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Sample records for array-based fmr1 sequencing

  1. Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndrome-like phenotype.

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    Stephen C Collins

    Full Text Available BACKGROUND: Fragile X syndrome (FXS is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract. METHODOLOGY/PRINCIPAL FINDINGS: To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations. CONCLUSIONS/SIGNIFICANCE: These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility.

  2. In Silico Analysis of FMR1 Gene Missense SNPs.

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    Tekcan, Akin

    2016-06-01

    The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1-related diseases.

  3. A nonsense mutation in FMR1 causing fragile X syndrome

    DEFF Research Database (Denmark)

    Grønskov, Karen; Brøndum-Nielsen, Karen; Dedic, Alma;

    2011-01-01

    Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5'UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent....... Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense...... mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should be...

  4. Methylization analysis of the FMR1 gene in carrier females

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    Meyers, S.; Cappon, S.; Khalifa, M.M. [Kingston General Hospital (Canada)] [and others

    1994-09-01

    The fragile X syndrome mutation is associated with an expansion of a CGG repeat sequence and methylation of the CpG island in the promoter of the FMR1 gene. Methylation of the CpG island silences the FMR1 gene, thereby generating the disease phenotypes. Previous studies suggest that the normal FMR1 gene has the properties of an X-linked housekeeping gene that is subject to X inactivation, i.e., its CpG island is unmethylated on the active X chromosome and methylated on the inactive X. Because methylation of the mutant FMR1 gene occurs in both males and females with the full mutation, inactivating the FMR1 gene in these females might be a localized event independent from X inactivation. To test this hypothesis we compared the methylation pattern of two housekeeping genes, PGK1 and androgen receptor (AR) with that of the FMR1 in 46 female carriers of the fragile X syndrome. Twenty eight females were in the premutation range (63-193 repeats) and 16 were carriers of the full mutation (263-996 repeats). The data revealed complete correlation between the methylation pattern of PGK1 and AR. There was also a close correlation between X inactivation pattern detected by PGK1 and/or AR and that detected by FMR1 in female carriers of the premutation. In all female carriers of the full mutation there was complete methylation of the BssHII site in the expanded FMR1 allele. The X chromosome inactivation pattern in these females as detected by PGK1 and/or AR was as follows: in 10 cases the X inactivation was skewed in favor of the mutant FMR1, i.e. the mutant allele was on the inactive X chromosome, in 3 the inactivation was random and in 3 the inactivation was skewed in favor of the normal allele. These data suggest that the methylation of the FMR1 gene in females with the full mutation is a localized event and methylation of the FMR1 gene in these females cannot be used as a predictor of X inactivation.

  5. Evolutionary insights from suffix array-based genome sequence analysis

    Indian Academy of Sciences (India)

    Anindya Poddar; Nagasuma Chandra; Madhavi Ganapathiraju; K Sekar; Judith Klein-Seetharaman; Raj Reddy; N Balakrishnan

    2007-08-01

    Gene and protein sequence analyses, central components of studies in modern biology are easily amenable to string matching and pattern recognition algorithms. The growing need of analysing whole genome sequences more efficiently and thoroughly, has led to the emergence of new computational methods. Suffix trees and suffix arrays are data structures, well known in many other areas and are highly suited for sequence analysis too. Here we report an improvement to the design of construction of suffix arrays. Enhancement in versatility and scalability, enabled by this approach, is demonstrated through the use of real-life examples. The scalability of the algorithm to whole genomes renders it suitable to address many biologically interesting problems. One example is the evolutionary insight gained by analysing unigrams, bi-grams and higher n-grams, indicating that the genetic code has a direct influence on the overall composition of the genome. Further, different proteomes have been analysed for the coverage of the possible peptide space, which indicate that as much as a quarter of the total space at the tetra-peptide level is left un-sampled in prokaryotic organisms, although almost all tri-peptides can be seen in one protein or another in a proteome. Besides, distinct patterns begin to emerge for the counts of particular tetra and higher peptides, indicative of a ‘meaning’ for tetra and higher n-grams. The toolkit has also been used to demonstrate the usefulness of identifying repeats in whole proteomes efficiently. As an example, 16 members of one COG, coded by the genome of Mycobacterium tuberculosis H37Rv have been found to contain a repeating sequence of 300 amino acids.

  6. Role of CTCF protein in regulating FMR1 locus transcription.

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    Stella Lanni

    Full Text Available Fragile X syndrome (FXS, the leading cause of inherited intellectual disability, is caused by epigenetic silencing of the FMR1 gene, through expansion and methylation of a CGG triplet repeat (methylated full mutation. An antisense transcript (FMR1-AS1, starting from both promoter and intron 2 of the FMR1 gene, was demonstrated in transcriptionally active alleles, but not in silent FXS alleles. Moreover, a DNA methylation boundary, which is lost in FXS, was recently identified upstream of the FMR1 gene. Several nuclear proteins bind to this region, like the insulator protein CTCF. Here we demonstrate for the first time that rare unmethylated full mutation (UFM alleles present the same boundary described in wild type (WT alleles and that CTCF binds to this region, as well as to the FMR1 gene promoter, exon 1 and intron 2 binding sites. Contrariwise, DNA methylation prevents CTCF binding to FXS alleles. Drug-induced CpGs demethylation does not restore this binding. CTCF knock-down experiments clearly established that CTCF does not act as insulator at the active FMR1 locus, despite the presence of a CGG expansion. CTCF depletion induces heterochromatinic histone configuration of the FMR1 locus and results in reduction of FMR1 transcription, which however is not accompanied by spreading of DNA methylation towards the FMR1 promoter. CTCF depletion is also associated with FMR1-AS1 mRNA reduction. Antisense RNA, like sense transcript, is upregulated in UFM and absent in FXS cells and its splicing is correlated to that of the FMR1-mRNA. We conclude that CTCF has a complex role in regulating FMR1 expression, probably through the organization of chromatin loops between sense/antisense transcriptional regulatory regions, as suggested by bioinformatics analysis.

  7. Differential Impact of the "FMR1" Gene on Visual Processing in Fragile X Syndrome

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    Kogan, Cary S.; Boutet, Isabelle; Cornish, Kim; Zangenehpour, Shahin; Mullen, Kathy T.; Holden, Jeanette J. A.; Kaloustian, Vazken M. Der; Andermann, Eva; Chaudhuri, Avi

    2004-01-01

    Fragile X syndrome (FXS) is the most common form of heritable mental retardation, affecting (~ around) 1 in 4000 males. The syndrome arises from expansion of a trinucleotide repeat in the 5'-untranslated region of the fragile X mental retardation 1 ("FMR1") gene, leading to methylation of the promoter sequence and lack of the fragile X mental…

  8. The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro

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    Tabolacci Elisabetta

    2012-03-01

    Full Text Available Abstract Background Fragile X syndrome (FXS, the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5, on fully methylated FXS patients respect to partially methylated FXS ones. Methods To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis. Results Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls. Conclusions These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1.

  9. Brief Report: Altered Social Behavior in Isolation-Reared "Fmr1" Knockout Mice

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    Heitzer, Andrew M.; Roth, Alexandra K.; Nawrocki, Lauren; Wrenn, Craige C.; Valdovinos, Maria G.

    2013-01-01

    Social behavior abnormalities in Fragile X syndrome (FXS) are characterized by social withdrawal, anxiety, and deficits in social cognition. To assess these deficits, a model of FXS, the "Fmr1" knockout mouse ("Fmr1" KO), has been utilized. This mouse model has a null mutation in the fragile X mental retardation 1 gene ("Fmr1") and displays…

  10. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

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    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  11. A microdeletion of less than 250 kb, including the proximal part of the FMR-1 gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome

    OpenAIRE

    Wöhrle, Doris; Kotzot, Dieter; Hirst, Mark C; Manca, Antonella; Korn, Bernhard; Schmidt, Angela; Barbi, Gotthold; Rott, Hans-Dieter; Poustka, Annemarie; Davies, Kay E.; Steinbach, Peter

    1992-01-01

    A gene designated “FMR-1” has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involve...

  12. Novel Polymorphism in the FMR1 Gene Resulting in a “Pseudodeletion” of FMR1 in a Commonly Used Fragile X Assay

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    Daly, Thomas M.; Rafii, Arash; Martin, Rick A.; Zehnbauer, Barbara A.

    2000-01-01

    The fragile X syndrome is the most commonly inherited cause of mental retardation. Genetic diagnosis of this disease relies on the detection of triplet repeat expansion in the FMR1 gene on the X chromosome. Although the majority of disease in fragile X patients is due to mutations involving triplet repeat expansion, deletion of various portions of FMR1 has also been described in association with the fragile X syndrome. Here we describe a rare polymorphism in the noncoding region of FMR1 that ...

  13. Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse

    DEFF Research Database (Denmark)

    Sørensen, Emilie M; Bertelsen, Freja; Weikop, Pia;

    2015-01-01

    The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three......-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed...... in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse...

  14. Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background

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    Ding, Qi; Sethna, Ferzin; Wang, Hongbing

    2014-01-01

    Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 K...

  15. Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma.

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    Albrecht, Bettina; Hausmann, Michael; Zitzelsberger, Horst; Stein, Hubert; Siewert, Jörg Rüdiger; Hopt, Ulrich; Langer, Rupert; Höfler, Heinz; Werner, Martin; Walch, Axel

    2004-07-01

    Array-based comparative genomic hybridization (aCGH) allows the identification of DNA sequence copy number changes at high resolution by co-hybridizing differentially labelled test and control DNAs to a micro-array of genomic clones. The present study has analysed a series of 23 formalin-fixed, paraffin wax-embedded tissue samples of Barrett's adenocarcinoma (BCA, n = 18) and non-neoplastic squamous oesophageal (n = 2) and gastric cardia mucosa (n = 3) by aCGH. The micro-arrays used contained 287 genomic targets covering oncogenes, tumour suppressor genes, and DNA sequences localized within chromosomal regions previously reported to be altered in BCA. DNA sequence copy number changes for a panel of approximately 50 genes were identified, most of which have not been previously described in BCA. DNA sequence copy number gains (mean 41 +/- 25/BCA) were more frequent than DNA sequence copy number losses (mean 20 +/- 15/BCA). The highest frequencies for DNA sequence copy number gains were detected for SNRPN (61%); GNLY (44%); NME1 (44%); DDX15, ABCB1 (MDR), ATM, LAMA3, MYBL2, ZNF217, and TNFRSF6B (39% each); and MSH2, TERC, SERPINE1, AFM137XA11, IGF1R, and PTPN1 (33% each). DNA sequence copy number losses were identified for PDGFB (44%); D17S125 (39%); AKT3 (28%); and RASSFI, FHIT, CDKN2A (p16), and SAS (CDK4) (28% each). In all non-neoplastic tissue samples of squamous oesophageal and gastric cardia mucosa, the measured mean ratios were 1.00 (squamous oesophageal mucosa) or 1.01 (gastric mucosa), indicating that no DNA sequence copy number chances were present. For validation, the DNA sequence copy number changes of selected clones (SNRPN, CMYC, HER2, ZNF217) detected by aCGH were confirmed by fluorescence in situ hybridization (FISH). These data show the sensitivity of aCGH for the identification of DNA sequence copy number changes at high resolution in BCA. The newly identified genes may include so far unknown biomarkers in BCA and are therefore a starting point for

  16. How the FMR1 gene became relevant to female fertility and reproductive medicine

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    Norbert eGleicher

    2014-08-01

    Full Text Available This manuscript describes the 6-year evolution of our center’s research into ovarian functions of the FMR1 gene, which led to the identification of a new normal CGGn range of 26-34. This new normal range, in turn, led to definitions of different alleles (haplotypes based on whether no, one or both alleles are within range. Specific alleles then were demonstrated to represent distinct ovarian aging patterns, suggesting an important FMR1 function in follicle recruitment and ovarian depletion of follicles. So called low alleles, characterized by CGGn34 alleles. Because low FMR1 alleles present in approximately 25% of all females, FMR1 testing at young ages may offer an opportunity for earlier diagnosis of OPOI than current practice allows. Earlier diagnosis of OPOI, in turn, would give young women the options of reassessing their reproductive schedules and/or pursue fertility preservation via oocyte cryopreservation when most effective.

