopy. The interaction of metallic nanoparticles with nearby fluorophores results in the increase of the dye fluorescence quantum yield, photostability and decrease of the lifetime parameter. The mentioned properties of platforms were applied to achieve a picosecond fluorescence lifetime (21 ps) of erythrosin B, used later as a better choice for deconvolution of fluorescence decays measured with 'color' sensitive photo-detectors. The ultra-short fluorescence standard based on combination of thin layers of silver film, silver colloidal nanoparticles (about 60 nm in diameter), and top layer of erythrosin B embedded in 0.2 % poly(vinyl) alcohol. The response functions were monitored on two photo-detectors; microchannel plate photomultiplier and single photon avalanche photodiode as a Rayleigh scattering and ultra-short fluorescence. We demonstrated that use of the plasmonic base fluorescence standard as an instrumental response function results in the absence of systematic error in lifetime measurements and analysis.

  17. An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

    Science.gov (United States)

    Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

    2008-10-01

    Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

  18. Análise dos haplótipos do gene da betaS-globina no Ceará Analysis of betaS-globin gene haplotypes in Ceará, Brazil

    Directory of Open Access Journals (Sweden)

    Gentil Claudino de Galiza Neto

    2005-10-01

    Full Text Available No presente trabalho abordam-se vários aspectos relacionados à natureza molecular da anemia falciforme (AF, desordem hematológica de caráter hereditário. A descoberta do polimorfismo do DNA no grupamento do gene betaS, originando diferentes haplótipos da doença, permitiu ampliar o conhecimento em torno da heterogeneidade clínica observada nos pacientes falcêmicos nas mais diversas regiões do mundo. Analisaram-se os diferentes haplótipos e seus parâmetros hematológicos, presentes em um grupo de 22 pacientes naturais e procedentes do estado do Ceará. A distribuição das freqüências dos haplótipos encontrados foi de 55,9% para Benin; 41,2% para República Centro-Africana (CAR; e de 2,9% para o haplótipo Senegal. Esses dados, em comparação com os demais estudos realizados no Brasil, mostram associação entre os seus valores para um alfa de 5% (p The present work deals with numerous aspects related to the molecular nature of sickle cell anemia. The discovery of the DNA polymorphism in the betas-globin gene cluster, gave origin to different haplotypes of the disease, making possible to enlarge the knowledge about the clinical heterogenity observed on the patients with sickle cell disease, in the various regions of the world. The different haplotypes and its hematological parameters were analysed in a group of 22 patients born in the State of Ceará, northeast of Brazil. The distribution found in the haplotypes frequency was of 55.9% for the Benin, of 41.2% for the CAR, and of 2.9% for Senegal haplotype. The data, compared to the others works done in Brazil, show relations among their values to alpha of 5% (p < 0,05. The results make possible a full understanding of the pathophisiology of the illness and of its clinical complexity in our State, as well as it allows a better knowledge of the sickle cell disease in our country.

  19. Risk of Death in Infants Who Have Experienced a Brief Resolved Unexplained Event: A Meta-Analysis.

    Science.gov (United States)

    Brand, Donald A; Fazzari, Melissa J

    2018-06-01

    To estimate an upper bound on the risk of death after a brief resolved unexplained event (BRUE), a sudden alteration in an infant's breathing, color, tone, or responsiveness, previously labeled "apparent life-threatening event" (ALTE). The meta-analysis incorporated observational studies of patients with ALTE that included data on in-hospital and post-discharge deaths with at least 1 week of follow-up after hospital discharge. Pertinent studies were identified from a published review of the literature from 1970 through 2014 and a supplementary PubMed query through February 2017. The 12 included studies (n = 3005) reported 12 deaths, of which 8 occurred within 4 months of the event. Applying a Poisson-normal random effects model to the 8 proximate deaths using a 4-month time horizon yielded a post-ALTE mortality rate of about 1 in 800, which constitutes an upper bound on the risk of death after a BRUE. This risk is about the same as the baseline risk of death during the first year of life. The meta-analysis therefore supports the return-home approach advocated in a recently published clinical practice guideline-not routine hospitalization-for BRUE patients who have been evaluated in the emergency department and determined to be at lower risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo

    DEFF Research Database (Denmark)

    Baraka, Vito; Delgado-Ratto, Christopher; Nag, Sidsel

    2017-01-01

    Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African.......3 and 7.7 kb) flanking the Pfdhps gene were assayed. Evolutionary analysis revealed a shared origin of Pfdhps haplotypes in East Africa, with a distinct population clustering in DR Congo. Furthermore, in Tanzania there was an independent distinct origin of Pfdhps SGEGA resistant haplotype. In Uganda...... and Tanzania, gene flow patterns contribute to the dispersal and shared origin of parasites carrying double- and triple-mutant Pfdhps haplotypes associated with poor outcomes of intermittent preventive treatment during pregnancy using SP (IPTp-SP). However, the origins of the Pfdhps haplotypes in DR Congo...

  1. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men.

    Directory of Open Access Journals (Sweden)

    Bruna Gigante

    Full Text Available The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R and the interleukin 6 (IL6 haplotypes modulates the risk of myocardial infarction (MI in the Stockholm Heart Epidemiology Program (SHEEP. Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S, indicates the presence of a synergy (S>1 or of an antagonism (S<1. None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI of 1.58 (1.05-2.41 (p = 0.02 in the crude and an OR of 1.72 (1.11-2.67 (p = 0.01 in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI of 2.24 (1.27-3.95 (p = 0.005 and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI of 1.56 (1.02-2.37 (p = 0.03 and S of 1.66 (0.89-31. In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

  2. Multilinear analysis of Time-Resolved Laser-Induced Fluorescence Spectra of U(VI containing natural water samples

    Directory of Open Access Journals (Sweden)

    Višňák Jakub

    2017-01-01

    Full Text Available Natural waters’ uranium level monitoring is of great importance for health and environmental protection. One possible detection method is the Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS, which offers the possibility to distinguish different uranium species. The analytical identification of aqueous uranium species in natural water samples is of distinct importance since individual species differ significantly in sorption properties and mobility in the environment. Samples originate from former uranium mine sites and have been provided by Wismut GmbH, Germany. They have been characterized by total elemental concentrations and TRLFS spectra. Uranium in the samples is supposed to be in form of uranyl(VI complexes mostly with carbonate (CO32− and bicarbonate (HCO3− and to lesser extend with sulphate (SO42− , arsenate (AsO43− , hydroxo (OH− , nitrate (NO3− and other ligands. Presence of alkaline earth metal dications (M = Ca2+ , Mg2+ , Sr2+ will cause most of uranyl to prefer ternary complex species, e.g. Mn(UO2(CO332n-4 (n ∊ {1; 2}. From species quenching the luminescence, Cl− and Fe2+ should be mentioned. Measurement has been done under cryogenic conditions to increase the luminescence signal. Data analysis has been based on Singular Value Decomposition and monoexponential fit of corresponding loadings (for separate TRLFS spectra, the “Factor analysis of Time Series” (FATS method and Parallel Factor Analysis (PARAFAC, all data analysed simultaneously. From individual component spectra, excitation energies T00, uranyl symmetric mode vibrational frequencies ωgs and excitation driven U-Oyl bond elongation ΔR have been determined and compared with quasirelativistic (TDDFT/B3LYP theoretical predictions to cross -check experimental data interpretation.

  3. Multilinear analysis of Time-Resolved Laser-Induced Fluorescence Spectra of U(VI) containing natural water samples

    Science.gov (United States)

    Višňák, Jakub; Steudtner, Robin; Kassahun, Andrea; Hoth, Nils

    2017-09-01

    Natural waters' uranium level monitoring is of great importance for health and environmental protection. One possible detection method is the Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), which offers the possibility to distinguish different uranium species. The analytical identification of aqueous uranium species in natural water samples is of distinct importance since individual species differ significantly in sorption properties and mobility in the environment. Samples originate from former uranium mine sites and have been provided by Wismut GmbH, Germany. They have been characterized by total elemental concentrations and TRLFS spectra. Uranium in the samples is supposed to be in form of uranyl(VI) complexes mostly with carbonate (CO32- ) and bicarbonate (HCO3- ) and to lesser extend with sulphate (SO42- ), arsenate (AsO43- ), hydroxo (OH- ), nitrate (NO3- ) and other ligands. Presence of alkaline earth metal dications (M = Ca2+ , Mg2+ , Sr2+ ) will cause most of uranyl to prefer ternary complex species, e.g. Mn(UO2)(CO3)32n-4 (n ɛ {1; 2}). From species quenching the luminescence, Cl- and Fe2+ should be mentioned. Measurement has been done under cryogenic conditions to increase the luminescence signal. Data analysis has been based on Singular Value Decomposition and monoexponential fit of corresponding loadings (for separate TRLFS spectra, the "Factor analysis of Time Series" (FATS) method) and Parallel Factor Analysis (PARAFAC, all data analysed simultaneously). From individual component spectra, excitation energies T00, uranyl symmetric mode vibrational frequencies ωgs and excitation driven U-Oyl bond elongation ΔR have been determined and compared with quasirelativistic (TD)DFT/B3LYP theoretical predictions to cross -check experimental data interpretation. Note to the reader: Several errors have been produced in the initial version of this article. This new version published on 23 October 2017 contains all the corrections.

  4. Dual analyzer system for surface analysis dedicated for angle-resolved photoelectron spectroscopy at liquid surfaces and interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Niedermaier, Inga; Kolbeck, Claudia; Steinrück, Hans-Peter; Maier, Florian, E-mail: florian.maier@fau.de [Lehrstuhl für Physikalische Chemie II, FAU Universität Erlangen-Nürnberg, Egerlandstraße 3, 91058 Erlangen (Germany)

    2016-04-15

    The investigation of liquid surfaces and interfaces with the powerful toolbox of ultra-high vacuum (UHV)-based surface science techniques generally has to overcome the issue of liquid evaporation within the vacuum system. In the last decade, however, new classes of liquids with negligible vapor pressure at room temperature—in particular, ionic liquids (ILs)—have emerged for surface science studies. It has been demonstrated that particularly angle-resolved X-ray Photoelectron Spectroscopy (ARXPS) allows for investigating phenomena that occur at gas-liquid and liquid-solid interfaces on the molecular level. The results are not only relevant for IL systems but also for liquids in general. In all of these previous ARXPS studies, the sample holder had to be tilted in order to change the polar detection angle of emitted photoelectrons, which restricted the liquid systems to very thin viscous IL films coating a flat solid support. We now report on the concept and realization of a new and unique laboratory “Dual Analyzer System for Surface Analysis (DASSA)” which enables fast ARXPS, UV photoelectron spectroscopy, imaging XPS, and low-energy ion scattering at the horizontal surface plane of macroscopically thick non-volatile liquid samples. It comprises a UHV chamber equipped with two electron analyzers mounted for simultaneous measurements in 0° and 80° emission relative to the surface normal. The performance of DASSA on a first macroscopic liquid system will be demonstrated.

  5. Dual analyzer system for surface analysis dedicated for angle-resolved photoelectron spectroscopy at liquid surfaces and interfaces

    International Nuclear Information System (INIS)

    Niedermaier, Inga; Kolbeck, Claudia; Steinrück, Hans-Peter; Maier, Florian

    2016-01-01

    The investigation of liquid surfaces and interfaces with the powerful toolbox of ultra-high vacuum (UHV)-based surface science techniques generally has to overcome the issue of liquid evaporation within the vacuum system. In the last decade, however, new classes of liquids with negligible vapor pressure at room temperature—in particular, ionic liquids (ILs)—have emerged for surface science studies. It has been demonstrated that particularly angle-resolved X-ray Photoelectron Spectroscopy (ARXPS) allows for investigating phenomena that occur at gas-liquid and liquid-solid interfaces on the molecular level. The results are not only relevant for IL systems but also for liquids in general. In all of these previous ARXPS studies, the sample holder had to be tilted in order to change the polar detection angle of emitted photoelectrons, which restricted the liquid systems to very thin viscous IL films coating a flat solid support. We now report on the concept and realization of a new and unique laboratory “Dual Analyzer System for Surface Analysis (DASSA)” which enables fast ARXPS, UV photoelectron spectroscopy, imaging XPS, and low-energy ion scattering at the horizontal surface plane of macroscopically thick non-volatile liquid samples. It comprises a UHV chamber equipped with two electron analyzers mounted for simultaneous measurements in 0° and 80° emission relative to the surface normal. The performance of DASSA on a first macroscopic liquid system will be demonstrated.

  6. Controlled dissolution of silicon dioxide layers for depth resolved multielement analysis by inductively coupled plasma-mass spectrometry

    International Nuclear Information System (INIS)

    Lorge, Susan E.; Houk, R.S.

    2009-01-01

    Dissolution procedures were developed to control the number of surface layers removed, in an attempt to achieve depth resolved analysis by inductively coupled plasma-mass spectrometry (ICP-MS). NIST 612 glass was chosen because it is a homogeneous material with many elements at interesting concentrations, ∼ 50 ppm. Varying dissolution time and HF concentration resulted in the reproducible removal of SiO 2 layers as thin as 70 A deep. Dissolved trace metals were determined after dilution by inductively coupled plasma-mass spectrometry (ICP-MS) with a magnetic sector instrument. The amount removed was determined from the concentration of a major element, Ca. With the exception of Zn, trace metal concentrations agreed reasonably well with their certified values for removal depths of 500, 300 and 150 A. Zinc concentration was significantly high in all dissolutions indicating either a contamination problem or that Zn is removed at a faster rate than Ca. For the dissolutions that removed 70 A of SiO 2 , Cr, Mn, Co, Sr, Cd, Ce, Dy, Er, Yb and U recovery results agreed with their certified values (∼ 50 ppm); Ti, As, Mo, Ba, and Th could not be determined because net intensities were below 3σ of the blank; and measured concentrations for Cu, Pb and Zn were well above the certified values.

  7. Measurement and analysis of thermal conductivity of isotopically controlled silicon layers by time-resolved X-ray scattering

    Energy Technology Data Exchange (ETDEWEB)

    Eon, S.; Frieling, R.; Bracht, H. [Institute for Materials Physics, University of Muenster, 48149 Muenster (Germany); Plech, A. [Institute for Photon Science and Synchrotron Radiation (IPS), 76344 Eggenstein-Leopoldshafen (Germany)

    2016-11-15

    Nanostructuring is considered to be an efficient way to tailor phonon scattering and to reduce the thermal conductivity while keeping good electronic properties. This can be ideally realized by mass modulation of chemical identical elements. In this work, we report measurements of the crossplane thermal conductivity of isotopically modulated {sup 28}Si/{sup 30}Si multilayer structures and of isotopically pure {sup 28}Si layers by means of time-resolved X-ray scattering. Compared to earlier investigations, an improved measurement technique has been applied to determine the cooling behavior of a top gold metal layer after laser excitation with picosecond time resolution until thermal equilibration is established. Detailed analysis of the cooling behavior not only confirms a reduced thermal conductivity of {sup 28}Si/{sup 30}Si multilayer structures compared to natural and isotopically enriched {sup 28}Si layers but also provides evidence of direct laser heating of the Si layer. This and extrinsic effects affecting the cooling behavior of the gold layer are taken into account to determine the thermal conductivity by means of the pump-and-probe measurement technique. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Time-resolved broadband analysis of slow-light propagation and superluminal transmission of electromagnetic waves in three-dimensional photonic crystals

    NARCIS (Netherlands)

    Gómez Rivas, J.; Farré Benet, A.; Niehusmann, J.; Haring Bolivar, P.; Kurz, H.

    2005-01-01

    A time-resolved analysis of the amplitude and phase of THz pulses propagating through three-dimensional photonic crystals is presented. Single-cycle pulses of THz radiation allow measurements over a wide frequency range, spanning more than an octave below, at and above the bandgap of strongly

  9. Time-resolved characterization and energy balance analysis of implosion core in shock-ignition experiments at OMEGA

    International Nuclear Information System (INIS)

    Florido, R.; Mancini, R. C.; Nagayama, T.; Tommasini, R.; Delettrez, J. A.; Regan, S. P.

    2014-01-01

    Time-resolved temperature and density conditions in the core of shock-ignition implosions have been determined for the first time. The diagnostic method relies on the observation, with a streaked crystal spectrometer, of the signature of an Ar tracer added to the deuterium gas fill. The data analysis confirms the importance of the shell attenuation effect previously noted on time-integrated spectroscopic measurements of thick-wall targets [R. Florido et al., Phys. Rev. E 83, 066408 (2011)]. This effect must be taken into account in order to obtain reliable results. The extracted temperature and density time-histories are representative of the state of the core during the implosion deceleration and burning phases. As a consequence of the ignitor shock launched by the sharp intensity spike at the end of the laser pulse, observed average core electron temperature and mass density reach T ∼ 1100 eV and ρ ∼ 2 g/cm 3 ; then temperature drops to T ∼ 920 eV while density rises to ρ ∼ 3.4 g/cm 3 about the time of peak compression. Compared to 1D hydrodynamic simulations, the experiment shows similar maximum temperatures and smaller densities. Simulations do not reproduce all observations. Differences are noted in the heating dynamics driven by the ignitor shock and the optical depth time-history of the compressed shell. Time-histories of core conditions extracted from spectroscopy show that the implosion can be interpreted as a two-stage polytropic process. Furthermore, an energy balance analysis of implosion core suggests an increase in total energy greater than what 1D hydrodynamic simulations predict. This new methodology can be implemented in other ICF experiments to look into implosion dynamics and help to understand the underlying physics

  10. Time-resolved characterization and energy balance analysis of implosion core in shock-ignition experiments at OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Florido, R., E-mail: ricardo.florido@ulpgc.es; Mancini, R. C.; Nagayama, T. [Department of Physics, University of Nevada, Reno, Nevada 89557 (United States); Tommasini, R. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Delettrez, J. A.; Regan, S. P. [Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623 (United States)

    2014-10-15

    Time-resolved temperature and density conditions in the core of shock-ignition implosions have been determined for the first time. The diagnostic method relies on the observation, with a streaked crystal spectrometer, of the signature of an Ar tracer added to the deuterium gas fill. The data analysis confirms the importance of the shell attenuation effect previously noted on time-integrated spectroscopic measurements of thick-wall targets [R. Florido et al., Phys. Rev. E 83, 066408 (2011)]. This effect must be taken into account in order to obtain reliable results. The extracted temperature and density time-histories are representative of the state of the core during the implosion deceleration and burning phases. As a consequence of the ignitor shock launched by the sharp intensity spike at the end of the laser pulse, observed average core electron temperature and mass density reach T ∼ 1100 eV and ρ ∼ 2 g/cm{sup 3}; then temperature drops to T ∼ 920 eV while density rises to ρ ∼ 3.4 g/cm{sup 3} about the time of peak compression. Compared to 1D hydrodynamic simulations, the experiment shows similar maximum temperatures and smaller densities. Simulations do not reproduce all observations. Differences are noted in the heating dynamics driven by the ignitor shock and the optical depth time-history of the compressed shell. Time-histories of core conditions extracted from spectroscopy show that the implosion can be interpreted as a two-stage polytropic process. Furthermore, an energy balance analysis of implosion core suggests an increase in total energy greater than what 1D hydrodynamic simulations predict. This new methodology can be implemented in other ICF experiments to look into implosion dynamics and help to understand the underlying physics.

  11. Time-resolved infrared stimulated luminescence signals in feldspars: Analysis based on exponential and stretched exponential functions

    International Nuclear Information System (INIS)

    Pagonis, V.; Morthekai, P.; Singhvi, A.K.; Thomas, J.; Balaram, V.; Kitis, G.; Chen, R.

    2012-01-01

    Time-resolved infrared-stimulated luminescence (TR-IRSL) signals from feldspar samples have been the subject of several recent experimental studies. These signals are of importance in the field of luminescence dating, since they exhibit smaller fading effects than the commonly employed continuous-wave infrared signals (CW-IRSL). This paper presents a semi-empirical analysis of TR-IRSL data from feldspar samples, by using a linear combination of exponential and stretched exponential (SE) functions. The best possible estimates of the five parameters in this semi-empirical approach are obtained using five popular commercially available software packages, and by employing a variety of global optimization techniques. The results from all types of software and from the different fitting algorithms were found to be in close agreement with each other, indicating that a global optimum solution has likely been reached during the fitting process. Four complete sets of TR-IRSL data on well-characterized natural feldspars were fitted by using such a linear combination of exponential and SE functions. The dependence of the extracted fitting parameters on the stimulation temperature is discussed within the context of a recently proposed model of luminescence processes in feldspar. Three of the four feldspar samples studied in this paper are K-rich, and these exhibited different behavior at higher stimulation temperatures, than the fourth sample which was a Na-rich feldspar. The new method of analysis proposed in this paper can help isolate mathematically the more thermally stable components, and hence could lead to better dating applications in these materials. - Highlights: ► TR-IRSL from four feldspars were analyzed using exponential and stretched exponential functions. ► A variety of global optimization techniques give good agreement. ► Na-rich sample behavior is different from the three K-rich samples. ► Experimental data are fitted for stimulation temperatures

  12. Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

    Science.gov (United States)

    Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

    2017-11-13

    Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

  13. HapCol : Accurate and memory-efficient haplotype assembly from long reads

    NARCIS (Netherlands)

    Pirola, Yuri; Zaccaria, Simone; Dondi, Riccardo; Klau, Gunnar W.; Pisanti, Nadia; Bonizzoni, Paola

    2016-01-01

    Motivation: Haplotype assembly is the computational problem of reconstructing haplotypes in diploid organisms and is of fundamental importance for characterizing the effects of single-nucleotide polymorphisms on the expression of phenotypic traits. Haplotype assembly highly benefits from the advent

  14. HapCol: Accurate and Memory-efficient Haplotype Assembly from Long Reads

    NARCIS (Netherlands)

    Y. Pirola (Yuri); S. Zaccaria (Simone); R. Dondi (Riccardo); G.W. Klau (Gunnar); N. Pisanti (Nadia); P. Bonizzoni (Paola)

    2015-01-01

    htmlabstractMotivation: Haplotype assembly is the computational problem of reconstructing haplotypes in diploid organisms and is of fundamental importance for characterizing the effects of single-nucleotide polymorphisms on the expression of phenotypic traits. Haplotype assembly highly benefits from

  15. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies.

    Directory of Open Access Journals (Sweden)

    Melanie Legrand

    2008-01-01

    Full Text Available Haplotype maps (HapMaps reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

  16. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    International Nuclear Information System (INIS)

    Hansen, Torben F.; Spindler, Karen-Lise G.; Andersen, Rikke F.; Lindebjerg, Jan; Kølvraa, Steen; Brandslund, Ivan; Jakobsen, Anders

    2010-01-01

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation

  17. Divergence at the casein haplotypes in dairy and meat goat breeds.

    Science.gov (United States)

    Küpper, Julia; Chessa, Stefania; Rignanese, Daniela; Caroli, Anna; Erhardt, Georg

    2010-02-01

    Casein genes have been proved to have an influence on milk properties, and are in addition appropriate for phylogeny studies. A large number of casein polymorphisms exist in goats, making their analysis quite complex. The four casein loci were analyzed by molecular techniques for genetic polymorphism detection in the two dairy goat breeds Bunte Deutsche Edelziege (BDE; n=96), Weisse Deutsche Edelziege (WDE; n=91), and the meat goat breed Buren (n=75). Of the 35 analyzed alleles, 18 were found in BDE, and 17 in Buren goats and WDE. In addition, a new allele was identified at the CSN1S1 locus in the BDE, showing a frequency of 0.05. This variant, named CSN1S1*A', is characterized by a t-->c transversion in intron 9. Linkage disequilibrium was found at the casein haplotype in all three breeds. A total of 30 haplotypes showed frequencies higher than 0.01. In the Buren breed only one haplotype showed a frequency higher than 0.1. The ancestral haplotype B-A-A-B (in the order: CSN1S1-CSN2-CSN1S2-CSN3) occurred in all three breeds, showing a very high frequency (>0.8) in the Buren.

  18. A class representative model for Pure Parsimony Haplotyping under uncertain data.

    Directory of Open Access Journals (Sweden)

    Daniele Catanzaro

    Full Text Available The Pure Parsimony Haplotyping (PPH problem is a NP-hard combinatorial optimization problem that consists of finding the minimum number of haplotypes necessary to explain a given set of genotypes. PPH has attracted more and more attention in recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from mapping complex disease genes to inferring population histories, passing through designing drugs, functional genomics and pharmacogenetics. In this article we investigate, for the first time, a recent version of PPH called the Pure Parsimony Haplotype problem under Uncertain Data (PPH-UD. This version mainly arises when the input genotypes are not accurate, i.e., when some single nucleotide polymorphisms are missing or affected by errors. We propose an exact approach to solution of PPH-UD based on an extended version of Catanzaro et al.[1] class representative model for PPH, currently the state-of-the-art integer programming model for PPH. The model is efficient, accurate, compact, polynomial-sized, easy to implement, solvable with any solver for mixed integer programming, and usable in all those cases for which the parsimony criterion is well suited for haplotype estimation.

  19. Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific

    Energy Technology Data Exchange (ETDEWEB)

    Rapacz, J.; Hasler-Rapacz, J.O. (Univ. of Wisconsin, Madison (United States)); Chen, L.; Wu, Mingjiuan; Schumaker, V.N. (Univ. of California, Los Angeles (United States)); Butler-Brunner, E.; Butler, R. (Swiss Red Cross Blood Transfusion Service, Bern (Switzerland))

    1991-02-15

    The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes.

  20. Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific

    International Nuclear Information System (INIS)

    Rapacz, J.; Hasler-Rapacz, J.O.; Chen, L.; Wu, Mingjiuan; Schumaker, V.N.; Butler-Brunner, E.; Butler, R.

    1991-01-01

    The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes

  1. A spatial haplotype copying model with applications to genotype imputation.

    Science.gov (United States)

    Yang, Wen-Yun; Hormozdiari, Farhad; Eskin, Eleazar; Pasaniuc, Bogdan

    2015-05-01

    Ever since its introduction, the haplotype copy model has proven to be one of the most successful approaches for modeling genetic variation in human populations, with applications ranging from ancestry inference to genotype phasing and imputation. Motivated by coalescent theory, this approach assumes that any chromosome (haplotype) can be modeled as a mosaic of segments copied from a set of chromosomes sampled from the same population. At the core of the model is the assumption that any chromosome from the sample is equally likely to contribute a priori to the copying process. Motivated by recent works that model genetic variation in a geographic continuum, we propose a new spatial-aware haplotype copy model that jointly models geography and the haplotype copying process. We extend hidden Markov models of haplotype diversity such that at any given location, haplotypes that are closest in the genetic-geographic continuum map are a priori more likely to contribute to the copying process than distant ones. Through simulations starting from the 1000 Genomes data, we show that our model achieves superior accuracy in genotype imputation over the standard spatial-unaware haplotype copy model. In addition, we show the utility of our model in selecting a small personalized reference panel for imputation that leads to both improved accuracy as well as to a lower computational runtime than the standard approach. Finally, we show our proposed model can be used to localize individuals on the genetic-geographical map on the basis of their genotype data.

  2. Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

    International Nuclear Information System (INIS)

    Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström

    2004-01-01

    Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk. We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA n , 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women

  3. Aeroacoustic analysis of a NACA 0015 airfoil with Gurney flap based on time-resolved PIV measurements

    NARCIS (Netherlands)

    Zhang, Xueqing; Sciacchitano, A.; Pröbsting, S.; von Estorff, O.; Kropp, W.; Schulte-Fortkamp, B.

    2016-01-01

    The present study investigates the feasibility of high-lift devices noise prediction based on measurements of time-resolved particle image velocimetry (TR-PIV). The model under investigation is a NACA 0015 airfoil with Gurney flap with height of 6% chord length. The velocity fields around and

  4. Minimal sharing of Y-chromosome STR haplotypes among five endogamous population groups from western and southwestern India.

    Science.gov (United States)

    Das, Birajalaxmi; Chauhan, P S; Seshadri, M

    2004-10-01

    We attempt to address the issue of genetic variation and the pattern of male gene flow among and between five Indian population groups of two different geographic and linguistic affiliations using Y-chromosome markers. We studied 221 males at three Y-chromosome biallelic loci and 184 males for the five Y-chromosome STRs. We observed 111 Y-chromosome STR haplotypes. An analysis of molecular variance (AMOVA) based on Y-chromosome STRs showed that the variation observed between the population groups belonging to two major regions (western and southwestern India) was 0.17%, which was significantly lower than the level of genetic variance among the five populations (0.59%) considered as a single group. Combined haplotype analysis of the five STRs and the biallelic locus 92R7 revealed minimal sharing of haplotypes among these five ethnic groups, irrespective of the similar origin of the linguistic and geographic affiliations; this minimal sharing indicates restricted male gene flow. As a consequence, most of the haplotypes were population specific. Network analysis showed that the haplotypes, which were shared between the populations, seem to have originated from different mutational pathways at different loci. Biallelic markers showed that all five ethnic groups have a similar ancestral origin despite their geographic and linguistic diversity.

  5. Fitchi: haplotype genealogy graphs based on the Fitch algorithm.

    Science.gov (United States)

    Matschiner, Michael

    2016-04-15

    : In population genetics and phylogeography, haplotype genealogy graphs are important tools for the visualization of population structure based on sequence data. In this type of graph, node sizes are often drawn in proportion to haplotype frequencies and edge lengths represent the minimum number of mutations separating adjacent nodes. I here present Fitchi, a new program that produces publication-ready haplotype genealogy graphs based on the Fitch algorithm. http://www.evoinformatics.eu/fitchi.htm : michaelmatschiner@mac.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. SLC22A1-ABCB1 haplotype profiles predict imatinib pharmacokinetics in Asian patients with chronic myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Onkar Singh

    Full Text Available OBJECTIVE: This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5 3 genetic polymorphisms on imatinib mesylate (IM pharmacokinetics in Asian patients with chronic myeloid leukemia (CML. PATIENTS AND METHODS: Healthy subjects belonging to three Asian populations (Chinese, Malay, Indian; n = 70 each and CML patients (n = 38 were enrolled in a prospective pharmacogenetics study. Imatinib trough (C(0h and clearance (CL were determined in the patients at steady state. Haplowalk method was applied to infer the haplotypes and generalized linear model (GLM to estimate haplotypic effects on IM pharmacokinetics. Association of haplotype copy numbers with IM pharmacokinetics was defined by Mann-Whitney U test. RESULTS: Global haplotype score statistics revealed a SLC22A1 sub-haplotypic region encompassing three polymorphisms (rs3798168, rs628031 and IVS7+850C>T, to be significantly associated with IM clearance (p = 0.013. Haplotype-specific GLM estimated that the haplotypes AGT and CGC were both associated with 22% decrease in clearance compared to CAC [CL (10(-2 L/hr/mg: CAC vs AGT: 4.03 vs 3.16, p = 0.017; CAC vs CGC: 4.03 vs 3.15, p = 0.017]. Patients harboring 2 copies of AGT or CGC haplotypes had 33.4% lower clearance and 50% higher C(0h than patients carrying 0 or 1 copy [CL (10(-2 L/hr/mg: 2.19 vs 3.29, p = 0.026; C(0h (10(-6 1/ml: 4.76 vs 3.17, p = 0.013, respectively]. Further subgroup analysis revealed SLC22A1 and ABCB1 haplotypic combinations to be significantly associated with clearance and C(0h (p = 0.002 and 0.009, respectively. CONCLUSION: This exploratory study suggests that SLC22A1-ABCB1 haplotypes may influence IM pharmacokinetics in Asian CML patients.