  17. PSP-CBS with Dopamine Deficiency in a Female with a FMR1 Premutation.

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    Paucar, Martin; Beniaminov, Stanislav; Paslawski, Wojciech; Svenningsson, Per

    2016-10-01

    Premutations in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related primary ovarian insufficiency (POI). Female FMR1 premutation carriers rarely develop motor features. Dual pathology is an emerging phenomenon among FMR1 premutation carriers. Here, we describe a family affected by FMR1-related disorders in which the female index case has developed a rapidly progressive and disabling syndrome of atypical parkinsonism. This syndrome consists of early onset postural instability, echolalia, dystonia, and varying types of apraxia like early onset orobuccal apraxia and oculomotor apraxia. She has also developed supranuclear gaze palsy, increased latency of saccade initiation, and slow saccades. These features are compatible with progressive supranuclear palsy (PSP) of a corticobasal syndrome (CBS) variant. Imaging displays a marked reduction of presynaptic dopaminergic uptake and cerebrospinal fluid analysis showed reduced dopamine metabolism; however, the patient is unresponsive to levodopa. Midbrain atrophy ("hummingbird sign") and mild cerebellar atrophy were found on brain MRI. Her father was affected by a typical FXTAS presentation but also displayed dopamine deficiency along with the hummingbird sign. The mechanisms by which FMR1 premutations predispose to atypical parkinsonism and dopamine deficiency await further elucidation. PMID:27230899

  18. Expression of GAD of cochlea in FMR1 gene Knock-out mice%Fmr1基因敲除小鼠耳蜗GAD的表达

    Institute of Scientific and Technical Information of China (English)

    李敏雄; 杜娜; 孙卫文; 黄月玲; 沈岩松; 戴丽军; 陈盛强; 马钊恩; 张建国

    2012-01-01

    目的 对4 周龄Fmr1 基因敲除小鼠的耳蜗的GAD 表达进行观察,探讨耳蜗GAD 的表达是否受FMRP 的影响.方法 使用PCR 技术对Fmr1 基因敲除小鼠鉴定后对4 周龄的Fmr1 基因敲除小鼠和野生型小鼠各15 只进行耳蜗的苏木精-伊红(HE) 染色和GAD 免疫组织化学的表达观察,数据采用多因素方差分析处理.结果 耳蜗HE 染色结果:4 周龄组KO 鼠较WT 鼠形态学观察无差异.4 周龄KO 小鼠的耳蜗中GAD 表达的平均阳性细胞数均高于WT 小鼠,P<0.01,差异具有统计学意义.结论 GAD 表达的改变可能与FMR1 基因KO 小鼠听源性惊厥发病有关.

  19. Ovarian dysfunction and FMR1 alleles in a large Italian family with POF and FRAXA disorders: case report

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    D'Urso Michele

    2007-04-01

    Full Text Available Abstract Background The association between premature ovarian failure (POF and the FMR1 repeat number (41> CGGnFMR1 alleles. Case presentation We describe the coexistence in a large Italian kindred of Fragile X syndrome and familial POF in females with ovarian dysfunctions who carried normal or expanded FMR1 alleles. Genetic analysis of the FMR1 gene in over three generations of females revealed that six carried pre-mutated alleles (61–200, of which two were also affected by POF. However a young woman, who presented a severe ovarian failure with early onset, carried normal FMR1 alleles ( Conclusion Our case study represents a helpful observation and will provide familial cases with heterogeneous etiology that could be further studied when candidate genes in addition to the FMR1 premutation will be available.

  20. Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice.

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    Sungchil Yang

    Full Text Available Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1 gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP is impaired in the developing auditory cortex of the Fmr1 knockout (KO mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.

  1. Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation

    Science.gov (United States)

    de Esch, Celine E.F.; Ghazvini, Mehrnaz; Loos, Friedemann; Schelling-Kazaryan, Nune; Widagdo, W.; Munshi, Shashini T.; van der Wal, Erik; Douben, Hannie; Gunhanlar, Nilhan; Kushner, Steven A.; Pijnappel, W.W.M. Pim; de Vrij, Femke M.S.; Geijsen, Niels; Gribnau, Joost; Willemsen, Rob

    2014-01-01

    Summary Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels. The FMR1 expression in the uFM line corresponds with the increased H3 acetylation and H3K4 methylation in combination with a reduced H3K9 methylation. After reprogramming, the FMR1 promoter region was methylated in all uFM iPSC clones. Two clones were analyzed further and showed a lack of FMR1 expression, whereas the presence of specific histone modifications also indicated a repressed FMR1 promoter. In conclusion, these findings demonstrate that the standard reprogramming procedure leads to epigenetic silencing of the fully mutated FMR1 gene. PMID:25358783

  2. Epigenetic Characterization of the FMR1 Promoter in Induced Pluripotent Stem Cells from Human Fibroblasts Carrying an Unmethylated Full Mutation

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    Celine E.F. de Esch

    2014-10-01

    Full Text Available Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs of an unmethylated full mutation (uFM individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels. The FMR1 expression in the uFM line corresponds with the increased H3 acetylation and H3K4 methylation in combination with a reduced H3K9 methylation. After reprogramming, the FMR1 promoter region was methylated in all uFM iPSC clones. Two clones were analyzed further and showed a lack of FMR1 expression, whereas the presence of specific histone modifications also indicated a repressed FMR1 promoter. In conclusion, these findings demonstrate that the standard reprogramming procedure leads to epigenetic silencing of the fully mutated FMR1 gene.

  3. The FMR1 Gene, Infertility and Reproductive Decision-Making: A Review

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    Lisa M Pastore

    2014-07-01

    Full Text Available The strongest association between FMR1 and the ovary in humans is the increased risk of premature ovarian failure in women who carry the premutation level of CGG repeats (55-199 CGGs. Research on the FMR1 gene has extended to other endpoints of relevance in the OB/GYN setting for women, including infertility and ovarian hormones. After reviewing the nomenclature changes that have occurred in recent years, this article reviews the evidence linking the length of the FMR1 repeat length to fertility and ovarian hormones (follicle stimulating hormone and anti-mullerian hormone as the primary methods to assess ovarian reserve in clinical settings. The literature is inconsistent on the association between the FMR1 trinucleotide repeat length and infertility. Elevated levels of follicle stimulating hormone have been found in women who carry the premutation; however the literature on the relationship between anti-mullerian hormone and the CGG repeat length are too disparate in design to make a summary statement. This article considers the implications of two transgenic mouse models (FXPM 130R and YAC90R for theories on pathogenesis related to ovarian endpoints. Given the current screening/testing recommendations for reproductive age females and the variability of screening protocols in clinics, future research is recommended on pretest and posttest genetic counseling needs. Future research is also needed on ovarian health measurements across a range of CGG repeat lengths in order to interpret FMR1 test results in reproductive age women; the inconsistencies in the literature make it quite challenging to advise women on their risks related to FMR1 repeat length.

  4. Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers.

    Science.gov (United States)

    Hall, Deborah A; Robertson, Erin; Shelton, Annie L; Losh, Molly C; Mila, Montserrat; Moreno, Esther Granell; Gomez-Anson, Beatriz; Martínez-Cerdeño, Verónica; Grigsby, Jim; Lozano, Reymundo; Hagerman, Randi; Maria, Lorena Santa; Berry-Kravis, Elizabeth; O'Keefe, Joan A

    2016-10-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder caused by a repeat expansion in the fragile X mental retardation 1 (FMR1) gene. The disorder is characterized by kinetic tremor and cerebellar ataxia, shows age-dependent penetrance, and occurs more frequently in men. This paper summarizes the key emerging issues in FXTAS as presented at the Second International Conference on the FMR1 Premutation: Basic Mechanisms & Clinical Involvement in 2015. The topics discussed include phenotype-genotype relationships, neurobehavioral function, and updates on FXTAS genetics and imaging. PMID:27287737

  5. Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.

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    Qiu, Guozhen; Chen, Shengqiang; Guo, Jialing; Wu, Jie; Yi, Yong-Hong

    2016-10-01

    Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity. PMID:27316341

  6. Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

    Directory of Open Access Journals (Sweden)

    Timmerman Stephanie

    2008-10-01

    Full Text Available Abstract Background Regulating synthesis of the Fragile X gene (FMR1 product, FMRP alters neural plasticity potentially through its role in the microRNA pathway. Cap-dependent translation of the FMR1 mRNA, a process requiring ribosomal scanning through the 5' leader, is likely impeded by the extensive secondary structure generated by the high guanosine/cytosine nucleotide content including the CGG triplet nucleotide repeats in the 5' leader. An alternative mechanism to initiate translation – internal initiation often utilizes secondary structure to recruit the translational machinery. Consequently, studies were undertaken to confirm and extend a previous observation that the FMR1 5' leader contains an internal ribosomal entry site (IRES. Results Cellular transfection of a dicistronic DNA construct containing the FMR1 5' leader inserted into the intercistronic region yielded significant translation of the second cistron, but the FMR1 5' leader was also found to contain a cryptic promoter possibly confounding interpretation of these results. However, transfection of dicistronic and monocistronic RNA ex vivo or in vitro confirmed that the FMR1 5' leader contains an IRES. Moreover, inhibiting cap-dependent translation ex vivo did not affect the expression level of endogenous FMRP indicating a role for IRES-dependent translation of FMR1 mRNA. Analysis of the FMR1 5' leader revealed that the CGG repeats and the 5' end of the leader were vital for internal initiation. Functionally, exposure to potassium chloride or intracellular acidification and addition of polyinosinic:polycytidylic acid as mimics of neural activity and double stranded RNA, respectively, differentially affected FMR1 IRES activity. Conclusion Our results indicate that multiple stimuli influence IRES-dependent translation of the FMR1 mRNA and suggest a functional role for the CGG nucleotide repeats.

  7. Mild clinical involvement in two males with a large FMR1 premutation

    Energy Technology Data Exchange (ETDEWEB)

    Hagerman, R.; O`Connor, R.; Staley, L. [Children`s Hospital, Denver, CO (United States)] [and others

    1994-09-01

    Both male and female individuals who carry the FMR1 premutation are considered to be clinically unaffected and have been reported to have normal transcription of their FMR1 gene and normal FMR1 protein (FMRP) production. We have evaluated two males who are mildly affected clinically with features of fragile X syndrome and demonstrate a large premutation on DNA studies. The first patient is a 2 year 8 month old boy who demonstrated the fragile X chromosome in 3% of his lymphocytes on cytogenetic testing. His physical features include mildly prominent ears and hyperextensible finger joints. He has language delays along with behavioral problems including tantrums and attention deficit. Developmental testing revealed a mental scale of 116 on the Bayley Scales of Infant Development, which is in the normal range. DNA testing demonstrated a premutation with 161 CGG repeats. This premutation was methylated in a small percent of his cells (<2%). These findings were observed in both blood leukocytes and buccal cells. Protein studies of transformed lymphocytes from this boy showed approximately 50 to 70% of the normal level of FMRP. The second patient is a 14 year old male who was cytogenetically negative for fragile X expression. His physical exam demonstrates a long face, a high palate and macroorchidism, (testicular volume of approximately 35 ml). His overall full scale IQ on the WISC-III is 73. He has language deficits and visual spatial perceptual deficits which have caused significant learning problems in school. Behaviorally he has problems with shyness and social anxiety, although he does not have attention deficit hyperactivity disorder. DNA testing revealed an FMR1 mutation of approximately 210 CGG repeats that is methylated in 4.7% of his cells.

  8. FIRING PROPERTY OF INFERIOR COLLICULUS NEURONS AFFECTED BY FMR1 GENE MUTATION

    Institute of Scientific and Technical Information of China (English)

    Brittany Mott; SUN Wei

    2014-01-01

    Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn-drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor-mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound (hyperacusis). The molecular basis of fragile X syndrome is thoroughly understood;however, the neural mechanisms underly-ing hyperacusis have not yet been determined. As the inferior colliculus (IC) is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob-served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.

  9. FMR1 fully expanded mutation with minimal methylation in a high functioning fragile X male.

    OpenAIRE

    Wang, Z.; Taylor, A K; Bridge, J.A.

    1996-01-01

    Cytogenetic and molecular genetic analysis of a peripheral blood sample from a 31 year old, non-mentally retarded male with a family history of fragile X syndrome showed unexpected results. Nine percent of cells evaluated cytogenetically expressed a fragile X chromosome and molecular examination of the FMR1 gene showed a highly unusual pattern defined as a minimally methylated fully expanded mutation. This case illustrates the need to recognise exceptional variations of fragile X syndrome mut...

  10. Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

    Science.gov (United States)

    Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

    2016-10-01

    Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. PMID:27291517

  11. MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xi [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Zhang, Kunshan [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Wang, Yanlu; Wang, Junbang; Cui, Yaru [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Li, Siguang, E-mail: siguangli@163.com [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Luo, Yuping, E-mail: luoyuping@163.com [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China)

    2013-10-04

    Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome.

  12. MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

    International Nuclear Information System (INIS)

    Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome

  13. Transcriptional Reactivation of the FMR1 Gene. A Possible Approach to the Treatment of the Fragile X Syndrome.

    Science.gov (United States)

    Tabolacci, Elisabetta; Palumbo, Federica; Nobile, Veronica; Neri, Giovanni

    2016-01-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability, caused by CGG expansion over 200 repeats (full mutation, FM) at the 5' untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene and subsequent DNA methylation of the promoter region, accompanied by additional epigenetic histone modifications that result in a block of transcription and absence of the fragile X mental retardation protein (FMRP). The lack of FMRP, involved in multiple aspects of mRNA metabolism in the brain, is thought to be the direct cause of the FXS phenotype. Restoration of FMR1 transcription and FMRP production can be obtained in vitro by treating FXS lymphoblastoid cell lines with the demethylating agent 5-azadeoxycytidine, demonstrating that DNA methylation is key to FMR1 inactivation. This concept is strengthened by the existence of rare male carriers of a FM, who are unable to methylate the FMR1 promoter. These individuals produce limited amounts of FMRP and are of normal intelligence. Their inability to methylate the FMR1 promoter, whose cause is not yet fully elucidated, rescues them from manifesting the FXS. These observations demonstrate that a therapeutic approach to FXS based on the pharmacological reactivation of the FMR1 gene is conceptually tenable and worthy of being further pursued. PMID:27548224

  14. Compact field programmable gate array-based pulse-sequencer and radio-frequency generator for experiments with trapped atoms

    Energy Technology Data Exchange (ETDEWEB)

    Pruttivarasin, Thaned, E-mail: thaned.pruttivarasin@riken.jp [Quantum Metrology Laboratory, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Katori, Hidetoshi [Quantum Metrology Laboratory, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Innovative Space-Time Project, ERATO, JST, Bunkyo-ku, Tokyo 113-8656 (Japan); Department of Applied Physics, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656 (Japan)

    2015-11-15

    We present a compact field-programmable gate array (FPGA) based pulse sequencer and radio-frequency (RF) generator suitable for experiments with cold trapped ions and atoms. The unit is capable of outputting a pulse sequence with at least 32 transistor-transistor logic (TTL) channels with a timing resolution of 40 ns and contains a built-in 100 MHz frequency counter for counting electrical pulses from a photo-multiplier tube. There are 16 independent direct-digital-synthesizers RF sources with fast (rise-time of ∼60 ns) amplitude switching and sub-mHz frequency tuning from 0 to 800 MHz.

  15. Fmr1基因敲除小鼠耳蜗的GABAα1受体的表达%Expression of GABAα1 receptor of cochlea in FMR1 gene knock-out mice

    Institute of Scientific and Technical Information of China (English)

    李敏雄; 杜娜; 孙卫文; 黄月玲; 沈岩松; 戴丽军; 陈盛强; 马钊恩; 张建国

    2012-01-01

    Objective To observe cochlea morphology and expression of GABA a 1 receptor of cochlea in 4 weeks FMR1 KO mice and WT mice. Methods Four-week old Fmrl knockout mice were identified using the PCR technique.and immunohistochemistry to compare with the changes of expression of GABA a 1 receptor between FMR1 KO mice and WT mice cochlea. Results There were no difference in cochlea morphology between FMR1 KO mice and WT mice by HE dyeing. The expression of GABA a 1 receptor in cochlear in FMR-1K0 mice was decreased. Conclusion The expression of GABA a 1 receptor is incerased in cochlear in four-week old FMR-1K0 mice that might be associated with audiogenic seizure susceptibility of Fmrl knockout mice.%目的 对4周龄Fmr1基因敲除小鼠耳蜗的GABAα1受体表达进行观察,探讨耳蜗GABAα1受体的表达是否受FMRP的影响.方法 使用PCR技术对Fmr1基因敲除小鼠鉴定后,对4周龄的Fmr1基因敲除小鼠和野生型小鼠进行耳蜗的GABAα1受体免疫组织化学的表达观察,数据采用多因素方差分析处理.结果 耳蜗HE染色结果:4周龄组KO鼠较WT鼠形态学观察无差异.4周龄KO小鼠的耳蜗中GABAα1受体表达的平均阳性细胞数均低于WT小鼠,P<0.01,差异具有统计学意义.结论 GABAα1受体表达的降低可能与FMR1基因KO小鼠听源性惊厥发病有关.

  16. Fmr1 KO Mice as a Possible Model of Autistic Features

    Directory of Open Access Journals (Sweden)

    Maude Bernardet

    2006-01-01

    Full Text Available Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude that Fmr1 KO mice display several autistic-like features, but more work is needed to validate this model.

  17. Refining transcriptional programs in kidney development by integration of deep RNA-sequencing and array-based spatial profiling

    Directory of Open Access Journals (Sweden)

    Rumballe Bree A

    2011-09-01

    Full Text Available Abstract Background The developing mouse kidney is currently the best-characterized model of organogenesis at a transcriptional level. Detailed spatial maps have been generated for gene expression profiling combined with systematic in situ screening. These studies, however, fall short of capturing the transcriptional complexity arising from each locus due to the limited scope of microarray-based technology, which is largely based on "gene-centric" models. Results To address this, the polyadenylated RNA and microRNA transcriptomes of the 15.5 dpc mouse kidney were profiled using strand-specific RNA-sequencing (RNA-Seq to a depth sufficient to complement spatial maps from pre-existing microarray datasets. The transcriptional complexity of RNAs arising from mouse RefSeq loci was catalogued; including 3568 alternatively spliced transcripts and 532 uncharacterized alternate 3' UTRs. Antisense expressions for 60% of RefSeq genes was also detected including uncharacterized non-coding transcripts overlapping kidney progenitor markers, Six2 and Sall1, and were validated by section in situ hybridization. Analysis of genes known to be involved in kidney development, particularly during mesenchymal-to-epithelial transition, showed an enrichment of non-coding antisense transcripts extended along protein-coding RNAs. Conclusion The resulting resource further refines the transcriptomic cartography of kidney organogenesis by integrating deep RNA sequencing data with locus-based information from previously published expression atlases. The added resolution of RNA-Seq has provided the basis for a transition from classical gene-centric models of kidney development towards more accurate and detailed "transcript-centric" representations, which highlights the extent of transcriptional complexity of genes that direct complex development events.

  18. Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice.

    Directory of Open Access Journals (Sweden)

    Susanna Pietropaolo

    Full Text Available BACKGROUND: No animal models of autism spectrum disorders (ASD with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6, which may explain some of the conflicting results that have been obtained with these mutants up till now. METHODS: Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors, as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events. RESULTS: Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. CONCLUSIONS: The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes.

  19. From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

    Directory of Open Access Journals (Sweden)

    Mégraud Francis

    2010-06-01

    Full Text Available Abstract Background elicobacter pylori infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach. Results A set of 254 H. pylori genes was used to perform array-based comparative genomic hybridization among 120 French H. pylori strains associated with chronic gastritis (n = 33, duodenal ulcers (n = 27, intestinal metaplasia (n = 17 or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43. Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with cagPAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released H. pylori genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470. B38 has the smallest H. pylori genome described thus far (1,576,758 base pairs containing 1,528 CDSs; it contains the vacAs2m2 allele and lacks the genes encoding the major virulence factors (absence of cagPAI, babB, babC, sabB, and homB. Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes. Pair-wise genomic synteny comparisons between B38 and the 6 H. pylori sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate and B38. Conclusion These isolates are deprived of the main H. pylori virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.

  20. Observation of tail suspension test in Fmr1 gene knockout mice%Fmr1基因敲除小鼠悬尾实验的观察

    Institute of Scientific and Technical Information of China (English)

    胡丽婵; 黄海樱; 郭艺; 孙祺章; 余国汉; 黄月玲; 戴丽军; 党亚梅; 黄雄; 陈盛强

    2016-01-01

    Objective To observe tail suspension test in Fmr1 gene knockout mice and to explore whether there are differences in mobility of KO and WT mice. Methods 1 80 test mice were divided into two groups:① KO group (4,6,8 weeks old,each age group of mice is 30,male and female in half,a total of 90)② WT group (4,6,8 weeks old,each group of mice is 30,male and female on half,a total of 90).Through forced swimming test and tail suspension test to observe gender, age effect on immobility time. Results With the same age of the same sex,the KO mice’s immobility time was longer than WT mice’s.P <0.05.With the same age,the male mice’s immobility time was shorter than female mice’s.With the age in-crease,the immobility time of KO mice was longer than WT mice.P <0.05. Conclusion Fmr1 gene knockout mice have anxiety and depressive behavior.%目的:对不同周龄的 KO 小鼠与 WT 小鼠进行悬尾实验进行观察,探讨 KO 小鼠与 WT 小鼠的行为差别。方法采用健康的试验动物180只分两组:①KO 组(4、6、8周龄,各周龄30只,雌雄各半,共90只)②WT 组(4、6、8周龄,各周龄30只,雌雄各半,共90只);通过悬尾实验观察性别,年龄对不动时间的影响。结果同龄 KO 雌性小鼠比雄性小鼠的静止时间差别不大;随着年龄增大,静止时间增长。同龄同性别的 KO 鼠比 WT 鼠的不动时间长。P <0.05;同龄雄性小鼠比雌性小鼠的不动时间短;随年龄增长各种系小鼠不动时间增长,KO 鼠的不动时间比 WT 鼠长,P <0.05。结论 KO 小鼠存在抑郁行为表型。

  1. Methylation analysis of CpG island DNA of FMR1 gene in the fragile X syndrome%脆性X综合征FMR1基因CpG岛的甲基化程度分析

    Institute of Scientific and Technical Information of China (English)

    吴鼎文; 竺智伟; 赵正言; 曲一平; 杨建滨

    2013-01-01

    目的 建立用甲基化敏感性限制性内切酶定量聚合酶链反应(methylation-sensitiverestriction enzymes-based quantitative PCR,MSRE-qPCR)分析FMR1基因CpG岛甲基化程度的方法,并探讨其对脆性X综合征的诊断价值.方法 以常规PCR初筛存在FMR1基因5′(CGG)n异常扩增的30例智力低下男童和20名母亲作为研究对象,用Eag Ⅰ酶消化DNA样品,针对FMR1基因CpG岛设计引物,定量PCR扩增Eag Ⅰ酶切前、后DNA,用2-△△Ct法计算CpG岛甲基化程度;以Southern印迹杂交确诊的3例患儿和正常体检男、女各30例DNA样品为质控样本,从而建立优化的MSRE-qPCR方法.结果 确立了正常甲基化、部分异常甲基化、全甲基化的区间值,并明确30例常规PCR初筛异常患儿中3例存在部分甲基化,27例为全甲基化,其中3例经Southern印迹杂交验证;13例母亲处于正常甲基化,7例存在异常甲基化.结论 MSRE-qPCR可以对FMR1基因CpG岛的甲基化程度进行快速可靠分析,为脆性X综合征的分子诊断提供新的策略.%Objective To establish a method of methylation-sensitive restriction enzymes-based quantitative PCR (MSRE-qPCR) for analysis of CpG island DNA of FMR1 gene,and to assess its value for molecular diagnosis of fragile X syndrome.Methods Thirty boys with mental retardation and abnormal repeats of 5' (CGG)n in the FMR1 gene and 20 mothers were analyzed by conventional PCR screening.Eag Ⅰ was used to digest genomic DNA,and qPCR was performed to amplify CpG island in the FMR1 gene using both undigested and digested templates.Raw Ct values were obtained through quantitative PCR amplification.The degree of CpG island methylation was calculated by 2-△△Ct.The result of MSRE-qPCR was verified by Southern blotting.30 healthy females and 30 healthy males were used as controls to optimize the established MSRE-qPCR method.Results The ranges of 2-△△Ct value for normal methylation,partial methylation and full methylation were

  2. FMR1基因敲除对雄性小鼠生殖功能的影响%The influence of FMR1 gene knockout on the reproduction of male mice

    Institute of Scientific and Technical Information of China (English)

    祝亚桥; 周兴; 陈盛强

    2012-01-01

    Objective To investigate the influence of fragile x mental retardation-1 (FMR1) gene on the spermatogenesis and reproduction of male mice. Methods FMR1 knockout (KO) male mice and wild type (WT) male mice were mated with wt female mice. The number of litters, pregnancy rate and male mice having offsprings were counted. Serum T, FSH and LH concentrations were also measured. The density, mortality and morphology of the left cauda epididymis sperms were analyzed, HE staining was performed on the right side. Results The pregnance rate of wt female mice mated with FMR1K0 males was significantly lower than the control group (41.7% vs. 87. 5% , P 0.05). Male fertility showed that 41.7% of KO mice had pups, whereas 91.7% of the mice had pups in the control group (P 0.05).两组小鼠血清T,FSH,LH浓度无统计学差异.KO组的睾丸附睾病理切片与WT组比较未见明显异常,其精子活率及各种畸形率与WT小鼠比较均没有统计学差异(P>0.05).结论:可以推测FMR1基因对雄性生殖系统发育有一定的影响,Fmr1基因的缺失降低了雄性小鼠生育率,但对精子生成、畸形率等未见明显影响,其对雄性生殖系统影响机制还有待进一步的实验研究.