  7. Introgression of a Rare Haplotype from Southeastern Africa to Breed California Blackeyes with Larger Seeds

    Directory of Open Access Journals (Sweden)

    Mitchell R Lucas

    2015-03-01

    Full Text Available Seed size distinguishes most crops from their wild relatives and is an important quality trait for the grain legume cowpea. In order to breed cowpea varieties with larger seeds we introgressed a rare haplotype associated with large seeds at the Css-1 locus from an African buff seed type cultivar, IT82E-18 (18.5g/100 seeds, into a blackeye seed type cultivar, CB27 (22g/100 seed. Four RILs derived from these two parents were chosen for marker-assisted breeding based on SNP genotyping with a goal of stacking large seed haplotypes into a CB27 background. Foreground and background selection were performed during two cycles of backcrossing based on genome-wide SNP markers. The average seed size of introgression lines homozygous for haplotypes associated with large seeds was 28.7g/100 seed and 24.8g/100 seed for cycles 1 and 2, respectively. One cycle 1 introgression line with desirable seed quality was selfed for two generations to make families with very large seeds (28-35g/100 seeds. Field-based performance trials helped identify breeding lines that not only have large seeds but are also desirable in terms of yield, maturity, and plant architecture when compared to industry standards. A principal component analysis was used to explore the relationships between the parents relative to a core set of landraces and improved varieties based on high-density SNP data. The geographic distribution of haplotypes at the Css-1 locus suggest the haplotype associated with large seeds is unique to accessions collected from Southeastern Africa. Therefore this QTL has a strong potential to develop larger seeded varieties for other growing regions which is demonstrated in this work using a California pedigree.

  8. The IGF1 small dog haplotype is derived from Middle Eastern grey wolves

    Directory of Open Access Journals (Sweden)

    Ostrander Elaine A

    2010-02-01

    Full Text Available Abstract Background A selective sweep containing the insulin-like growth factor 1 (IGF1 gene is associated with size variation in domestic dogs. Intron 2 of IGF1 contains a SINE element and single nucleotide polymorphism (SNP found in all small dog breeds that is almost entirely absent from large breeds. In this study, we surveyed a large sample of grey wolf populations to better understand the ancestral pattern of variation at IGF1 with a particular focus on the distribution of the small dog haplotype and its relationship to the origin of the dog. Results We present DNA sequence data that confirms the absence of the derived small SNP allele in the intron 2 region of IGF1 in a large sample of grey wolves and further establishes the absence of a small dog associated SINE element in all wild canids and most large dog breeds. Grey wolf haplotypes from the Middle East have higher nucleotide diversity suggesting an origin there. Additionally, PCA and phylogenetic analyses suggests a closer kinship of the small domestic dog IGF1 haplotype with those from Middle Eastern grey wolves. Conclusions The absence of both the SINE element and SNP allele in grey wolves suggests that the mutation for small body size post-dates the domestication of dogs. However, because all small dogs possess these diagnostic mutations, the mutations likely arose early in the history of domestic dogs. Our results show that the small dog haplotype is closely related to those in Middle Eastern wolves and is consistent with an ancient origin of the small dog haplotype there. Thus, in concordance with past archeological studies, our molecular analysis is consistent with the early evolution of small size in dogs from the Middle East. See associated opinion by Driscoll and Macdonald: http://jbiol.com/content/9/2/10

  9. Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity

    Directory of Open Access Journals (Sweden)

    Dallol Ashraf

    2012-09-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is caused by one or more mutations in the G6PD gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established. Methods In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction. Results All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr was the most common variant in the cohort (30% in males patients followed by the Mediterranean variant (p.Ser188Phe detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females were identified. Five of these were previously unreported (Jeddah A, B, C, D and E and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency. Conclusions Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.

  10. HERC1 polymorphisms: population-specific variations in haplotype composition.

    Science.gov (United States)

    Yuasa, Isao; Umetsu, Kazuo; Nishimukai, Hiroaki; Fukumori, Yasuo; Harihara, Shinji; Saitou, Naruya; Jin, Feng; Chattopadhyay, Prasanta K; Henke, Lotte; Henke, Jürgen

    2009-08-01

    Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations. The results confirmed remarked differences in the allele and haplotype frequencies between East Asian and non-East Asian populations. One of the three common haplotypes observed was found to be characteristic of East Asians, who showed a relatively uniform distribution of haplotypes. Information on haplotypes would be useful for testing the function of polymorphisms in the HERC1 gene. This is the first study to investigate the distribution of HERC1 polymorphisms in various populations. (c) 2009 John Wiley & Sons, Ltd.

  11. Honey bee-inspired algorithms for SNP haplotype reconstruction problem

    Science.gov (United States)

    PourkamaliAnaraki, Maryam; Sadeghi, Mehdi

    2016-03-01

    Reconstructing haplotypes from SNP fragments is an important problem in computational biology. There have been a lot of interests in this field because haplotypes have been shown to contain promising data for disease association research. It is proved that haplotype reconstruction in Minimum Error Correction model is an NP-hard problem. Therefore, several methods such as clustering techniques, evolutionary algorithms, neural networks and swarm intelligence approaches have been proposed in order to solve this problem in appropriate time. In this paper, we have focused on various evolutionary clustering techniques and try to find an efficient technique for solving haplotype reconstruction problem. It can be referred from our experiments that the clustering methods relying on the behaviour of honey bee colony in nature, specifically bees algorithm and artificial bee colony methods, are expected to result in more efficient solutions. An application program of the methods is available at the following link. http://www.bioinf.cs.ipm.ir/software/haprs/

  12. Haplotype inference in general pedigrees with two sites

    Directory of Open Access Journals (Sweden)

    Doan Duong D

    2011-04-01

    Full Text Available Abstract Background Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with two sites for all members. Results We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem and therefore can be solved by an O(2k · n2 exact algorithm, where n is the number of members and k is the number of recombination events. Conclusions Our work can therefore be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.

  13. Identification of Tribolium castaneum (Herbst) haplotypes, the pest of ...

    African Journals Online (AJOL)

    SARAH

    2016-07-31

    Jul 31, 2016 ... haplotypes of T. castaneum and their distribution in Senegal. Methodology ... very strong marketing of cereals and vegetables in that area. The mutations ..... for each channel by sampling the various parameters every 1000 ...

  14. Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification

    Science.gov (United States)

    Janson, Marleen M.; Roesler, Mark R.; Avner, Ellis D.; Strawn, Estil Y.; Bick, David P.

    2010-01-01

    Purpose To develop a reliable preimplantation genetic diagnosis protocol for couples who both carry a mutant PKHD1 gene wishing to conceive children unaffected with autosomal recessive polycystic kidney disease (ARPKD). Methods Development of a unique protocol for preimplantation genetic testing using whole genome amplification of single blastomeres by multiple displacement amplification (MDA), and haplotype analysis with novel short tandem repeat (STR) markers from the PKHD1 gene and flanking sequences, and a case report of successful utilization of the protocol followed by successful IVF resulting in the birth of an infant unaffected with ARPKD. Results We have developed 20 polymorphic STR markers suitable for linkage analysis of ARPKD. These linked STR markers have enabled unambiguous identification of the PKHD1 haplotypes of embryos produced by at-risk couples. Conclusions We have developed a reliable protocol for preimplantation genetic diagnosis of ARPKD using single-cell MDA products for PKHD1 haplotyping. PMID:20490649

  15. Sequence variation of bovine mitochondrial ND-5 between haplotypes of composite and Hereford Breeds of beef cattle

    Directory of Open Access Journals (Sweden)

    SUTARNO

    2002-07-01

    Full Text Available The aims of the study were to: Investigate polymorphisms in the ND-5 region of bovine mitochondrial DNA in the composite and purebred Hereford herds from the Wokalup selection experiment, sequencing and compare the sequences between haplotypes and published sequence from Genebank. A total of 194 Hereford and 235 composite breed cattle from Wokalup Research Station were used in this study. The mitochondrial DNA was extracted using Wizard genomic DNA purification system from Promega. ND-5 fragment of mitochondrial DNA was amplified using PCR and continued with RFLP. Each haplotypes were sequenced. PCR products of each haplotype were cloned into pCR II, transformed, colonies selection, plasmid DNA extraction continued with cycle sequencing. Polymorphisms were found in both breeds of cattle in ND-5 region of mitochondrial DNA by PCR-RFLP analysis. Sequencing analysis confirmed the RFLPs data.

  16. MHC Class II haplotypes of Colombian Amerindian tribes

    Science.gov (United States)

    Yunis, Juan J.; Yunis, Edmond J.; Yunis, Emilio

    2013-01-01

    We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America. PMID:23885196

  17. Strategies for haplotype-based association mapping in complex pedigreed populations

    DEFF Research Database (Denmark)

    Boleckova, J; Christensen, Ole Fredslund; Sørensen, Peter

    2012-01-01

    In association mapping, haplotype-based methods are generally regarded to provide higher power and increased precision than methods based on single markers. For haplotype-based association mapping most studies use a fixed haplotype effect in the model. However, an increase in haplotype length inc...

  18. Texture analysis with neutron bending on geological/mineralogical multi-phase samples using a locally resolving detector and profile analysis

    International Nuclear Information System (INIS)

    Merz, P.L.

    1991-02-01

    In the context of this work, the NANCY four circuit diffractometer of the University of Bonn at the RRJ2 research reactor at KFA Juelich was equipped with a linear locally resolving scintillation detector JULIOS. To evaluate the diffractogram occurring at a pole figure measurement, user-friendly profile analysis and other evaluation programs were developed on the PC. The course of evaluation was largely automated, so that only a few interactive steps are required. The measuring period of a sample is usually two to three days. Up to 35 pole figures are produced, depending on the phase conditions of the examined sample. The evaluation of up to 900 diffractograms with the aid of the automatically running profile analysis program takes between 30 and 100 minutes on a 20 MHz PC 386. Pole figure datafiles are produced from the intensity data obtained in this way by a conversion program. The texture analyses of copper pyrites ores introduced here are connected with geological questions. (orig.) [de

  19. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

    Czech Academy of Sciences Publication Activity Database

    Tulupová, Elena; Kumar, R.; Hánová, Monika; Slyšková, Jana; Pardini, Barbara; Poláková, Veronika; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Halamková, J.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 648, 1-2 (2008), s. 40-45 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA mismatch repair * Genetic polymorphism * Haplotype analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  20. Analysis of a photon number resolving detector based on fluorescence readout of an ion Coulomb crystal quantum memory inside an optical cavity

    DEFF Research Database (Denmark)

    Clausen, Christoph; Sangouard, N.; Drewsen, M.

    2013-01-01

    The ability to detect single photons with a high efficiency is a crucial requirement for various quantum information applications. By combining the storage process of a quantum memory for photons with fluorescence-based quantum state measurement, it is, in principle, possible to achieve high......-efficiency photon counting in large ensembles of atoms. The large number of atoms can, however, pose significant problems in terms of noise stemming from imperfect initial state preparation and off-resonant fluorescence. We identify and analyse a concrete implementation of a photon number resolving detector based...... larger than 93%. Moderate experimental parameters allow for repetition rates of about 3 kHz, limited by the time needed for fluorescence collection and re-cooling of the ions between trials. Our analysis may lead to the first implementation of a photon number resolving detector in atomic ensembles....

  1. Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor ( Gene

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhang

    2015-10-01

    Full Text Available The AT motif-binding factor (ATBF1 not only interacts with protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3 (PIAS3 to suppress STAT3 signaling regulating embryo early development and cell differentiation, but is required for early activation of the pituitary specific transcription factor 1 (Pit1 gene (also known as POU1F1 critically affecting mammalian growth and development. The goal of this study was to detect novel nucleotide variations and haplotypes structure of the ATBF1 gene, as well as to test their associations with growth-related traits in goats. Herein, a total of seven novel single nucleotide polymorphisms (SNPs (SNP 1-7 within this gene were found in two well-known Chinese native goat breeds. Haplotypes structure analysis demonstrated that there were four haplotypes in Hainan black goat while seventeen haplotypes in Xinong Saanen dairy goat, and both breeds only shared one haplotype (hap1. Association testing revealed that the SNP2, SNP5, SNP6, and SNP7 loci were also found to significantly associate with growth-related traits in goats, respectively. Moreover, one diplotype in Xinong Saanen dairy goats significantly linked to growth related traits. These preliminary findings not only would extend the spectrum of genetic variations of the goat ATBF1 gene, but also would contribute to implementing marker-assisted selection in genetics and breeding in goats.

  2. Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

    Science.gov (United States)

    Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

    2008-11-01

    Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

  3. Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

    Directory of Open Access Journals (Sweden)

    Srinivasan Pugazhendhi

    Full Text Available Inflammatory bowel disease (IBD is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs in the autophagy related 16 like 1 (ATG16L1 gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD, 249 patients with ulcerative colitis (UC and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0 and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC. SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

  4. A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families.

    Science.gov (United States)

    Hettinger, Joe A; Liu, Xudong; Schwartz, Charles E; Michaelis, Ron C; Holden, Jeanette J A

    2008-07-05

    Individuals with autism spectrum disorders (ASDs) have impairments in executive function and social cognition, with males generally being more severely affected in these areas than females. Because the dopamine D1 receptor (encoded by DRD1) is integral to the neural circuitry mediating these processes, we examined the DRD1 gene for its role in susceptibility to ASDs by performing single marker and haplotype case-control comparisons, family-based association tests, and genotype-phenotype assessments (quantitative transmission disequilibrium tests: QTDT) using three DRD1 polymorphisms, rs265981C/T, rs4532A/G, and rs686T/C. Our previous findings suggested that the dopaminergic system may be more integrally involved in families with affected males only than in other families. We therefore restricted our study to families with two or more affected males (N = 112). There was over-transmission of rs265981-C and rs4532-A in these families (P = 0.040, P = 0.038), with haplotype TDT analysis showing over-transmission of the C-A-T haplotype (P = 0.022) from mothers to affected sons (P = 0.013). In addition, haplotype case-control comparisons revealed an increase of this putative risk haplotype in affected individuals relative to a comparison group (P = 0.004). QTDT analyses showed associations of the rs265981-C, rs4532-A, rs686-T alleles, and the C-A-T haplotype with more severe problems in social interaction, greater difficulties with nonverbal communication and increased stereotypies compared to individuals with other haplotypes. Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of ASD in families having only affected males. Copyright 2008 Wiley-Liss, Inc.

  5. Dimensional Anxiety Mediates Linkage of GABRA2 Haplotypes With Alcoholism

    Science.gov (United States)

    Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2015-01-01

    The GABAAα2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P α0.007, OR α2.1, Plains Indians: P α0.040, OR α1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

  6. New Cases of Thelazia callipaeda Haplotype 1 in Dogs Suggest a Wider Distribution in Romania.

    Science.gov (United States)

    Ioniţă, Mariana; Mitrea, Ioan Liviu; Ionică, Angela Monica; Morariu, Sorin; Mihalca, Andrei Daniel

    2016-03-01

    Thelazia callipaeda is an emerging vector-borne zoonotic helminth parasitizing the conjunctival sac of a broad spectrum of definitive hosts, such as dogs, cats, rabbits, wild carnivores, and humans. Its presence is associated with mild to severe ocular disease. Here, we report two new clinical cases in dogs originating from western and southern Romania, with no travel history. On clinical examination, the nematodes were retrieved from the conjunctival sac and identified using morphological keys and molecular tools. Twenty-two adult nematodes (8 males, 14 females) were collected and were identified as T. callipaeda by morphology. The molecular analysis revealed a 100% identity with haplotype h1 of T. callipaeda. This study describes the occurrence of new autochthonous cases of thelaziosis in Romania, reinforcing the spreading trend of this zoonotic eyeworm and highlighting the need for increased awareness among medical and veterinary practitioners. Moreover, we provide additional molecular evidence for the exclusive distribution of haplotype 1 of T. callipaeda in Europe.

  7. Should prenatal hydronephrosis that resolves before birth be followed postnatally? Analysis and comparison to persistent prenatal hydronephrosis.

    Science.gov (United States)

    Scarborough, Patrick L; Ferrara, Elizabeth; Storm, Douglas W

    2015-09-01

    Prenatal ultrasonography has greatly enhanced detection of congenital genitourinary abnormalities. However, although persistent prenatal hydronephrosis (PPH) is typically imaged and followed postnatally, it remains unclear if prenatal hydronephrosis that resolves in utero (RPH) should be similarly managed. We determined postnatal abnormalities associated with RPH and compared these to those associated with PPH. We performed a retrospective review of all consecutive patients evaluated for prenatal hydronephrosis over 24 months. Patients were followed prenatally with serial ultrasounds and postnatally with ultrasonography and a voiding cystourethrogram. Of the consecutive 165 patients enrolled in the study, 72 had RPH. The average prenatal anterior-posterior renal pelvis length was significantly longer in patients with PPH (5.5 mm) than in those with RPH (4.9 mm) (p = 0.01). Recurrent postnatal hydronephrosis occurred in 44% of patients with RPH, with eventual resolution in 34% of those affected. In comparison, 29% of PPH cases resolved postnatally. Mean time to resolution was statistically shorter for PPH (116 days) than for RPH (175 days) (p = 0.01). Seven PPH patients required surgery, while no RPH patients needed intervention (difference was statistically significant). A significant number of RPH children had postnatal hydronephrosis. Despite a slower resolution time, no children with RPH required intervention. Although RPH may recur postnatally, the significantly lower chance of intervention being required suggests that these children may not require postnatal imaging.

  8. Genomic identification of founding haplotypes reveals the history of the selfing species Capsella rubella.

    Directory of Open Access Journals (Sweden)

    Yaniv Brandvain

    Full Text Available The shift from outcrossing to self-fertilization is among the most common evolutionary transitions in flowering plants. Until recently, however, a genome-wide view of this transition has been obscured by both a dearth of appropriate data and the lack of appropriate population genomic methods to interpret such data. Here, we present a novel population genomic analysis detailing the origin of the selfing species, Capsella rubella, which recently split from its outcrossing sister, Capsella grandiflora. Due to the recency of the split, much of the variation within C. rubella is also found within C. grandiflora. We can therefore identify genomic regions where two C. rubella individuals have inherited the same or different segments of ancestral diversity (i.e. founding haplotypes present in C. rubella's founder(s. Based on this analysis, we show that C. rubella was founded by multiple individuals drawn from a diverse ancestral population closely related to extant C. grandiflora, that drift and selection have rapidly homogenized most of this ancestral variation since C. rubella's founding, and that little novel variation has accumulated within this time. Despite the extensive loss of ancestral variation, the approximately 25% of the genome for which two C. rubella individuals have inherited different founding haplotypes makes up roughly 90% of the genetic variation between them. To extend these findings, we develop a coalescent model that utilizes the inferred frequency of founding haplotypes and variation within founding haplotypes to estimate that C. rubella was founded by a potentially large number of individuals between 50 and 100 kya, and has subsequently experienced a twenty-fold reduction in its effective population size. As population genomic data from an increasing number of outcrossing/selfing pairs are generated, analyses like the one developed here will facilitate a fine-scaled view of the evolutionary and demographic impact of the

  9. Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

    Science.gov (United States)

    Furgeri, Daniela Tenório; Marson, Fernando Augusto Lima; Correia, Cyntia Arivabeni Araújo; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia

    2018-01-30

    Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible. Therefore, silent polymorphisms can be used to label the mutant allele in households of patients with CF. To verify the haplotypes of four polymorphisms at the CFTR locus in households of patients with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation diagnosis to provide better genetic counseling for families and patients with CF and to associate the genotypes/haplotypes with the F508del mutation screening. GATT polymorphism analysis was performed using direct polymerase chain reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses were performed using restriction fragment length polymorphism. Nine haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of households analyzed, at least one informative polymorphism can be used for the indirect diagnostic test. CFTR polymorphisms are genetic markers that are useful for identifying the mutant CFTR alleles in households of patients with CF when it is not possible to establish the complete CFTR genotype. Moreover, the polymorphisms can be used for indirect CFTR mutation identification in cases of pre-fertilization, pre-implantation and prenatal analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    NARCIS (Netherlands)

    Calus, M.P.L.; Meuwissen, T.H.E.; Windig, J.J.; Knol, E.F.; Schrooten, C.; Vereijken, A.L.J.; Veerkamp, R.F.

    2009-01-01

    The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD) probabilities between haplotypes, various haplotype definitions were tested i.e.

  11. Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing.

    Science.gov (United States)

    Hamstra, D A; de Kloet, E R; van Hemert, A M; de Rijk, R H; Van der Does, A J W

    2015-02-12

    Oral contraceptives (OCs) affect mood in some women and may have more subtle effects on emotional information processing in many more users. Female carriers of mineralocorticoid receptor (MR) haplotype 2 have been shown to be more optimistic and less vulnerable to depression. To investigate the effects of oral contraceptives on emotional information processing and a possible moderating effect of MR haplotype. Cross-sectional study in 85 healthy premenopausal women of West-European descent. We found significant main effects of oral contraceptives on facial expression recognition, emotional memory and decision-making. Furthermore, carriers of MR haplotype 1 or 3 were sensitive to the impact of OCs on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. Different compounds of OCs were included. No hormonal measures were taken. Most naturally cycling participants were assessed in the luteal phase of their menstrual cycle. Carriers of MR haplotype 2 may be less sensitive to depressogenic side-effects of OCs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. In Vivo Characterization of Human APOA5 Haplotypes

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila; Pennacchio, Len A.

    2006-10-01

    Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

  13. Time-resolved analysis of thickness-dependent dewetting and ablation of silver films upon nanosecond laser irradiation

    International Nuclear Information System (INIS)

    Qi, Dongfeng; Paeng, Dongwoo; Yeo, Junyeob; Kim, Eunpa; Wang, Letian; Grigoropoulos, Costas P.; Chen, Songyan

    2016-01-01

    Nanosecond pulsed laser dewetting and ablation of thin silver films is investigated by time-resolved imaging. Laser pulses of 532 nm wavelength and 5 ns temporal width are irradiated on silver films of different thicknesses (50 nm, 80 nm, and 350 nm). Below the ablation threshold, it is observed that the dewetting process does not conclude until 630 ns after the laser irradiation for all samples, forming droplet-like particles in the spot central region. At higher laser intensities, ablative material removal occurs in the spot center. Cylindrical rims are formed in the peripheral dewetting zone due to the solidification of transported matter at about 700 ns following the laser pulse exposure. In addition to these features, droplet fingers are superposed upon irradiation of 350-nm thick silver films with higher intensity.

  14. Time-resolved analysis of thickness-dependent dewetting and ablation of silver films upon nanosecond laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Dongfeng [Laser Thermal Laboratory, Department of Mechanical Engineering, University of California, Berkeley, California 94720-1740 (United States); Semiconductor Photonics Research Center, Department of Physics, Xiamen University, Xiamen 361005 (China); Paeng, Dongwoo; Yeo, Junyeob; Kim, Eunpa; Wang, Letian; Grigoropoulos, Costas P., E-mail: cgrigoro@berkeley.edu [Laser Thermal Laboratory, Department of Mechanical Engineering, University of California, Berkeley, California 94720-1740 (United States); Chen, Songyan [Semiconductor Photonics Research Center, Department of Physics, Xiamen University, Xiamen 361005 (China)

    2016-05-23

    Nanosecond pulsed laser dewetting and ablation of thin silver films is investigated by time-resolved imaging. Laser pulses of 532 nm wavelength and 5 ns temporal width are irradiated on silver films of different thicknesses (50 nm, 80 nm, and 350 nm). Below the ablation threshold, it is observed that the dewetting process does not conclude until 630 ns after the laser irradiation for all samples, forming droplet-like particles in the spot central region. At higher laser intensities, ablative material removal occurs in the spot center. Cylindrical rims are formed in the peripheral dewetting zone due to the solidification of transported matter at about 700 ns following the laser pulse exposure. In addition to these features, droplet fingers are superposed upon irradiation of 350-nm thick silver films with higher intensity.

  15. Spatial-Resolved Measurement and Analysis of Extreme-Ultraviolet Emission Spectra from Laser-Produced Al Plasmas

    International Nuclear Information System (INIS)

    Cao Shi-Quan; Su Mao-Gen; Sun Dui-Xiong; Min Qi; Dong Chen-Zhong

    2016-01-01

    Extreme ultraviolet emission from laser-produced Al plasma is experimentally and theoretically investigated. Spatial-evolution emission spectra are measured by using the spatio-temporally resolved laser produced plasma technique. Based on the assumptions of a normalized Boltzmann distribution among the excited states and a steady-state collisional-radiative model, we succeed in reproducing the spectra at different detection positions, which are in good agreement with experiments. The decay curves about the electron temperature and electron density, as well as the fractions of individual Al ions and average ionization stage with increasing the detection distance are obtained by comparison with the experimental measurements. These parameters are critical points for deeply understanding the expanding and cooling of laser produced plasmas in vacuum. (paper)

  16. BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes.

    Science.gov (United States)

    Salles, José Inácio; Amaral, Marcus Vinícius; Aguiar, Diego Pinheiro; Lira, Daisy Anne; Quinelato, Valquiria; Bonato, Letícia Ladeira; Duarte, Maria Eugenia Leite; Vieira, Alexandre Rezende; Casado, Priscila Ladeira

    2015-03-01

    To investigate whether genetic variants can be correlated with tendinopathy in elite male volleyball athletes. Case-control study. Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1 genes were investigated in 138 elite volleyball athletes, aged between 18 and 35 years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and hip abductors tendons. The clinical diagnostic criterion was progressive pain during training, confirmed by magnetic resonance image. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR. Chi-square test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of covariates and incidence of tendinopathy. Statistical analysis revealed participant age (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379. FGFR1 showed no association with disease. These findings indicate that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease process in elite volleyball athletes. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Shrinkage Estimators for Robust and Efficient Inference in Haplotype-Based Case-Control Studies

    KAUST Repository

    Chen, Yi-Hau

    2009-03-01

    Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can adaptively relax the model assumptions of Hardy-Weinberg-Equilibrium and gene-environment independence required by recently proposed efficient "retrospective" methods. Our proposal involves first development of a novel retrospective approach to the analysis of case-control data, one that is robust to the nature of the gene-environment distribution in the underlying population. Next, it involves shrinkage of the robust retrospective estimator toward a more precise, but model-dependent, retrospective estimator using novel empirical Bayes and penalized regression techniques. Methods for variance estimation are proposed based on asymptotic theories. Simulations and two data examples illustrate both the robustness and efficiency of the proposed methods.

  18. Shrinkage Estimators for Robust and Efficient Inference in Haplotype-Based Case-Control Studies

    KAUST Repository

    Chen, Yi-Hau; Chatterjee, Nilanjan; Carroll, Raymond J.

    2009-01-01

    Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can adaptively relax the model assumptions of Hardy-Weinberg-Equilibrium and gene-environment independence required by recently proposed efficient "retrospective" methods. Our proposal involves first development of a novel retrospective approach to the analysis of case-control data, one that is robust to the nature of the gene-environment distribution in the underlying population. Next, it involves shrinkage of the robust retrospective estimator toward a more precise, but model-dependent, retrospective estimator using novel empirical Bayes and penalized regression techniques. Methods for variance estimation are proposed based on asymptotic theories. Simulations and two data examples illustrate both the robustness and efficiency of the proposed methods.

  19. More powerful haplotype sharing by accounting for the mode of inheritance.

    Science.gov (United States)

    Ziegler, Andreas; Ewhida, Adel; Brendel, Michael; Kleensang, André

    2009-04-01

    The concept of haplotype sharing (HS) has received considerable attention recently, and several haplotype association methods have been proposed. Here, we extend the work of Beckmann and colleagues [2005 Hum. Hered. 59:67-78] who derived an HS statistic (BHS) as special case of Mantel's space-time clustering approach. The Mantel-type HS statistic correlates genetic similarity with phenotypic similarity across pairs of individuals. While phenotypic similarity is measured as the mean-corrected cross product of phenotypes, we propose to incorporate information of the underlying genetic model in the measurement of the genetic similarity. Specifically, for the recessive and dominant modes of inheritance we suggest the use of the minimum and maximum of shared length of haplotypes around a marker locus for pairs of individuals. If the underlying genetic model is unknown, we propose a model-free HS Mantel statistic using the max-test approach. We compare our novel HS statistics to BHS using simulated case-control data and illustrate its use by re-analyzing data from a candidate region of chromosome 18q from the Rheumatoid Arthritis (RA) Consortium. We demonstrate that our approach is point-wise valid and superior to BHS. In the re-analysis of the RA data, we identified three regions with point-wise P-values<0.005 containing six known genes (PMIP1, MC4R, PIGN, KIAA1468, TNFRSF11A and ZCCHC2) which might be worth follow-up.

  20. Effect of genetic type and casein haplotype on antioxidant activity of yogurts during storage.

    Science.gov (United States)

    Perna, A; Intaglietta, I; Simonetti, A; Gambacorta, E

    2013-06-01

    The aim of this work was to investigate the antioxidant activity of yogurt made from the milk of 2 breeds-Italian Brown and Italian Holstein-characterized by different casein haplotypes (αS1-, β-, and κ-caseins) during storage up to 15 d. The casein haplotype was determined by isoelectric focusing; antioxidant activity of yogurt was measured using 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid). The statistical analysis showed a significant effect of the studied factors. Antioxidant activity increased during storage of both yogurt types, but yogurt produced with Italian Brown milk showed higher antioxidant activity than those produced with Italian Holstein milk. A high scavenging activity was present in yogurts with the allelic combination of BB-A(2)A(2)-BB. The results of this study suggest that the genetic type and the haplotype make a significant contribution in the production of yogurts with high nutraceutical value. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Shindo, Hiroyuki; Chigira, Hiroshi; Nagaoka, Tomoyo; Inoue, Masato [Department of Electrical Engineering and Bioscience, School of Advanced Science and Engineering, Waseda University, 3-4-1, Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Kamatani, Naoyuki, E-mail: masato.inoue@eb.waseda.ac.j [Institute of Rheumatology, Tokyo Women' s Medical University, 10-22, Kawada-cho, Shinjuku-ku, Tokyo 162-0054 (Japan)

    2009-12-01

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

  3. HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

    Directory of Open Access Journals (Sweden)

    Camille Ribeyre

    2018-02-01

    Full Text Available Human leukocyte antigen (HLA-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC. Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing, thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF binding sites and alternative splicing sites. HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a

  4. Prion gene haplotypes of U.S. cattle

    Directory of Open Access Journals (Sweden)

    Harhay Gregory P

    2006-11-01

    Full Text Available Abstract Background Bovine spongiform encephalopathy (BSE is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD and haplotype networks within the bovine prion gene (PRNP is important for 1 testing rare or common PRNP variation for an association with BSE and 2 interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb. PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb. Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS which characterize variation within and across PRNP. Conclusion The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle.

  5. On the relationship between instantaneous phase synchrony and correlation-based sliding windows for time-resolved fMRI connectivity analysis.