  3. Microdeletions including FMR1 in three female patients with intellectual disability - further delineation of the phenotype and expression studies

    DEFF Research Database (Denmark)

    Zink, A M; Wohlleber, E; Engels, H;

    2014-01-01

    Fragile X syndrome (FXS) is one of the most common causes of intellectual disability/developmental delay (ID/DD), especially in males. It is caused most often by CGG trinucleotide repeat expansions, and less frequently by point mutations and partial or full deletions of the FMR1 gene. The wide...

  4. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    Science.gov (United States)

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS.

  5. Reversion of FMR1 Methylation and Silencing by Editing the Triplet Repeats in Fragile X iPSC-Derived Neurons

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    Chul-Yong Park

    2015-10-01

    Full Text Available Fragile X syndrome (FXS is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1 gene. Here, we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders.

  6. The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells.

    Science.gov (United States)

    Gerhardt, Jeannine; Tomishima, Mark J; Zaninovic, Nikica; Colak, Dilek; Yan, Zi; Zhan, Qiansheng; Rosenwaks, Zev; Jaffrey, Samie R; Schildkraut, Carl L

    2014-01-01

    Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene that appears to occur during oogenesis and during early embryogenesis. One model proposes that repeat instability depends on the replication fork direction through the repeats such that (CNG)n hairpin-like structures form, causing DNA polymerase to stall and slip. Examining DNA replication fork progression on single DNA molecules at the endogenous FMR1 locus revealed that replication forks stall at CGG repeats in human cells. Furthermore, replication profiles of FXS human embryonic stem cells (hESCs) compared to nonaffected hESCs showed that fork direction through the repeats is altered at the FMR1 locus in FXS hESCs, such that predominantly the CCG strand serves as the lagging-strand template. This is due to the absence of replication initiation that would typically occur upstream of FMR1, suggesting that altered replication origin usage combined with fork stalling promotes repeat instability during early embryonic development.

  7. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    Science.gov (United States)

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS. PMID:25168779

  8. Fmr1 knockout mice show reduced anxiety and alterations in neurogenesis that are specific to the ventral dentate gyrus.

    Science.gov (United States)

    Eadie, B D; Zhang, W N; Boehme, F; Gil-Mohapel, J; Kainer, L; Simpson, J M; Christie, B R

    2009-11-01

    Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the selective loss of the expression of the Fmr1 gene. Key symptoms in FXS include intellectual impairment and abnormal anxiety-related behaviors. Fmr1 knockout (KO) mice exhibited reduced anxiety on two behavioral tests as well as a blunted corticosterone response to acute stress. Spatial learning and memory was not impaired when tested with both the classic Morris water and Plus-shaped mazes. Adult hippocampal neurogenesis has been associated with spatial learning and memory and emotions such as anxiety and depression. The process of neurogenesis appears abnormal in young adult Fmr1 KO mice, with significantly fewer bromodeoxyuridine-positive cells surviving for at least 4 weeks in the ventral subregion of the dentate gyrus (DG), a hippocampal subregion more closely associated with emotion than the dorsal DG. Within this smaller pool of surviving cells, we observed a concomitant increase in the proportion of surviving cells that acquire a neuronal phenotype. We did not observe a clear difference in cell proliferation using both endogenous and exogenous markers. This work indicates that loss of Fmr1 expression can alter anxiety-related behaviors in mice as well as produce region-specific alterations in hippocampal adult neurogenesis.

  9. Pragmatic Language Features of Mothers with the "FMR1" Premutation Are Associated with the Language Outcomes of Adolescents and Young Adults with Fragile X Syndrome

    Science.gov (United States)

    Klusek, Jessica; McGrath, Sara E.; Abbeduto, Leonard; Roberts, Jane E.

    2016-01-01

    Purpose: Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the "FMR1"…

  10. FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile.

    Science.gov (United States)

    Santa María, Lorena; Aliaga, Solange; Faundes, Víctor; Morales, Paulina; Pugin, Ángela; Curotto, Bianca; Soto, Paula; Peña, M Ignacia; Salas, Isabel; Alliende, M Angélica

    2016-01-01

    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8·8%), the average age of diagnosis was 8·8 ± 5·4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS. PMID:27350105

  11. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

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    Karen eUsdin

    2014-07-01

    Full Text Available AbstractThe Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor and ataxia syndrome (FXTAS, the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI and the intellectual disability, Fragile X syndrome (FXS. The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5’ UTR of the FMR1 gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, FMRP. Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by reduced FMRP levels, the clinical picture is turning out to be more complex than once appreciated. Added complications are generated by the fact that increasing repeat numbers make the alleles somatically unstable, generating resulting in individuals sometimes having a complex mixture of different sized alleles. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects.

  12. Fmr1基因敲除雄性小鼠生长指标的变化%Observation on the results of body weight and length of male mince with Fmr1 gene knockout.

    Institute of Scientific and Technical Information of China (English)

    杨乙; 刘国彬; 刘绪红; 林波; 黄月玲; 沈岩松; 张维雯; 孙卫文; 李敏雄; 陈盛强

    2011-01-01

    目的 对出生后0~56d的清洁级FVB小鼠和Fmr1基因敲除雄性小鼠的体重和体长指标进行分析比较,同时比较出生后28d的睾丸大小变化.方法 挑选10周龄FVB小鼠和Fmr1基因敲除小鼠各20只(雌、雄各半),采取1:I同居,全同胞兄妹近交繁殖,测定雄性子代生长发育指标,进行统计分析.结果 出生后0~56d清洁级Fmr1基因敲除雄性小鼠体重与体长的增长与FVB小鼠差异无统计学意义(t=0.93,t=1.24,P>0.05),但出生后28d的FVB小鼠和Fmr1基因敲除雄性小鼠睾丸大小差别有统计学意义(t=4.12,P<0.05).结论 Fmr1基因敲除不影响雄性小鼠正常的体重和体长的发育,但出生后28d的Fmr1基因敲除小鼠有巨睾征.%Objective To characterize the growth performance of FVB mice and Fmrl gene knockout mice. Methods There 20 seed FVB micedO males and 10 females,aged 10 weeks)were chosen and monogamously mated. The parameters of growth performance were analyzed. And these analysis also conducted on male Fmrl gene knockout mice. Results There no significant statistical differences in average weight and length of the newboms FVB and Fmrl gene knockout mice within 56 days after borth were observed. While significant differences were observed in size of testes of FVB mice and Fmrl gene knockout mice 28 days after birth. Conclusion Fmrl gene knockout does not affect the growth and weight of the mice but the mice may have giant testes.

  13. Behavioural comparision on Fmr1 knockout mice at 30 days age in spontaneous activity test%30日龄Fmr1基因敲除小鼠的自主活动观察

    Institute of Scientific and Technical Information of China (English)

    张伟雯; 黄越玲; 刘国彬; 沈岩松; 孙卫文; 李敏雄; 戴丽军; 陈盛强

    2011-01-01

    Objective To compare the behavioural differences at 30 days age in spontaneous activity test. Methods Fmr1 knockout mice were identified using the PCR technica. and spontaneous activity test was used in the study .The data was analyzed with Multifactor Variance Analysis. Results Activities in their own experiments, as compared with WT mice, KO mice in the experiment of self-activity increase in the number of activities and reduction in the number of standing, with statistical significance ( P<0.05 ), but there were no significant differences on manure behaviour between two groups. Conclusion Fmr1 knockout animals exhibited higher locomotor activity in the spontaneous activity test at 30 days age.%目的 对30日龄的Fmr1基因敲除小鼠的自主活动进行观察.方法 采用30日龄的KO鼠和WT鼠分别连续进行2天的自主活动实验,根据所获得的数据进行多因素方差分析处理.结果 通过第1天的学习与第2天的记忆再现,在自主活动实验中,与WT鼠相比,KO鼠在自主活动实验中的活动和站立次数均增多,具有统计学意义(P<0.05),粪便数相比无明显差异.结论 30日龄Fmr1基因敲除小鼠的自主活动异常,运动性和兴奋性较野生型小鼠增高.

  14. FMR1基因敲除对雌性小鼠生殖功能的影响%Influence of FMR1 gene knockout on the reproduction of female mice

    Institute of Scientific and Technical Information of China (English)

    肖国宏; 叶球仙; 杨洁; 陈盛强; 孙卫文; 黄晓虹; 甘婷

    2014-01-01

    目的 利用FMR1基因敲除小鼠,研究FMR1基因缺失对雌性小鼠生殖功能的影响,并对其影响机制进行探讨.方法 将成年的KO纯合子、KO杂合子、WT雌鼠分别和成年的WT雄鼠合笼,观察合笼时间及产仔数;随机取10周的上述3种基因型雌鼠,HE染色观察卵巢形态;免疫组化测定NPY和GABA在下丘脑的分布,Image Pro Plus 6.0分析平均光密度值;ELISA测定血清NPY水平.结果 3组小鼠中,KO纯合子雌鼠的产仔数少于WT雌鼠(6.39±2.30)、(7.60±2.69)和(8.00±1.88);KO纯合子雌鼠的卵泡总数少于WT雌鼠(36.00±5)、(39.33±7.87)和(45.45±7.85);KO纯合子雌鼠下丘脑NPY的表达弱于WT雌鼠(0.27±0.016)、(0.29±0.04)和(0.31±0.041);血清NPY及下丘脑GABA的表达三组间差异均无显著性(P>0.05).结论 FMR1基因敲除可导致雌鼠生育功能下降,FMR1基因可能是通过下调NPY的表达来降低其生殖功能的.

  15. Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the Fmr1 Knockout Mouse Model of Fragile X Syndrome.

    Science.gov (United States)

    Martin, Henry G S; Lassalle, Olivier; Brown, Jonathan T; Manzoni, Olivier J

    2016-05-01

    The most common inherited monogenetic cause of intellectual disability is Fragile X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood; however, neurophysiological data exploring this phenomenon are limited. TheFmr1knockout (Fmr1KO) mouse models FXS, but studies in these mice of prefrontal cortex (PFC) function are underrepresented, and aging linked data are absent. We studied synaptic physiology and activity-dependent synaptic plasticity in the medial PFC ofFmr1KO mice from 2 to 12 months. In young adultFmr1KO mice, NMDA receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12-month-old mice this LTP is impaired. In parallel, there was an increase in the AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12-month-oldFmr1KO mice. We found that acute pharmacological blockade of mGlu5receptor in 12-month-oldFmr1KO mice restored a normal AMPAR/NMDAR ratio and LTP. Taken together, the data reveal an age-dependent deficit in LTP inFmr1KO mice, which may correlate to some of the complex age-related deficits in FXS. PMID:25750254

  16. Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks

    Directory of Open Access Journals (Sweden)

    Zarnescu Daniela C

    2008-11-01

    Full Text Available Abstract Background In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation. Results We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions. Conclusion These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.

  17. Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

    Science.gov (United States)

    Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

    2016-01-01

    STUDY QUESTION Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause? SUMMARY ANSWER The length of repeat alleles within the normal range does not substantially affect risk of early menopause. WHAT IS KNOWN ALREADY There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait. STUDY DESIGN, SIZE, DURATION We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS, SETTING, METHOD We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We

  18. Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qin; Zhu, Zhiwei; Xu, Jialu [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Gu, Weizhong [Department of Pathology, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Zhao, Zhengyan [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China)

    2012-10-05

    Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5′-GTGGCCATCGTGTCCTACCATAC-3′ and 5′-GTTTCGAGGCAGGTGGAAGCTA-3′ were used for the detection of nNOS and primers 5′-CCGTTTCTCCTGGCTCAGTTTA-3′ and 5′-CCCCAATACCACATCATCCAT-3′ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

  19. Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

    Directory of Open Access Journals (Sweden)

    Qin Xu

    2012-12-01

    Full Text Available Nitric oxide (NO, synthesized as needed by NO synthase (NOS, is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS. The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS and male wild-type mice (WT at postnatal day 7 (P7, P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7 and nNOS protein was estimated by Western blot (N = 3 and immunohistochemistry (N = 1. In the PCR assessment, primers 5’-GTGGCCATCGTGTCCTACCATAC-3’ and 5’-GTTTCGAGGCAGGTGGAAGCTA-3’ were used for the detection of nNOS and primers 5’-CCGTTTCTCCTGGCTCAGTTTA-3’ and 5’-CCCCAATACCACATCATCCAT-3’ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05. Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05. These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

  20. Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

    International Nuclear Information System (INIS)

    Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5′-GTGGCCATCGTGTCCTACCATAC-3′ and 5′-GTTTCGAGGCAGGTGGAAGCTA-3′ were used for the detection of nNOS and primers 5′-CCGTTTCTCCTGGCTCAGTTTA-3′ and 5′-CCCCAATACCACATCATCCAT-3′ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS

  1. Towards a Better Molecular Diagnosis of FMR1-Related Disorders-A Multiyear Experience from a Reference Lab.

    Science.gov (United States)

    Rzońca, Sylwia Olimpia; Gos, Monika; Szopa, Daniel; Sielska-Rotblum, Danuta; Landowska, Aleksandra; Szpecht-Potocka, Agnieszka; Milewski, Michał; Czekajska, Jolanta; Abramowicz, Anna; Obersztyn, Ewa; Maciejko, Dorota; Mazurczak, Tadeusz; Bal, Jerzy

    2016-01-01

    The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1) molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5'UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%), 4/43 (9.3%) and 3/11 (27.3%) of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used. PMID:27598204

  2. FMR1 gene mutation screening by TP-PCR in patients with premature ovarian failure and fragile-X.

    Science.gov (United States)

    Tural, Sengul; Tekcan, Akın; Kara, Nurten; Elbistan, Mehmet; Güven, Davut; Ali Tasdemir, Haydar

    2015-03-01

    CGG repeat expansion in the FMR1 gene is associated with fragile X syndrome, fragile X-associated tremor/ ataxia syndrome and fragile X-associated primary ovarian insufficiency. In this study, FMR1 gene mutation screening was carried out in 50 patients. Among them, 12 (%24) were POF and 19 (%38) were Fragile-X. We also examined the parents of the Fragile-X patients. DNA was extracted from blood with kit procedure. To examine expansion of the fragile-X CGG repeat, TP-PCR assay was performed and all amplicons were evaluated on an ABI3130XL Genetic Analyzer System by Fragman analysis. The data were analyzed by Gene Mapper Program. As a result of this study, the patients were identified with the fragile-X whose FMR1 gene CGG alleles have been observed in normal range. However, in patients who were referred with premature ovarian failure, pre-mutation frequency was observed as 6.6%. Only limited study in Turkish population reported frequency of pre-mutation carrier in POF and Fragile-X. Detection of pre-mutation carrier is important for next generation to have healthy siblings. We emphasize that TP-PCR technique is clear, reliable, sensitive, easy and fast method to detect pre-mutation. However, full mutations have to be examined by the technique of Southern blot in the diagnosis of fragile-X. PMID:25366135

  3. Towards a Better Molecular Diagnosis of FMR1-Related Disorders—A Multiyear Experience from a Reference Lab

    Directory of Open Access Journals (Sweden)

    Sylwia Olimpia Rzońca

    2016-09-01

    Full Text Available The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1 molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS, fragile X-associated primary ovarian insufficiency (FXPOI and fragile X-associated tremor/ataxia syndrome (FXTAS, which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5′UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%, 4/43 (9.3% and 3/11 (27.3% of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used.

  4. Towards a Better Molecular Diagnosis of FMR1-Related Disorders—A Multiyear Experience from a Reference Lab

    Science.gov (United States)

    Rzońca, Sylwia Olimpia; Gos, Monika; Szopa, Daniel; Sielska-Rotblum, Danuta; Landowska, Aleksandra; Szpecht-Potocka, Agnieszka; Milewski, Michał; Czekajska, Jolanta; Abramowicz, Anna; Obersztyn, Ewa; Maciejko, Dorota; Mazurczak, Tadeusz; Bal, Jerzy

    2016-01-01

    The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1) molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5′UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%), 4/43 (9.3%) and 3/11 (27.3%) of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used. PMID:27598204

  5. The fragile x mental retardation syndrome 20 years after the FMR1 gene discovery: an expanding universe of knowledge.

    Science.gov (United States)

    Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

    2011-08-01

    The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations.

  6. Estudios de la región 5'UTRTR del gen FMR-1 en pacientes con falla ovárica prematura Studies of the 5' - UTRTR region in the FMR-1 gene in patients withe Premature Ovarian Failure

    Directory of Open Access Journals (Sweden)

    V.A. Chiauzzi

    2010-12-01

    Full Text Available La falla ovárica prematura (FOP es un síndrome de patogénesis multicausal que afecta aproximadamente al 1% de las mujeres en edad reproductiva. Numerosos estudios asocian el estado de premutación (amplificación del número de tripletes CGG entre 50/55 y 200 repeticiones en el gen FMR-1 y FOP. Alrededor de un 4% de las pacientes FOP presentan alelos con premutación. La amplificación del número de tripletes por encima de 200 repeticiones causa el Síndrome de Fragilidad del X (SFX. El objetivo del presente trabajo fue estudiar la región 5´ no codificante del gen en un grupo de pacientes FOP de Argentina. La región de interés se amplificó por PCR a partir de muestras de ADN de 100 pacientes FOP y 145 mujeres controles. Los alelos de las pacientes y controles fueron agrupados en 7 categorías de acuerdo al número de tripletes obtenidos. Se observó que el número de repeticiones más frecuente se encuentra en el rango de 26 a 30 tripletes, tanto en pacientes como en controles. En el grupo de pacientes FOP, 5/197 (2.6% alelos no relacionados estudiados presentaron un número de tripletes CGG mayor a 50, mientras que sólo 1 de 290 (0.34% para el grupo control. Todas las pacientes FOP con valores de tripletes CGG mayor a 50 presentaron amenorrea secundaria. Estos resultados están en concordancia con lo comunicado para otras poblaciones acerca de la existencia de una asociación entre la premutación del gen FMR-1 y el desarrollo de FOP. Asimismo, los resultados obtenidos refuerzan la importancia de la genotipificación del gen FMR-1 en las pacientes FOP, a los efectos de estimar el riesgo de su descendencia para el SFX.Premature ovarian failure (POF is a syndrome of multicausal pathogenesis that affects 1% of women before the age of 40. Several studies associate the premutation state (CGG repeats increased in number between 50/55 and 200 in the FMR-1 gene and POF. About 4% of POF women have alleles in the FMR-1 gene in the permutation

  7. Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

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    Giulia eCuria

    2013-04-01

    Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

  8. Differences in ovarian aging patterns between races are associated with ovarian genotypes and sub-genotypes of the FMR1 gene

    Directory of Open Access Journals (Sweden)

    Gleicher Norbert

    2012-09-01

    Full Text Available Abstract Background Ovarian aging patterns differ between races, and appear to affect fertility treatment outcomes. What causes these differences is, however, unknown. Variations in ovarian aging patterns have recently been associated with specific ovarian genotypes and sub-genotypes of the FMR1 gene. We, therefore, attempted to determine differences in how functional ovarian reserve (FOR changes with advancing age between races, and whether changes are associated with differences in distribution of ovarian genotypes and sub-genotypes of the FMR1 gene. Methods We determined in association with in vitro fertilization (IVF FOR in 62 young Caucasian, African and Asian oocyte donors and 536 older infertility patients of all three races, based on follicle stimulating hormone (FSH, anti-Müllerian hormone (AMH and oocyte yields, and investigated whether differences between races are associated with differences in distribution of FMR1 genotypes and sub-genotypes. Results Changes in distribution of mean FSH, AMH and oocyte yields between young donors and older infertility patients were significant (all P FMR1 genotypes and sub-genotypes in patients varied significantly between races, with Asians demonstrating fewer het-norm/low sub-genotypes than Caucasians and Africans (P = 0.012. Conclusion FOR changes in different races at different rates, and appears to parallel ovarian FMR1 genotypes and sub-genotype distributions. Differences in ovarian aging between races may, therefore, be FMR1-associated.

  9. A viable model for the study of GABAergic neurons in fmr1 knockout mice%fmr1基因敲除小鼠中间神经元发育研究的新方法

    Institute of Scientific and Technical Information of China (English)

    欧阳梅; 徐明明; 卢韬; 黄越玲; 易咏红

    2011-01-01

    目的:通过杂交技术获得能表达GAD67 -GFP的fmr1基因敲除小鼠模型.方法:fmr1基因敲除(fmr1-ko)雌性小鼠(X-X-)和GAD67-GFP敲入基因杂合雄性小鼠(2+2-)杂交.鼠尾巴提取基因组DNA,用PCR方法鉴定所有子代基因型.对杂交后代小鼠进行行为学观察,并行脑组织切片观察绿色荧光蛋白在γ-氨基丁酸能神经元的表达.结果:PCR方法证实通过杂交繁殖出四种基因型小鼠:同时带有杂合fmr1 ko及GAD67-GFP位点的雌性小鼠(X+ X-/2 +2-)、带有纯合fmr1-ko及GAD67-GFP位点的雄性小鼠(X-Y/2 +2-)、不带有GAD67-GFP的雌性和雄性小鼠(X+X-/2-2-,X-Y/2-2-).观察发现X-Y/2+2-小鼠具有fmr1 -ko小鼠类似的行为学表现,同时在显微镜下观察到X-Y/2+2-小鼠脑组织切片有发绿色荧光的GABA神经元.结论:该杂交小鼠成功表达了GAD67-GFP,为研究γ-氨基丁酸能神经元在脆性X综合征发病机制中的作用提供一种可靠的模型.%Objective: To obtain Fragile X syndrome rat models with GAD67-GFP expression by hybridization technique. Methods; One fmrl-knockout female (X~X~) rat was mated with GAD67-CFP heterozygous male (2 + 2-). All hybrid offspring were genotyped by polymerase chain reaction ( PCR) according to genomic DNA extracted from the tail. The behaviors and the expression of GFP on GABAergic neurons of brain slice were also observed. Results: Four genotypes of mice have been generated: the heterozygous female mice with both the fmrl-gfp-ko and GAD67-GFP locus (X+XV2-2-) , fmrl-ko male mice heterozygous with GAD67-GFP locus (X-Y/2+2-) .female and male mice without GAD67-GFP locus(X+ X/-2-2-,X-Y/2-2-). Mice X-Y2+2-were noted to have similar behaviors with fmrl ko mice. Morphological observation of GABAergic neuron had a good match between the mice X-Y/2+2~and fmrl ko mice. Conclusions:The hybrid mice X-Y/2-2- successfully expressed the GAD67-GFP protein, which provides a viable model for the study on the pathogenetic effect of

  10. Investigation on the mechanism of descended reproductive function in FMR1 gene knockout male mice%FMR1基因敲除雄鼠生殖功能下降的机制探讨

    Institute of Scientific and Technical Information of China (English)

    叶球仙; 杨洁; 罗虹; 陈盛强; 黄晓虹; 甘婷; 陈燕; 肖国宏

    2013-01-01

    Objective To investigate the mechanism of descended reproductive function induced by FMR1 gene knockout in male FMR1 gene knockout mice (KO) and male wild mice (WT).Methods The morphology of the testis of 10 weeks old KO and WT male mice were observed by HE staining.The mean optical density (MOD) of the expressions of neuropeptide Y (NPY) and gamma aminobutyricacid (GABA) in hypothalamus were tested and analyzed by immunohistochemistry and Image Pro Plus 6.0.Serum NPY concentrations were measured by ELISA.Results No obvious pathological differences in testis were found between KO and WT mice.The MOD of NPY in hypothalamus and the expression of NPY in serum in KO mice were weaken than those in WT mice,respectively [0.27 ± 0.031 vs.0.31 ± 0.031,P < 0.05; (179.21 ± 50.773)ng/L vs.(225.24 ± 52.293) ng/L,P <0.05].There was no significant difference in the MOD of GABA in hypothalamus between KO and WT mice (0.29 ±0.017 vs.0.28 ± 0.009,P > 0.05).Conclusions FMR1 gene may down-regulate the reproductive function of male mice through reducing the expression of NPY.%目的:利用FMR1基因敲除鼠(KO)和野生型FVB鼠(WT),研究FMR1基因敲除引起雄鼠生殖功能下降的可能机制.方法:随机取10周的KO及WT雄鼠,HE染色观察睾丸形态;免疫组化及Image ProPlus 6.0测定分析下丘脑神经肽Y(NPY)及γ-氨基丁酸(GABA)表达的平均光密度值;ELISA测定血清NPY水平.结果:KO、WT小鼠睾丸形态未见明显不同;KO雄鼠下丘脑NPY的表达弱于WT雄鼠(0.27±0.031,0.31±0.031,P<0.05);KO雄鼠血清NPY的表达弱于WT雄鼠(179.21±50.773,225.24±52.293,P< 0.05);两种基因型小鼠下丘脑GABA的表达差异无统计学意义(0.29±0.017,0.28±0.009,P> 0.05).结论:FMR1基因可能是通过下调NPY的表达来降低雄鼠生殖功能的.