    Science.gov (United States)

    Pedersen, Mangor; Omidvarnia, Amir; Zalesky, Andrew; Jackson, Graeme D

    2018-06-08

    Correlation-based sliding window analysis (CSWA) is the most commonly used method to estimate time-resolved functional MRI (fMRI) connectivity. However, instantaneous phase synchrony analysis (IPSA) is gaining popularity mainly because it offers single time-point resolution of time-resolved fMRI connectivity. We aim to provide a systematic comparison between these two approaches, on both temporal and topological levels. For this purpose, we used resting-state fMRI data from two separate cohorts with different temporal resolutions (45 healthy subjects from Human Connectome Project fMRI data with repetition time of 0.72 s and 25 healthy subjects from a separate validation fMRI dataset with a repetition time of 3 s). For time-resolved functional connectivity analysis, we calculated tapered CSWA over a wide range of different window lengths that were temporally and topologically compared to IPSA. We found a strong association in connectivity dynamics between IPSA and CSWA when considering the absolute values of CSWA. The association between CSWA and IPSA was stronger for a window length of ∼20 s (shorter than filtered fMRI wavelength) than ∼100 s (longer than filtered fMRI wavelength), irrespective of the sampling rate of the underlying fMRI data. Narrow-band filtering of fMRI data (0.03-0.07 Hz) yielded a stronger relationship between IPSA and CSWA than wider-band (0.01-0.1 Hz). On a topological level, time-averaged IPSA and CSWA nodes were non-linearly correlated for both short (∼20 s) and long (∼100 s) windows, mainly because nodes with strong negative correlations (CSWA) displayed high phase synchrony (IPSA). IPSA and CSWA were anatomically similar in the default mode network, sensory cortex, insula and cerebellum. Our results suggest that IPSA and CSWA provide comparable characterizations of time-resolved fMRI connectivity for appropriately chosen window lengths. Although IPSA requires narrow-band fMRI filtering, we recommend the use of

  6. Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Quataert, Ina; Jansen, Myrthe; Van der Does, Willem

    2017-02-01

    Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week. At both sessions E2 and P4 were assessed in saliva. Tests included implicit and explicit positive and negative affect, attentional blink accuracy, emotional memory, emotion recognition, and risky decision-making (gambling). MR-haplotype 2 homozygotes had higher implicit happiness scores than MR-haplotype 2 heterozygotes (p=0.031) and MR-haplotype 1/3 carriers (pemotion recognition test than MR-haplotype 1/3 (p=0.001). Practice effects were observed for most measures. The pattern of correlations between information processing and P4 or E2 differed between sessions, as well as the moderating effects of the MR genotype. In the first session the MR-genotype moderated the influence of P4 on implicit anxiety (sr=-0.30; p=0.005): higher P4 was associated with reduction in implicit anxiety, but only in MR-haplotype 2 homozygotes (sr=-0.61; p=0.012). In the second session the MR-genotype moderated the influence of E2 on the recognition of facial expressions of happiness (sr=-0.21; p=0.035): only in MR-haplotype 1/3 higher E2 was correlated with happiness recognition (sr=0.29; p=0.005). In the second session higher E2 and P4 were negatively correlated with accuracy in lag2 trials of the attentional blink task (pemotional information processing. This moderating effect may depend on the novelty of the situation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Analysis of the environments of seven Mediterranean tropical-like storms using an axisymmetric, nonhydrostatic, cloud resolving model

    Directory of Open Access Journals (Sweden)

    L. Fita

    2007-01-01

    Full Text Available Tropical-like storms on the Mediterranean Sea are occasionally observed on satellite images, often with a clear eye surrounded by an axysimmetric cloud structure. These storms sometimes attain hurricane intensity and can severely affect coastal lands. A deep, cut-off, cold-core low is usually observed at mid-upper tropospheric levels in association with the development of these tropical-like systems. In this study we attempt to apply some tools previously used in studies of tropical hurricanes to characterise the environments in which seven known Mediterranean events developed. In particular, an axisymmetric, nonhydrostatic, cloud resolving model is applied to simulate the tropical-like storm genesis and evolution. Results are compared to surface observations when landfall occurred and with satellite microwave derived wind speed measurements over the sea. Finally, sensitivities of the numerical simulations to different factors (e.g. sea surface temperature, vertical humidity profile and size of the initial precursor of the storm are examined.

  8. Time-resolved spectral analysis of prompt emission from long gamma-ray bursts with GeV emission

    International Nuclear Information System (INIS)

    Rao Arikkala Raghurama; Basak Rupal; Bhattacharya Jishnu; Chandra Sarthak; Maheshwari Nikunj; Choudhury Manojendu; Misra Ranjeev

    2014-01-01

    We performed detailed time-resolved spectroscopy of bright long gamma-ray bursts (GRBs) which show significant GeV emissions (GRB 080916C, GRB 090902B and GRB 090926A). In addition to the standard Band model, we also use a model consisting of a black body and a power law to fit the spectra. We find that for the latter model there are indications of an additional soft component in the spectra. While previous studies have shown that such models are required for GRB 090902B, here we find that a composite spectral model consisting of two blackbodies and a power law adequately fits the data of all the three bright GRBs. We investigate the evolution of the spectral parameters and find several interesting features that appear in all three GRBs, like (a) temperatures of the blackbodies are strongly correlated with each other, (b) fluxes in the black body components are strongly correlated with each other, (c) the temperatures of the black body trace the profile of the individual pulses of the GRBs, and (d) the characteristics of power law components like the spectral index and the delayed onset bear a close similarity to the emission characteristics in the GeV regions. We discuss the implications of these results and the possibility of identifying the radiation mechanisms during the prompt emission of GRBs. (research papers)

  9. Improving representation of convective transport for scale-aware parameterization: 2. Analysis of cloud-resolving model simulations

    Science.gov (United States)

    Liu, Yi-Chin; Fan, Jiwen; Zhang, Guang J.; Xu, Kuan-Man; Ghan, Steven J.

    2015-04-01

    Following Part I, in which 3-D cloud-resolving model (CRM) simulations of a squall line and mesoscale convective complex in the midlatitude continental and the tropical regions are conducted and evaluated, we examine the scale dependence of eddy transport of water vapor, evaluate different eddy transport formulations, and improve the representation of convective transport across all scales by proposing a new formulation that more accurately represents the CRM-calculated eddy flux. CRM results show that there are strong grid-spacing dependencies of updraft and downdraft fractions regardless of altitudes, cloud life stage, and geographical location. As for the eddy transport of water vapor, updraft eddy flux is a major contributor to total eddy flux in the lower and middle troposphere. However, downdraft eddy transport can be as large as updraft eddy transport in the lower atmosphere especially at the mature stage of midlatitude continental convection. We show that the single-updraft approach significantly underestimates updraft eddy transport of water vapor because it fails to account for the large internal variability of updrafts, while a single downdraft represents the downdraft eddy transport of water vapor well. We find that using as few as three updrafts can account for the internal variability of updrafts well. Based on the evaluation with the CRM simulated data, we recommend a simplified eddy transport formulation that considers three updrafts and one downdraft. Such formulation is similar to the conventional one but much more accurately represents CRM-simulated eddy flux across all grid scales.

  10. Aeroacoustic analysis of an airfoil with Gurney flap based on time-resolved particle image velocimetry measurements

    Science.gov (United States)

    Zhang, Xueqing; Sciacchitano, Andrea; Pröbsting, Stefan

    2018-05-01

    Particle image velocimetry for the experimental assessment of trailing edge noise sources has become focus of research in recent years. The present study investigates the feasibility of the noise prediction for high-lift devices based on time-resolved particle image velocimetry (PIV). The model under investigation is a NACA 0015 airfoil with a Gurney flap with a height of 6% of the chord length. The velocity fields around and downstream of the Gurney flap were measured by PIV and used to compute the corresponding pressure fields by solving the Poisson equation for incompressible flows. The reconstructed pressure fluctuations on the airfoil surface constitute the source term for Curle's aeroacoustic analogy, which was employed in both the distributed and compact formulation to estimate the noise emission from PIV. The results of the two formulations are compared with the simultaneous far-field microphone measurements in the temporal and spectral domains. Both formulations of Curle's analogy yield acoustic sound pressure levels in good agreement with the simultaneous microphone measurements for the tonal component. The estimated far-field sound power spectra (SPL) from the PIV measurements reproduce the peak at the vortex shedding frequency, which also agrees well with the acoustic measurements.

  11. Fast Fenton footprinting: a laboratory-based method for the time-resolved analysis of DNA, RNA and proteins

    Science.gov (United States)

    Shcherbakova, Inna; Mitra, Somdeb; Beer, Robert H.; Brenowitz, Michael

    2006-01-01

    ‘Footprinting’ describes assays in which ligand binding or structure formation protects polymers such as nucleic acids and proteins from either cleavage or modification; footprinting allows the accessibility of individual residues to be mapped in solution. Equilibrium and time-dependent footprinting links site-specific structural information with thermodynamic and kinetic transitions. The hydroxyl radical (·OH) is a particularly valuable footprinting probe by virtue of it being among the most reactive of chemical oxidants; it reports the solvent accessibility of reactive sites on macromolecules with as fine as a single residue resolution. A novel method of millisecond time-resolved ·OH footprinting has been developed based on the Fenton reaction, Fe(II) + H2O2 → Fe(III) + ·OH + OH−. This method can be implemented in laboratories using widely available three-syringe quench flow mixers and inexpensive reagents to study local changes in the solvent accessibility of DNA, RNA and proteins associated with their biological function. PMID:16582097

  12. Analysis of time- and space-resolved Na-, Ne-, and F-like emission from a laser-produced bromine plasma

    International Nuclear Information System (INIS)

    Goldstein, W.H.; Young, B.K.F.; Osterheld, A.L.; Stewart, R.E.; Walling, R.S.; Bar-Shalom, A.

    1991-01-01

    Advances in the efficiency and accuracy of computational atomic physics and collisional radiative modeling promise to place the analysis and diagnostic application of L-shell emission on a par with the simpler K-shell regime. Coincident improvements in spectroscopic plasma measurements yield optically thin emission spectra from small, homogeneous regions of plasma, localized both in space and time. Together, these developments can severely test models for high-density, high-temperature plasma formation and evolution, and non-LTE atomic kinetics. In this paper we present highly resolved measurements of n=3 to n=2 X-ray line emission from a laser-produced bromine micro plasma. The emission is both space- and time-resolved, allowing us to apply simple, steady-state, 0-dimensional spectroscopic models to the analysis. These relativistic, multi-configurational, distorted wave collisional-radiative models were created using the HULLAC atomic physics package. Using these models, we have analyzed the F-like, Ne-like and Na-like (satellite) spectra with respect to temperature, density and charge-state distribution. This procedure leads to a full characterization of the plasma conditions. 9 refs., 3 figs

  13. Time- and energy resolved photoemission electron microscopy-imaging of photoelectron time-of-flight analysis by means of pulsed excitations

    International Nuclear Information System (INIS)

    Oelsner, Andreas; Rohmer, Martin; Schneider, Christian; Bayer, Daniela; Schoenhense, Gerd; Aeschlimann, Martin

    2010-01-01

    The present work enlightens the developments in time- and energy resolved photoemission electron microscopy over the past few years. We describe basic principles of the technique and demonstrate different applications. An energy- and time-filtering photoemission electron microscopy (PEEM) for real-time spectroscopic imaging can be realized either by a retarding field or hemispherical energy analyzer or by using time-of-flight optics with a delay line detector. The latter method has the advantage of no data loss at all as all randomly incoming particles are measured not only by position but also by time. This is of particular interest for pump-probe experiments in the femtosecond and attosecond time scale where space charge processes drastically limit the maximum number of photoemitted electrons per laser pulse. This work focuses particularly on time-of-flight analysis using a novel delay line detector. Time and energy resolved PEEM instruments with delay line detectors enable 4D imaging (x, y, Δt, E Kin ) on a true counting basis. This allows a broad range of applications from real-time observation of dynamic phenomena at surfaces to fs time-of-flight spectro-microscopy and even aberration correction. By now, these time-of-flight analysis instruments achieve intrinsic time resolutions of 108 ps absolute and 13.5 ps relative. Very high permanent measurement speeds of more than 4 million events per second in random detection regimes have been realized using a standard USB2.0 interface. By means of this performance, the time-resolved PEEM technique enables to display evolutions of spatially resolved (<25 nm) and temporal sliced images life on any modern computer. The method allows dynamics investigations of variable electrical, magnetic, and optical near fields at surfaces and great prospects in dynamical adaptive photoelectron optics. For dynamical processes in the ps time scale such as magnetic domain wall movements, the time resolution of the delay line detectors

  14. Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients.

    Science.gov (United States)

    Chowbay, Balram; Cumaraswamy, Sivathasan; Cheung, Yin Bun; Zhou, Qingyu; Lee, Edmund J D

    2003-02-01

    Intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) both play a vital role in the metabolism of oral cyclosporine (CsA). We investigated the genetic polymorphisms in CYP3A4(promoter region and exons 5, 7 and 9) and MDR1 (exons 12, 21 and 26) genes and the impact of these polymorphisms on the pharmacokinetics of oral CsA in stable heart transplant patients (n = 14). CYP3A4 polymorphisms were rare in the Asian population and transplant patients. Haplotype analysis revealed 12 haplotypes in the Chinese, eight in the Malays and 10 in the Indians. T-T-T was the most common haplotype in all ethnic groups. The frequency of the homozygous mutant genotype at all three loci (TT-TT-TT) was highest in the Indians (31%) compared to 19% and 15% in the Chinese and Malays, respectively. In heart transplant patients, CsA exposure (AUC(0-4 h), AUC(0-12 h) and C(max)) was high in patients with the T-T-T haplotypes compared to those with C-G-C haplotypes. These findings suggest that haplotypes rather than genotypes influence CsA disposition in transplant patients.

  15. Time-resolved analysis of particle emissions from residential biomass combustion - Emissions of refractory black carbon, PAHs and organic tracers

    Science.gov (United States)

    Nielsen, Ingeborg E.; Eriksson, Axel C.; Lindgren, Robert; Martinsson, Johan; Nyström, Robin; Nordin, Erik Z.; Sadiktsis, Ioannis; Boman, Christoffer; Nøjgaard, Jacob K.; Pagels, Joakim

    2017-09-01

    Time-resolved particle emissions from a conventional wood stove were investigated with aerosol mass spectrometry to provide links between combustion conditions, emission factors, mixing state of refractory black carbon and implications for organic tracer methods. The addition of a new batch of fuel results in low temperature pyrolysis as the fuel heats up, resulting in strong, short-lived, variable emission peaks of organic aerosol-containing markers of anhydrous sugars, such as levoglucosan (fragment at m/z 60). Flaming combustion results in emissions dominated by refractory black carbon co-emitted with minor fractions of organic aerosol and markers of anhydrous sugars. Full cycle emissions are an external mixture of larger organic aerosol-dominated and smaller thinly coated refractory black carbon particles. A very high burn rate results in increased full cycle mass emission factors of 66, 2.7, 2.8 and 1.3 for particulate polycyclic aromatic hydrocarbons, refractory black carbon, total organic aerosol and m/z 60, respectively, compared to nominal burn rate. Polycyclic aromatic hydrocarbons are primarily associated with refractory black carbon-containing particles. We hypothesize that at very high burn rates, the central parts of the combustion zone become air starved, leading to a locally reduced combustion temperature that reduces the conversion rates from polycyclic aromatic hydrocarbons to refractory black carbon. This facilitates a strong increase of polycyclic aromatic hydrocarbons emissions. At nominal burn rates, full cycle emissions based on m/z 60 correlate well with organic aerosol, refractory black carbon and particulate matter. However, at higher burn rates, m/z 60 does not correlate with increased emissions of polycyclic aromatic hydrocarbons, refractory black carbon and organic aerosol in the flaming phase. The new knowledge can be used to advance source apportionment studies, reduce emissions of genotoxic compounds and model the climate impacts of

  16. Angle resolved x-ray photoelectron spectroscopy (ARXPS) analysis of lanthanum oxide for micro-flexography printing

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, S., E-mail: suhaimihas@uthm.edu.my; Yusof, M. S., E-mail: mdsalleh@uthm.edu.my; Maksud, M. I., E-mail: midris1973@gmail.com [Faculty of Mechanical and Manufacturing Engineering, Universiti Tun Hussein Onn Malaysia, 86400 Batu Pahat, Johor (Malaysia); Embong, Z., E-mail: zaidi@uthm.edu.my [Faculty of Science, Technology and Human Development, Universiti Tun Hussein Onn Malaysia, 86400 Batu Pahat, Johor (Malaysia)

    2016-01-22

    Micro-flexography printing was developed in patterning technique from micron to nano scale range to be used for graphic, electronic and bio-medical device on variable substrates. In this work, lanthanum oxide (La{sub 2}O{sub 3}) has been used as a rare earth metal candidate as depositing agent. This metal deposit was embedded on Carbon (C) and Silica (Si) wafer substrate using Magnetron Sputtering technique. The choose of Lanthanum as a target is due to its wide application in producing electronic devices such as thin film battery and printed circuit board. The La{sub 2}O{sub 3} deposited on the surface of Si wafer substrate was then analyzed using Angle Resolve X-Ray Photoelectron Spectroscopy (ARXPS). The position for each synthetic component in the narrow scan of Lanthanum (La) 3d and O 1s are referred to the electron binding energy (eV). The La 3d narrow scan revealed that the oxide species of this particular metal is mainly contributed by La{sub 2}O{sub 3} and La(OH){sub 3}. The information of oxygen species, O{sup 2-} component from O 1s narrow scan indicated that there are four types of species which are contributed from the bulk (O{sup 2−}), two chemisorb component (La{sub 2}O{sub 3}) and La(OH){sub 3} and physisorp component (OH). Here, it is proposed that from the adhesive and surface chemical properties of La, it is suitable as an alternative medium for micro-flexography printing technique in printing multiple fine solid lines at nano scale. Hence, this paper will describe the capability of this particular metal as rare earth metal for use in of micro-flexography printing practice. The review of other parameters contributing to print fine lines will also be described later.

  17. Angle resolved x-ray photoelectron spectroscopy (ARXPS) analysis of lanthanum oxide for micro-flexography printing

    Science.gov (United States)

    Hassan, S.; Yusof, M. S.; Embong, Z.; Maksud, M. I.

    2016-01-01

    Micro-flexography printing was developed in patterning technique from micron to nano scale range to be used for graphic, electronic and bio-medical device on variable substrates. In this work, lanthanum oxide (La2O3) has been used as a rare earth metal candidate as depositing agent. This metal deposit was embedded on Carbon (C) and Silica (Si) wafer substrate using Magnetron Sputtering technique. The choose of Lanthanum as a target is due to its wide application in producing electronic devices such as thin film battery and printed circuit board. The La2O3 deposited on the surface of Si wafer substrate was then analyzed using Angle Resolve X-Ray Photoelectron Spectroscopy (ARXPS). The position for each synthetic component in the narrow scan of Lanthanum (La) 3d and O 1s are referred to the electron binding energy (eV). The La 3d narrow scan revealed that the oxide species of this particular metal is mainly contributed by La2O3 and La(OH)3. The information of oxygen species, O2- component from O 1s narrow scan indicated that there are four types of species which are contributed from the bulk (O2-), two chemisorb component (La2O3) and La(OH)3 and physisorp component (OH). Here, it is proposed that from the adhesive and surface chemical properties of La, it is suitable as an alternative medium for micro-flexography printing technique in printing multiple fine solid lines at nano scale. Hence, this paper will describe the capability of this particular metal as rare earth metal for use in of micro-flexography printing practice. The review of other parameters contributing to print fine lines will also be described later.

  18. Stability analysis of the Backward Euler time discretization for the pin-resolved transport transient reactor calculation

    International Nuclear Information System (INIS)

    Zhu, Ang; Xu, Yunlin; Downar, Thomas

    2016-01-01

    Three-dimensional, full core transport modeling with pin-resolved detail for reactor dynamic simulation is important for some multi-physics reactor applications. However, it can be computationally intensive due to the difficulty in maintaining accuracy while minimizing the number of time steps. A recently proposed Transient Multi-Level (TML) methodology overcomes this difficulty by use multi-level transient solvers to capture the physical phenomenal in different time domains and thus maximize the numerical accuracy and computational efficiency. One major problem with the TML method is the negative flux/precursor number density generated using large time steps for the MOC solver, which is due to the Backward Euler discretization scheme. In this paper, the stability issue of Backward Euler discretization is first investigated using the Point Kinetics Equations (PKEs), and the predicted maximum allowed time step for SPERT test 60 case is shown to be less than 10 ms. To overcome this difficulty, linear and exponential transformations are investigated using the PKEs. The linear transformation is shown to increase the maximum time step by a factor of 2, and the exponential transformation is shown to increase the maximum time step by a factor of 5, as well as provide unconditionally stability above a specified threshold. The two sets of transformations are then applied to TML scheme in the MPACT code, and the numerical results presented show good agreement for standard, linear transformed, and exponential transformed maximum time step between the PKEs model and the MPACT whole core transport solution for three different cases, including a pin cell case, a 3D SPERT assembly case and a row of assemblies (“striped assembly case”) from the SPERT model. Finally, the successful whole transient execution of the stripe assembly case shows the ability of the exponential transformation method to use 10 ms and 20 ms time steps, which all failed using the standard method.

  19. Bayesian genomic selection: the effect of haplotype lenghts and priors

    DEFF Research Database (Denmark)

    Villumsen, Trine Michelle; Janss, Luc

    2009-01-01

    Breeding values for animals with marker data are estimated using a genomic selection approach where data is analyzed using Bayesian multi-marker association models. Fourteen model scenarios with varying haplotype lengths, hyper parameter and prior distributions were compared to find the scenario ...

  20. Direct chromosome-length haplotyping by single-cell sequencing

    NARCIS (Netherlands)

    Porubský, David; Sanders, Ashley D; van Wietmarschen, Niek; Falconer, Ester; Hills, Mark; Spierings, Diana C J; Bevova, Marianna R; Guryev, Victor; Lansdorp, Peter Michael

    Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid

  1. Dense and accurate whole-chromosome haplotyping of individual genomes

    NARCIS (Netherlands)

    Porubsky, David; Garg, Shilpa; Sanders, Ashley D.; Korbel, Jan O.; Guryev, Victor; Lansdorp, Peter M.; Marschall, Tobias

    2017-01-01

    The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate

  2. Geographical distribution of a specific mitochondrial haplotype of Zymoseptoria tritici

    Directory of Open Access Journals (Sweden)

    Sameh BOUKEF

    2014-01-01

    Full Text Available Severity of disease caused by the fungus Zymoseptoria tritici throughout world cereal growing regions has elicited much debate on the potential evolutionary mechanism conferring high adaptability of the pathogen to diverse climate conditions and different wheat hosts (Triticum durum and T. aestivum. Specific mitochondrial DNA sequence was used to investigate geographic distribution of the type 4 haplotype (mtRFLP4 within 1363 isolates of Z. tritici originating from 21 countries. The mtRFLP4 haplotype was detected from both durum and bread wheat hosts with greater frequency on durum wheat. The distribution of mtRFLP4 was limited to populations sampled from the Mediterranean and the Red Sea region. Greater frequencies of mtRFLP4 were found in Tunisia (87% and Algeria (60%. The haplotype was absent within European, Australian, North and South American populations except Argentina. While alternative hypotheses such as climatic adaptation could not be ruled out, it is postulated that mtRFLP4 originated in North Africa (e.g. Tunisia or Algeria as an adaptation to durum wheat as the prevailing cereal crop. The specialized haplotype has subsequently spread as indicated by lower frequency of occurrence in the surrounding Mediterranean countries and on bread wheat hosts.

  3. Association of specific haplotype of TNFα with Helicobacter pylori ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 87; Issue 3. Association of specific haplotype of TNF with Helicobacter pylori-mediated duodenal ulcer in eastern Indian population. Meenakshi Chakravorty Dipanjana Datta De Abhijit Choudhury Amal Santra Susanta Roychoudhury. Research Note Volume 87 Issue 3 ...

  4. Genetics of chloroquine-resistant malaria: a haplotypic view

    Directory of Open Access Journals (Sweden)

    Gauri Awasthi

    2013-12-01

    Full Text Available The development and rapid spread of chloroquine resistance (CQR in Plasmodium falciparum have triggered the identification of several genetic target(s in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76, are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria.

  5. Exact algorithms for haplotype assembly from whole-genome sequence data.

    Science.gov (United States)

    Chen, Zhi-Zhong; Deng, Fei; Wang, Lusheng

    2013-08-15

    Haplotypes play a crucial role in genetic analysis and have many applications such as gene disease diagnoses, association studies, ancestry inference and so forth. The development of DNA sequencing technologies makes it possible to obtain haplotypes from a set of aligned reads originated from both copies of a chromosome of a single individual. This approach is often known as haplotype assembly. Exact algorithms that can give optimal solutions to the haplotype assembly problem are highly demanded. Unfortunately, previous algorithms for this problem either fail to output optimal solutions or take too long time even executed on a PC cluster. We develop an approach to finding optimal solutions for the haplotype assembly problem under the minimum-error-correction (MEC) model. Most of the previous approaches assume that the columns in the input matrix correspond to (putative) heterozygous sites. This all-heterozygous assumption is correct for most columns, but it may be incorrect for a small number of columns. In this article, we consider the MEC model with or without the all-heterozygous assumption. In our approach, we first use new methods to decompose the input read matrix into small independent blocks and then model the problem for each block as an integer linear programming problem, which is then solved by an integer linear programming solver. We have tested our program on a single PC [a Linux (x64) desktop PC with i7-3960X CPU], using the filtered HuRef and the NA 12878 datasets (after applying some variant calling methods). With the all-heterozygous assumption, our approach can optimally solve the whole HuRef data set within a total time of 31 h (26 h for the most difficult block of the 15th chromosome and only 5 h for the other blocks). To our knowledge, this is the first time that MEC optimal solutions are completely obtained for the filtered HuRef dataset. Moreover, in the general case (without the all-heterozygous assumption), for the HuRef dataset our

  6. How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

    DEFF Research Database (Denmark)

    Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

    1994-01-01

    how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

  7. Time-Resolved Analysis of a Highly Sensitive Förster Resonance Energy Transfer Immunoassay Using Terbium Complexes as Donors and Quantum Dots as Acceptors

    Directory of Open Access Journals (Sweden)

    Niko Hildebrandt

    2007-01-01

    Full Text Available CdSe/ZnS core/shell quantum dots (QDs are used as efficient Förster Resonance Energy Transfer (FRET acceptors in a time-resolved immunoassays with Tb complexes as donors providing a long-lived luminescence decay. A detailed decay time analysis of the FRET process is presented. QD FRET sensitization is evidenced by a more than 1000-fold increase of the QD luminescence decay time reaching ca. 0.5 milliseconds, the same value to which the Tb donor decay time is quenched due to FRET to the QD acceptors. The FRET system has an extremely large Förster radius of approx. 100 Å and more than 70% FRET efficiency with a mean donor-acceptor distance of ca. 84 Å, confirming the applied biotin-streptavidin binding system. Time-resolved measurement allows for suppression of short-lived emission due to background fluorescence and directly excited QDs. By this means a detection limit of 18 attomol QDs within the immunoassay is accomplished, an improvement of more than two orders of magnitude compared to commercial systems.

  8. An angle-resolved, wavelength-dispersive x-ray fluorescence spectrometer for depth profile analysis of ion-implanted semiconductors using synchrotron radiation

    Science.gov (United States)

    Schmitt, W.; Hormes, J.; Kuetgens, U.; Gries, W. H.

    1992-01-01

    An apparatus for angle-resolved, wavelength-dispersive x-ray fluorescence spectroscopy with synchrotron radiation has been built and tested at the beam line BN2 of the Bonn electron stretcher and accelerator (ELSA). The apparatus is to be used for nondestructive depth profile analysis of ion-implanted semiconductors as part of the multinational Versailles Project of Advanced Materials and Standards (VAMAS) project on ion-implanted reference materials. In particular, the centroid depths of depth profiles of various implants is to be determined by use of the angle-resolved signal ratio technique. First results of measurements on implants of phosphorus (100 keV, 1016 cm-2) and sulfur (200 keV, 1014 cm-2) in silicon wafers using ``white'' synchrotron radiation are presented and suggest that it should be generally possible to measure the centroid depth of an implant at dose densities as low as 1014 cm-2. Some of the apparative and technical requirements are discussed which are peculiar to the use of synchrotron radiation in general and to the use of nonmonochromatized radiation in particular.

  9. An angle-resolved, wavelength-dispersive x-ray fluorescence spectrometer for depth profile analysis of ion-implanted semiconductors using synchrotron radiation

    International Nuclear Information System (INIS)

    Schmitt, W.; Hormes, J.; Kuetgens, U.; Gries, W.H.

    1992-01-01

    An apparatus for angle-resolved, wavelength-dispersive x-ray fluorescence spectroscopy with synchrotron radiation has been built and tested at the beam line BN2 of the Bonn electron stretcher and accelerator (ELSA). The apparatus is to be used for nondestructive depth profile analysis of ion-implanted semiconductors as part of the multinational Versailles Project of Advanced Materials and Standards (VAMAS) project on ion-implanted reference materials. In particular, the centroid depths of depth profiles of various implants is to be determined by use of the angle-resolved signal ratio technique. First results of measurements on implants of phosphorus (100 keV, 10 16 cm -2 ) and sulfur (200 keV, 10 14 cm -2 ) in silicon wafers using ''white'' synchrotron radiation are presented and suggest that it should be generally possible to measure the centroid depth of an implant at dose densities as low as 10 14 cm -2 . Some of the apparative and technical requirements are discussed which are peculiar to the use of synchrotron radiation in general and to the use of nonmonochromatized radiation in particular

  10. Size-resolved aerosol chemical analysis of extreme haze pollution events during early 2013 in urban Beijing, China

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shili; Pan, Yuepeng, E-mail: panyuepeng@mail.iap.ac.cn; Liu, Zirui; Wen, Tianxue; Wang, Yuesi, E-mail: wys@mail.iap.ac.cn

    2014-08-30

    Highlights: • Anthropogenic species substantially accumulated in both fine and coarse particles. • Secondary organic carbon in PM{sub 1.1} decreased from clear to haze days. • The mass peak shifted to larger particles from clear to haze days. • The NO{sub 3}{sup −}/SO{sub 4}{sup 2−} ratio decreased with enhanced haze pollution. • Both mobile local and stationary regional sources were vital for haze formation. - Abstract: Using size-resolved filter sampling and chemical characterization, high concentrations of water-soluble ions, carbonaceous species and heavy metals were found in both fine (PM{sub 2.1}) and coarse (PM{sub 2.1–9}) particles in Beijing during haze events in early 2013. Even on clear days, average mass concentration of submicron particles (PM{sub 1.1}) was several times higher than that previously measured in most of abroad urban areas. A high concentration of particulate matter on haze days weakens the incident solar radiation, which reduces the generation rate of secondary organic carbon in PM{sub 1.1}. We show that the peak mass concentration of particles shifted from 0.43–0.65 μm on clear days to 0.65–1.1 μm on lightly polluted days and to 1.1–2.1 μm on heavily polluted days. The peak shifts were also found for the following species: organic carbon, elemental carbon, NH{sub 4}{sup +}, SO{sub 4}{sup 2−}, NO{sub 3}{sup −}, K, Cu, Zn, Cd and Pb. Our findings demonstrate that secondary inorganic aerosols (36%) and organic matter (26%) dominated the fine particle mass on heavily polluted days, while their contribution reduced to 29% and 18%, respectively, on clear days. Besides fine particles, anthropogenic chemical species also substantially accumulated in the coarse mode, which suggests that particles with aerodynamic diameter larger than 2.1 μm cannot be neglected during severe haze events.

  11. Beta-globin gene cluster haplotypes of Amerindian populations from the Brazilian Amazon region.

    Science.gov (United States)

    Guerreiro, J F; Figueiredo, M S; Zago, M A

    1994-01-01

    We have determined the beta-globin cluster haplotypes for 80 Indians from four Brazilian Amazon tribes: Kayapó, Wayampí, Wayana-Apalaí, and Arára. The results are analyzed together with 20 Yanomámi previously studied. From 2 to 4 different haplotypes were identified for each tribe, and 7 of the possible 32 haplotypes were found in a sample of 172 chromosomes for which the beta haplotypes were directly determined or derived from family studies. The haplotype distribution does not differ significantly among the five populations. The two most common haplotypes in all tribes were haplotypes 2 and 6, with average frequencies of 0.843 and 0.122, respectively. The genetic affinities between Brazilian Indians and other human populations were evaluated by estimates of genetic distance based on haplotype data. The lowest values were observed in relation to Asians, especially Chinese, Polynesians, and Micronesians.