  11. Concurrent array-based queue

    Energy Technology Data Exchange (ETDEWEB)

    Heidelberger, Philip; Steinmacher-Burow, Burkhard

    2015-01-06

    According to one embodiment, a method for implementing an array-based queue in memory of a memory system that includes a controller includes configuring, in the memory, metadata of the array-based queue. The configuring comprises defining, in metadata, an array start location in the memory for the array-based queue, defining, in the metadata, an array size for the array-based queue, defining, in the metadata, a queue top for the array-based queue and defining, in the metadata, a queue bottom for the array-based queue. The method also includes the controller serving a request for an operation on the queue, the request providing the location in the memory of the metadata of the queue.

  12. The impact in older women of ovarian FMR1 genotypes and sub-genotypes on ovarian reserve.

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    Norbert Gleicher

    Full Text Available We recently associated ovarian FMR1genotypes and sub-genotypes with distinct ovarian aging patterns. How they impact older females is, however, unknown. We, therefore, investigated 217 consecutive first in vitro fertilization (IVF cycles in women >40 assessing oocyte yields, stratified for better (anti-Müllerian hormone, AMH >1.05 ng/mL or poorer (AMH ≤ 1.05 ng/mL functional reserve (FOR. Mean age was 42.4 ± 2.0 years, mean AMH 0.76 ± 0.92 ng/mL and mean oocyte yield 5.3 ± 5.4. Overall, and in women with better FOR, FMR1 did not affect oocyte yields. With poorer FOR (AMH ≤ 1.05 ng/mL women with het-norm/high, however, demonstrated higher oocyte yields (5.0 ± 3.8 than those with het-norm/low sub-genotype 3.1 ± 2.5; P = 0.03, confirmed after log conversion. Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions.

  13. Mosaicism for FMR1 gene full mutation and intermediate allele in a female foetus: a postzygotic retraction event.

    Science.gov (United States)

    Ferreira, Susana Isabel; Pires, Luís Miguel; Ferrão, José; Sá, Joaquim; Serra, Armando; Carreira, Isabel Marques

    2013-09-15

    Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5'UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus--amniotic fluid, skin biopsy and blood--the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling.

  14. 三十日龄Fmr1基因敲除小鼠的水迷宫实验观察%Behavioural comparision on Fmr1 knockout mice at 30 days age in Morris water maze experiment

    Institute of Scientific and Technical Information of China (English)

    孙卫文; 黄越玲; 张维雯; 刘国彬; 沈岩松; 李敏雄; 戴丽军; 陈盛强

    2011-01-01

    目的 实验对30日龄的Fmr1基因敲除(KO)小鼠的经典Morris水迷宫实验进行观察.方法 采用Morris水迷宫实验,测试1月龄KO小鼠与WT小鼠的学习记忆功能.水迷宫实验共训练4 d,记录每天的潜伏期与游泳轨迹,第5天去除平台,记录小鼠停留各象限的时间百分比.根据所获得的数据进行多因素方差分析处理.结果 ①空间航行实验第1天至第3天实验中KO鼠与WT鼠的潜伏期和穿越平台次数差异无统计学意义(P>0.05);在第4天实验中KO鼠的潜伏期和穿越平台次数比WT鼠差异有统计学意义(JP<0.05).②空间搜索实验4周龄WT鼠在目标象限停留时间比其它象限停留时间长;4周龄KO鼠在第二象限停留时间长.结论 30日龄KO小鼠存在认知功能障碍.%Objective To compare the behaviour defferences at 30 days age in Morris water maze experiment.Methods Fmr1 knockout mice were identified using the PCR technique , and Morris water maze experiment were used in the study.The data was analyzed with Multifactor Variance Analysis.Results ①space navigation experiment from the first day to the third day, KO mice have no obviously difference with the WT mice in the Latency and number of crossing platform (P> 0.05) , but on the fourth day , there was a statistical significance (P< 0.05) ; ②Space search experiment.The four-week WT mice will stay longer than the other mice at the target quadrants; the four-week KO mice stay at the second quadrant longer.Conclusion Fmr1 knockout animals exhihited low ability of learning and memorizing in the Morris water maze task at 30 days Age.

  15. 钙结合蛋白Calbindin在FMR1基因敲除小鼠脑组织中的表达%The expression of calcium combined with protein Calbindin in little FMR-1 gene knockout rat brain tissue

    Institute of Scientific and Technical Information of China (English)

    郭阳; 易咏红; 孙卫文

    2006-01-01

    目的探讨脆性X综合征中钙结合蛋白Calbindin在神经元树突棘形态异常中的作用.方法我们选用FVB品系的FMR1基因敲除型(KO)和野生型(WT)小鼠,分别取新生1、3、5、7、10、14 d,及成年(6周)的KO小鼠以及WT小鼠用免疫组织化学方法检测钙结合蛋白Calbindin在脑组织中的分布和表达情况,分别对大脑纹状皮质、海马、颞叶听区、梨状皮质、丘脑及小脑的免疫阳性显色细胞进行检测.结果在新生1 d龄WT型及KO型小鼠中Calbindin免疫阳性细胞首先出现于梨状皮质和小脑皮质中,随着天龄的增长脑内其他各区逐渐出现Calbindin免疫阳性细胞的表达,且≤10 dKO型小鼠Calbindin免疫阳性细胞平均光密度均显著高于WT型小鼠(P<0.05). 结论FMRP通过负性调节脑内钙结合蛋白Calbindin的表达,这推测与FMR1基因敲除小鼠神经元树突和树突棘形态异常有关.

  16. 针刺长强穴对FMR1基因敲除小鼠海马CA1区BDNF和SYN表达的影响%Effects of Acupuncturing at Changqiang on Expressions of BDNF and SYN in Hippocampal CA1 Area of FMR1 Gene Knockout Mice

    Institute of Scientific and Technical Information of China (English)

    韩平; 俞萍; 陈可爱; 林栋; 张学君; 吴强

    2012-01-01

    目的 研究针刺长强穴对FMR1基因敲除小鼠海马CA1区脑源性神经营养因子(BDNF)与突触素(SYN)的表达. 方法 选取28日龄脆性X智力低下基因1(FMR1)缺失KO小鼠与野生型(WT)小鼠各30只,分为KO长强组、KO非穴组、KO空白组和WT长强组、WT非穴组、WT空白组,每组10只,检测小鼠海马CA1区BDNF、SYN蛋白的表达. 结果 FMR1基因敲除小鼠海马区BDNF的表达低于野生型小鼠;FMR1基因敲除小鼠长强组BDNF的表达明显高于非穴组和空白组;FMR1基因敲除小鼠海马区SYN的表达低于野生型小鼠;FMR1基因敲除小鼠长强组SYN的表达明显高于非穴组和空白组. 结论 针刺长强穴能上调FMR1基因敲除小鼠海马CA1区BDNF和SYN的表达.

  17. The RNA-binding proteins FMR1, rasputin and caprin act together with the UBA protein lingerer to restrict tissue growth in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Roland Baumgartner

    Full Text Available Appropriate expression of growth-regulatory genes is essential to ensure normal animal development and to prevent diseases like cancer. Gene regulation at the levels of transcription and translational initiation mediated by the Hippo and Insulin signaling pathways and by the TORC1 complex, respectively, has been well documented. Whether translational control mediated by RNA-binding proteins contributes to the regulation of cellular growth is less clear. Here, we identify Lingerer (Lig, an UBA domain-containing protein, as growth suppressor that associates with the RNA-binding proteins Fragile X mental retardation protein 1 (FMR1 and Caprin (Capr and directly interacts with and regulates the RNA-binding protein Rasputin (Rin in Drosophila melanogaster. lig mutant organs overgrow due to increased proliferation, and a reporter for the JAK/STAT signaling pathway is upregulated in a lig mutant situation. rin, Capr or FMR1 in combination as double mutants, but not the respective single mutants, display lig like phenotypes, implicating a redundant function of Rin, Capr and FMR1 in growth control in epithelial tissues. Thus, Lig regulates cell proliferation during development in concert with Rin, Capr and FMR1.

  18. The RNA-binding proteins FMR1, rasputin and caprin act together with the UBA protein lingerer to restrict tissue growth in Drosophila melanogaster.

    Science.gov (United States)

    Baumgartner, Roland; Stocker, Hugo; Hafen, Ernst

    2013-01-01

    Appropriate expression of growth-regulatory genes is essential to ensure normal animal development and to prevent diseases like cancer. Gene regulation at the levels of transcription and translational initiation mediated by the Hippo and Insulin signaling pathways and by the TORC1 complex, respectively, has been well documented. Whether translational control mediated by RNA-binding proteins contributes to the regulation of cellular growth is less clear. Here, we identify Lingerer (Lig), an UBA domain-containing protein, as growth suppressor that associates with the RNA-binding proteins Fragile X mental retardation protein 1 (FMR1) and Caprin (Capr) and directly interacts with and regulates the RNA-binding protein Rasputin (Rin) in Drosophila melanogaster. lig mutant organs overgrow due to increased proliferation, and a reporter for the JAK/STAT signaling pathway is upregulated in a lig mutant situation. rin, Capr or FMR1 in combination as double mutants, but not the respective single mutants, display lig like phenotypes, implicating a redundant function of Rin, Capr and FMR1 in growth control in epithelial tissues. Thus, Lig regulates cell proliferation during development in concert with Rin, Capr and FMR1.

  19. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Steven D Sheridan

    Full Text Available Fragile X syndrome (FXS is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5' untranslated region of the Fragile X Mental Retardation (FMR1 gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP. Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid

  20. 30日龄Fmr1基因敲除小鼠的跳台实验观察%Behavioural Comparison of Fmr1 Knockout Mice at 30 Days Age in Step-down Test

    Institute of Scientific and Technical Information of China (English)

    黄月玲; 沈岩松; 张维雯; 孙卫文; 李敏雄; 陈盛强; 戴丽军

    2011-01-01

    目的 对30日龄的Fmr1基因敲除小鼠的跳台实验进行观察.方法 采用30日龄的KO鼠和WT鼠分别连续进行2d的跳台实验,根据所获得的数据进行多因素方差分析处理.结果 同周龄KO鼠的潜伏期比WT鼠明显少(P<0.05);而KO鼠的错误次数比WT鼠明显多(P<0.05);不同周龄KO鼠或WT鼠的潜伏期、错误次数无差异(P>0.05);第1天KO鼠的潜伏期和错误次数与第2天相比无差异(P>0.05);第1天WT鼠的潜伏期和错误次数与第2天相比有显著差异(P<0.05).结论 30日龄Fmr1基因敲除小鼠存在认知功能障碍.%Objective This study was designed to observe the cognition of Fmrl knockout mice at 30 days Age instep-down test. Method Fmrl knockout mice were identified using the PCR technical and step-down test were used in the study. Animals were tested for two days. The latency and the number of errors were recorded. The data was analyzed with multifactor variance analysis. Result KO mice obviously had the shorter latency than WT mice, and KO mice obviously had more errors than WT mice ( P 0. 05 ) ; On the first day, the latency and number of errors of WT mice had significant difference compared with the second day ( P < 0.05 ). Conclusion Fmrl knockout mice displayed cognitive impairment in the step-down test.

  1. 中国女性对于FMR1突变产前筛查的态度调查%Acceptance of prenatal screening for FMR1 mutation in Chinese female population

    Institute of Scientific and Technical Information of China (English)

    张岚; 章远志

    2012-01-01

    Objective Study the attitude of Chinese female population on prenatal screening of FXS in order to investigate the feasibility of offering prenatal screening.Methods Two hundred and eighty four women with no family history of mental retardation or FXS were recruited in the study.They were grouped into:females married with child (ren) (67/284),females married without child (54/284),unmarried single women (163/284).Then the participants were tested whether they retained the basic genetic knowledge of fragile X by using the adapted questionnaire.Results The proportions of the women who preferred to have prenatal screening for FXS in each group were 77.6%,66.7% and 74.9%.Further more,95.5% of the women in the first female group would like to terminate the pregnancy if a positive result of FXS was reported,so did 92.6% of the women in the second female group and 90.2% of women in the third female group.Conclusion There is a big acceptance of prenatal screening for FMR1 mutation in Chinese female population.Most people would like to take prenatal screening of fragile X syndrome.%目的 调查中国女性对于脆性X综合征产前筛查的态度.方法 随机调查284位没有智力发育障碍及脆性X综合征家族史的女性,分为已婚已育(67/284)、已婚未育(54/284)及未婚未育(163/284)三组.结果 各组愿意接受产前筛查的比率分别为77.6%、66.7%及74.9%.而各组选择在得知产前筛查结果阳性时愿意终止妊娠的比率分别为95.5%、92.6%及90.2%.结论 在中国女性群体中对FMR1基因突变进行产前筛查有较高的接受度.大多数人选择接受针对脆X综合征的产前筛查.

  2. FMR1 CGG Repeats: Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women's Health Across the Nation).

    Science.gov (United States)

    Pastore, Lisa M; Manichaikul, Ani; Wang, Xin Q; Finkelstein, Joel S

    2016-09-01

    FMR1 premutation carriers (55-199 CGG repeats), and potentially women with high normal (35-44) or low normal (scarcity of population data on CGG repeats <45 CGG, and variation in race-ethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had ≥1 menses in the 3 months before enrollment, ≥1 pregnancy, no history of infertility or hormonal therapy, and menopause ≥46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P = .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the "normal" range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele. PMID:26905421

  3. Extended gene diversity at the FMR1 locus and neighbouring CA repeats in a sub-Saharan population

    Energy Technology Data Exchange (ETDEWEB)

    Chiurazzi, Genuardi, M.; Neri, G. [Instituto di Genetica Medica, Roma (Italy)] [and others

    1996-07-12

    We report on the allele distributions in a normal black African population at two microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5{prime} end of the FMR1 gene, which causes the fragile X syndrome. The CGG repeat distribution was found to be similar to that of other ethnic groups, as well as to that of other non-human primates, possibly predicting a comparable prevalence of fragile X in Africa. Significant linkage disequilibrium has been observed between fragile X mutations and alleles of the DXS548 and FRAXAC1 loci in European and Asian populations, and some founder chromosomes may be extremely old. Those associated with FRAXAC1-A and DXS548-2 alleles are not present in the Asian fragile X samples. We searched for these alleles and their frequency in the well defined Bamileke population of Cameroon. All previously described alleles and some new ones were found in this sample, supporting the hypothesis of their pre-existence and subsequent loss in Asian populations. Finally, the heterozygosity of the Bamileke sample was significantly higher at both marker loci and comparable to that of Europeans at the CGG repeat, confirming the notion that genetic diversity is greater in Africans than in other groups and supporting the view that evolution of modern man started in Africa. 31 refs., 1 fig., 1 tab.

  4. Health and reproductive experiences of women with an FMR1 premutation with and without fragile X premature ovarian insufficiency

    Directory of Open Access Journals (Sweden)

    Anne Caroline Wheeler

    2014-09-01

    Full Text Available Recently, research has indicated an increased risk for greater medical and emotional comorbidity and physical health symptoms among women with an FMR1 expansion. However, these studies have generally been limited in their ability to model multiple risk factors associated with these symptoms by small numbers (n = 112 to 146 of participants. This study used survey methodology to examine the health experiences of 458 adult women with the premutation with and without a history of an FXPOI diagnosis. Results suggest similar findings to those reported in the literature with regard to the frequency of medical, emotional, and reproductive experiences of women with the premutation. In addition to expected reproductive differences, women with a diagnosis of FXPOI were also more likely to experience dizziness, nausea, and muscle weakness than women without a diagnosis of FXPOI. Women with and without FXPOI were more likely to have used reproductive assistance and were more likely to have experienced preeclampsia during at least one pregnancy than is reported in the general population. Having comorbid depression and anxiety was predictive of increased medical conditions and increased daily physical health symptoms.

  5. Expression of neuregulin 1 and its significance in brain tissues of FMR1 gene knockout mice%Fmr1基因敲除小鼠脑组织神经调节蛋白1表达的改变及其意义

    Institute of Scientific and Technical Information of China (English)

    卢韬; 欧阳梅; 周林涛; 易咏红

    2013-01-01

    目的 明确神经调节蛋白1 (NRG1)在Fmr1基因敲除(KO)小鼠中的变化,探讨其在脆性X综合征发病机制中的作用. 方法 应用免疫组织化学染色法检测FVB近交系雄性2周龄Fmr1 KO小鼠(KO2w)、4周龄Fmr1 KO小鼠(KO4w)和同龄野生型(WT)小鼠大脑皮层及海马CA1区、CA3区、齿状回中神经调节蛋白1的阳性神经元的数量;Western blotting检测上述小鼠大脑皮层和海马组织NRG1蛋白的含量. 结果 与同龄WT小鼠相比,KO2w、KO4w小鼠大脑皮层、海马CA1和CA3区NRG1阳性神经元的数量明显减少,在海马齿状回却明显增多,差异均有统计学意义(P<0.05);KO2w、KO4w小鼠大脑皮层、海马中NRG1含量(相对分子质量为55 000亚型)分别较同龄的WT小鼠明显减少,差异亦有统计学意义(P<0.05). 结论 Fmr1 KO小鼠大脑皮层和海马组织NRG1阳性神经元及NRG1蛋白表达明显减少,NRG1可能参与脆性X综合征发病机制.%Objective To explore the expression changes ofneuregulin 1 (NRG1) in Fmr1 gene knockout (Fmr1 KO) mice,and its possible role in fragile X syndrome pathogenesis.Methods Immunohistochemistry and Western blotting were simultaneously employed to detect the expression levels of NRG 1 in the hippocampus and the cortex of FVB strain Fmr1 KO mice and wild type (WT) controls at the age of 2 and 4 weeks.Results The number of NRG1-positive cells in the CA1 and CA3 regions of hippocampus and the cortex of Fmr1 KO mice at the age of 2 and 4 weeks was significantly smaller than that in the age-matched WT mice (P<0.05).The NRG1 protein levels in the hippocampus and cerebral cortex of Fmr1 KO mice at the age of 2 and 4 weeks were also decreased as compared with those in the age-matched WT mice (P<0.05).Conclusion The number of NRG1-positive cells and NRG1 protein levels in the CA1 and CA3 regions of hippocampus and the cortex of Fmr1 KO mice are decreased,indicating that NRG 1 might involve in the pathogenesis of Fragile X

  6. Fmr1基因在大鼠快速眼动睡眠剥夺后脑皮质、海马和丘脑区的表达%Expressions of gene Fmr1 in rat cortex, hippocampus and thalamus areas after the rapid eyes movement sleep deprivation

    Institute of Scientific and Technical Information of China (English)

    范贵民; 武冬梅; 王培君; 熊慧; 杨迎峰; 范洪儒; 王景涛

    2014-01-01

    Objective To investigate the expression of gene Fmr1 in rats cortex, hippocampus and hypothalamus areas after the rapid eyes movement ( REM ) sleep deprivation .Methods Using the modified multiple platform method (MMPM), 126 rats were randomly and averagely divided into three groups , the normal control group ( CC), the environmental control group (TC) and the sleep deprivation group (SD).Each group was detected on day 1, day 2, day 3, day 5, day 7, and day 9, and the sample tissues were extracted from 7 rats at each time point.Immunohistochemistry and RT-PCR were operated to analysis the expression of gene Fmr 1.Results The expressions of gene Fmr1 were increased gradually in the cortex and thalamus of the SD group after 3 days ( P 0.05).The expressions of gene Fmr1 were decreased gradually in hippocampus for SD after 3 days ( P 0.05 ) . Conclusion The expressions of gene Fmr 1 were increased gradually in the cortex and thalamus but decreased in the hippocampus in the SD group after 3 days.%目的:探讨快速眼动( REM)睡眠剥夺过程中Fmr1基因在大鼠皮质、海马和丘脑区的表达及变化。方法采用改良多平台水环境法( MMPM )制作大鼠睡眠剥夺模型,采用免疫组织化学法及RT-PCR方法检测Fmr1基因的表达变化。结果在皮质和丘脑中,与CC组和TC组相比,SD1d和SD2d组的Fmr1基因表达无明显变化,SD3d组开始增高(P<0.05),SD5d、SD7d组和SD9d组显著增高(P<0.01);在海马中,与CC组和TC组相比,SD1d和SD2d组的Fmr1基因表达无明显变化,SD3d组开始降低(P<0.05),SD5d、SD7d组和SD9d组显著降低(P<0.01)。结论Fmr1基因在大鼠睡眠剥夺第3天开始表达发生变化,在皮质和丘脑中表达增高,在海马中表达降低。

  7. Array-based techniques for fingerprinting medicinal herbs

    Directory of Open Access Journals (Sweden)

    Xue Charlie

    2011-05-01

    Full Text Available Abstract Poor quality control of medicinal herbs has led to instances of toxicity, poisoning and even deaths. The fundamental step in quality control of herbal medicine is accurate identification of herbs. Array-based techniques have recently been adapted to authenticate or identify herbal plants. This article reviews the current array-based techniques, eg oligonucleotides microarrays, gene-based probe microarrays, Suppression Subtractive Hybridization (SSH-based arrays, Diversity Array Technology (DArT and Subtracted Diversity Array (SDA. We further compare these techniques according to important parameters such as markers, polymorphism rates, restriction enzymes and sample type. The applicability of the array-based methods for fingerprinting depends on the availability of genomics and genetics of the species to be fingerprinted. For the species with few genome sequence information but high polymorphism rates, SDA techniques are particularly recommended because they require less labour and lower material cost.

  8. Effects of FMR1 Gene Knockout on Reproductive Performance of C57BL/6 Mice Based on Gene Identification%基于子代基因型鉴定技术研究FMR1敲除对C57BL/6小鼠繁殖性能的影响

    Institute of Scientific and Technical Information of China (English)

    谢金东; 杨燕燕; 林玮; 俞春英; 周建华; 刘德强; 王训立

    2015-01-01

    为探讨FMR1基因敲除对C57BL/6小鼠繁殖性能的影响,将FMR1基因敲除杂合子小鼠饲养于SPF环境,依照遗传学规则进行繁育,并采用PCR法利用小鼠尾部组织鉴定子代小鼠的基因型.结果表明,PCR技术可以检测小鼠的基因型,且具有方便快捷、直观可靠的特点.子代经过检测可得野生型、杂合子和纯合子3种基因型;在此鉴定基础上,挑选10周龄C57BL/6 FMR1 KO和同源SPF级C57BL/6种鼠各10对,采取1∶1全同胞兄妹近亲繁殖的方法,测定各对第2胎仔鼠的繁殖性能,并进行比较分析.结果显示,C57BL/6 FMR1 KO小鼠在窝产仔数、离乳率、初生鼠体重和体长、离乳体长及雌雄比例等数值偏低,但均差异不显著(P>0.05);而两者的离乳体重差异极显著(P<0.01).

  9. Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia.

    Science.gov (United States)

    Larsen, L A; Vuust, J; Nystad, M; Evseeva, I; Van Ghelue, M; Tranebjaerg, L

    2001-09-01

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by expansion of a (CGG)(n) repeat located in the FMR1 gene. The molecular factors involved in the mutation process from stable (CGG)(n) alleles towards unstable alleles are largely unknown, although family transmission studies and population studies have suggested that loss of AGG interruptions in the (CGG)(n) repeat is essential. We have analysed the AGG interspersion pattern of the FMR1 (CGG)(n) repeat and the haplotype distribution of closely located microsatellite markers DXS548 and FRAXAC1, in three circumarctic populations: Norwegians, Nenets and Saami. The data confirm the conservation, reported in all human populations studied so far, of an AGG interruption for each 9-10 CGG and support the stabilising effect of AGG interruptions. The data also indicate the existence of chromosomes of Asian origin in the Saami and Nenets population, thereby confirming a genetic relationship between Northern Europe and Asia. DXS548-FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males and 119 normal males. Significant linkage disequilibrium were found between the fragile X mutation and haplotype 6-4 and between normal (CGG)(n) alleles and haplotype 7-3.

  10. A Special Extract of Bacopa monnieri (CDRI-08-Restored Memory in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation of Fmr-1 Gene Expression in Hippocampus

    Directory of Open Access Journals (Sweden)

    Anupama Rani

    2015-01-01

    Full Text Available Fragile X mental retardation protein (FMRP is a neuronal translational repressor and has been implicated in learning, memory, and cognition. However, the role of Bacopa monnieri extract (CDRI-08 in enhancing cognitive abilities in hypoxia-induced memory impairment via Fmr-1 gene expression is not known. Here, we have studied effects of CDRI-08 on the expression of Fmr-1 gene in the hippocampus of well validated cobalt chloride (CoCl2-induced hypoxia mimetic mice and analyzed the data with alterations in spatial memory. Results obtained from Morris water maze test suggest that CoCl2 treatment causes severe loss of spatial memory and CDRI-08 is capable of reversing it towards that in the normal control mice. Our semiquantitative RT-PCR, Western blot, and immunofluorescence microscopic data reveal that CoCl2-induced hypoxia significantly upregulates the expression of Hif-1α and downregulates the Fmr-1 expression in the hippocampus, respectively. Further, CDRI-08 administration reverses the memory loss and this is correlated with significant downregulation of Hif-1α and upregulation of Fmr-1 expression. Our data are novel and may provide mechanisms of hypoxia-induced impairments in the spatial memory and action of CDRI-08 in the recovery of hypoxia led memory impairment involving Fmr-1 gene encoded protein called FMRP.