  12. Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle

    Directory of Open Access Journals (Sweden)

    Hayes Ben J

    2011-08-01

    Full Text Available Abstract Background Previous fine mapping studies in Norwegian Red cattle (NRC in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6 has revealed a quantitative trait locus (QTL for protein yield (PY around 88 Mb and a QTL for clinical mastitis (CM around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. Results Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and αS2-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of

  13. The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach

    Directory of Open Access Journals (Sweden)

    Knapp Michael

    2010-07-01

    Full Text Available Abstract Background The DAOA/G30 (D-amino acid oxidase activator gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. Methods In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188 we examined seven single nucleotide polymorphisms (SNPs around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575 for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification. Results No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022 and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036. Conclusion Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.

  14. PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

    Science.gov (United States)

    Begnini, A; Tessari, G; Turco, A; Malerba, G; Naldi, L; Gotti, E; Boschiero, L; Forni, A; Rugiu, C; Piaserico, S; Fortina, A B; Brunello, A; Cascone, C; Girolomoni, G; Gomez Lira, M

    2010-08-01

    Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5

  15. Antifolate drug resistance: Novel mutations and haplotype ...

    Indian Academy of Sciences (India)

    N P Sarmah

    2017-09-27

    Sep 27, 2017 ... distribution in dhps and dhfr from Northeast India ... The findings of this study strongly discourage the use SP as a partner drug in ACT. ... led to critical hindrances in controlling of Plasmodium fal- ciparum (Pf) malaria in this part of India. ..... alignment editor and analysis programme for Windows95/98/. NT.

  16. Radiative and magnetic properties of solar active regions. II. Spatially resolved analysis of O V 62.97 nm transition region emission

    Science.gov (United States)

    Fludra, A.; Warren, H.

    2010-11-01

    Context. Global relationships between the photospheric magnetic flux and the extreme ultraviolet emission integrated over active region area have been studied in a previous paper by Fludra & Ireland (2008, A&A, 483, 609). Spatially integrated EUV line intensities are tightly correlated with the total unsigned magnetic flux, and yet these global power laws have been shown to be insufficient for accurately determining the coronal heating mechanism owing to the mathematical ill-conditioning of the inverse problem. Aims: Our aim is to establish a relationship between the EUV line intensities and the photospheric magnetic flux density on small spatial scales in active regions and investigate whether it provides a way of identifying the process that heats the coronal loops. Methods: We compare spatially resolved EUV transition region emission and the photospheric magnetic flux density. This analysis is based on the O V 62.97 nm line recorded by the SOHO Coronal Diagnostic Spectrometer (CDS) and SOHO MDI magnetograms for six solar active regions. The magnetic flux density ϕ is converted to a simulated O V intensity using a model relationship I(ϕ, L) = Cϕδ Lλ, where the loop length L is obtained from potential magnetic field extrapolations. This simulated spatial distribution of O V intensities is convolved with the CDS instrument's point spread function and compared pixel by pixel with the observed O V line intensity. Parameters δ and λ are derived to give the best fit for the observed and simulated intensities. Results: Spatially-resolved analysis of the transition region emission reveals the complex nature of the heating processes in active regions. In some active regions, particularly large, local intensity enhancements up to a factor of five are present. When areas with O V intensities above 3000 erg cm-2 s-1 sr-1 are ignored, a power law has been fitted to the relationship between the local O V line intensity and the photospheric magnetic flux density in each

  17. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

    NARCIS (Netherlands)

    Betz, Regina C; Petukhova, Lynn; Ripke, Stephan; Huang, Hailiang; Menelaou, Androniki; Redler, Silke; Becker, Tim; Heilmann, Stefanie; Yamany, Tarek; Duvic, Madeliene; Hordinsky, Maria; Norris, David; Price, Vera H; Mackay-Wiggan, Julian; de Jong, Annemieke; DeStefano, Gina M; Moebus, Susanne; Böhm, Markus; Blume-Peytavi, Ulrike; Wolff, Hans; Lutz, Gerhard; Kruse, Roland; Bian, Li; Amos, Christopher I; Lee, Annette; Gregersen, Peter K; Blaumeiser, Bettina; Altshuler, David; Clynes, Raphael; de Bakker, Paul I W; Nöthen, Markus M; Daly, Mark J; Christiano, Angela M

    2015-01-01

    Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and

  18. HLA alleles and haplotypes distribution in Dai population in Yunnan province, Southwest China.

    Science.gov (United States)

    Shi, L; Yao, Y F; Shi, L; Matsushita, M; Yu, L; Lin, Q K; Tao, Y F; Oka, T; Chu, J Y; Tokunaga, K

    2010-02-01

    Human leukocyte antigen (HLA) analysis would be a useful tool to trace the origin of modern humans. In this study, we provided the first four digital HLA-A, -B, -C and -DRB1 allele and haplotype data in the Dai ethnic population, which is a unique and representative Kam-Tai-speaking ethnic minority living in the Yunnan province of Southwestern China. Our results showed that the Dai population has unique HLA characteristic that are most closely related to the Southeastern Asia group and similar to the Kam-Tai speaking populations in China and Thailand.

  19. Identifying haplotypes for flowering and QTLs for fruit quality in the RosBREED Michigan and Oregon strawberry (Fragaria ×ananassa) breeding sets using pedigree-based analysis [abstract

    Science.gov (United States)

    Strawberry (Fragaria ×ananassa) is consumed for its flavor and health benefits. Over the last two decades, several quantitative trait loci (QTL) analysis studies for consumer traits were conducted using low-density genetic maps. The previous studies utilized low-throughput genotyping methodologies. ...

  20. Development of a new analysis technique to measure low radial-order p modes in spatially-resolved helioseismic data

    Energy Technology Data Exchange (ETDEWEB)

    Salabert, David; Leibacher, John W [National Solar Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Appourchaux, Thierry [Institut d' Astrophysique Spatiale, CNRS-Universite Paris XI UMR 8617, 91405 Orsay Cedex (France)], E-mail: dsalabert@nso.edu

    2008-10-15

    In order to take full advantage of the long time series collected by the GONG and MDI helioseismic projects, we present here an adaptation of the rotation-corrected m-averaged spectrum technique in order to observe low radial-order solar p modes. Modeled profiles of the solar rotation demonstrated the potential advantage of such a technique. Here we develop a new analysis procedure which finds the best estimates of the shift of each m of a given (n, {iota}) multiplet, commonly expressed as an expansion in a set of orthogonal polynomials, which yield the narrowest mode in the m-averaged spectrum. We apply the technique to the GONG data for modes with 1 {<=} {iota} {<=} 25 and show that it allows us to measure lower-frequency modes than with classic peak-fitting analysis of the individual-m spectra.

  1. Single molecule manipulation at low temperature and laser scanning tunnelling photo-induced processes analysis through time-resolved studies

    International Nuclear Information System (INIS)

    Riedel, Damien

    2010-01-01

    This paper describes, firstly, the statistical analysis used to determine the processes that occur during the manipulation of a single molecule through electronically induced excitations with a low temperature (5 K) scanning tunnelling microscope (STM). Various molecular operation examples are described and the ability to probe the ensuing molecular manipulation dynamics is discussed within the excitation context. It is, in particular, shown that such studies can reveal reversible manipulation for tuning dynamics through variation of the excitation energy. Secondly, the photo-induced process arising from the irradiation of the STM junction is also studied through feedback loop dynamics analysis, allowing us to distinguish between photo-thermally and photo-electronically induced signals.

  2. Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops

    Directory of Open Access Journals (Sweden)

    Lunwen Qian

    2017-09-01

    Full Text Available In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP–trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately

  3. Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops.

    Science.gov (United States)

    Qian, Lunwen; Hickey, Lee T; Stahl, Andreas; Werner, Christian R; Hayes, Ben; Snowdon, Rod J; Voss-Fels, Kai P

    2017-01-01

    In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS) strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP) markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP-trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately providing an effective tool

  4. Haplotype and genetic relationship of 27 Y-STR loci in Han population of Chaoshan area of China

    Directory of Open Access Journals (Sweden)

    Qing-hua TIAN

    2017-04-01

    Full Text Available Objective  To investigate the genetic polymorphisms of 27 Y-chromosomal short tandem repeats (Y-STR loci included in Yfiler® Plus kit in Han population of Chaoshan area, and explore the population genetic relationships and evaluate its application value on forensic medicine. Methods  By detecting 795 unrelated Chaoshan Han males with Yfiler® Plus kit, haplotype frequencies and population genetics parameters of the 27 Y-STR loci were statistically analyzed and compared with available data of other populations from different races and regions for analyzing the genetic distance and clustering relation of Chaoshan Han population. Results  Seven hundred and eighty-seven different haplotypes were observed in 795 unrelated male individuals, of which 779 haplotypes were unique, and 8 haplotypes occurred twice. The haplotype diversity (HD was 0.999975 with discriminative capacity (DC of 98.99%. The gene diversity (GD at the 27 Y-STR loci ranged from 0.3637(DYS391 to 0.9559(DYS385a/b. Comparing with Asian reference populations, the genetic distance (Rst between Chaoshan Han and Guangdong Han was the smallest (0.0036, while it was relatively larger between Chaoshan Han and Gansu Tibetan population (0.0935. The multi-dimensional scaling (MDS plot based on Rst values was similar to the results of clustering analysis. Conclusion  Multiplex detection of the 27 Y-STR loci reveals a highly polymorphic genetic distribution in Chaoshan Han population, which demonstrates the important significance of Yfiler® Plus kit for establishing a Y-STR database, studying population genetics, and for good practice in forensic medicine. DOI: 10.11855/j.issn.0577-7402.2017.03.08

  5. Two extended haplotype blocks are associated with adaptation to high altitude habitats in East African honey bees.

    Directory of Open Access Journals (Sweden)

    Andreas Wallberg

    2017-05-01

    Full Text Available Understanding the genetic basis of adaption is a central task in biology. Populations of the honey bee Apis mellifera that inhabit the mountain forests of East Africa differ in behavior and morphology from those inhabiting the surrounding lowland savannahs, which likely reflects adaptation to these habitats. We performed whole genome sequencing on 39 samples of highland and lowland bees from two pairs of populations to determine their evolutionary affinities and identify the genetic basis of these putative adaptations. We find that in general, levels of genetic differentiation between highland and lowland populations are very low, consistent with them being a single panmictic population. However, we identify two loci on chromosomes 7 and 9, each several hundred kilobases in length, which exhibit near fixation for different haplotypes between highland and lowland populations. The highland haplotypes at these loci are extremely rare in samples from the rest of the world. Patterns of segregation of genetic variants suggest that recombination between haplotypes at each locus is suppressed, indicating that they comprise independent structural variants. The haplotype on chromosome 7 harbors nearly all octopamine receptor genes in the honey bee genome. These have a role in learning and foraging behavior in honey bees and are strong candidates for adaptation to highland habitats. Molecular analysis of a putative breakpoint indicates that it may disrupt the coding sequence of one of these genes. Divergence between the highland and lowland haplotypes at both loci is extremely high suggesting that they are ancient balanced polymorphisms that greatly predate divergence between the extant honey bee subspecies.

  6. Two extended haplotype blocks are associated with adaptation to high altitude habitats in East African honey bees

    Science.gov (United States)

    Schöning, Caspar

    2017-01-01

    Understanding the genetic basis of adaption is a central task in biology. Populations of the honey bee Apis mellifera that inhabit the mountain forests of East Africa differ in behavior and morphology from those inhabiting the surrounding lowland savannahs, which likely reflects adaptation to these habitats. We performed whole genome sequencing on 39 samples of highland and lowland bees from two pairs of populations to determine their evolutionary affinities and identify the genetic basis of these putative adaptations. We find that in general, levels of genetic differentiation between highland and lowland populations are very low, consistent with them being a single panmictic population. However, we identify two loci on chromosomes 7 and 9, each several hundred kilobases in length, which exhibit near fixation for different haplotypes between highland and lowland populations. The highland haplotypes at these loci are extremely rare in samples from the rest of the world. Patterns of segregation of genetic variants suggest that recombination between haplotypes at each locus is suppressed, indicating that they comprise independent structural variants. The haplotype on chromosome 7 harbors nearly all octopamine receptor genes in the honey bee genome. These have a role in learning and foraging behavior in honey bees and are strong candidates for adaptation to highland habitats. Molecular analysis of a putative breakpoint indicates that it may disrupt the coding sequence of one of these genes. Divergence between the highland and lowland haplotypes at both loci is extremely high suggesting that they are ancient balanced polymorphisms that greatly predate divergence between the extant honey bee subspecies. PMID:28542163

  7. Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

    Directory of Open Access Journals (Sweden)

    Amin El-Heliebi

    Full Text Available The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells. The population of cells consists of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous cells. To date analysis was only performed on bulk tumor mass because of its rare incidence, lack of suited model systems and technical limitations thereby neglecting its heterogeneous composition. We intended to clarify whether the observed cell types are derived from genetically distinct clones or represent different phenotypes. Furthermore, we aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Phenotype-specific analyses of small non-vacuolated and large physaliferous cells in two independent chordoma cell lines yielded four candidate genes involved in chordoma cell development. UCHL3, coding for an ubiquitin hydrolase, was found to be over-expressed in the large physaliferous cell phenotype of MUG-Chor1 (18.7-fold and U-CH1 (3.7-fold cells. The mannosyltransferase ALG11 (695-fold and the phosphatase subunit PPP2CB (18.6-fold were found to be up-regulated in large physaliferous MUG-Chor1 cells showing a similar trend in U-CH1 cells. TMEM144, an orphan 10-transmembrane family receptor, yielded contradictory data as cDNA microarray analysis showed up- but RT-qPCR data down-regulation in large physaliferous MUG-Chor1 cells. Isolation of few but morphologically identical cells allowed us to overcome the limitations of bulk analysis in chordoma research. We identified the different chordoma cell phenotypes to be part of a developmental process and discovered new genes linked to chordoma cell development representing potential targets for further research in chordoma tumor biology.

  8. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.

    Science.gov (United States)

    Betz, Regina C; Petukhova, Lynn; Ripke, Stephan; Huang, Hailiang; Menelaou, Androniki; Redler, Silke; Becker, Tim; Heilmann, Stefanie; Yamany, Tarek; Duvic, Madeliene; Hordinsky, Maria; Norris, David; Price, Vera H; Mackay-Wiggan, Julian; de Jong, Annemieke; DeStefano, Gina M; Moebus, Susanne; Böhm, Markus; Blume-Peytavi, Ulrike; Wolff, Hans; Lutz, Gerhard; Kruse, Roland; Bian, Li; Amos, Christopher I; Lee, Annette; Gregersen, Peter K; Blaumeiser, Bettina; Altshuler, David; Clynes, Raphael; de Bakker, Paul I W; Nöthen, Markus M; Daly, Mark J; Christiano, Angela M

    2015-01-22

    Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.

  9. The interpretation of dream meaning: Resolving ambiguity using Latent Semantic Analysis in a small corpus of text.

    Science.gov (United States)

    Altszyler, Edgar; Ribeiro, Sidarta; Sigman, Mariano; Fernández Slezak, Diego

    2017-11-01

    Computer-based dreams content analysis relies on word frequencies within predefined categories in order to identify different elements in text. As a complementary approach, we explored the capabilities and limitations of word-embedding techniques to identify word usage patterns among dream reports. These tools allow us to quantify words associations in text and to identify the meaning of target words. Word-embeddings have been extensively studied in large datasets, but only a few studies analyze semantic representations in small corpora. To fill this gap, we compared Skip-gram and Latent Semantic Analysis (LSA) capabilities to extract semantic associations from dream reports. LSA showed better performance than Skip-gram in small size corpora in two tests. Furthermore, LSA captured relevant word associations in dream collection, even in cases with low-frequency words or small numbers of dreams. Word associations in dreams reports can thus be quantified by LSA, which opens new avenues for dream interpretation and decoding. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A deep view in cultural heritage - confocal micro X-ray spectroscopy for depth resolved elemental analysis

    International Nuclear Information System (INIS)

    Kanngiesser, B.; Malzer, W.; Mantouvalou, I.; Sokaras, D.; Karydas, A.G.

    2012-01-01

    Quantitative X-ray fluorescence (XRF) and particle induced X-ray emission (PIXE) techniques have been developed mostly for the elemental analysis of homogeneous bulk or very simple layered materials. Further on, the microprobe version of both techniques is applied for 2D elemental mapping of surface heterogeneities. At typical XRF/PIXE fixed geometries and exciting energies (15-25 keV and 2-3 MeV, respectively), the analytical signal (characteristic X-ray radiation) emanates from a variable but rather extended depth within the analyzed material, according to the exciting probe energy, set-up geometry, specimen matrix composition and analyte. Consequently, the in-depth resolution offered by XRF and PIXE techniques is rather limited for the characterization of materials with micrometer-scale stratigraphy or 3D heterogeneous structures. This difficulty has been over-passed to some extent in the case of an X-ray or charged particle microprobe by creating the so-called confocal geometry. The field of view of the X-ray spectrometer is spatially restricted by a polycapillary X-ray lens within a sensitive microvolume formed by the two inter-sectioned focal regions. The precise scanning of the analyzed specimen through the confocal microvolume results in depth-sensitive measurements, whereas the additional 2D scanning microprobe possibilities render to element-specific 3D spatial resolution (3D micro-XRF and 3D micro-PIXE). These developments have contributed since 2003 to a variety of fields of applications in environmental, material and life sciences. In contrast to other elemental imaging methods, no size restriction of the objects investigated and the non-destructive character of analysis have been found indispensable for cultural heritage (CH) related applications. The review presents a summary of the experimental set-up developments at synchrotron radiation beamlines, particle accelerators and desktop spectrometers that have driven methodological developments and

  11. A Dynamic Programming Algorithm for the k-Haplotyping Problem

    Institute of Scientific and Technical Information of China (English)

    Zhen-ping Li; Ling-yun Wu; Yu-ying Zhao; Xiang-sun Zhang

    2006-01-01

    The Minimum Fragments Removal (MFR) problem is one of the haplotyping problems: given a set of fragments, remove the minimum number of fragments so that the resulting fragments can be partitioned into k classes of non-conflicting subsets. In this paper, we formulate the k-MFR problem as an integer linear programming problem, and develop a dynamic programming approach to solve the k-MFR problem for both the gapless and gap cases.

  12. Combinatorial aspects of genome rearrangements and haplotype networks

    OpenAIRE

    Labarre , Anthony

    2008-01-01

    The dissertation covers two problems motivated by computational biology: genome rearrangements, and haplotype networks. Genome rearrangement problems are a particular case of edit distance problems, where one seeks to transform two given objects into one another using as few operations as possible, with the additional constraint that the set of allowed operations is fixed beforehand; we are also interested in computing the corresponding distances between those objects, i.e. merely computing t...

  13. Exploring Nuclear Photorelaxation of Pyranine in Aqueous Solution: an Integrated Ab-Initio Molecular Dynamics and Time Resolved Vibrational Analysis Approach.

    Science.gov (United States)

    Chiariello, Maria Gabriella; Rega, Nadia

    2018-03-22

    Advances in time-resolved vibrational spectroscopy techniques provided a new stimulus for understanding the transient molecular dynamics triggered by the electronic excitation. The detailed interpretation of such time-dependent spectroscopic signals is a challenging task from both experimental and theoretical points of view. We simulated and analyzed the transient photorelaxation of the pyranine photoacid in aqueous solution, with special focus on structural parameters and low frequency skeleton modes that are possibly preparatory for the photoreaction occurring at later time, as suggested by experimental spectroscopic studies. To this aim, we adopted an accurate computational protocol that combines excited state ab initio molecular dynamics within an hybrid quantum mechanical/molecular mechanics framework and a time-resolved vibrational analysis based on the Wavelet transform. According to our results, the main nuclear relaxation on the excited potential energy surface is completed in about 500 fs, in agreement with experimental data. The rearrangement of C-C bonds occurs according to a complex vibrational dynamics, showing oscillatory patterns that are out of phase and modulated by modes below 200 cm -1 . We also analyzed in both the ground and the excited state the evolution of some structural parameters involved in excited state proton transfer reaction, namely, those involving the pyranine and the water molecule hydrogen bonded to the phenolic O-H group. Both the hydrogen bond distance and the intermolecular orientation are optimized in the excited state, resulting in a tighter proton donor-acceptor couple. Indeed, we found evidence that collective low frequency skeleton modes, such as the out of plane wagging at 108 cm -1 and the deformation at 280 cm -1 , are photoactivated by the ultrafast part of the relaxation and modulate the pyranine-water molecule rearrangement, favoring the preparatory step for the photoreactivity.

  14. Solid-phase nano-extraction and laser-excited time-resolved Shpol'skii spectroscopy for the analysis of polycyclic aromatic hydrocarbons in drinking water samples.

    Science.gov (United States)

    Wang, Huiyong; Yu, Shenjiang; Campiglia, Andres D

    2009-02-15

    A unique method for screening polycyclic aromatic hydrocarbons in drinking water samples is reported. Water samples (500 microl) are mixed and centrifuged with 950 microl of a commercial solution of 20 nm gold nanoparticles for pollutants extraction. The precipitate is treated with 2 microl of 1-pentanethiol and 48 microl of n-octane, and the supernatant is then analyzed via laser-excited time-resolved Shpol'skii spectroscopy. Fifteen priority pollutants are directly determined at liquid helium temperature (4.2 K) with the aid of a cryogenic fiber-optic probe. Unambiguous pollutant determination is carried out via spectral and lifetime analysis. Limits of detection are at the parts-per-trillion level. Analytical recoveries are similar to those obtained via high-performance liquid chromatography. The simplicity of the experimental procedure, use of microliters of organic solvent, short analysis time, selectivity, and excellent analytical figures of merit demonstrate the advantages of this environmentally friendly approach for routine analysis of numerous samples.

  15. The effect of using genealogy-based haplotypes for genomic prediction.

    Science.gov (United States)

    Edriss, Vahid; Fernando, Rohan L; Su, Guosheng; Lund, Mogens S; Guldbrandtsen, Bernt

    2013-03-06

    Genomic prediction uses two sources of information: linkage disequilibrium between markers and quantitative trait loci, and additive genetic relationships between individuals. One way to increase the accuracy of genomic prediction is to capture more linkage disequilibrium by regression on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (π) of the haplotype covariates had zero effect, i.e. a Bayesian mixture method. About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some cases, decreased the bias of prediction. With the Bayesian method, accuracy of prediction was less sensitive to parameter π when fitting haplotypes compared to fitting markers. Use of haplotypes based on genealogy can slightly increase the accuracy of genomic prediction. Improved methods to cluster the haplotypes constructed from local genealogy could lead to additional gains in accuracy.

  16. Haplotype reconstruction error as a classical misclassification problem: introducing sensitivity and specificity as error measures.

    Directory of Open Access Journals (Sweden)

    Claudia Lamina

    Full Text Available BACKGROUND: Statistically reconstructing haplotypes from single nucleotide polymorphism (SNP genotypes, can lead to falsely classified haplotypes. This can be an issue when interpreting haplotype association results or when selecting subjects with certain haplotypes for subsequent functional studies. It was our aim to quantify haplotype reconstruction error and to provide tools for it. METHODS AND RESULTS: By numerous simulation scenarios, we systematically investigated several error measures, including discrepancy, error rate, and R(2, and introduced the sensitivity and specificity to this context. We exemplified several measures in the KORA study, a large population-based study from Southern Germany. We find that the specificity is slightly reduced only for common haplotypes, while the sensitivity was decreased for some, but not all rare haplotypes. The overall error rate was generally increasing with increasing number of loci, increasing minor allele frequency of SNPs, decreasing correlation between the alleles and increasing ambiguity. CONCLUSIONS: We conclude that, with the analytical approach presented here, haplotype-specific error measures can be computed to gain insight into the haplotype uncertainty. This method provides the information, if a specific risk haplotype can be expected to be reconstructed with rather no or high misclassification and thus on the magnitude of expected bias in association estimates. We also illustrate that sensitivity and specificity separate two dimensions of the haplotype reconstruction error, which completely describe the misclassification matrix and thus provide the prerequisite for methods accounting for misclassification.

  17. Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

    Directory of Open Access Journals (Sweden)

    Eric J Brunner

    2008-08-01

    Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

  18. Overview of worldwide diversity of Diaphorina citri Kuwayama mitochondrial cytochrome oxidase 1 haplotypes: two Old World lineages and a New World invasion

    Science.gov (United States)

    Boykin, L.M.; De Barro, P.; Hall, D.G.; Hunter, W.B.; McKenzie, C.L.; Powell, C.A.; Shatters, R.G.

    2012-01-01

    Relationships among worldwide collections of Diaphorina citri (Asian citrus psyllid) were analyzed using mitochondrial cytochrome oxidase I (mtCOI) haplotypes from novel primers. Sequences were produced from PCR amplicons of an 821bp portion of the mtCOI gene using D. citri specific primers, derived from an existing EST library. An alignment was constructed using 612bps of this fragment and consisted of 212 individuals from 52 collections representing 15 countries. There were a total of eight polymorphic sites that separated the sequences into eight different haplotypes (Dcit-1 through Dcit-8). Phylogenetic network analysis using the statistical parsimony software, TCS, suggests two major haplotype groups with preliminary geographic bias between southwestern Asia (SWA) and southeastern Asia (SEA). The recent (within the last 15 to 25 years) invasion into the New World originated from only the SWA group in the northern hemisphere (USA and Mexico) and from both the SEA and SWA groups in the southern hemisphere (Brazil). In only one case, Reunion Island, did haplotypes from both the SEA and SWA group appear in the same location. In Brazil, both groups were present, but in separate locations. The Dcit-1 SWA haplotype was the most frequently encountered, including ~50% of the countries sampled and 87% of the total sequences obtained from India, Pakistan and Saudi Arabia. The second most frequently encountered haplotype, Dcit-2, the basis of the SEA group, represented ~50% of the countries and contained most of the sequences from Southeast Asia and China. Interestingly, only the Caribbean collections (Puerto Rico and Guadeloupe) represented a unique haplotype not found in other countries, indicating no relationship between the USA (Florida) and Caribbean introductions. There is no evidence for cryptic speciation for D. citri based on the COI region included in this study. PMID:22717059

  19. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  20. Undergraduate ALFALFA Team: Analysis of Spatially-Resolved Star-Formation in Nearby Galaxy Groups and Clusters

    Science.gov (United States)

    Finn, Rose; Collova, Natasha; Spicer, Sandy; Whalen, Kelly; Koopmann, Rebecca A.; Durbala, Adriana; Haynes, Martha P.; Undergraduate ALFALFA Team

    2017-01-01

    As part of the Undergraduate ALFALFA Team, we are conducting a survey of the gas and star-formation properties of galaxies in 36 groups and clusters in the local universe. The galaxies in our sample span a large range of galactic environments, from the centers of galaxy groups and clusters to the surrounding infall regions. One goal of the project is to map the spatial distribution of star-formation; the relative extent of the star-forming and stellar disks provides important information about the internal and external processes that deplete gas and thus drive galaxy evolution. We obtained wide-field H-alpha observations with the WIYN 0.9m telescope at Kitt Peak National Observatory for galaxies in the vicinity of the MKW11 and NRGb004 galaxy groups and the Abell 1367 cluster. We present a preliminary analysis of the relative size of the star-forming and stellar disks as a function of galaxy morphology and local galaxy density, and we calculate gas depletion times using star-formation rates and HI gas mass. We will combine these results with those from other UAT members to determine if and how environmentally-driven gas depletion varies with the mass and X-ray properties of the host group or cluster. This work has supported by NSF grants AST-0847430, AST-1211005 and AST-1637339.

  1. [Resolving excitation emission matrix spectroscopy of estuarine CDOM with parallel factor analysis and its application in organic pollution monitoring].

    Science.gov (United States)

    Guo, Wei-Dong; Huang, Jian-Ping; Hong, Hua-Sheng; Xu, Jing; Deng, Xun

    2010-06-01

    The distribution and estuarine behavior of fluorescent components of chromophoric dissolved organic matter (CDOM) from Jiulong Estuary were determined by fluorescence excitation emission matrix spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC). The feasibility of these components as tracers for organic pollution in estuarine environments was also evaluated. Four separate fluorescent components were identified by PARAFAC, including three humic-like components (C1: 240, 310/382 nm; C2: 230, 250, 340/422 nm; C4: 260, 390/482 nm) and one protein-like components (C3: 225, 275/342 nm). These results indicated that UV humic-like peak A area designated by traditional "peak-picking method" was not a single peak but actually a combination of several fluorescent components, and it also had inherent links to so-called marine humic-like peak M or terrestrial humic-like peak C. Component C2 which include peak M decreased with increase of salinity in Jiulong Estuary, demonstrating that peak M can not be thought as the specific indicator of the "marine" humic-like component. Two humic-like components C1 and C2 showed additional behavior in the turbidity maximum region (salinity CDOM may provide a fast in-situ way to monitor the variation of the degree of organic pollution in estuarine environments.

  2. Resolving piping analysis issues to minimize impact on installation activities during refueling outage at nuclear power plants

    International Nuclear Information System (INIS)

    Bhavnani, D.

    1996-01-01

    While it is required to maintain piping code compliance for all phases of installation activities during outages at a nuclear plant, it is equally essential to reduce challenges to the installation personnel on how plant modification work should be performed. Plant betterment activities that incorporate proposed design changes are continually implemented during the outages. Supporting analysis are performed to back these activities for operable systems. The goal is to reduce engineering and craft man-hours and minimize outage time. This paper outlines how plant modification process can be streamlined to facilitate construction teams to do their tasks that involve safety related piping. In this manner, installation can proceed by minimizing on the spot analytical effort and reduce downtime to support the proposed modifications. Examples are provided that permit performance of installation work in any sequence. Piping and hangers including the branch lines are prequalified and determined operable. The system is up front analyzed for all possible scenarios. The modification instructions in the work packages is flexible enough to permit any possible installation sequence. The benefit to this approach is large enough in the sense that valuable outage time is not extended and on site analytical work is not required

  3. Serpin peptidase inhibitor (SERPINB5) haplotypes are associated with susceptibility to hepatocellular carcinoma

    Science.gov (United States)

    Yang, Shun-Fa; Yeh, Chao-Bin; Chou, Ying-Erh; Lee, Hsiang-Lin; Liu, Yu-Fan

    2016-05-01

    Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. The serpin peptidase inhibitor SERPINB5 is a tumour-suppressor gene that promotes the development of various cancers in humans. However, whether SERPINB5 gene variants play a role in HCC susceptibility remains unknown. In this study, we genotyped 6 SNPs of the SERPINB5 gene in an independent cohort from a replicate population comprising 302 cases and 590 controls. Additionally, patients who had at least one rs2289520 C allele in SERPINB5 tended to exhibit better liver function than patients with genotype GG (Child-Pugh grade A vs. B or C; P = 0.047). Next, haplotype blocks were reconstructed according to the linkage disequilibrium structure of the SERPINB5 gene. A haplotype “C-C-C” (rs17071138 + rs3744941 + rs8089204) in SERPINB5-correlated promoter showed a significant association with an increased HCC risk (AOR = 1.450 P = 0.031). Haplotypes “T-C-A” and “C-C-C” (rs2289519 + rs2289520 + rs1455555) located in the SERPINB5 coding region had a decreased (AOR = 0.744 P = 0.031) and increased (AOR = 1.981 P = 0.001) HCC risk, respectively. Finally, an additional integrated in silico analysis confirmed that these SNPs affected SERPINB5 expression and protein stability, which significantly correlated with tumour expression and subsequently with tumour development and aggressiveness. Taken together, our findings regarding these biomarkers provide a prediction model for risk assessment.

  4. Worldwide genealogy of Entamoeba histolytica: an overview to understand haplotype distribution and infection outcome.

    Science.gov (United States)

    Zermeño, Valeria; Ximénez, Cecilia; Morán, Patricia; Valadez, Alicia; Valenzuela, Olivia; Rascón, Edgar; Diaz, Daniel; Cerritos, René

    2013-07-01

    Although Entamoeba histolytica is one of the most prevalent intestinal parasites, how the different strains of this species are distributed all over the world and how different genotypes are associated with the infection outcome are yet to be fully understood. Recently, the use of a number of molecular markers has made the characterization of several genotypes in those regions with high incidence of amoebiasis possible. This work proposes the first genealogy of E. histolytica, with an haplotype network based on two tRNA gene-linked array of Short Tandem Repeats (STRs) reported until today, and 47 sequences from 39 new isolates of Mexican Amoebic Liver Abscesses (ALA) samples. One hundred and three sequences were obtained from D-A locus, their information about the geographic region of isolation as well as clinical diagnosis were also collected. One hundred and five sequences from N-K2 locus were also obtained as well as the region of isolation, but the information about clinical diagnosis was not available in all cases. The most abundant and widely distributed haplotype in the world is the one of E. histolytica HM1:IMSS strain. This was found in Mexico, Bangladesh, Japan, China and USA and is associated to symptomatic patients as well as asymptomatic cyst passers. Many other haplotypes were found only in a single country. Both genealogies suggest that there are no lineages within the networks that may be related to a particular geographic region or infection outcome. A concatenated analysis of the two molecular markers revealed 12 different combinations, which suggests the possibility of genetic recombination events. The present study is the first to propose a global genealogy of this species and suggests that there are still many genotypes to be discovered. The genotyping of new isolates will help to understand the great diversity and genetic structure of this parasite. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Mice, humans and haplotypes--the hunt for disease genes in SLE.

    Science.gov (United States)

    Rigby, R J; Fernando, M M A; Vyse, T J

    2006-09-01

    Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

  6. Direct on-strip analysis of size- and time-resolved aerosol impactor samples using laser induced fluorescence spectra excited at 263 and 351 nm

    International Nuclear Information System (INIS)

    Wang, Chuji; Pan, Yong-Le; James, Deryck; Wetmore, Alan E.; Redding, Brandon

    2014-01-01

    Highlights: • A dual wavelength UV-LIF spectra-rotating drum impactor (RDI) technique was developed. • The technique was demonstrated by direct on-strip analysis of size- and time-resolved LIF spectra of atmospheric aerosol particles. • More than 2000 LIF spectra of atmospheric aerosol particles collected over three weeks in Djibouti were obtained and assigned to various fluorescence clusters. • The LIF spectra showed size- and time-sensitivity behavior with a time resolution of 3.6 h. - Abstract: We report a novel atmospheric aerosol characterization technique, in which dual wavelength UV laser induced fluorescence (LIF) spectrometry marries an eight-stage rotating drum impactor (RDI), namely UV-LIF-RDI, to achieve size- and time-resolved analysis of aerosol particles on-strip. The UV-LIF-RDI technique measured LIF spectra via direct laser beam illumination onto the particles that were impacted on a RDI strip with a spatial resolution of 1.2 mm, equivalent to an averaged time resolution in the aerosol sampling of 3.6 h. Excited by a 263 nm or 351 nm laser, more than 2000 LIF spectra within a 3-week aerosol collection time period were obtained from the eight individual RDI strips that collected particles in eight different sizes ranging from 0.09 to 10 μm in Djibouti. Based on the known fluorescence database from atmospheric aerosols in the US, the LIF spectra obtained from the Djibouti aerosol samples were found to be dominated by fluorescence clusters 2, 5, and 8 (peaked at 330, 370, and 475 nm) when excited at 263 nm and by fluorescence clusters 1, 2, 5, and 6 (peaked at 390 and 460 nm) when excited at 351 nm. Size- and time-dependent variations of the fluorescence spectra revealed some size and time evolution behavior of organic and biological aerosols from the atmosphere in Djibouti. Moreover, this analytical technique could locate the possible sources and chemical compositions contributing to these fluorescence clusters. Advantages, limitations, and

  7. Direct on-strip analysis of size- and time-resolved aerosol impactor samples using laser induced fluorescence spectra excited at 263 and 351 nm

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chuji [U.S. Army Research Laboratory, Adelphi, MD 20783 (United States); Mississippi State University, Starkville, MS, 39759 (United States); Pan, Yong-Le, E-mail: yongle.pan.civ@mail.mil [U.S. Army Research Laboratory, Adelphi, MD 20783 (United States); James, Deryck; Wetmore, Alan E. [U.S. Army Research Laboratory, Adelphi, MD 20783 (United States); Redding, Brandon [Yale University, New Haven, CT 06510 (United States)

    2014-04-01

    Highlights: • A dual wavelength UV-LIF spectra-rotating drum impactor (RDI) technique was developed. • The technique was demonstrated by direct on-strip analysis of size- and time-resolved LIF spectra of atmospheric aerosol particles. • More than 2000 LIF spectra of atmospheric aerosol particles collected over three weeks in Djibouti were obtained and assigned to various fluorescence clusters. • The LIF spectra showed size- and time-sensitivity behavior with a time resolution of 3.6 h. - Abstract: We report a novel atmospheric aerosol characterization technique, in which dual wavelength UV laser induced fluorescence (LIF) spectrometry marries an eight-stage rotating drum impactor (RDI), namely UV-LIF-RDI, to achieve size- and time-resolved analysis of aerosol particles on-strip. The UV-LIF-RDI technique measured LIF spectra via direct laser beam illumination onto the particles that were impacted on a RDI strip with a spatial resolution of 1.2 mm, equivalent to an averaged time resolution in the aerosol sampling of 3.6 h. Excited by a 263 nm or 351 nm laser, more than 2000 LIF spectra within a 3-week aerosol collection time period were obtained from the eight individual RDI strips that collected particles in eight different sizes ranging from 0.09 to 10 μm in Djibouti. Based on the known fluorescence database from atmospheric aerosols in the US, the LIF spectra obtained from the Djibouti aerosol samples were found to be dominated by fluorescence clusters 2, 5, and 8 (peaked at 330, 370, and 475 nm) when excited at 263 nm and by fluorescence clusters 1, 2, 5, and 6 (peaked at 390 and 460 nm) when excited at 351 nm. Size- and time-dependent variations of the fluorescence spectra revealed some size and time evolution behavior of organic and biological aerosols from the atmosphere in Djibouti. Moreover, this analytical technique could locate the possible sources and chemical compositions contributing to these fluorescence clusters. Advantages, limitations, and

  8. Time-resolved, single-cell analysis of induced and programmed cell death via non-invasive propidium iodide and counterstain perfusion.

    Science.gov (United States)

    Krämer, Christina E M; Wiechert, Wolfgang; Kohlheyer, Dietrich

    2016-09-01

    Conventional propidium iodide (PI) staining requires the execution of multiple steps prior to analysis, potentially affecting assay results as well as cell vitality. In this study, this multistep analysis method has been transformed into a single-step, non-toxic, real-time method via live-cell imaging during perfusion with 0.1 μM PI inside a microfluidic cultivation device. Dynamic PI staining was an effective live/dead analytical tool and demonstrated consistent results for single-cell death initiated by direct or indirect triggers. Application of this method for the first time revealed the apparent antibiotic tolerance of wild-type Corynebacterium glutamicum cells, as indicated by the conversion of violet fluorogenic calcein acetoxymethyl ester (CvAM). Additional implementation of this method provided insight into the induced cell lysis of Escherichia coli cells expressing a lytic toxin-antitoxin module, providing evidence for non-lytic cell death and cell resistance to toxin production. Finally, our dynamic PI staining method distinguished necrotic-like and apoptotic-like cell death phenotypes in Saccharomyces cerevisiae among predisposed descendants of nutrient-deprived ancestor cells using PO-PRO-1 or green fluorogenic calcein acetoxymethyl ester (CgAM) as counterstains. The combination of single-cell cultivation, fluorescent time-lapse imaging, and PI perfusion facilitates spatiotemporally resolved observations that deliver new insights into the dynamics of cellular behaviour.

  9. Spatially-resolved in-situ quantification of biofouling using optical coherence tomography (OCT) and 3D image analysis in a spacer filled channel

    KAUST Repository

    Fortunato, Luca

    2016-11-21

    The use of optical coherence tomography (OCT) to investigate biomass in membrane systems has increased with time. OCT is able to characterize the biomass in-situ and non-destructively. In this study, a novel approach to process three-dimensional (3D) OCT scans is proposed. The approach allows obtaining spatially-resolved detailed structural biomass information. The 3D biomass reconstruction enables analysis of the biomass only, obtained by subtracting the time zero scan to all images. A 3D time series analysis of biomass development in a spacer filled channel under representative conditions (cross flow velocity) for a spiral wound membrane element was performed. The flow cell was operated for five days with monitoring of ultrafiltration membrane performance: feed channel pressure drop and permeate flux. The biomass development in the flow cell was detected by OCT before a performance decline was observed. Feed channel pressure drop continuously increased with increasing biomass volume, while flux decline was mainly affected in the initial phase of biomass accumulation. The novel OCT imaging approach enabled the assessment of spatial biomass distribution in the flow cell, discriminating the total biomass volume between the membrane, feed spacer and glass window. Biomass accumulation was stronger on the feed spacer during the early stage of biofouling, impacting the feed channel pressure drop stronger than permeate flux.

  10. Nucleotide polymorphisms and haplotype diversity of RTCS gene in China elite maize inbred lines.

    Directory of Open Access Journals (Sweden)

    Enying Zhang

    Full Text Available The maize RTCS gene, encoding a LOB domain transcription factor, plays important roles in the initiation of embryonic seminal and postembryonic shoot-borne root. In this study, the genomic sequences of this gene in 73 China elite inbred lines, including 63 lines from 5 temperate heteroric groups and 10 tropic germplasms, were obtained, and the nucleotide polymorphisms and haplotype diversity were detected. A total of 63 sequence variants, including 44 SNPs and 19 indels, were identified at this locus, and most of them were found to be located in the regions of UTR and intron. The coding region of this gene in all tested inbred lines carried 14 haplotypes, which encoding 7 deferring RTCS proteins. Analysis of the polymorphism sites revealed that at least 6 recombination events have occurred. Among all 6 groups tested, only the P heterotic group had a much lower nucleotide diversity than the whole set, and selection analysis also revealed that only this group was under strong negative selection. However, the set of Huangzaosi and its derived lines possessed a higher nucleotide diversity than the whole set, and no selection signal were identified.

  11. Rapid DNA haplotyping using a multiplex heteroduplex approach: Application to Duchenne muscula dystrophy carrier detection

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Wenger, G.D.; Moore, J. [Ohio State Univ., Columbus, OH (United States)] [and others

    1994-09-01

    A new strategy has been developed for rapid haplotype analysis. It is based on an initial multiplex amplification of several polymorphic sites, followed by heteroduplex detection. Heteroduplexes formed between two different alleles are detected because they migrate differently than the corresponding homoduplexes in Hydrolink-MDE gel. The method is simple, rapid, does not depend on specific sequences such as restriction enzyme sites or CA boxes and does not require the use of isotope. This approach has been tested using 12 commonly occurring polymorphisms spanning the dystrophin gene as a model. We describe the use of the method to assign the carrier status of females in Duchenne muscular dystrophy (DMD) pedigrees. As a result of expanding the number of detectable polymorphisms throughout the dystrophin gene, we show how the method can easily be combined with dinucleotide analysis to improve the accuracy of carrier detection in the nondeletion cases. The technique is also shown to be used as an effective screen for improving carrier detection in several families with deletions. The finding of heterozygosity within the deletion identifies the at-risk female as a noncarrier. Using this method, we have identified and incorporated 3 new dystrophin polymorphisms (one of which in exon 16 is unique to African Americans). The method may be used other genetic diseases when mutations are unknown, or there are few dinucleotide markers in the gene proximity, or for the identification of haplotype backgrounds of mutant alleles.

  12. The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis

    Science.gov (United States)

    Beretta, Lorenzo; Simeón, Carmen P.; Carreira, Patricia E.; Callejas, José Luis; Fernández-Castro, Mónica; Sáez-Comet, Luis; Beltrán, Emma; Camps, María Teresa; Egurbide, María Victoria; Airó, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H. W.; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M.; Fonseca, Carmen; Denton, Christopher; Herrick, Ariane; Worthington, Jane; Schuerwegh, Annemie J.; Vonk, Madelon C.; Voskuyl, Alexandre E.; Radstake, Timothy R. D. J.; Martín, Javier

    2013-01-01

    Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10−8, OR  = 1.22, CI 95%  = 1.14–1.30; rs2004640: P  = 4.60×10−7, OR  = 0.84, CI 95%  = 0.78–0.90; rs10488631: P  = 7.53×10−20, OR  = 1.63, CI 95%  = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10−22, OR  = 1.75, CI 95%  = 1.56–1.97) better explained the observed association (likelihood P-value  = 1.48×10−4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that

  13. Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

    Science.gov (United States)

    Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

    2018-05-01

    Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

  14. Mechanisms of haplotype divergence at the RGA08 nucleotide-binding leucine-rich repeat gene locus in wild banana (Musa balbisiana).

    Science.gov (United States)

    Baurens, Franc-Christophe; Bocs, Stéphanie; Rouard, Mathieu; Matsumoto, Takashi; Miller, Robert N G; Rodier-Goud, Marguerite; MBéguié-A-MBéguié, Didier; Yahiaoui, Nabila

    2010-07-16

    Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW). Sequence comparison revealed two regions of contrasting features. The first is a highly colinear gene-rich region where the two haplotypes diverge only by single nucleotide polymorphisms and two repetitive element insertions. The second corresponds to a large cluster of RGA08 genes, with 13 and 18 predicted RGA genes and pseudogenes spread over 131 and 152 kb respectively on each haplotype. The RGA08 cluster is enriched in repetitive element insertions, in duplicated non-coding intergenic sequences including low complexity regions and shows structural variations between haplotypes. Although some allelic relationships are retained, a large diversity of RGA08 genes occurs in this single M. balbisiana genotype, with several RGA08 paralogs specific to each haplotype. The RGA08 gene family has evolved by mechanisms of unequal recombination, intragenic sequence exchange and diversifying selection. An unequal recombination event taking place between duplicated non-coding intergenic sequences resulted in a different RGA08 gene content between haplotypes pointing out the role of such duplicated regions in the evolution of RGA clusters. Based on the synonymous substitution rate in coding sequences, we estimated a 1 million year divergence time for these M. balbisiana haplotypes. A

  15. Intragenic haplotype analysis of common HFE mutations in the ...

    Indian Academy of Sciences (India)

    mutation <100 generations ago in the Celtic populations of mainland Europe, with a ... 0.9–5.8%, evidencing regional differences in distribution across the ..... and H63D alleles in the HFE gene among various Jewish ethnic groups in Israel: a ...

  16. SNP and haplotype mapping for genetic analysis in the rat

    Czech Academy of Sciences Publication Activity Database

    Saar, K.; Beck, A.; Bihoreau, M. T.; Birney, E.; Brocklebank, D.; Chen, Y.; Cuppen, E.; Demonchy, S.; Dopazo, J.; Flicek, P.; Foglio, M.; Fujiyama, A.; Gut, I. G.; Gauguier, D.; Guigo, R.; Guryev, V.; Heinig, M.; Hummel, O.; Jahn, N.; Klages, S.; Křen, Vladimír; Kube, M.; Kuhl, H.; Kuramoto, T.; Pravenec, Michal

    2008-01-01

    Roč. 40, č. 5 (2008), s. 560-566 ISSN 1061-4036 R&D Projects: GA MŠk(CZ) 1P05ME791; GA MŠk(CZ) 1M0520; GA MŠk(CZ) ME08006 Grant - others:HHMI(US) 55005624; -(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Source of funding: N - neverejné zdroje ; R - rámcový projekt EK Keywords : SNP * rat * complete map Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 30.259, year: 2008

  17. CFTR mutation analysis and haplotype associations in CF patients☆

    OpenAIRE

    Cordovado, S.K.; Hendrix, M.; Greene, C.N.; Mochal, S.; Earley, M.C.; Farrell, P.M.; Kharrazi, M.; Hannon, W.H.; Mueller, P.W.

    2011-01-01

    Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention’s NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and por...

  18. Spatially resolved regression analysis of pre-treatment FDG, FLT and Cu-ATSM PET from post-treatment FDG PET: an exploratory study

    Science.gov (United States)

    Bowen, Stephen R; Chappell, Richard J; Bentzen, Søren M; Deveau, Michael A; Forrest, Lisa J; Jeraj, Robert

    2012-01-01

    Purpose To quantify associations between pre-radiotherapy and post-radiotherapy PET parameters via spatially resolved regression. Materials and methods Ten canine sinonasal cancer patients underwent PET/CT scans of [18F]FDG (FDGpre), [18F]FLT (FLTpre), and [61Cu]Cu-ATSM (Cu-ATSMpre). Following radiotherapy regimens of 50 Gy in 10 fractions, veterinary patients underwent FDG PET/CT scans at three months (FDGpost). Regression of standardized uptake values in baseline FDGpre, FLTpre and Cu-ATSMpre tumour voxels to those in FDGpost images was performed for linear, log-linear, generalized-linear and mixed-fit linear models. Goodness-of-fit in regression coefficients was assessed by R2. Hypothesis testing of coefficients over the patient population was performed. Results Multivariate linear model fits of FDGpre to FDGpost were significantly positive over the population (FDGpost~0.17 FDGpre, p=0.03), and classified slopes of RECIST non-responders and responders to be different (0.37 vs. 0.07, p=0.01). Generalized-linear model fits related FDGpre to FDGpost by a linear power law (FDGpost~FDGpre0.93, pregression analysis indicates that pre-treatment FDG PET uptake is most strongly associated with three-month post-treatment FDG PET uptake in this patient population, though associations are histopathology-dependent. PMID:22682748

  19. Pathway markers for pro-resolving lipid mediators in maternal and umbilical cord blood: A Secondary analysis of the Mothers, Omega-3, & Mental Health Study

    Directory of Open Access Journals (Sweden)

    Ellen L Mozurkewich

    2016-09-01

    Full Text Available The omega-3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA are precursors to immune regulatory and specialized pro-resolving mediators (SPM of inflammation termed resolvins, maresins, and protections. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX and 15-LOX metabolic pathway precursors and downstream metabolites: We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA- rich fish oil supplementation increased SPM precursor 17-HDHA concentrations in maternal and umbilical cord blood (P=0.02 We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P=0.049. Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P<0.001, both.

  20. Chemical transitions of Areca semen during the thermal processing revealed by temperature-resolved ATR-FTIR spectroscopy and two-dimensional correlation analysis

    Science.gov (United States)

    Wang, Zhibiao; Wang, Xu; Pei, Wenxuan; Li, Sen; Sun, Suqin; Zhou, Qun; Chen, Jianbo

    2018-03-01

    Areca semen is a common herb used in traditional Chinese medicine, but alkaloids in this herb are categorized as Group I carcinogens by IARC. It has been proven that the stir-baking process can reduce alkaloids in Areca semen while keep the activity for promoting digestion. However, the changes of compositions other than alkaloids during the thermal processing are unclear. Understanding the thermal chemical transitions of Areca semen is necessary to explore the processing mechanisms and optimize the procedures. In this research, FTIR spectroscopy with a temperature-controlled ATR accessory is employed to study the heating process of Areca semen. Principal component analysis and two-dimensional correlation spectroscopy are used to interpret the spectra to reveal the chemical transitions of Areca semen in different temperature ranges. The loss of a few volatile compounds in the testa and sperm happens below 105 °C, while some esters in the sperm decreases above 105 °C. As the heating temperature is close to 210 °C, Areca semen begins to be scorched and the decomposition of many compounds can be observed. This research shows the potential of the temperature-resolved ATR-FTIR spectroscopy in exploring the chemical transitions of the thermal processing of herbal materials.

  1. The Energy-Water Nexus: Spatially-Resolved Analysis of the Potential for Desalinating Brackish Groundwater by Use of Solar Energy

    Directory of Open Access Journals (Sweden)

    Jill B. Kjellsson

    2015-06-01

    Full Text Available This research looks at coupling desalination with renewable energy sources to create a high-value product (treated water from two low value resources (brackish groundwater and intermittent solar energy. Desalination of brackish groundwater is already being considered as a potential new water supply in Texas. This research uses Texas as a testbed for spatially-resolved analysis techniques while considering depth to brackish groundwater, water quality, and solar radiation across Texas to determine the locations with the best potential for integrating solar energy with brackish groundwater desalination. The framework presented herein can be useful for policymakers, regional planners, and project developers as they consider where to site desalination facilities coupled with solar photovoltaics. Results suggest that the northwestern region of Texas—with abundant sunshine and groundwater at relatively shallow depths and low salinity in areas with freshwater scarcity—has the highest potential for solar powered desalination. The range in capacity for solar photovoltaic powered reverse osmosis desalination was found to be 1.56 × 10—6 to 2.93 × 10—5 cubic meters of water per second per square meter of solar panel (m3/s/m2.

  2. Time-Resolved Analysis of Cytosolic and Surface-Associated Proteins of Staphylococcus aureus HG001 under Planktonic and Biofilm Conditions.

    Science.gov (United States)

    Moche, Martin; Schlüter, Rabea; Bernhardt, Jörg; Plate, Kristina; Riedel, Katharina; Hecker, Michael; Becher, Dörte

    2015-09-04

    Staphylococcal biofilms are associated with persistent infections due to their capacity to protect bacteria against the host's immune system and antibiotics. Cell-surface-associated proteins are of great importance during biofilm formation. In the present study, an optimized biotinylation approach for quantitative GeLC-MS-based analysis of the staphylococcal cell-surface proteome was applied and the cytoplasmic protein fraction was analyzed to elucidate proteomic differences between colony biofilms and planktonic cells. The experimental setup enabled a time-resolved monitoring of the proteome under both culture conditions and the comparison of biofilm cells to planktonic cells at several time points. This allowed discrimination of differences attributed to delayed growth phases from responses provoked by biofilm conditions. Biofilm cells expressed CcpA-dependent catabolic proteins earlier than planktonic cells and strongly accumulated proteins that belong to the SigB stress regulon. The amount of the cell-surface protein and virulence gene regulator Rot decreased within biofilms and MgrA-dependent regulations appeared more pronounced. Biofilm cells simultaneously up-regulated activators (e.g., SarZ) as well as repressors (e.g., SarX) of RNAIII. A decreased amount of high-affinity iron uptake systems and an increased amount of the iron-storage protein FtnA possibly indicated a lower demand of iron in biofilms.

  3. Compound haplotypes at Xp11.23 and human population growth in Eurasia.

    Science.gov (United States)

    Alonso, S; Armour, J A L

    2004-09-01

    To investigate patterns of diversity and the evolutionary history of Eurasians, we have sequenced a 2.8 kb region at Xp11.23 in a sample of African and Eurasian chromosomes. This region is in a long intron of CLCN5 and is immediately flanked by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE. Compared to Africans, Eurasians showed a marked reduction in sequence diversity. The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole sample. Coalescent simulations, including recombination and exponential growth, indicate a median length of strong linkage disequilibrium, up to approximately 9 kb for this area. The Ka/Ks ratio between the coding sequence of human CLCN5 and its mouse orthologue is much less than 1. This implies that the region sequenced is unlikely to be under the strong influence of positive selective processes on CLCN5, mutations in which have been associated with disorders such as Dent's disease. In contrast, a scenario based on a population bottleneck and exponential growth seems a more likely explanation for the reduced diversity observed in Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches a gene diversity value greater than 98% in Eurasians) suggest an estimated age of origin of the Euro-Asiatic diversity compatible with a recent out-of-Africa model for colonization of Eurasia by modern Homo sapiens.

  4. Deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes

    International Nuclear Information System (INIS)

    Nepom, B.S.; Kim, S.J.; Nepom, G.T.

    1986-01-01

    We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A-10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ''3.1''. The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ''3.1'' allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity

  5. Quantitative trait loci and the relevance of phased haplotypes

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl

    Genetic control of different production traits and diseases within livestock has been of great interest since domenstication. SNPs have greatly facilitated the use of QTL studies in the search of genomic regions affecting different phenotypes. The studies have been conducted to identify regions...... underlying gentic control both as traditional linkage studies relying on genetic maps and as GWAS where an approach of phasing haplotypes within the QTL have been conducted to validate the regions. Overall, regions of interest have been identified for chronic pleuritis and osteochondrosis in addition to meat...... quality and boar taint in pigs, and for improved chees production within cows...

  6. Operation: Inherent Resolve

    DEFF Research Database (Denmark)

    Cramer-Larsen, Lars

    2015-01-01

    Kapitlet giver læseren indsigt i den internationale koalitions engagement mod IS igennem Operaton Inherent Resolve; herunder koalitionens strategi i forhold til IS strategi, ligesom det belyser kampagnens legalitet og folkeretlige grundlag, ligesom det giver et bud på overvejelser om kampagnens...

  7. Regolith and Environment Science and Oxygen and Lunar Volatile Extraction (RESOLVE): Lunar Advanced Volatile Analysis (LAVA) Capillary Fluid Dynamic Restriction Effects on Gas Chromatography

    Science.gov (United States)

    Gonzalez, Marianne; Quinn, Jacqueline; Captain, Janine; Santiago-Bond, Josephine; Starr, Stanley

    2015-01-01

    The Resource Prospector (RP) mission with the Regolith and Environment Science and Oxygen Lunar Volatile Extraction (RESOLVE) payload aims to show the presence of water in lunar regolith, and establish a proving ground for NASAs mission to Mars. One of the analysis is performed by the Lunar Advanced Volatiles Analysis (LAVA) subsystem, which consists of a fluid network that facilitates the transport of volatile samples to a gas chromatograph and mass spectrometer (GC-MS) instrument. The understanding of fluid dynamics directed from the GC to the MS is important due to the influence of flow rates and pressures that affect the accuracy of and prevent the damage to the overall GC-MS instrument. The micro-scale capillary fluid network within the GC alone has various lengths and inner-diameters; therefore, determination of pressure differentials and flow rates are difficult to model computationally, with additional complexity from the vacuum conditions in space and lack of a lunar atmosphere. A series of tests were performed on an experimental set-up of the system where the inner diameters of the GC transfer line connecting to the MS were varied. The effect on chromatography readings were also studied by applying these lines onto a GC instrument. It was found that a smaller inner diameter transfer line resulted in a lower flow rate, as well as a lower pressure differential across the thermal conductivity detector (TCD) unit of the GC and a negligible pressure drop across the mock-up capillary column. The chromatography was affected with longer retention times and broader peak integrations. It was concluded that a 0.050 mm inner diameter line still proved most suitable for the systems flow rate preferences. In addition, it was evident that this small transfer line portrayed some expense to GC signal characteristics and the wait time for steady-state operation.

  8. Observation of a rainbow of visible colors in a near infrared cascaded Raman fiber laser and its novel application as a diagnostic tool for length resolved spectral analysis

    Science.gov (United States)

    Aparanji, Santosh; Balaswamy, V.; Arun, S.; Supradeepa, V. R.

    2018-02-01

    In this work, we report and analyse the surprising observation of a rainbow of visible colors, spanning 390nm to 620nm, in silica-based, Near Infrared, continuous-wave, cascaded Raman fiber lasers. The cascaded Raman laser is pumped at 1117nm at around 200W and at full power we obtain 100 W at 1480nm. With increasing pump power at 1117nm, the fiber constituting the Raman laser glows in various hues along its length. From spectroscopic analysis of the emitted visible light, it was identified to be harmonic and sum-frequency components of various locally propagating wavelength components. In addition to third harmonic components, surprisingly, even 2nd harmonic components were observed. Despite being a continuous-wave laser, we expect the phase-matching occurring between the core-propagating NIR light with the cladding-propagating visible wavelengths and the intensity fluctuations characteristic of Raman lasers to have played a major role in generation of visible light. In addition, this surprising generation of visible light provides us a powerful non-contact method to deduce the spectrum of light propagating in the fiber. Using static images of the fiber captured by a standard visible camera such as a DSLR, we demonstrate novel, image-processing based techniques to deduce the wavelength component propagating in the fiber at any given spatial location. This provides a powerful diagnostic tool for both length and power resolved spectral analysis in Raman fiber lasers. This helps accurate prediction of the optimal length of fiber required for complete and efficient conversion to a given Stokes wavelength.

  9. Exploring climate niches of ponderosa pine (Pinus ponderosa Douglas ex Lawson) haplotypes in the western United States: implications for evolutionary history and conservation

    Science.gov (United States)

    Douglas J. Shinneman; Robert E. Means; Kevin M. Potter; Valerie D. Hipkins; Tzen-Yuh Chiang

    2016-01-01

    Ponderosa pine (Pinus ponderosa Douglas ex Lawson) occupies montane environments throughout western North America, where it is both an ecologically and economically important tree species. A recent study using mitochondrial DNA analysis demonstrated substantial genetic variation among ponderosa pine populations in the western U.S., identifying 10 haplotypes with unique...

  10. The evolutionary history of the DMRT3 'Gait keeper' haplotype.

    Science.gov (United States)

    Staiger, E A; Almén, M S; Promerová, M; Brooks, S; Cothran, E G; Imsland, F; Jäderkvist Fegraeus, K; Lindgren, G; Mehrabani Yeganeh, H; Mikko, S; Vega-Pla, J L; Tozaki, T; Rubin, C J; Andersson, L

    2017-10-01

    A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits. © 2017 Stichting International Foundation for Animal Genetics.

  11. HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population.

    Science.gov (United States)

    Pimentel-Santos, F M; Matos, M; Ligeiro, D; Mourão, A F; Ribeiro, C; Costa, J; Santos, H; Barcelos, A; Pinto, P; Cruz, M; Sousa, E; Santos, R A; Fonseca, J E; Trindade, H; Guedes-Pinto, H; Branco, J C

    2013-12-01

    Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension.

    Science.gov (United States)

    Zhang, Hao; Li, Xueyan; Zhou, Li; Zhang, Keyong; Zhang, Qi; Li, Jingping; Wang, Ningning; Jin, Ming; Wu, Nan; Cong, Mingyu; Qiu, Changchun

    2017-09-01

    Low-frequency variants showed that there is more power to detect risk variants than to detect protective variants in complex diseases. Aldosterone plays an important role in the renin-angiotensin-aldosterone system, and aldosterone synthase catalyzes the speed-controlled steps of aldosterone biosynthesis. Polymorphisms of the aldosterone synthase gene (CYP11B2) have been reported to be associated with essential hypertension (EH). CYP11B2 polymorphisms such as -344T/C, have been extensively reported, but others are less well known. This study aimed to assess the association between human CYP11B2 and EH using a haplotype-based case-control study. A total of 1024 EH patients and 956 normotensive controls, which consist of north Han population peasants, were enrolled. Seven single nucleotide polymorphisms (SNPs) (rs28659182, rs10087214, rs73715282, rs542092383, rs4543, rs28491316, and rs7463212) covering the entire human CYP11B2 gene were genotyped as markers using the MassARRAY system. The major allele G frequency of rs542092383 was found to be risk against hypertension [odds ratio (OR) 3.478, 95% confidence interval (95% CI) 1.407-8.597, P = .004]. The AG genotype frequency of SNP rs542092383 was significantly associated with an increased risk of hypertension (OR 4.513, 95% CI 1.426-14.287, P = .010). In the haplotype-based case-control analysis, the frequency of the T-G-T haplotype was higher for EH patients than for controls (OR 5.729, 95% CI 1.889-17.371, P = .000495). All |D'| values of the seven SNPs were >0.9, and r values for rs28659182- rs10087214-rs28491316-rs7463212 SNPs were >0.8 and showed strong linkage intensity. Haplotype T-G-T may therefore be a useful genetic marker for EH.

  13. Haplotype diversity of 17 Y-chromosomal STRs in three native Sarawak populations (Iban, Bidayuh and Melanau) in East Malaysia.

    Science.gov (United States)

    Chang, Yuet Meng; Swaran, Yuvaneswari; Phoon, Yoong Keat; Sothirasan, Kavin; Sim, Hang Thiew; Lim, Kong Boon; Kuehn, Daniel

    2009-06-01

    17 Y-STRs (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) have been analyzed in 320 male individuals from Sarawak, an eastern state of Malaysia on the Borneo island using the AmpFlSTR Y-filer (Applied Biosystems, Foster City, CA). These individuals were from three indigenous ethnic groups in Sarawak comprising of 103 Ibans, 113 Bidayuhs and 104 Melanaus. The observed 17-loci haplotypes and the individual allele frequencies for each locus were estimated, whilst the locus diversity, haplotype diversity and discrimination capacity were calculated in the three groups. Analysis of molecular variance (AMOVA) indicated that 87.6% of the haplotypic variation was found within population and 12.4% between populations (fixation index F(ST)=0.124, p=0.000). This study has revealed that the indigenous populations in Sarawak are distinctly different to each other, and to the three major ethnic groups in Malaysia (Malays, Chinese and Indians), with the Melanaus having a strikingly high degree of shared haplotypes within. There are rare unusual variants and microvariants that were not present in Malaysian Malay, Chinese or Indian groups. In addition, occurrences of DYS385 duplications which were only noticeably present in Chinese group previously was also observed in the Iban group whilst null alleles were detected at several Y-loci (namely DYS19, DYS392, DYS389II and DYS448) in the Iban and Melanau groups.

  14. Novel Tenascin-C Haplotype Modifies the Risk for a Failure to Heal After Rotator Cuff Repair.

    Science.gov (United States)

    Kluger, Rainer; Huber, Klaus R; Seely, Philipp G; Berger, Christian E; Frommlet, Florian

    2017-11-01

    Several single-nucleotide polymorphisms (SNPs) in the TNC gene have recently been found to be associated with degenerative rotator cuff tears. Exonic SNPs in the TNC gene are related to the risk for a failure to heal after rotator cuff repair. Case-control study; Level of evidence, 3. A total of 302 patients from the Vienna area and European Caucasian ancestry underwent mini-open rotator cuff repair for a full-thickness superior or posterosuperior tear and were assessed for the integrity of the repair 1 year postoperatively with a real-time 7.5- to 10-MHz ultrasound linear array transducer. Outcomes were classified as intact (complete footprint coverage), small (T] was protective for a large recurrent defect (odds ratio = 0.16; 95% CI, 0.09-0.31). The role of rs1138545 was further backed by haplotype analysis, which showed that the combination of the C allele at rs1138545 [C>T], the A allele at rs2104772 [A>T], and the G allele at rs10759752 [A>G] formed the risk-related haplotype [CAG]. The CAG haplotype was associated with large recurrent defects ( P rotator cuff repairs are clinically relevant, and a heritable component of the disorder is plausible on the basis of a genetic association with 8 TNC variants. Characterization of TNC sequences that favor tendon healing will help engineer new products in regenerative medicine.

  15. Haplotype diversity of 16 Y-chromosomal STRs in three main ethnic populations (Malays, Chinese and Indians) in Malaysia.

    Science.gov (United States)

    Chang, Yuet Meng; Perumal, Revathi; Keat, Phoon Yoong; Kuehn, Daniel L C

    2007-03-22

    We have analyzed 16 Y-STR loci (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) from the non-recombining region of the human Y-chromosome in 980 male individuals from three main ethnic populations in Malaysia (Malay, Chinese, Indian) using the AmpFlSTR((R)) Y-filertrade mark (Applied Biosystems, Foster City, CA). The observed 17-loci haplotypes and the individual allele frequencies for each locus were estimated, whilst the locus diversity, haplotype diversity and discrimination capacity were calculated in the three ethnic populations. Analysis of molecular variance indicated that 88.7% of the haplotypic variation is found within population and 11.3% is between populations (fixation index F(ST)=0.113, p=0.000). This study has revealed Y-chromosomes with null alleles at several Y-loci, namely DYS458, DYS392, DYS389I, DYS389II, DYS439, DYS448 and Y-GATA H4; and several occurrences of duplications at the highly polymorphic DYS385 loci. Some of these deleted loci were in regions of the Y(q) arm that have been implicated in the occurrence of male infertility.

  16. Antioxidant activity of yogurt made from milk characterized by different casein haplotypes and fortified with chestnut and sulla honeys.

    Science.gov (United States)

    Perna, Annamaria; Intaglietta, Immacolata; Simonetti, Amalia; Gambacorta, Emilio

    2014-11-01

    The aim of this work was to evaluate the antioxidant activity of yogurt made from milk characterized by different casein (CN) haplotypes (αs1-, β-, κ-CN) and fortified with chestnut and sulla honeys. The CN haplotype was determined by isoelectric focusing, whereas antioxidant activity of yogurt was measured using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and ferric-reducing antioxidant power. The statistical analysis showed a significant effect of the studied factors. The results showed that chestnut honey presented the highest phenolic acid and flavonoid contents, which are closely associated with its high antioxidant activity. The antioxidant activity of fortified yogurt samples was affected both by different CN haplotypes and by type of honey added. Yogurts fortified with chestnut honey showed higher antioxidant activity than those fortified with sulla honey. The different behavior observed among the fortified yogurts led us to hypothesize that the effects of protein-polyphenol complex on antioxidant activity are interactive. The results suggest that milk proteins polymorphism and polyphenols play different roles in affecting the bioavailability and the antioxidant activity of yogurt. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

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    Pamela Thompson

    Full Text Available Childhood Acute Lymphoblastic Leukemia (ALL is a malignant lymphoid disease of which B-cell precursor- (BCP and T-cell- (T ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3, adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3 differed significantly between BCP-ALL and controls (P = 0.002 and in Block 4 (including HLA-DPB1 between T-ALL and controls (P = 0.049. Of specific common (>5% haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

  18. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2010-03-01

    Full Text Available Abstract Background Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI. The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3. Results The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.

  19. Characterization of weakly absorbing thin films by multiple linear regression analysis of absolute unwrapped phase in angle-resolved spectral reflectometry.

    Science.gov (United States)

    Dong, Jingtao; Lu, Rongsheng

    2018-04-30

    The simultaneous determination of t, n(λ), and κ(λ) of thin films can be a tough task for the high correlation of fit parameters. The strong assumptions about the type of dispersion relation are commonly used as a consequence to alleviate correlation concerns by reducing the free parameters before the nonlinear regression analysis. Here we present an angle-resolved spectral reflectometry for the simultaneous determination of weakly absorbing thin film parameters, where a reflectance interferogram is recorded in both angular and spectral domains in a single-shot measurement for the point of the sample being illuminated. The variations of the phase recovered from the interferogram as functions of t, n, and κ reveals that the unwrapped phase is monotonically related to t, n, and κ, thereby allowing the problem of correlation to be alleviated by multiple linear regression. After removing the 2π ambiguity of the unwrapped phase, the merit function based on the absolute unwrapped phase performs a 3D data cube with variables of t, n and κ at each wavelength. The unique solution of t, n, and κ can then be directly determined from the extremum of the 3D data cube at each wavelength with no need of dispersion relation. A sample of GaN thin film grown on a polished sapphire substrate is tested. The experimental data of t and [n(λ), κ(λ)] are confirmed by the scanning electron microscopy and the comparison with the results of other related works, respectively. The consistency of the results shows the proposed method provides a useful tool for the determination of the thickness and optical constants of weakly absorbing thin films.

  20. In vivo hemodynamic analysis of intracranial aneurysms obtained by magnetic resonance fluid dynamics (MRFD) based on time-resolved three-dimensional phase-contrast MRI

    International Nuclear Information System (INIS)

    Isoda, Haruo; Takeda, Hiroyasu; Yamashita, Shuhei; Takehara, Yasuo; Sakahara, Harumi; Ohkura, Yasuhide; Kosugi, Takashi; Hirano, Masaya; Hiramatsu, Hisaya; Namba, Hiroki; Alley, Marcus T.; Bammer, Roland; Pelc, Norbert J.

    2010-01-01

    Hemodynamics is thought to play a very important role in the initiation, growth, and rupture of intracranial aneurysms. The purpose of our study was to perform in vivo hemodynamic analysis of unruptured intracranial aneurysms of magnetic resonance fluid dynamics using time-resolved three-dimensional phase-contrast MRI (4D-Flow) at 1.5 T and to analyze relationships between hemodynamics and wall shear stress (WSS) and oscillatory shear index (OSI). This study included nine subjects with 14 unruptured aneurysms. 4D-Flow was performed by a 1.5-T magnetic resonance scanner with a head coil. We calculated in vivo streamlines, WSS, and OSI of intracranial aneurysms based on 4D-Flow with our software. We evaluated the number of spiral flows in the aneurysms and compared the differences in WSS or OSI between the vessel and aneurysm and between whole aneurysm and the apex of the spiral flow. 3D streamlines, WSS, and OSI distribution maps in arbitrary direction during the cardiac phase were obtained for all intracranial aneurysms. Twelve aneurysms had one spiral flow each, and two aneurysms had two spiral flows each. The WSS was lower and the OSI was higher in the aneurysm compared to the vessel. The apex of the spiral flow had a lower WSS and higher OSI relative to the whole aneurysm. Each intracranial aneurysm in this study had at least one spiral flow. The WSS was lower and OSI was higher at the apex of the spiral flow than the whole aneurysmal wall. (orig.)

  1. In vivo hemodynamic analysis of intracranial aneurysms obtained by magnetic resonance fluid dynamics (MRFD) based on time-resolved three-dimensional phase-contrast MRI.

    Science.gov (United States)

    Isoda, Haruo; Ohkura, Yasuhide; Kosugi, Takashi; Hirano, Masaya; Takeda, Hiroyasu; Hiramatsu, Hisaya; Yamashita, Shuhei; Takehara, Yasuo; Alley, Marcus T; Bammer, Roland; Pelc, Norbert J; Namba, Hiroki; Sakahara, Harumi

    2010-10-01

    Hemodynamics is thought to play a very important role in the initiation, growth, and rupture of intracranial aneurysms. The purpose of our study was to perform in vivo hemodynamic analysis of unruptured intracranial aneurysms of magnetic resonance fluid dynamics using time-resolved three-dimensional phase-contrast MRI (4D-Flow) at 1.5 T and to analyze relationships between hemodynamics and wall shear stress (WSS) and oscillatory shear index (OSI). This study included nine subjects with 14 unruptured aneurysms. 4D-Flow was performed by a 1.5-T magnetic resonance scanner with a head coil. We calculated in vivo streamlines, WSS, and OSI of intracranial aneurysms based on 4D-Flow with our software. We evaluated the number of spiral flows in the aneurysms and compared the differences in WSS or OSI between the vessel and aneurysm and between whole aneurysm and the apex of the spiral flow. 3D streamlines, WSS, and OSI distribution maps in arbitrary direction during the cardiac phase were obtained for all intracranial aneurysms. Twelve aneurysms had one spiral flow each, and two aneurysms had two spiral flows each. The WSS was lower and the OSI was higher in the aneurysm compared to the vessel. The apex of the spiral flow had a lower WSS and higher OSI relative to the whole aneurysm. Each intracranial aneurysm in this study had at least one spiral flow. The WSS was lower and OSI was higher at the apex of the spiral flow than the whole aneurysmal wall.

  2. Historical biogeography of the land snail Cornu aspersum: a new scenario inferred from haplotype distribution in the Western Mediterranean basin

    Directory of Open Access Journals (Sweden)

    Madec Luc

    2010-01-01

    Full Text Available Abstract Background Despite its key location between the rest of the continent and Europe, research on the phylogeography of north African species remains very limited compared to European and North American taxa. The Mediterranean land mollusc Cornu aspersum (= Helix aspersa is part of the few species widely sampled in north Africa for biogeographical analysis. It then provides an excellent biological model to understand phylogeographical patterns across the Mediterranean basin, and to evaluate hypotheses of population differentiation. We investigated here the phylogeography of this land snail to reassess the evolutionary scenario we previously considered for explaining its scattered distribution in the western Mediterranean, and to help to resolve the question of the direction of its range expansion (from north Africa to Europe or vice versa. By analysing simultaneously individuals from 73 sites sampled in its putative native range, the present work provides the first broad-scale screening of mitochondrial variation (cyt b and 16S rRNA genes of C. aspersum. Results Phylogeographical structure mirrored previous patterns inferred from anatomy and nuclear data, since all haplotypes could be ascribed to a B (West or a C (East lineage. Alternative migration models tested confirmed that C. aspersum most likely spread from north Africa to Europe. In addition to Kabylia in Algeria, which would have been successively a centre of dispersal and a zone of secondary contacts, we identified an area in Galicia where genetically distinct west and east type populations would have regained contact. Conclusions Vicariant and dispersal processes are reviewed and discussed in the light of signatures left in the geographical distribution of the genetic variation. In referring to Mediterranean taxa which show similar phylogeographical patterns, we proposed a parsimonious scenario to account for the "east-west" genetic splitting and the northward expansion of the

  3. Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

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    Luciana Takada

    Full Text Available Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth as fixed effect and parent of the animal (sire effect as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05 on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2, two in the Estrogen-related receptor gamma gene (ESRRG, and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A, Kell blood group complex subunit-related family (XKR4 and mannose-binding lectin genes (MBL-1 genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

  4. Genetic relationships among native americans based on beta-globin gene cluster haplotype frequencies

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    Rita de Cassia Mousinho-Ribeiro

    2003-01-01

    Full Text Available The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village, Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13 had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - - was the most common in all groups studied, with frequencies varying from 70% to 100%, followed by haplotype 6 (- + + - +, with frequencies between 7% and 18%. The frequency distribution of the b-globin gene haplotypes in the eighteen Brazilian Amerindian populations studied to date is characterized by a reduced number of haplotypes (average of 3.5 and low levels of heterozygosity and intrapopulational differentiation, with a single clearly predominant haplotype in most tribes (haplotype 2. The Parakanã, Urubú-Kaapór, Tiriyó and Xavante tribes constitute exceptions, presenting at least four haplotypes with relatively high frequencies. The closest genetic relationships were observed between the Brazilian and the Colombian Amerindians (Wayuu, Kamsa and Inga, and, to a lesser extent, with the Huichol of Mexico. North-American Amerindians are more differentiated and clearly separated from all other tribes, except the Xavante, from Brazil, and the Mapuche, from Argentina. A restricted pool of ancestral haplotypes may explain the low diversity observed among most present-day Brazilian and Colombian Amerindian groups, while interethnic admixture could be the most important factor to explain the high number of haplotypes and high levels of diversity observed in some South-American and most North-American tribes.

  5. Performance test of Spectran-F and Spectran-III computer programs for resolving the 137Cs-110Ag double peak in gamma-ray spectrometric analysis

    International Nuclear Information System (INIS)

    Terada, H.; Malinowski, J.; Blick, H.

    1981-09-01

    The performance of the computer programs (Spectran F and Spectran-III) in resolving the 137 Cs-sup(110m)Ag double peak at 661.6-657.7 keV in the gamma-ray spectrum was investigated. In the experiments, the intensity ratios of both lines in the double peak were varied from 0.1 to 60. The results obtained show, that both programs have almost the same performance in resolving the double peak investigated, with slight superiority of Spectran-F. If accuracy better than 5% is desired, the peak intensity ratio in the dublet must be kept below 10. (orig.)

  6. Musical aptitude is associated with AVPR1A-haplotypes.

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    Liisa T Ukkola

    Full Text Available Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A, serotonin transporter (SLC6A4, catecol-O-methyltranferase (COMT, dopamin receptor D2 (DRD2 and tyrosine hydroxylase 1 (TPH1, genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT and Carl Seashores tests for pitch (SP and for time (ST. Data on creativity in music (composing, improvising and/or arranging music was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2 = .84; composing h(2 = .40; arranging h(2 = .46; improvising h(2 = .62 in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001. We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3 and KMT (p = 0.0008; corrected p = 0.00002, SP (p = 0.0261; corrected p = 0.0072 and combined music test scores (COMB (p = 0.0056; corrected p = 0.0006. AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184 and COMB (p = 0.0083; corrected p = 0.0040 using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment

  7. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

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    Schrooten Chris

    2009-01-01

    Full Text Available Abstract The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD probabilities between haplotypes, various haplotype definitions were tested i.e. including 2, 6, 12 or 20 marker alleles and clustering base haplotypes related with an IBD probability of > 0.55, 0.75 or 0.95. Simulated data contained 1100 animals with known genotypes and phenotypes and 1000 animals with known genotypes and unknown phenotypes. Genomes comprising 3 Morgan were simulated and contained 74 polymorphic QTL and 383 polymorphic SNP markers with an average r2 value of 0.14 between adjacent markers. The total number of haplotypes decreased up to 50% when the window size was increased from two to 20 markers and decreased by at least 50% when haplotypes related with an IBD probability of > 0.55 instead of > 0.95 were clustered. An intermediate window size led to more precise QTL mapping. Window size and clustering had a limited effect on the accuracy of predicted total breeding values, ranging from 0.79 to 0.81. Our conclusion is that different optimal window sizes should be used in QTL-mapping versus genome-wide breeding value prediction.

  8. Discovery, evaluation and distribution of haplotypes of the wheat Ppd-D1 gene.

    Science.gov (United States)

    Guo, Zhiai; Song, Yanxia; Zhou, Ronghua; Ren, Zhenglong; Jia, Jizeng

    2010-02-01

    Ppd-D1 is one of the most potent genes affecting the photoperiod response of wheat (Triticum aestivum). Only two alleles, insensitive Ppd-D1a and sensitive Ppd-D1b, were known previously, and these did not adequately explain the broad adaptation of wheat to photoperiod variation. In this study, five diagnostic molecular markers were employed to identify Ppd-D1 haplotypes in 492 wheat varieties from diverse geographic locations and 55 accessions of Aegilops tauschii, the D genome donor species of wheat. Six Ppd-D1 haplotypes, designated I-VI, were identified. Types II, V and VI were considered to be more ancient and types I, III and IV were considered to be derived from type II. The transcript abundances of the Ppd-D1 haplotypes showed continuous variation, being highest for haplotype I, lowest for haplotype III, and correlating negatively with varietal differences in heading time. These haplotypes also significantly affected other agronomic traits. The distribution frequency of Ppd-D1 haplotypes showed partial correlations with both latitudes and altitudes of wheat cultivation regions. The evolution, expression and distribution of Ppd-D1 haplotypes were consistent evidentially with each other. What was regarded as a pair of alleles in the past can now be considered a series of alleles leading to continuous variation.

  9. Identification of a functional enhancer variant within the chronic pancreatitis-associated SPINK1 c.101A>G (p.Asn34Ser)-containing haplotype.

    Science.gov (United States)

    Boulling, Arnaud; Masson, Emmanuelle; Zou, Wen-Bin; Paliwal, Sumit; Wu, Hao; Issarapu, Prachand; Bhaskar, Seema; Génin, Emmanuelle; Cooper, David N; Li, Zhao-Shen; Chandak, Giriraj R; Liao, Zhuan; Chen, Jian-Min; Férec, Claude

    2017-08-01

    The haplotype harboring the SPINK1 c.101A>G (p.Asn34Ser) variant (also known as rs17107315:T>C) represents the most important heritable risk factor for idiopathic chronic pancreatitis identified to date. The causal variant contained within this risk haplotype has however remained stubbornly elusive. Herein, we set out to resolve this enigma by employing a hypothesis-driven approach. First, we searched for variants in strong linkage disequilibrium (LD) with rs17107315:T>C using HaploReg v4.1. Second, we identified two candidate SNPs by visual inspection of sequences spanning all 25 SNPs found to be in LD with rs17107315:T>C, guided by prior knowledge of pancreas-specific transcription factors and their cognate binding sites. Third, employing a novel cis-regulatory module (CRM)-guided approach to further filter the two candidate SNPs yielded a solitary candidate causal variant. Finally, combining data from phylogenetic conservation and chromatin accessibility, cotransfection transactivation experiments, and population genetic studies, we suggest that rs142703147:C>A, which disrupts a PTF1L-binding site within an evolutionarily conserved HNF1A-PTF1L CRM located ∼4 kb upstream of the SPINK1 promoter, contributes to the aforementioned chronic pancreatitis risk haplotype. Further studies are required not only to improve the characterization of this functional SNP but also to identify other functional components that might contribute to this high-risk haplotype. © 2017 Wiley Periodicals, Inc.

  10. Musical Aptitude Is Associated with AVPR1A-Haplotypes

    Science.gov (United States)

    Ukkola, Liisa T.; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-01-01

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h2 = .84; composing h2 = .40; arranging h2 = .46; improvising h2 = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (pmusic test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment behavior. PMID:19461995

  11. Musical aptitude is associated with AVPR1A-haplotypes.

    Science.gov (United States)

    Ukkola, Liisa T; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-05-20

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2) = .84; composing h(2) = .40; arranging h(2) = .46; improvising h(2) = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (pmusic test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment behavior.

  12. Haplotype assembly in polyploid genomes and identical by descent shared tracts.

    Science.gov (United States)

    Aguiar, Derek; Istrail, Sorin

    2013-07-01

    Genome-wide haplotype reconstruction from sequence data, or haplotype assembly, is at the center of major challenges in molecular biology and life sciences. For complex eukaryotic organisms like humans, the genome is vast and the population samples are growing so rapidly that algorithms processing high-throughput sequencing data must scale favorably in terms of both accuracy and computational efficiency. Furthermore, current models and methodologies for haplotype assembly (i) do not consider individuals sharing haplotypes jointly, which reduces the size and accuracy of assembled haplotypes, and (ii) are unable to model genomes having more than two sets of homologous chromosomes (polyploidy). Polyploid organisms are increasingly becoming the target of many research groups interested in the genomics of disease, phylogenetics, botany and evolution but there is an absence of theory and methods for polyploid haplotype reconstruction. In this work, we present a number of results, extensions and generalizations of compass graphs and our HapCompass framework. We prove the theoretical complexity of two haplotype assembly optimizations, thereby motivating the use of heuristics. Furthermore, we present graph theory-based algorithms for the problem of haplotype assembly using our previously developed HapCompass framework for (i) novel implementations of haplotype assembly optimizations (minimum error correction), (ii) assembly of a pair of individuals sharing a haplotype tract identical by descent and (iii) assembly of polyploid genomes. We evaluate our methods on 1000 Genomes Project, Pacific Biosciences and simulated sequence data. HapCompass is available for download at http://www.brown.edu/Research/Istrail_Lab/. Supplementary data are available at Bioinformatics online.

  13. MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

    Science.gov (United States)

    Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

    2016-10-01

    The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

  14. Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene

    Science.gov (United States)

    2010-01-01

    Background Effective treatment remains a mainstay of malaria control, but it is unfortunately strongly compromised by drug resistance, particularly in Plasmodium falciparum, the most important human malaria parasite. Although P. falciparum chemoresistance is well recognized all over the world, limited data are available on the distribution and prevalence of pfcrt and pfmdr1 haplotypes that mediate resistance to commonly used drugs and that show distinct geographic differences. Methods Plasmodium falciparum-infected blood samples collected in 2007 at four municipalities of Luanda, Angola, were genotyped using PCR and direct DNA sequencing. Single nucleotide polymorphisms in the P. falciparum pfcrt and pfmdr1 genes were assessed and haplotype prevalences were determined. Results and Discussion The most prevalent pfcrt haplotype was StctVMNT (representing amino acids at codons 72-76). This result was unexpected, since the StctVMNT haplotype has previously been seen mainly in parasites from South America and India. The CVIET, CVMNT and CVINT drug-resistance haplotypes were also found, and one previously undescribed haplotype (CVMDT) was detected. Regarding pfmdr1, the most prevalent haplotype was YEYSNVD (representing amino acids at codons 86, 130, 184, 1034, 1042, 1109 and 1246). Wild haplotypes for pfcrt and pfmdr1 were uncommon; 3% of field isolates harbored wild type pfcrt (CVMNK), whereas 21% had wild type pfmdr1 (NEYSNVD). The observed predominance of the StctVMNT haplotype in Angola could be a result of frequent travel between Brazil and Angola citizens in the context of selective pressure of heavy CQ use. Conclusions The high prevalence of the pfcrt SVMNT haplotype and the pfmdr1 86Y mutation confirm high-level chloroquine resistance and might suggest reduced efficacy of amodiaquine in Angola. Further studies must be encouraged to examine the in vitro sensitivity of pfcrt SVMNT parasites to artesunate and amodiaquine for better conclusive data. PMID:20565881

  15. MalHaploFreq: A computer programme for estimating malaria haplotype frequencies from blood samples

    Directory of Open Access Journals (Sweden)

    Smith Thomas A

    2008-07-01

    Full Text Available Abstract Background Molecular markers, particularly those associated with drug resistance, are important surveillance tools that can inform policy choice. People infected with falciparum malaria often contain several genetically-distinct clones of the parasite; genotyping the patients' blood reveals whether or not the marker is present (i.e. its prevalence, but does not reveal its frequency. For example a person with four malaria clones may contain both mutant and wildtype forms of a marker but it is not possible to distinguish the relative frequencies of the mutant and wildtypes i.e. 1:3, 2:2 or 3:1. Methods An appropriate method for obtaining frequencies from prevalence data is by Maximum Likelihood analysis. A computer programme has been developed that allows the frequency of markers, and haplotypes defined by up to three codons, to be estimated from blood phenotype data. Results The programme has been fully documented [see Additional File 1] and provided with a user-friendly interface suitable for large scale analyses. It returns accurate frequencies and 95% confidence intervals from simulated dataset sets and has been extensively tested on field data sets. Additional File 1 User manual for MalHaploFreq. Click here for file Conclusion The programme is included [see Additional File 2] and/or may be freely downloaded from 1. It can then be used to extract molecular marker and haplotype frequencies from their prevalence in human blood samples. This should enhance the use of frequency data to inform antimalarial drug policy choice. Additional File 2 executable programme compiled for use on DOS or windows Click here for file

  16. Novel CYP2E1 haplotype identified in a South African cohort

    Directory of Open Access Journals (Sweden)

    Laura J. Heathfield

    2014-09-01

    Full Text Available Alcohol abuse accounts for approximately 2.5 million deaths annually and is the third highest risk factor for disease and disability. Alcohol is metabolised by polymorphic enzymes and the status of an individual with respect to alcohol metabolising enzymes may have forensic relevance in post-mortems. Baseline frequencies of gene variants involved in alcohol metabolism need to be established to aid the identification of suitable population-specific polymorphisms to genotype during molecular autopsies. The principal alcohol metabolising enzymes include alcohol dehydrogenase (ADH, aldehyde dehydrogenase (ALDH and cytochrome P450 2E1 (CYP2E1. Six single nucleotide polymorphisms (SNPs – rs1229984G>A and rs2066702C>T in ADH1B, rs671G>A in ALDH2, and rs3813867G>C, rs2031920C>T and rs6413432T>A in CYP2E1 – were genotyped in 150 individuals from four South African populations: Xhosa, Zulu, South African white and South African coloured. Allele frequencies for each SNP in the four population groups were 0–10% for rs1229984A, 2–12% for rs2066702T, 0–2% for rs671A, 1–4% for rs3813867C, 0–1% for rs2031920T and 3–15% for rs6413432A. Haplotype analysis revealed a novel combination of three SNPs in CYP2E1 whose effects on alcohol metabolism need further investigation. Establishment of baseline frequencies adds to our knowledge of genetic variation in alcohol metabolising enzymes and additional research is required to determine the functional significance of this novel CYP2E1 haplotype.

  17. Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

    Science.gov (United States)

    Stram, Daniel O; Leigh Pearce, Celeste; Bretsky, Phillip; Freedman, Matthew; Hirschhorn, Joel N; Altshuler, David; Kolonel, Laurence N; Henderson, Brian E; Thomas, Duncan C

    2003-01-01

    The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both

  18. Highly resolving computerized tomography

    International Nuclear Information System (INIS)

    Kurtz, B.; Petersen, D.; Walter, E.

    1984-01-01

    With the development of highly-resolving devices for computerized tomography, CT diagnosis of the lumbar vertebral column has gained increasing importance. As an ambulatory, non-invasive method it has proved in comparative studies to be at least equivalent to myelography in the detection of dislocations of inter-vertebral disks (4,6,7,15). Because with modern devices not alone the bones, but especially the spinal soft part structures are clearly and precisely presented with a resolution of distinctly below 1 mm, a further improvement of the results is expected as experience will increase. The authors report on the diagnosis of the lumbar vertebral column with the aid of a modern device for computerized tomography and wish to draw particular attention to the possibility of doing this investigation as a routine, and to the diagnostic value of secondary reconstructions. (BWU) [de

  19. Highly resolving computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, B.; Petersen, D.; Walter, E.

    1984-01-01

    With the development of highly-resolving devices for computerized tomography, CT diagnosis of the lumbar vertebral column has gained increasing importance. As an ambulatory, non-invasive method it has proved in comparative studies to be at least equivalent to myelography in the detection of dislocations of inter-vertebral disks (4,6,7,15). Because with modern devices not alone the bones, but especially the spinal soft part structures are clearly and precisely presented with a resolution of distinctly below 1 mm, a further improvement of the results is expected as experience will increase. The authors report on the diagnosis of the lumbar vertebral column with the aid of a modern device for computerized tomography and wish to draw particular attention to the possibility of doing this investigation as a routine, and to the diagnostic value of secondary reconstructions.

  20. HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment.

    Science.gov (United States)

    Costa, Cynthia Hernandes; Gelmini, Georgia Fernanda; Wowk, Pryscilla Fanini; Mattar, Sibelle Botogosque; Vargas, Rafael Gustavo; Roxo, Valéria Maria Munhoz Sperandio; Schuffner, Alessandro; Bicalho, Maria da Graça

    2012-09-01

    The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART. Copyright © 2012. Published by Elsevier Inc.

  1. Mineralocorticoid receptor haplotype moderates the effects of oral contraceptives and menstrual cycle on emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Tollenaar, Marieke; Verkuil, Bart; Manai, Meriem; Putman, Peter; Van der Does, Willem

    2016-10-01

    The processing of emotional information is affected by menstrual cycle phase and by the use of oral contraceptives (OCs). The stress hormone cortisol is known to affect emotional information processing via the limbic mineralocorticoid receptor (MR). We investigated in an exploratory study whether the MR-genotype moderates the effect of both OC-use and menstrual cycle phase on emotional cognition. Healthy premenopausal volunteers (n=93) of West-European descent completed a battery of emotional cognition tests. Forty-nine participants were OC users and 44 naturally cycling, 21 of whom were tested in the early follicular (EF) and 23 in the mid-luteal (ML) phase of the menstrual cycle. In MR-haplotype 1/3 carriers, ML women gambled more than EF women when their risk to lose was relatively small. In MR-haplotype 2, ML women gambled more than EF women, regardless of their odds of winning. OC-users with MR-haplotype 1/3 recognised fewer facial expressions than ML women with MR-haplotype 1/3. MR-haplotype 1/3 carriers may be more sensitive to the influence of their female hormonal status. MR-haplotype 2 carriers showed more risky decision-making. As this may reflect optimistic expectations, this finding may support previous observations in female carriers of MR-haplotype 2 in a naturalistic cohort study. © The Author(s) 2016.

  2. Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents.

    Science.gov (United States)

    Habara, Alawi H; Shaikho, Elmutaz M; Steinberg, Martin H

    2017-11-01

    Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly twofold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. © 2017 Wiley Periodicals, Inc.

  3. Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe

    DEFF Research Database (Denmark)

    Nagirnaja, Liina; Nõmmemees, Diana; Rull, Kristiina

    2015-01-01

    and recurrent pregnancy loss (RPL), however with inconclusive results. STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia...... compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%). CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic...

  4. Genetic and molecular characterization of three novel S-haplotypes in sour cherry (Prunus cerasus L.).

    Science.gov (United States)

    Tsukamoto, Tatsuya; Potter, Daniel; Tao, Ryutaro; Vieira, Cristina P; Vieira, Jorge; Iezzoni, Amy F

    2008-01-01

    Tetraploid sour cherry (Prunus cerasus L.) exhibits gametophytic self-incompatibility (GSI) whereby the specificity of self-pollen rejection is controlled by alleles of the stylar and pollen specificity genes, S-RNase and SFB (S haplotype-specific F-box protein gene), respectively. As sour cherry selections can be either self-compatible (SC) or self-incompatible (SI), polyploidy per se does not result in SC. Instead the genotype-dependent loss of SI in sour cherry is due to the accumulation of non-functional S-haplotypes. The presence of two or more non-functional S-haplotypes within sour cherry 2x pollen renders that pollen SC. Two new S-haplotypes from sour cherry, S(33) and S(34), that are presumed to be contributed by the P. fruticosa species parent, the complete S-RNase and SFB sequences of a third S-haplotype, S(35), plus the presence of two previously identified sweet cherry S-haplotypes, S(14) and S(16) are described here. Genetic segregation data demonstrated that the S(16)-, S(33)-, S(34)-, and S(35)-haplotypes present in sour cherry are fully functional. This result is consistent with our previous finding that 'hetero-allelic' pollen is incompatible in sour cherry. Phylogenetic analyses of the SFB and S-RNase sequences from available Prunus species reveal that the relationships among S-haplotypes show no correspondence to known organismal relationships at any taxonomic level within Prunus, indicating that polymorphisms at the S-locus have been maintained throughout the evolution of the genus. Furthermore, the phylogenetic relationships among SFB sequences are generally incongruent with those among S-RNase sequences for the same S-haplotypes. Hypotheses compatible with these results are discussed.

  5. Effects of Single Nucleotide Polymorphism Marker Density on Haplotype Block Partition

    Directory of Open Access Journals (Sweden)

    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.

  6. Analysis of the influence of the plasma thermodynamic regime in the spectrally resolved and mean radiative opacity calculations of carbon plasmas in a wide range of density and temperature

    International Nuclear Information System (INIS)

    Gil, J.M.; Rodriguez, R.; Martel, P.; Florido, R.; Rubiano, J.G.; Mendoza, M.A.; Minguez, E.

    2013-01-01

    In this work the spectrally resolved, multigroup and mean radiative opacities of carbon plasmas are calculated for a wide range of plasma conditions which cover situations where corona, local thermodynamic and non-local thermodynamic equilibrium regimes are found. An analysis of the influence of the thermodynamic regime on these magnitudes is also carried out by means of comparisons of the results obtained from collisional-radiative, corona or Saha–Boltzmann equations. All the calculations presented in this work were performed using ABAKO/RAPCAL code. -- Highlights: ► Spectrally resolved, multigroup and mean radiative opacities of carbon plasmas are calculated. ► Corona, local thermodynamic and non-local thermodynamic equilibrium regimes are analyzed. ► Simulations performed using the computational package ABAKO/RAPCAL. ► A criterion for the establishment of the thermodynamic regime is proposed.

  7. Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease

    DEFF Research Database (Denmark)

    Lund, Flemming; Hermansen, Mette N; Pedersen, Merete F

    2015-01-01

    BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group...... of Danish CD patients using the SNP technique. METHODS: Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2...

  8. Genetic relationships among native americans based on b-globin gene cluster haplotype frequencies

    OpenAIRE

    Mousinho-Ribeiro Rita de Cassia; Pante-de-Sousa Gabriella; Santos Eduardo José Melo dos; Guerreiro João Farias

    2003-01-01

    The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village), Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13) had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - -) was the most common in all groups studied, with frequencies varying from 70% to 100%, followed...

  9. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    Abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study...... using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible...... findings in a second and independent cohort. Haplotype combinations call for further investigation. Keywords: colorectal neoplasm; single nucleotide polymorphisms; haplotypes; vascular endothelial growth factor A; survival...

  10. Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.

    Directory of Open Access Journals (Sweden)

    Shabeesh Balan

    Full Text Available The post-synaptic density (PSD of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects. Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02, although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects or in a Japanese case-control sample (n = 4182 subjects. The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009 and Chinese (p = 0.0007 schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes.

  11. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    Directory of Open Access Journals (Sweden)

    Mojca Simčič

    Full Text Available The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which

  12. Globin haplotypes of human T-cell lymphotropic virus type I-infected individuals in Salvador, Bahia, Brazil, suggest a post-Columbian African origin of this virus.

    Science.gov (United States)

    Alcantara, Luiz Carlos; Van Dooren, Sonia; Gonçalves, Marilda Souza; Kashima, Simone; Costa, Maria Cristina Ramos; Santos, Fred Luciano Neves; Bittencourt, Achilea Lisboa; Dourado, Inês; Filho, Antonio Andrade; Covas, Dimas Tadeu; Vandamme, Anne-Mieke; Galvão-Castro, Bernardo

    2003-08-01

    The city of Salvador, Bahia, Brazil, has sociodemographic characteristics similar to some African cities. Up to now, it has had the highest prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection (1.74%) in the country. To investigate which strains of HTLV-I are circulating in Salvador, we studied isolates from 82 patients infected with HTLV-I: 19 from the general population, 21 from pregnant women, 16 from intravenous drug users, and 26 from patients and their family attending a neurologic clinic. Phylogenetic analysis from part of the LTR fragments showed that most of these isolates belonged to the Transcontinental subgroup of the Cosmopolitan subtype (HTLV-Ia). Only one sample from a pregnant woman was closely related to the Japanese subgroup, suggesting recent introduction of a Japanese HTLV-I lineage into Salvador. betaA-Globin haplotypes were examined in 34 infected individuals and found to be atypical, confirming the racial heterogeneity of this population. A total of 20 chromosomes were characterized as Central African Republic (CAR) haplotype (29.4%), 31 (45.6%) were characterized as Benin (BEN) haplotype, and 17 (25%) were characterized as Senegal (SEN) haplotype. Five patients' genotypes (14.7%) were CAR/CAR; 10 (29,4%), BEN/BEN; 9 (26.5%), CAR/BEN; 2 (5.9%), BEN/SEN; and 7 (20.6%), SEN/SEN. One patient's genotype (2.9%) was CAR/SEN. The betaA-globin haplotype distribution in Salvador is unusual compared with other Brazilian states. Our data support the hypothesis of multiple post-Columbian introductions of African HTLV-Ia strains in Salvador, Bahia, Brazil.

  13. Strong association between a splice mutation (IVS12+5G{r_arrow}A) and haplotype 6 in hereditary tyrosinemia type I

    Energy Technology Data Exchange (ETDEWEB)

    Tanguay, R.M.; St-Louis, M.; Gibson, K. [Universite Laval, Ste-Foy (Canada)] [and others

    1994-09-01

    Hereditary tyrosinemia type I (HT I; McKusick 276700) is a severe inborn error of tyrosine catabolism pathway caused by a deficiency of fumarylacetoacetate hydrolase (FAH). The highest frequency reported is the one in Saguenay-Lac St-Jean (Quebec, Canada) where 1:1,846 births are affected. The FAH gene has been cloned and several mutations have been described. Allele specific oligonucleotide (ASO) hybridization was used to examine the frequency of a splice (IVS12-5G{r_arrow}A) mutation recently reported and RFLP analysis was done to identify haplotypes related to HT I. The splice mutation was found on 45/50 alleles (90%) in patients from SLSJ and 12/66 (18%) alleles from patients world-wide. All 25 patients from the SLSJ region were positive with 20 being homozygous, indicating that this mutation is the major cause of HT I in French Canada. Of these 25 patients, 96% were positive for one haplotype called no 6 which is these 25 patients, 96% were positive for one haplotype called no 6 which is identified by TaqI, RsaI, BglII, MspI and KpnI digestions. These data show a really strong association between the mutation (IVS12+5G{r_arrow}A) and haplotype 6. Among our patients from around the world, {approximately}52% were positive for haplotype 6 indicating its strong relation with HT I. These results provide the rationale for DNA-based carrier testing for HT I in the F-C population at risk as well as in HT I patients in general.

  14. MDR1 haplotypes conferring an increased expression of intestinal CYP3A4 rather than MDR1 in female living-donor liver transplant patients.

    Science.gov (United States)

    Hosohata, Keiko; Masuda, Satohiro; Yonezawa, Atsushi; Katsura, Toshiya; Oike, Fumitaka; Ogura, Yasuhiro; Takada, Yasutsugu; Egawa, Hiroto; Uemoto, Shinji; Inui, Ken-Ichi

    2009-07-01

    This study investigated whether haplotypes in the multidrug resistance 1 (MDR1) gene had effects on mRNA expression levels of MDR1 and cytochrome P450 (CYP) 3A4, and on the pharmacokinetics of tacrolimus in living-donor liver transplant (LDLT) patients, considering the gender difference. Haplotype analysis of MDR1 with G2677T/A and C3435T was performed in 63 de novo Japanese LDLT patients (17 to 55 years; 44.4% women). The expression levels of MDR1 and CYP3A4 mRNAs in jejunal biopsy specimens were quantified by real-time PCR. Intestinal CYP3A4 mRNA expression levels (amol/microg total RNA) showed significantly higher values in women carrying the 2677TT-3435TT haplotype (median, 10.7; range, 5.92-15.2) than those with 2677GG-3435CC (3.03; range 1.38-4.68) and 2677GT-3435CT (median, 4.31; range, 0.07-9.42) (P = 0.022), but not in men (P = 0.81). However, MDR1 haplotype did not influence mRNA expression levels of MDR1 nor the concentration/dose ratio [(ng/mL)/(mg/day)] of oral tacrolimus for the postoperative 7 days, irrespective of gender. MDR1 haplotype may have a minor association with the tacrolimus pharmacokinetics after LDLT, but could be a good predictor of the inter-individual variation of intestinal expression of CYP3A4 in women.

  15. Exploring climate niches of ponderosa pine (Pinus ponderosa Douglas ex Lawson) haplotypes in the western United States: Implications for evolutionary history and conservation

    Science.gov (United States)

    Shinneman, Douglas; Means, Robert E.; Potter, Kevin M.; Hipkins, Valerie D.

    2016-01-01

    Ponderosa pine (Pinus ponderosa Douglas ex Lawson) occupies montane environments throughout western North America, where it is both an ecologically and economically important tree species. A recent study using mitochondrial DNA analysis demonstrated substantial genetic variation among ponderosa pine populations in the western U.S., identifying 10 haplotypes with unique evolutionary lineages that generally correspond spatially with distributions of the Pacific (P. p. var. ponderosa) and Rocky Mountain (P. p. var. scopulorum) varieties. To elucidate the role of climate in shaping the phylogeographic history of ponderosa pine, we used nonparametric multiplicative regression to develop predictive climate niche models for two varieties and 10 haplotypes and to hindcast potential distribution of the varieties during the last glacial maximum (LGM), ~22,000 yr BP. Our climate niche models performed well for the varieties, but haplotype models were constrained in some cases by small datasets and unmeasured microclimate influences. The models suggest strong relationships between genetic lineages and climate. Particularly evident was the role of seasonal precipitation balance in most models, with winter- and summer-dominated precipitation regimes strongly associated with P. p. vars. ponderosa and scopulorum, respectively. Indeed, where present-day climate niches overlap between the varieties, introgression of two haplotypes also occurs along a steep clinal divide in western Montana. Reconstructed climate niches for the LGM suggest potentially suitable climate existed for the Pacific variety in the California Floristic province, the Great Basin, and Arizona highlands, while suitable climate for the Rocky Mountain variety may have existed across the southwestern interior highlands. These findings underscore potentially unique phylogeographic origins of modern ponderosa pine evolutionary lineages, including potential adaptations to Pleistocene climates associated with

  16. Exploring Climate Niches of Ponderosa Pine (Pinus ponderosa Douglas ex Lawson) Haplotypes in the Western United States: Implications for Evolutionary History and Conservation.

    Science.gov (United States)

    Shinneman, Douglas J; Means, Robert E; Potter, Kevin M; Hipkins, Valerie D

    2016-01-01

    Ponderosa pine (Pinus ponderosa Douglas ex Lawson) occupies montane environments throughout western North America, where it is both an ecologically and economically important tree species. A recent study using mitochondrial DNA analysis demonstrated substantial genetic variation among ponderosa pine populations in the western U.S., identifying 10 haplotypes with unique evolutionary lineages that generally correspond spatially with distributions of the Pacific (P. p. var. ponderosa) and Rocky Mountain (P. p. var. scopulorum) varieties. To elucidate the role of climate in shaping the phylogeographic history of ponderosa pine, we used nonparametric multiplicative regression to develop predictive climate niche models for two varieties and 10 haplotypes and to hindcast potential distribution of the varieties during the last glacial maximum (LGM), ~22,000 yr BP. Our climate niche models performed well for the varieties, but haplotype models were constrained in some cases by small datasets and unmeasured microclimate influences. The models suggest strong relationships between genetic lineages and climate. Particularly evident was the role of seasonal precipitation balance in most models, with winter- and summer-dominated precipitation regimes strongly associated with P. p. vars. ponderosa and scopulorum, respectively. Indeed, where present-day climate niches overlap between the varieties, introgression of two haplotypes also occurs along a steep clinal divide in western Montana. Reconstructed climate niches for the LGM suggest potentially suitable climate existed for the Pacific variety in the California Floristic province, the Great Basin, and Arizona highlands, while suitable climate for the Rocky Mountain variety may have existed across the southwestern interior highlands. These findings underscore potentially unique phylogeographic origins of modern ponderosa pine evolutionary lineages, including potential adaptations to Pleistocene climates associated with discrete

  17. Exploring Climate Niches of Ponderosa Pine (Pinus ponderosa Douglas ex Lawson Haplotypes in the Western United States: Implications for Evolutionary History and Conservation.

    Directory of Open Access Journals (Sweden)

    Douglas J Shinneman

    Full Text Available Ponderosa pine (Pinus ponderosa Douglas ex Lawson occupies montane environments throughout western North America, where it is both an ecologically and economically important tree species. A recent study using mitochondrial DNA analysis demonstrated substantial genetic variation among ponderosa pine populations in the western U.S., identifying 10 haplotypes with unique evolutionary lineages that generally correspond spatially with distributions of the Pacific (P. p. var. ponderosa and Rocky Mountain (P. p. var. scopulorum varieties. To elucidate the role of climate in shaping the phylogeographic history of ponderosa pine, we used nonparametric multiplicative regression to develop predictive climate niche models for two varieties and 10 haplotypes and to hindcast potential distribution of the varieties during the last glacial maximum (LGM, ~22,000 yr BP. Our climate niche models performed well for the varieties, but haplotype models were constrained in some cases by small datasets and unmeasured microclimate influences. The models suggest strong relationships between genetic lineages and climate. Particularly evident was the role of seasonal precipitation balance in most models, with winter- and summer-dominated precipitation regimes strongly associated with P. p. vars. ponderosa and scopulorum, respectively. Indeed, where present-day climate niches overlap between the varieties, introgression of two haplotypes also occurs along a steep clinal divide in western Montana. Reconstructed climate niches for the LGM suggest potentially suitable climate existed for the Pacific variety in the California Floristic province, the Great Basin, and Arizona highlands, while suitable climate for the Rocky Mountain variety may have existed across the southwestern interior highlands. These findings underscore potentially unique phylogeographic origins of modern ponderosa pine evolutionary lineages, including potential adaptations to Pleistocene climates associated

  18. Haplotype-based case-control study on human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 gene and essential hypertension.

    Science.gov (United States)

    Naganuma, Takahiro; Nakayama, Tomohiro; Sato, Naoyuki; Fu, Zhenyan; Soma, Masayoshi; Yamaguchi, Mai; Shimodaira, Masanori; Aoi, Noriko; Usami, Ron

    2010-02-01

    Oxidative DNA damage is involved in the pathophysiology of essential hypertension (EH), which is a multifactorial disorder. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/REF-1) is an essential endonuclease in the base excision repair pathway of oxidatively damaged DNA, in addition to having reducing properties that promote the binding of redox-sensitive transcription factors. Blood pressure in APE1/REF-1-knockout mice is reported to be significantly higher than in wild-type mice. The aim of this study was to investigate the relationship between EH and the human APE1/REF-1 gene through a haplotype-based case-control study using single-nucleotide polymorphisms (SNPs). We selected five SNPs in the human APE1/REF-1 gene (rs1760944, rs3136814, rs17111967, rs3136817, and rs1130409), and performed case-control studies in 265 EH patients and 266 age-matched normotensive (NT) subjects. rs17111967 was found to show nonheterogeneity among Japanese subjects. There were no significant differences in the overall distribution of genotypes or alleles for each SNP between EH and NT groups. In the overall distribution of the haplotype-based case-control study constructed based on rs1760944, rs3136817, and rs1130409, the frequency of the G-T-T haplotype was significantly higher in the EH group than in the NT group (2.1% vs. 0.0%, P = 0.001). Multiple logistic regression analysis also revealed significant differences for the G-T-T haplotype, even after adjustment for confounding factors (OR = 8.600, 95% CI: 1.073-68.951, P = 0.043). Based on the present results, the G-T-T haplotype appears to be a genetic marker of EH, and the APE1/REF-1 gene appears to be a susceptibility gene for EH.

  19. Resolving inventory differences

    International Nuclear Information System (INIS)

    Weber, J.H.; Clark, J.P.

    1991-01-01

    Determining the cause of an inventory difference (ID) that exceeds warning or alarm limits should not only involve investigation into measurement methods and reexamination of the model assumptions used in the calculation of the limits, but also result in corrective actions that improve the quality of the accountability measurements. An example illustrating methods used by Savannah River Site (SRS) personnel to resolve an ID is presented that may be useful to other facilities faced with a similar problem. After first determining that no theft or diversion of material occurred and correcting any accountability calculation errors, investigation into the IDs focused on volume and analytical measurements, limit of error of inventory difference (LEID) modeling assumptions, and changes in the measurement procedures and methods prior to the alarm. There had been a gradual gain trend in IDs prior to the alarm which was reversed by the alarm inventory. The majority of the NM in the facility was stored in four large tanks which helped identify causes for the alarm. The investigation, while indicating no diversion or theft, resulted in changes in the analytical method and in improvements in the measurement and accountability that produced a 67% improvement in the LEID

  20. On detecting incomplete soft or hard selective sweeps using haplotype structure

    DEFF Research Database (Denmark)

    Ferrer-Admetlla, Anna; Liang, Mason; Korneliussen, Thorfinn Sand

    2014-01-01

    We present a new haplotype-based statistic (nSL) for detecting both soft and hard sweeps in population genomic data from a single population. We compare our new method with classic single-population haplotype and site frequency spectrum (SFS)-based methods and show that it is more robust, particu......We present a new haplotype-based statistic (nSL) for detecting both soft and hard sweeps in population genomic data from a single population. We compare our new method with classic single-population haplotype and site frequency spectrum (SFS)-based methods and show that it is more robust......, particularly to recombination rate variation. However, all statistics show some sensitivity to the assumptions of the demographic model. Additionally, we show that nSL has at least as much power as other methods under a number of different selection scenarios, most notably in the cases of sweeps from standing...

  1. Y-STR haplotypes of Native American populations from the Brazilian Amazon region.

    Science.gov (United States)

    Palha, Teresinha Jesus Brabo Ferreira; Rodrigues, Elzemar Martins Ribeiro; dos Santos, Sidney Emanuel Batista

    2010-10-01

    The allele and haplotype frequencies of nine Y-STRs (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385 I/II) were determined in a sample of six native tribes from the Brazilian Amazon (Tiriyó, Awa-Guajá, Waiãpi, Urubu-Kaapor, Zoé and Parakanã). Forty-eight different haplotypes were identified, 28 of which unique. Five haplotypes are very frequent and were shared by over 10 individuals. The estimated haplotype diversity (0.9114) was very low compared to other geographic groups, including Africans, Europeans and Asians. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Time-resolved studies

    International Nuclear Information System (INIS)

    Mills, D.M.

    1992-01-01

    When new or more powerful probes become available that offer both shorter data-collection times and the opportunity to apply innovative approaches to established techniques, it is natural that investigators consider the feasibility of exploring the kinetics of time-evolving systems. This stimulating area of research not only can lead to insights into the metastable or excited states that a system may populate on its way to a ground state, but can also lead to a better understanding of that final state. Synchrotron radiation, with its unique properties, offers just such a tool to extend X-ray measurements from the static to the time-resolved regime. The most straight-forward application of synchrotron radiation to the study of transient phenomena is directly through the possibility of decreased data-collection times via the enormous increase in flux over that of a laboratory X-ray system. Even further increases in intensity can be obtained through the use of novel X-ray optical devices. Widebandpass monochromators, e.g., that utilize the continuous spectral distribution of synchrotron radiation, can increase flux on the sample several orders of magnitude over conventional X-ray optical systems thereby allowing a further shortening of the data-collection time. Another approach that uses the continuous spectral nature of synchrotron radiation to decrease data-collection times is the open-quote parallel data collectionclose quotes method. Using this technique, intensities as a function of X-ray energy are recorded simultaneously for all energies rather than sequentially recording data at each energy, allowing for a dramatic decrease in the data-collection time

  3. Haplotypes of the porcine peroxisome proliferator-activated receptor delta gene are associated with backfat thickness

    Directory of Open Access Journals (Sweden)

    Blöcker Helmut

    2009-11-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor delta belongs to the nuclear receptor superfamily of ligand-inducible transcription factors. It is a key regulator of lipid metabolism. The peroxisome proliferator-activated receptor delta gene (PPARD has been assigned to a region on porcine chromosome 7, which harbours a quantitative trait locus for backfat. Thus, PPARD is considered a functional and positional candidate gene for backfat thickness. The purpose of this study was to test this candidate gene hypothesis in a cross of breeds that were highly divergent in lipid deposition characteristics. Results Screening for genetic variation in porcine PPARD revealed only silent mutations. Nevertheless, significant associations between PPARD haplotypes and backfat thickness were observed in the F2 generation of the Mangalitsa × Piétrain cross as well as a commercial German Landrace population. Haplotype 5 is associated with increased backfat in F2 Mangalitsa × Piétrain pigs, whereas haplotype 4 is associated with lower backfat thickness in the German Landrace population. Haplotype 4 and 5 carry the same alleles at all but one SNP. Interestingly, the opposite effects of PPARD haplotypes 4 and 5 on backfat thickness are reflected by opposite effects of these two haplotypes on PPAR-δ mRNA levels. Haplotype 4 significantly increases PPAR-δ mRNA levels, whereas haplotype 5 decreases mRNA levels of PPAR-δ. Conclusion This study provides evidence for an association between PPARD and backfat thickness. The association is substantiated by mRNA quantification. Further studies are required to clarify, whether the observed associations are caused by PPARD or are the result of linkage disequilibrium with a causal variant in a neighbouring gene.

  4. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  5. Interrelationships between Amerindian tribes of lower Amazonia as manifest by HLA haplotype disequilibria.

    OpenAIRE

    Black, F L

    1984-01-01

    HLA B-C haplotypes exhibit common disequilibria in populations drawn from four continents, indicating that they are subject to broadly active selective forces. However, the A-B and A-C associations we have examined show no consistent disequilibrium pattern, leaving open the possibility that these disequilibria are due to descent from common progenitors. By examining HLA haplotype distributions, I have explored the implications that would follow from the hypothesis that biological selection pl...

  6. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

    Directory of Open Access Journals (Sweden)

    Sergio eTofanelli

    2014-11-01

    Full Text Available Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA and the non-recombining portion of the Y chromosome (NRY to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their classical 6 STR marker format or in the extended 12 STR format, as well as four founder mtDNA lineages (HVS-I segments accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same haplotype signatures. Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

  7. Haplotypes in the Dystrophin DNA Segment Point to a Mosaic Origin of Modern Human Diversity

    OpenAIRE

    Ziętkiewicz, Ewa; Yotova, Vania; Gehl, Dominik; Wambach, Tina; Arrieta, Isabel; Batzer, Mark; Cole, David E.C.; Hechtman, Peter; Kaplan, Feige; Modiano, David; Moisan, Jean-Paul; Michalski, Roman; Labuda, Damian

    2003-01-01

    Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one Tn microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences re...

  8. A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ p.Thr124Met mutation shares the Belgian haplotype

    Directory of Open Access Journals (Sweden)

    Alejandro Leal

    2014-12-01

    Full Text Available The p.Thr124Met mutation in the myelin protein zero (MPZ causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers´ sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch, the founder effect hypothesis for this allele migration is suggestive. Rev. Biol. Trop. 62 (4: 1285-1293. Epub 2014 December 01.

  9. Genetic variability and haplotypes of Echinococcus isolates from Tunisia.

    Science.gov (United States)

    Boufana, Belgees; Lahmar, Samia; Rebaï, Waël; Ben Safta, Zoubeir; Jebabli, Leïla; Ammar, Adel; Kachti, Mahmoud; Aouadi, Soufia; Craig, Philip S

    2014-11-01

    The species/genotypes of Echinococcus infecting a range of intermediate, canid and human hosts were examined as well as the intraspecific variation and population structure of Echinococcus granulosus sensu lato (s.l.) within these hosts. A total of 174 Echinococcus isolates from humans and ungulate intermediate hosts and adult tapeworms from dogs and jackals were used. Genomic DNA was used to amplify a fragment within a mitochondrial gene and a nuclear gene, coding for cytochrome c oxidase subunit 1 (cox1; 828 bp) and elongation factor 1-alpha (ef1a; 656 bp), respectively. E. granulosus sensu stricto was identified from all host species examined, E. canadensis (G6) in a camel and, for the first time, fertile cysts of E. granulosus (s.s.) and E. equinus in equids (donkeys) and E. granulosus (s.s.) from wild boars and goats. Considerable genetic variation was seen only for the cox1 sequences of E. granulosus (s.s.). The pairwise fixation index (Fst) for cox1 E. granulosus (s.s.) sequences from donkeys was high and was statistically significant compared with that of E. granulosus populations from other intermediate hosts. A single haplotype (EqTu01) was identified for the cox1 nucleotide sequences of E. equinus. The role of donkeys in the epidemiology of echinococcosis in Tunisia requires further investigation. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Vitamin D Receptor Gene Polymorphisms and Haplotypes in Hungarian Patients with Idiopathic Inflammatory Myopathy

    Directory of Open Access Journals (Sweden)

    Levente Bodoki

    2015-01-01

    Full Text Available Idiopathic inflammatory myopathies are autoimmune diseases characterized by symmetrical proximal muscle weakness. Our aim was to identify a correlation between VDR polymorphisms or haplotypes and myositis. We studied VDR-BsmI, VDR-ApaI, VDR-TaqI, and VDR-FokI polymorphisms and haplotypes in 89 Hungarian poly-/dermatomyositis patients (69 females and 93 controls (52 females. We did not obtain any significant differences for VDR-FokI, BsmI, ApaI, and TaqI genotypes and allele frequencies between patients with myositis and healthy individuals. There was no association of VDR polymorphisms with clinical manifestations and laboratory profiles in myositis patients. Men with myositis had a significantly different distribution of BB, Bb, and bb genotypes than female patients, control male individuals, and the entire control group. Distribution of TT, Tt, and tt genotypes was significantly different in males than in females in patient group. According to four-marker haplotype prevalence, frequencies of sixteen possible haplotypes showed significant differences between patient and control groups. The three most frequent haplotypes in patients were the fbAt, FBaT, and fbAT. Our findings may reveal that there is a significant association: Bb and Tt genotypes can be associated with myositis in the Hungarian population we studied. We underline the importance of our result in the estimated prevalence of four-marker haplotypes.

  11. The JAK2 GGCC (46/1 Haplotype in Myeloproliferative Neoplasms: Causal or Random?

    Directory of Open Access Journals (Sweden)

    Luisa Anelli

    2018-04-01

    Full Text Available The germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1 consists of a combination of single nucleotide polymorphisms (SNPs mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4 gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782 generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin receptor (MPL and calreticulin (CALR, or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival, or disease progression.

  12. Interrelationships between Amerindian tribes of lower Amazonia as manifest by HLA haplotype disequilibria.

    Science.gov (United States)

    Black, F L

    1984-11-01

    HLA B-C haplotypes exhibit common disequilibria in populations drawn from four continents, indicating that they are subject to broadly active selective forces. However, the A-B and A-C associations we have examined show no consistent disequilibrium pattern, leaving open the possibility that these disequilibria are due to descent from common progenitors. By examining HLA haplotype distributions, I have explored the implications that would follow from the hypothesis that biological selection played no role in determining A-C disequilibria in 10 diverse tribes of the lower Amazon Basin. Certain haplotypes are in strong positive disequilibria across a broad geographic area, suggesting that members of diverse tribes descend from common ancestors. On the basis of the extent of diffusion of the components of these haplotypes, one can estimate that the progenitors lived less than 6,000 years ago. One widely encountered lineage entered the area within the last 1,200 years. When haplotype frequencies are used in genetic distance measurements, they give a pattern of relationships very similar to that obtained by conventional chord measurements based on several genetic markers; but more than that, when individual haplotype disequilibria in the several tribes are compared, multiple origins of a single tribe are discernible and relationships are revealed that correlate more closely to geographic and linguistic patterns than do the genetic distance measurements.

  13. An accurate clone-based haplotyping method by overlapping pool sequencing.

    Science.gov (United States)

    Li, Cheng; Cao, Changchang; Tu, Jing; Sun, Xiao

    2016-07-08

    Chromosome-long haplotyping of human genomes is important to identify genetic variants with differing gene expression, in human evolution studies, clinical diagnosis, and other biological and medical fields. Although several methods have realized haplotyping based on sequencing technologies or population statistics, accuracy and cost are factors that prohibit their wide use. Borrowing ideas from group testing theories, we proposed a clone-based haplotyping method by overlapping pool sequencing. The clones from a single individual were pooled combinatorially and then sequenced. According to the distinct pooling pattern for each clone in the overlapping pool sequencing, alleles for the recovered variants could be assigned to their original clones precisely. Subsequently, the clone sequences could be reconstructed by linking these alleles accordingly and assembling them into haplotypes with high accuracy. To verify the utility of our method, we constructed 130 110 clones in silico for the individual NA12878 and simulated the pooling and sequencing process. Ultimately, 99.9% of variants on chromosome 1 that were covered by clones from both parental chromosomes were recovered correctly, and 112 haplotype contigs were assembled with an N50 length of 3.4 Mb and no switch errors. A comparison with current clone-based haplotyping methods indicated our method was more accurate. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Role of the extended MAPT haplotype in the worsening of psychotic symptoms and treatment response in Alzheimer disease.

    Science.gov (United States)

    Creese, Byron; Corbett, Anne; Jones, Emma; Fox, Chris; Ballard, Clive

    2014-12-01

    There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic symptoms in Alzheimer disease (AD). However, it is not clear whether this association is direct or mediated through the increased cognitive impairment associated with NFTs. We sought to determine whether the extended MAPT haplotype was associated with the worsening of delusions and hallucinations in a combined cohort of 95 patients who participated in 2 clinical trials of treatment with memantine. After controlling for baseline dementia severity, exposure to memantine, and antipsychotics, analysis shows that carriers of at least one H2 allele had a 5.4-fold (P = .03) increased risk of worsening hallucinations. There was some evidence of association with worsening delusions but only in analysis by allele. These results are the first to indicate that the H2 allele of the extended MAPT haplotype negatively affects the course of psychotic symptoms in AD independently of disease severity. It will be important for future research to examine MAPT transcription in people with AD with and without psychotic symptoms to understand the exact mechanisms underlying these findings. Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  15. Analysis of electronic structure of amorphous InGaZnO/SiO2 interface by angle-resolved X-ray photoelectron spectroscopy

    International Nuclear Information System (INIS)

    Ueoka, Y.; Ishikawa, Y.; Maejima, N.; Matsui, F.; Matsui, H.; Yamazaki, H.; Urakawa, S.; Horita, M.; Daimon, H.; Uraoka, Y.

    2013-01-01

    The electronic structures of amorphous indium gallium zinc oxide (a-IGZO) on a SiO 2 layers before and after annealing were observed by constant final state X-ray photoelectron spectroscopy (CFS-XPS) and X-ray adsorption near-edge structure spectroscopy (XANES). From the results of angle-resolved CFS-XPS, the change in the electronic state was clearly observed in the a-IGZO bulk rather than in the a-IGZO/SiO 2 interface. This suggests that the electronic structures of the a-IGZO bulk strongly affected the thin-film transistor characteristics. The results of XANES indicated an increase in the number of tail states upon atmospheric annealing (AT). We consider that the increase in the number of tail states decreased the channel mobility of AT samples

  16. A mixed integer linear programming model to reconstruct phylogenies from single nucleotide polymorphism haplotypes under the maximum parsimony criterion

    Science.gov (United States)

    2013-01-01

    Background Phylogeny estimation from aligned haplotype sequences has attracted more and more attention in the recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from medical research, to drug discovery, to epidemiology, to population dynamics. The literature on molecular phylogenetics proposes a number of criteria for selecting a phylogeny from among plausible alternatives. Usually, such criteria can be expressed by means of objective functions, and the phylogenies that optimize them are referred to as optimal. One of the most important estimation criteria is the parsimony which states that the optimal phylogeny T∗for a set H of n haplotype sequences over a common set of variable loci is the one that satisfies the following requirements: (i) it has the shortest length and (ii) it is such that, for each pair of distinct haplotypes hi,hj∈H, the sum of the edge weights belonging to the path from hi to hj in T∗ is not smaller than the observed number of changes between hi and hj. Finding the most parsimonious phylogeny for H involves solving an optimization problem, called the Most Parsimonious Phylogeny Estimation Problem (MPPEP), which is NP-hard in many of its versions. Results In this article we investigate a recent version of the MPPEP that arises when input data consist of single nucleotide polymorphism haplotypes extracted from a population of individuals on a common genomic region. Specifically, we explore the prospects for improving on the implicit enumeration strategy of implicit enumeration strategy used in previous work using a novel problem formulation and a series of strengthening valid inequalities and preliminary symmetry breaking constraints to more precisely bound the solution space and accelerate implicit enumeration of possible optimal phylogenies. We present the basic formulation and then introduce a series of provable valid constraints to reduce the solution space. We then prove

  17. Exploring Climate Niches of Ponderosa Pine (Pinus ponderosa Douglas ex Lawson) Haplotypes in the Western United States: Implications for Evolutionary History and Conservation

    OpenAIRE

    Shinneman, Douglas J.; Means, Robert E.; Potter, Kevin M.; Hipkins, Valerie D.

    2016-01-01

    Ponderosa pine (Pinus ponderosa Douglas ex Lawson) occupies montane environments throughout western North America, where it is both an ecologically and economically important tree species. A recent study using mitochondrial DNA analysis demonstrated substantial genetic variation among ponderosa pine populations in the western U.S., identifying 10 haplotypes with unique evolutionary lineages that generally correspond spatially with distributions of the Pacific (P. p. var. ponderosa) and Rocky ...

  18. Photon number projection using non-number-resolving detectors

    International Nuclear Information System (INIS)

    Rohde, Peter P; Webb, James G; Huntington, Elanor H; Ralph, Timothy C

    2007-01-01

    Number-resolving photo-detection is necessary for many quantum optics experiments, especially in the application of entangled state preparation. Several schemes have been proposed for approximating number-resolving photo-detection using non-number-resolving detectors. Such techniques include multi-port detection and time-division multiplexing. We provide a detailed analysis and comparison of different number-resolving detection schemes, with a view to creating a useful reference for experimentalists. We show that the ideal architecture for projective measurements is a function of the detector's dark count and efficiency parameters. We also describe a process for selecting an appropriate topology given actual experimental component parameters

  19. Identification of a two-marker-haplotype on Bos taurus autosome 18 associated with somatic cell score in German Holstein cattle

    Directory of Open Access Journals (Sweden)

    Reinsch Norbert

    2009-09-01

    Full Text Available Abstract Background The somatic cell score (SCS is implemented in routine sire evaluations in many countries as an indicator trait for udder health. Somatic cell score is highly correlated with clinical mastitis, and in the German Holstein population quantitative trait loci (QTL for SCS have been repeatedly mapped on Bos taurus autosome 18 (BTA18. In the present study, we report a refined analysis of previously detected QTL regions on BTA18 with the aim of identifying marker and marker haplotypes in linkage disequilibrium with SCS. A combined linkage and linkage disequilibrium approach was implemented, and association analyses of marker genotypes and maternally inherited two-marker-haplotypes were conducted to identify marker and haplotypes in linkage disequilibrium with a locus affecting SCS in the German Holstein population. Results We detected a genome-wide significant QTL within marker interval 9 (HAMP_c.366+109G>A - BMS833 in the middle to telomeric region on BTA18 and a second putative QTL in marker interval 12-13 (BB710 - PVRL2_c.392G>A. Association analyses with genotypes of markers flanking the most likely QTL positions revealed the microsatellite marker BMS833 (interval 9 to be associated with a locus affecting SCS within the families investigated. A further analysis of maternally inherited two-marker haplotypes and effects of maternally inherited two-marker-interval gametes indicated haplotype 249-G in marker interval 12-13 (BB710 - PVRL2_c.392G>A to be associated with SCS in the German Holstein population. Conclusion Our results confirmed previous QTL mapping results for SCS and support the hypothesis that more than one locus presumably affects udder health in the middle to telomeric region of BTA18. However, a subsequent investigation of the reported QTL regions is necessary to verify the two-QTL hypothesis and confirm the association of two-marker-haplotype 249-G in marker interval 12-13 (BB710 - PVRL2_c.392G>A with SCS. For this

  20. Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

    Science.gov (United States)

    Rogenhofer, Nina; Nienaber, Lara R M; Amshoff, Lea C; Bogdanova, Nadia; Petroff, David; Wieacker, Peter; Thaler, Christian J; Markoff, Arseni

    2018-01-01

    The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage. Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533). Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners. These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.

  1. Decreased calcium pump expression in human erythrocytes is connected to a minor haplotype in the ATP2B4 gene.

    Science.gov (United States)

    Zámbó, Boglárka; Várady, György; Padányi, Rita; Szabó, Edit; Németh, Adrienn; Langó, Tamás; Enyedi, Ágnes; Sarkadi, Balázs

    2017-07-01

    Plasma membrane Ca 2+ -ATPases are key calcium exporter proteins in most tissues, and PMCA4b is the main calcium transporter in the human red blood cells (RBCs). In order to assess the expression level of PMCA4b, we have developed a flow cytometry and specific antibody binding method to quantitatively detect this protein in the erythrocyte membrane. Interestingly, we found several healthy volunteers showing significantly reduced expression of RBC-PMCA4b. Western blot analysis of isolated RBC membranes confirmed this observation, and indicated that there are no compensatory alterations in other PMCA isoforms. In addition, reduced PMCA4b levels correlated with a lower calcium extrusion capacity in these erythrocytes. When exploring the potential genetic background of the reduced PMCA4b levels, we found no missense mutations in the ATP2B4 coding regions, while a formerly unrecognized minor haplotype in the predicted second promoter region closely correlated with lower erythrocyte PMCA4b protein levels. In recent GWA studies, SNPs in this ATP2B4 haplotype have been linked to reduced mean corpuscular hemoglobin concentrations (MCHC), and to protection against malaria infection. Our data suggest that an altered regulation of gene expression is responsible for the reduced RBC-PMCA4b levels that is probably linked to the development of human disease-related phenotypes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Inference of haplotypic phase and missing genotypes in polyploid organisms and variable copy number genomic regions

    Directory of Open Access Journals (Sweden)

    Balding David J

    2008-12-01

    Full Text Available Abstract Background The power of haplotype-based methods for association studies, identification of regions under selection, and ancestral inference, is well-established for diploid organisms. For polyploids, however, the difficulty of determining phase has limited such approaches. Polyploidy is common in plants and is also observed in animals. Partial polyploidy is sometimes observed in humans (e.g. trisomy 21; Down's syndrome, and it arises more frequently in some human tissues. Local changes in ploidy, known as copy number variations (CNV, arise throughout the genome. Here we present a method, implemented in the software polyHap, for the inference of haplotype phase and missing observations from polyploid genotypes. PolyHap allows each individual to have a different ploidy, but ploidy cannot vary over the genomic region analysed. It employs a hidden Markov model (HMM and a sampling algorithm to infer haplotypes jointly in multiple individuals and to obtain a measure of uncertainty in its inferences. Results In the simulation study, we combine real haplotype data to create artificial diploid, triploid, and tetraploid genotypes, and use these to demonstrate that polyHap performs well, in terms of both switch error rate in recovering phase and imputation error rate for missing genotypes. To our knowledge, there is no comparable software for phasing a large, densely genotyped region of chromosome from triploids and tetraploids, while for diploids we found polyHap to be more accurate than fastPhase. We also compare the results of polyHap to SATlotyper on an experimentally haplotyped tetraploid dataset of 12 SNPs, and show that polyHap is more accurate. Conclusion With the availability of large SNP data in polyploids and CNV regions, we believe that polyHap, our proposed method for inferring haplotypic phase from genotype data, will be useful in enabling researchers analysing such data to exploit the power of haplotype-based analyses.

  3. Identification of the Mislabeled Breast Cancer Samples by Mitochondrial DNA Haplotyping

    Directory of Open Access Journals (Sweden)

    Xiaogang Chen

    2015-01-01

    Full Text Available The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetics. The nuclear DNA (nDNA markers were affected by the aberration of tumor cells, so they were not suitable for personal identification when the tumor tissues were tested. In this study, we focused on a new solution - mitochondrial single nucleotide polymorphism (mtSNP haplotyping by a multiplex SNaPshot assay. To validate our strategy of haplotyping with 25 mtSNPs, we analyzed 15 pairs of cancerous/healthy tissues taken from patients with ductal breast carcinoma. The haplotypes of all the fifteen breast cancer tissues were matched with their paired breast tissues. The heteroplasmy at 2 sites, 14783A/G and 16519C/T was observed in one breast tissue, which indicated a mixture of related mitochondrial haplotypes. However, only one haplotype was retained in the paired breast cancer tissue, which could be considered the result of proliferation of tumor subclone. The allele drop-out and allele drop-in were observed when 39 STRs and 20 tri-allelic SNPs of nDNA were applied. Compared to nDNA markers applied, 25 mtSNPs were more stable without interference from aberrance of breast cancer. Also, two cases were presented where the investigation of haplotype with 25 mtSNPs was used to prove the origin of biopsy specimen with breast cancer. The mislabeling of biopsy specimen with breast cancer could be certified in one case but could not be supported in the other case. We highlight the importance of stability of mtSNP haplotype in breast cancer. It was implied that our multiplex SNaPshot assay with 25 mtSNPs was a useful strategy to identify mislabeled breast cancer specimen.

  4. Three Novel Haplotypes of Theileria bicornis in Black and White Rhinoceros in Kenya.

    Science.gov (United States)

    Otiende, M Y; Kivata, M W; Jowers, M J; Makumi, J N; Runo, S; Obanda, V; Gakuya, F; Mutinda, M; Kariuki, L; Alasaad, S

    2016-02-01

    Piroplasms, especially those in the genera Babesia and Theileria, have been found to naturally infect rhinoceros. Due to natural or human-induced stress factors such as capture and translocations, animals often develop fatal clinical piroplasmosis, which causes death if not treated. This study examines the genetic diversity and occurrence of novel Theileria species infecting both black and white rhinoceros in Kenya. Samples collected opportunistically during routine translocations and clinical interventions from 15 rhinoceros were analysed by polymerase chain reaction (PCR) using a nested amplification of the small subunit ribosomal RNA (18S rRNA) gene fragments of Babesia and Theileria. Our study revealed for the first time in Kenya the presence of Theileria bicornis in white (Ceratotherium simum simum) and black (Diceros bicornis michaeli) rhinoceros and the existence of three new haplotypes: haplotypes H1 and H3 were present in white rhinoceros, while H2 was present in black rhinoceros. No specific haplotype was correlated to any specific geographical location. The Bayesian inference 50% consensus phylogram recovered the three haplotypes monophyleticly, and Theileria bicornis had very high support (BPP: 0.98). Furthermore, the genetic p-uncorrected distances and substitutions between T. bicornis and the three haplotypes were the same in all three haplotypes, indicating a very close genetic affinity. This is the first report of the occurrence of Theileria species in white and black rhinoceros from Kenya. The three new haplotypes reported here for the first time have important ecological and conservational implications, especially for population management and translocation programs and as a means of avoiding the transport of infected animals into non-affected areas. © 2014 Blackwell Verlag GmbH.

  5. Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs

    DEFF Research Database (Denmark)

    Jacobsen, Mette Juul; Kracht, Steffen Skaarup; Esteso, G.

    2009-01-01

    Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility....../resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used...... for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markes. By a targeted approach, the candidate...

  6. Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

    Directory of Open Access Journals (Sweden)

    Cynthia Hatsue Kitayama Cabral

    2011-01-01

    Full Text Available βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5% were identified with genotype CAR/CAR, 9 (19.1% CAR/BEN, 6 (12.8% CAR/CAM, 1 (2.1% BEN/BEN, 2 (4.3% CAR/Atp, 1 (2.1% BEN/Atp and 1 (2.1% with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte.

  7. Chlorine levels and species in fine and size resolved atmospheric particles by X-ray absorption near-edge structure spectroscopy analysis in Beijing, China.

    Science.gov (United States)

    Ouyang, Jie; Yang, Guo-Sheng; Ma, Ling-Ling; Luo, Min; Zheng, Lei; Huo, Qing; Zhao, Yi-Dong; Hu, Tian-Dou; Cai, Zhen-Feng; Xu, Dian-Dou

    2018-04-01

    An understanding of the species of chlorine is crucial in the metropolis-Beijing, which is suffering serious haze pollution with high frequency. Particulate Matters (PMs) with five different sizes were collected in Beijing from July 2009 to March 2016, and characterized non-destructively by X-ray absorption near edge structure spectroscopy. PM 2.5 contributed for the major PMs mass in spring and summer, PM 0.5-1.0 and PM 1.0-2.5 contributed for the major PMs mass in autumn and winter. The concentrations of the three chlorine species were in the order of inorganic chlorine (Cl inorg ) > aliphatic chlorine (Cl ali ) > aromatic chlorine (Cl aro ), indicating that Cl inorg constituted the primary chlorine fraction and less toxic Cl ali constituted the primary total organic chlorine (Cl ali  + Cl aro , abbreviated as Cl org ) in the PMs in Beijing. In addition, these three chlorine species exhibited identical seasonal variation in PM 2.5 : winter > autumn > spring > summer. Wet precipitation is an important factor to result in the lower mass concentrations of these three chlorine species in summer. The temporal variations of both size resolved PM mass concentrations and chlorine species concentrations suggested that the air pollution prevention and control in Beijing has just won initial success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Spatially resolved ozone densities and gas temperatures in a time modulated RF driven atmospheric pressure plasma jet: an analysis of the production and destruction mechanisms

    International Nuclear Information System (INIS)

    Zhang Shiqiang; Van Gessel, Bram; Hofmann, Sven; Van Veldhuizen, Eddie; Bruggeman, Peter; Van Gaens, Wouter; Bogaerts, Annemie

    2013-01-01

    In this work, a time modulated RF driven DBD-like atmospheric pressure plasma jet in Ar + 2%O 2 , operating at a time averaged power of 6.5 W is investigated. Spatially resolved ozone densities and gas temperatures are obtained by UV absorption and Rayleigh scattering, respectively. Significant gas heating in the core of the plasma up to 700 K is found and at the position of this increased gas temperature a depletion of the ozone density is found. The production and destruction reactions of O 3 in the jet effluent as a function of the distance from the nozzle are obtained from a zero-dimensional chemical kinetics model in plug flow mode which considers relevant air chemistry due to air entrainment in the jet fluent. A comparison of the measurements and the models show that the depletion of O 3 in the core of the plasma is mainly caused by an enhanced destruction of O 3 due to a large atomic oxygen density. (paper)

  9. Resolving deconvolution ambiguity in gene alternative splicing

    Directory of Open Access Journals (Sweden)

    Hubbell Earl

    2009-08-01

    Full Text Available Abstract Background For many gene structures it is impossible to resolve intensity data uniquely to establish abundances of splice variants. This was empirically noted by Wang et al. in which it was called a "degeneracy problem". The ambiguity results from an ill-posed problem where additional information is needed in order to obtain an unique answer in splice variant deconvolution. Results In this paper, we analyze the situations under which the problem occurs and perform a rigorous mathematical study which gives necessary and sufficient conditions on how many and what type of constraints are needed to resolve all ambiguity. This analysis is generally applicable to matrix models of splice variants. We explore the proposal that probe sequence information may provide sufficient additional constraints to resolve real-world instances. However, probe behavior cannot be predicted with sufficient accuracy by any existing probe sequence model, and so we present a Bayesian framework for estimating variant abundances by incorporating the prediction uncertainty from the micro-model of probe responsiveness into the macro-model of probe intensities. Conclusion The matrix analysis of constraints provides a tool for detecting real-world instances in which additional constraints may be necessary to resolve splice variants. While purely mathematical constraints can be stated without error, real-world constraints may themselves be poorly resolved. Our Bayesian framework provides a generic solution to the problem of uniquely estimating transcript abundances given additional constraints that themselves may be uncertain, such as regression fit to probe sequence models. We demonstrate the efficacy of it by extensive simulations as well as various biological data.

  10. β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

    Science.gov (United States)

    Wu, Pingsheng; Larkin, Emma K; Reiss, Sara S; Carroll, Kecia N; Summar, Marshall L; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Islam, Jessica Y; Hartert, Tina V; Moore, Paul E

    2015-09-14

    Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence

  11. Direct sequencing of mitochondrial DNA detects highly divergent haplotypes in blue marlin (Makaira nigricans).

    Science.gov (United States)

    Finnerty, J R; Block, B A

    1992-06-01

    We were able to differentiate between species of billfish (Istiophoridae family) and to detect considerable intraspecific variation in the blue marlin (Makaira nigricans) by directly sequencing a polymerase chain reaction (PCR)-amplified, 612-bp fragment of the mitochondrial cytochrome b gene. Thirteen variable nucleotide sites separated blue marlin (n = 26) into 7 genotypes. On average, these genotypes differed by 5.7 base substitutions. A smaller sample of swordfish from an equally broad geographic distribution displayed relatively little intraspecific variation, with an average of 1.3 substitutions separating different genotypes. A cladistic analysis of blue marlin cytochrome b variants indicates two major divergent evolutionary lines within the species. The frequencies of these two major evolutionary lines differ significantly between Atlantic and Pacific ocean basins. This finding is important given that the Atlantic stocks of blue marlin are considered endangered. Migration from the Pacific can help replenish the numbers of blue marlin in the Atlantic, but the loss of certain mitochondrial DNA haplotypes in the Atlantic due to overfishing probably could not be remedied by an influx of Pacific fish because of their absence in the Pacific population. Fishery management strategies should attempt to preserve the genetic diversity within the species. The detection of DNA sequence polymorphism indicates the utility of PCR technology in pelagic fishery genetics.

  12. Quality control of radiolabeled antibodies through simultaneous determination of antibody concentration and specific activity using time-resolved interaction analysis and reverse kinetic fit

    International Nuclear Information System (INIS)

    Andersson, K.; Mihaylova, D.; Wang, E.; Abrahamsen, L.; Buijs, J.; Bjoerkelund, H.

    2015-01-01

    Full text of publication follows. With the advent of efficient methods for producing proteins that bind to a defined target, the number of radiolabeled proteins, and in particular antibodies, used for medical imaging and cancer therapy is increasing rapidly. In line with this increase, focus should be put on methods for the quality control (QC). Proper antibody quality is of fundamental importance to guarantee safety and consistent efficacy for the patient. Adequate QC procedures exist for small radiolabeled synthetic compounds like FDG, but antibody based radiopharmaceuticals are different. Proteins are much more complex and fragile than the synthetic compounds, and hence require new methods for adequate characterization and QC. Yet another complication is the labeling where there is a risk that a subpopulation of the protein is damaged to the level that it no longer binds the target. Therefore, a new toolbox is required to fulfill the quality characterization of radiolabeled antibodies. We have developed a QC assay for the simultaneous determination of antibody function, concentration and specific activity. The assay is based on time-resolved detection of the antibody interaction with antigen-coated magnetic beads in LigandTracer instruments. The resulting binding curve is evaluated using reverse kinetic fits, where the known interaction parameters of the antibody-antigen interaction are set constant while as the concentration and signal level are fitted. The assay takes approximately 2 hours and the majority of the time constitutes automated data collection in the instrument. The QC assay has been tested on multiple antibody-antigen interactions and consistently provides repeatable results for concentration and specific activity, both with coefficient of variation (CV) less than 15%. We believe that this QC assay can improve the quality of radiolabeled therapeutic antibodies. (authors)

  13. A suggested procedure for resolving an anomaly in least-squares data analysis known as ''Peelle's Pertinent Puzzle'' and the general implications for nuclear data evaluation

    International Nuclear Information System (INIS)

    Chiba, Satoshi; Smith, D.L.

    1991-09-01

    Modern nuclear-data evaluation methodology is based largely on statistical inference, with the least-squares technique being chosen most often to generate best estimates for physical quantities and their uncertainties. It has been observed that those least-squares evaluations which employ covariance matrices based on absolute errors that are derived directly from the reported experimental data often tend to produce results which appear to be too low. This anomaly is discussed briefly in this report, and a procedure for resolving it is suggested. The method involves employing data uncertainties which are derived from errors expressed in percent. These percent errors are used, in conjunction with reasonable a priori estimates for the quantities to be evaluated, to derive the covariance matrices which are required for applications of the least-squares procedure. This approach appears to lead to more rational weighting of the experimental data and, thus, to more realistic evaluated results than are obtained when the errors are based on the actual data. The procedure is very straightforward when only one parameter must be estimated. However, for those evaluation exercises involving more than one parameter, this technique demands that a priori estimates be provided at the outset for all of the parameters in question. Then, the least-squares method is applied iteratively to produce a sequence of sets of estimated values which are anticipated to convergence toward a particular set of parameters which one then designates as the ''best'' evaluated results from the exercise. It is found that convergence usually occurs very rapidly when the a priori estimates approximate the final solution reasonably well

  14. Infection Frequency of Hepatitis C Virus and IL28B Haplotypes in Papua New Guinea, Fiji, and Kiribati

    Science.gov (United States)

    Harrison, G. L. Abby; Pryor, Jan; Malani, Joji; Supuri, Mathias; Masta, Andrew; Teriboriki, Burentau; Toatu, Tebuka; Penny, David; Allain, Jean-Pierre; Barnes, Eleanor; Pybus, Oliver G.; Klenerman, Paul

    2013-01-01

    It has been estimated that there are more than 60 million Hepatitis C virus (HCV) carriers in the World Health Organisation's Western Pacific region (WHO-WPR), where liver cancer is among the top three causes of cancer death. WHO and the US Centres for Disease Control and Prevention report the prevalence of HCV in the South Pacific islands (countries within the WHO-WPR) to be high (5–10% and >2% respectively). However, since HCV is not tested for in many of these countries, there is sparse data available to support this assertion. We screened ∼2000 apparently healthy individuals from Papua New Guinea, Fiji and Kiribati and found a sero-prevalence of 2.0%, 0.1% and 0%, respectively. All sero-positive samples tested negative for HCV RNA. Curious as to why all the sero-positive individuals were negative for HCV-RNA, we also screened them for the HCV protective IL28B SNP markers rs12979860 and rs8099917. All antibody-positive participants bar one had HCV protective haplotypes. Our results suggest that HCV is present in these Pacific island countries, albeit at a prevalence lower than previous estimates. As none of our participants had undergone antiviral treatment, and therefore must have cleared infection naturally, we hypothesise that genotypes 1 and/or 4 are circulating in South Pacific Island people and that these peoples are genetically predisposed to be more likely to spontaneous resolve HCV infection than to become chronic carriers. PMID:23976941

  15. Chromatographic background drift correction coupled with parallel factor analysis to resolve coelution problems in three-dimensional chromatographic data: quantification of eleven antibiotics in tap water samples by high-performance liquid chromatography coupled with a diode array detector.

    Science.gov (United States)

    Yu, Yong-Jie; Wu, Hai-Long; Fu, Hai-Yan; Zhao, Juan; Li, Yuan-Na; Li, Shu-Fang; Kang, Chao; Yu, Ru-Qin

    2013-08-09

    Chromatographic background drift correction has been an important field of research in chromatographic analysis. In the present work, orthogonal spectral space projection for background drift correction of three-dimensional chromatographic data was described in detail and combined with parallel factor analysis (PARAFAC) to resolve overlapped chromatographic peaks and obtain the second-order advantage. This strategy was verified by simulated chromatographic data and afforded significant improvement in quantitative results. Finally, this strategy was successfully utilized to quantify eleven antibiotics in tap water samples. Compared with the traditional methodology of introducing excessive factors for the PARAFAC model to eliminate the effect of background drift, clear improvement in the quantitative performance of PARAFAC was observed after background drift correction by orthogonal spectral space projection. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

    Directory of Open Access Journals (Sweden)

    Maria Guadalupe Zavala-Cerna

    2013-01-01

    Full Text Available Peptidyl arginine deiminase IV (PAD 4 is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA. Four SNPs (single nucleotide polymorphisms have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA; nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC. There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

  17. The impact of sample size and marker selection on the study of haplotype structures

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2004-03-01

    Full Text Available Abstract Several studies of haplotype structures in the human genome in various populations have found that the human chromosomes are structured such that each chromosome can be divided into many blocks, within which there is limited haplotype diversity. In addition, only a few genetic markers in a putative block are needed to capture most of the diversity within a block. There has been no systematic empirical study of the effects of sample size and marker set on the identified block structures and representative marker sets, however. The purpose of this study was to conduct a detailed empirical study to examine such impacts. Towards this goal, we have analysed three representative autosomal regions from a large genome-wide study of haplotypes with samples consisting of African-Americans and samples consisting of Japanese and Chinese individuals. For both populations, we have found that the sample size and marker set have significant impact on the number of blocks and the total number of representative markers identified. The marker set in particular has very strong impacts, and our results indicate that the marker density in the original datasets may not be adequate to allow a meaningful characterisation of haplotype structures. In general, we conclude that we need a relatively large sample size and a very dense marker panel in the study of haplotype structures in human populations.

  18. Haplotypes in the dystrophin DNA segment point to a mosaic origin of modern human diversity.

    Science.gov (United States)

    Zietkiewicz, Ewa; Yotova, Vania; Gehl, Dominik; Wambach, Tina; Arrieta, Isabel; Batzer, Mark; Cole, David E C; Hechtman, Peter; Kaplan, Feige; Modiano, David; Moisan, Jean-Paul; Michalski, Roman; Labuda, Damian

    2003-11-01

    Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences reveals three lineages accounting for present-day diversity. The proportion of new recombinants and the diversity of the T(n) microsatellite were used to estimate the age of haplotype lineages and the time of colonization events. The lineage that underwent the great expansion originated in Africa prior to the Upper Paleolithic (27,000-56,000 years ago). A second group, of structurally distinct haplotypes that occupy a central position on the tree, has never left Africa. The third lineage is represented by the haplotype that lies closest to the root, is virtually absent in Africa, and appears older than the recent out-of-Africa expansion. We propose that this lineage could have left Africa before the expansion (as early as 160,000 years ago) and admixed, outside of Africa, with the expanding lineage. Contemporary human diversity, although dominated by the recently expanded African lineage, thus represents a mosaic of different contributions.

  19. Resolving Turbine Degradation

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Matthew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kruizenga, Alan Michael [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Withey, Elizabeth Ann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-08-01

    The supercritical carbon dioxide (S-CO2) Brayton Cycle has gained significant attention in the last decade as an advanced power cycle capable of achieving high efficiency power conversion. Sandia National Laboratories, with support from the U.S. Department of Energy Office of Nuclear Energy (US DOE-NE), has been conducting research and development in order to deliver a technology that is ready for commercialization. Root cause analysis has been performed on the Recompression Loop at Sandia National Laboratories. It was found that particles throughout the loop are stainless steel, likely alloy 316 based upon the elemental composition. Deployment of a filter scheme is underway to both protect the turbomachinery and also for purposes of determining the specific cause for the particulate. Shake down tests of electric resistance (ER) as a potential in-situ monitoring scheme shows promise in high temperature systems. A modified instrument was purchased and held at 650°C for more than 1.5 months to date without issue. Quantitative measurements of this instrument will be benchmarked against witness samples in the future, but all qualitative trends to date are as to be expected. ER is a robust method for corrosion monitoring, but very slow at responding and can take several weeks under conditions to see obvious changes in behavior. Electrochemical noise was identified as an advanced technique that should be pursued for the ability to identify transients that would lead to poor material performance.

  20. Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

    Science.gov (United States)

    Patente, Thiago A; Monteiro, Maria B; Vieira, Suzana M; Rossi da Silva, Maria E; Nery, Márcia; Queiroz, Márcia; Azevedo, Mirela J; Canani, Luis H; Parisi, Maria C; Pavin, Elizabeth J; Mainardi, Débora; Javor, Juraj; Velho, Gilberto; Coimbra, Cássio N; Corrêa-Giannella, Maria Lúcia

    2015-08-15

    A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  2. Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility.

    Science.gov (United States)

    Han, Xia; Liu, Lili; Niu, Jiamin; Yang, Jun; Zhang, Zengtang; Zhang, Zhiqiang

    2015-01-01

    Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.

  3. Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach

    Science.gov (United States)

    Kotnik, Barbara Faganel; Jazbec, Janez; Grabar, Petra Bohanec; Rodriguez-Antona, Cristina

    2017-01-01

    Abstract Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030). Conclusions SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results. PMID:29333125

  4. HLA alleles and haplotypes in Burmese (Myanmarese) and Karen in Thailand.

    Science.gov (United States)

    Kongmaroeng, C; Romphruk, A; Puapairoj, C; Leelayuwat, C; Kulski, J K; Inoko, H; Dunn, D S; Romphruk, A V

    2015-09-01

    This is the first report on human leukocyte antigen (HLA) allele and haplotype frequencies at three class I loci and two class II loci in unrelated healthy individuals from two ethnic groups, 170 Burmese and 200 Karen, orig