  11. FMR1基因敲除小鼠脑组织微白蛋白表达的改变及其意义%Changes and significance of expression of parvalbumin in brain tissues of FMR1 gene knockout mice

    Institute of Scientific and Technical Information of China (English)

    邸伟; 易咏红; 曾志涌; 徐明明; 王玉良; 孙卫文; 廖卫平

    2010-01-01

    目的 探讨微白蛋白(PV)阳性中间神经元在脆性X综合征(FXS)癫痫易感性增加中的作用. 方法 应用免疫组织化学染色检测FVB近交系雄性2、4、6 W龄FMR1基因敲除型(KO)(KO2W、KO4W、KO6W)和同龄野生型(WT)(WT2W、WT4W、WT6W)小鼠大脑纹状皮质、颞听皮质、梨状皮质及海马CA1区、CA3区、齿状回中PV的表达(n=6);应用Western blot法检测上述小鼠大脑皮层、海马组织PV的含量(n=6). 结果 KO2W、KO44W小鼠的大脑纹状皮质、颞听皮质、梨状皮质、海马CA1和CA3区PV阳性中间神经元的数量分别较WT2W、WT4-小鼠减少,差异有统计学意义(P<0.05);KO2W和KO4W小鼠大脑皮层、海马中PV含量分别较WT2W、WT4W小鼠减少,差异有统计学意义(P<0.05). 结论 PV阳性中间神经元及PV含量的减少.可能是引起FXS模型鼠癫痫易感性增加的主要原因.%Objective To explore the possible role of parvalbumin (PV)-positive interneuron in the pathogenesis of increased susceptibility to epileptic seizures in FMR1 gene knockout (FMR1 KO)mice. Methods Immunohistochemistry was employed to determine the expression of PV in CA1 and CA3 regions of the hippocampus, the striate cortex, the temporal auditory cortex and the piriform cortex of FVB strain FMR1 KO mice and wild type (WT) controls at the age of 2, 4 and 6 w. Western blotting was used to detect the level of PV in the cerebral cortex and hippocampus of the above mice. Results The numbers of PV-positive interneuron in CA1 and CA3 regions of the hippocampus, the striate cortex,the temporal auditory cortex and the piriform cortex of FMR1 KO mice at the age of 2 and 4 w were significantly decreased as compared with those in the age-matched WT mice (P<0.05). The level of PV in the cerebral cortex and hippocampus in FMR1 KO mice at the age of 2 and 4 w was also significantly decreased than that in the age-matched WT mice (P<0.05). Conclusion Decreased numbers of PV-positive interneuron and level of PV

  12. Premutation in the Fragile X Mental Retardation 1 (FMR1 Gene Affects Maternal Zn-milk and Perinatal Brain Bioenergetics and Scaffolding

    Directory of Open Access Journals (Sweden)

    Eleonora eNapoli

    2016-04-01

    Full Text Available Fragile X premutation alleles have 55-200 CGG repeats in the 5' UTR of the FMR1 gene. Altered zinc (Zn homeostasis has been reported in fibroblasts from > 60 y old premutation carriers, in which Zn supplementation significantly restored Zn-dependent mitochondrial protein import/processing and function. Given that mitochondria play a critical role in synaptic transmission, brain function, and cognition, we tested FMRP protein expression, brain bioenergetics and expression of the Zn-dependent synaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (Shank3 in a knock-in (KI premutation mouse model with 180 CGG repeats. Mitochondrial outcomes correlated with FMRP protein expression (but not FMR1 gene expression in KI mice and human fibroblasts from carriers of the pre- and full mutation. Significant deficits in brain bioenergetics, Zn levels, and Shank3 protein expression were observed in the Zn-rich regions KI hippocampus and cerebellum at PND21, with some of these effects lasting into adulthood (PND210. A strong genotype x age interaction was observed for most of the outcomes tested in hippocampus and cerebellum, whereas in cortex, age played a major role. Given that the most significant effects were observed at the end of the lactation period, we hypothesized that KI milk might have a role at compounding the deleterious effects on the FMR1 genetic background. A higher gene expression of ZnT4 and ZnT6, Zn transporters abundant in brain and lactating mammary glands, was observed in the latter tissue of KI dams. A cross-fostering experiment allowed improving cortex bioenergetics in KI pups nursing on WT milk. Conversely, WT pups nursing on KI milk showed deficits in hippocampus and cerebellum bioenergetics. A highly significant milk type x genotype interaction was observed for all three-brain regions, being cortex the most influenced. Finally, lower milk-Zn levels were recorded in milk from lactating women carrying the premutation as

  13. Premutation in the Fragile X Mental Retardation 1 (FMR1) Gene Affects Maternal Zn-milk and Perinatal Brain Bioenergetics and Scaffolding

    Science.gov (United States)

    Napoli, Eleonora; Ross-Inta, Catherine; Song, Gyu; Wong, Sarah; Hagerman, Randi; Gane, Louise W.; Smilowitz, Jennifer T.; Tassone, Flora; Giulivi, Cecilia

    2016-01-01

    Fragile X premutation alleles have 55–200 CGG repeats in the 5′ UTR of the FMR1 gene. Altered zinc (Zn) homeostasis has been reported in fibroblasts from >60 years old premutation carriers, in which Zn supplementation significantly restored Zn-dependent mitochondrial protein import/processing and function. Given that mitochondria play a critical role in synaptic transmission, brain function, and cognition, we tested FMRP protein expression, brain bioenergetics, and expression of the Zn-dependent synaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (Shank3) in a knock-in (KI) premutation mouse model with 180 CGG repeats. Mitochondrial outcomes correlated with FMRP protein expression (but not FMR1 gene expression) in KI mice and human fibroblasts from carriers of the pre- and full-mutation. Significant deficits in brain bioenergetics, Zn levels, and Shank3 protein expression were observed in the Zn-rich regions KI hippocampus and cerebellum at PND21, with some of these effects lasting into adulthood (PND210). A strong genotype × age interaction was observed for most of the outcomes tested in hippocampus and cerebellum, whereas in cortex, age played a major role. Given that the most significant effects were observed at the end of the lactation period, we hypothesized that KI milk might have a role at compounding the deleterious effects on the FMR1 genetic background. A higher gene expression of ZnT4 and ZnT6, Zn transporters abundant in brain and lactating mammary glands, was observed in the latter tissue of KI dams. A cross-fostering experiment allowed improving cortex bioenergetics in KI pups nursing on WT milk. Conversely, WT pups nursing on KI milk showed deficits in hippocampus and cerebellum bioenergetics. A highly significant milk type × genotype interaction was observed for all three-brain regions, being cortex the most influenced. Finally, lower milk-Zn levels were recorded in milk from lactating women carrying the premutation as well

  14. Intervention Effect of α-Asarone on the Locomotor Activity in Fmr1 Gene Knockout Mice%α-细辛醚对Fmr1基因敲除小鼠的自主活动的干预作用

    Institute of Scientific and Technical Information of China (English)

    吴杰贤; 陈希; 张伟雯; 黄月玲; 孙祺章; 黄小燕; 陈盛强; 孙卫文; 戴丽军

    2014-01-01

    目的 探讨α-细辛醚对Fmr1基因敲除小鼠的自主活动的干预作用.方法 选取30日龄Fmr1基因敲除小鼠(KO小鼠)和FVB野生型小鼠(WT小鼠)为研究对象,将KO和WT两种类型的小鼠分别分为7小组,每组15只.其中1组作为对照组给予生理盐水,另外6小组连续腹腔注射不同剂量α-细辛醚(3 mg/kg、6 mg/kg、9 mg/kg、12 mg/kg、24 mg/kg、36mg/kg)5天,用药第5天进行自主活动行为学实验,观察α-细辛醚能否改善KO鼠的过度活动的表型.结果 在行为学自主活动实验中,KO鼠的活动次数比WT鼠的活动次数多,站立次数比WT鼠的站立次数少,差异具有统计学意义(P<0.05);使用α-细辛醚后,KO鼠的活动次数明显减少,站立次数明显增多,差异均具有统计学意义(P均<0.05).结论 α-细辛醚能改善KO鼠的的活动过度的表型,可能对Fmr1基因敲除小鼠有治疗作用.

  15. 智力低下儿童X染色体脆性位点及FMR1基因突变的研究%Study on X chromosome fragile site and FMR1 gene mutation in children with metal retardation

    Institute of Scientific and Technical Information of China (English)

    陈冬萍; 曾素芬; 张素贞

    2014-01-01

    目的 探讨智力低下(Mental Retardation,MR)儿童染色体遗传学原因.方法 选择智力低下患儿及其父母作为研究对象,采用细胞遗传学方法检测X染色体脆性位点,以及采用多重连接探针扩增(Multiplex ligation-dependent Probe Amplificaton,MLPA)技术分析FMRl (Fragile X mental retardation gene 1)基因的缺失与重复.结果 266例患儿共查出X脆性综合征18例,与父母同一脆性位点的7例,其中6例为FMR1基因突变.结论 MR患儿可与表型正常的父母有同一X染色体脆性位点,但FMR1基因突变是X脆性综合征(Fragile X syndrome,Fra X)临床表型的真正原因.

  16. 柴胡桂枝汤挥发油对Fmr1基因敲除小鼠脑组织超氧化物歧化酶和丙二醛及一氧化氮的影响%Influence of Bupleuri and Ramuli Cinnamomi Decoction on Levels of Malondialdehyde,Nitrogen Monoxidum and Superoxide Dismutase in FMR-1 Gene Knockout Mice

    Institute of Scientific and Technical Information of China (English)

    高飞; 黄庆晖; 黄越玲; 孙卫文; 戴丽军; 沈岩松; 李敏雄; 陈盛强; 刘忠民

    2010-01-01

    目的 利用超临界二氧化碳(CO2)萃取法获取柴胡桂枝汤挥发油,并在Fmr1基因敲除小鼠(脆性基因敲除小鼠)模型上观察柴胡桂枝汤挥发油的抗癫痫作用,及其与超氧化物歧化酶(SOD )、丙二醛(MDA)、一氧化氮(NO)的关系.方法 将30只30日龄的Fmr1基因敲除小鼠(KO)和30只30日龄的野生型小鼠(WT)分别分成两组(KO空白组和KO用药组,WT空白组和WT用药组),按1.7 ml/kg的剂量腹腔注射柴胡桂枝汤挥发油,观察柴胡桂枝汤挥发油对小鼠旷场行为的影响,并取不同部位的小鼠脑组织制成1∶ 10(重量体积比) 的组织匀浆,测定SOD活性及MDA、NO的水平.结果 与空白组比较,用药组小鼠在旷场实验中运动的平均速度、总路程、穿过各区的次数减少;脑组织中SOD活性增高,而MDA、NO水平均降低,差异有统计学意义(P<0.05).结论 柴胡桂枝汤挥发油对Fmr1基因敲除小鼠的探索性、兴奋性、运动性均有抑制作用;其抗癫痫作用与清除自由基、阻止过氧化物生成,减少NO的神经毒性相关.

  17. Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study

    Science.gov (United States)

    Merino, Sonia; Ibarluzea, Nekane; Maortua, Hiart; Prieto, Begoña; Rouco, Idoia; López-Aríztegui, Maria-Asunción; Tejada, Maria-Isabel

    2016-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) are definitely related to the fragile X mental retardation 1 (FMR1) premutation (PM). Additional medical problems have also been associated with the PM, such as fibromyalgia, endocrine, and psychiatric disorders. To improve our understanding in the field, we reviewed all PM carriers and their reasons for any medical referrals from 104 fragile X families molecularly diagnosed in our laboratory and living in the Spanish Basque Country. After signing the written informed consent, we studied their electronic medical records in order to identify the disorders associated with the PM and their frequencies. We obtained clinical data in 188 PM carriers (147 women and 41 men). In women, the frequency of FXPOI (22.61%) was similar to that previously reported in PM carriers. In men, the frequency of definite FXTAS (28.57%) was lower than reported elsewhere. Furthermore, thyroid pathology was associated with the PM, the frequency of hypothyroidism being much higher in the studied region than in the general population (8.84% vs. 0.93%). Finally, we found no association with fibromyalgia or psychiatric problems. These findings represent another population contribution in this field and may be useful for the clinical management of PM carriers. PMID:27775646

  18. Normal number of CGG repeats in the FMR-1 gene and abnormal incorporation of fibrillin into the extracellular matrix in Lujan Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Greenhaw, G.A.; Stone, C.; Milewicz, D. [Univ. of Texas Health Science Center, Houston, TX (United States)

    1994-09-01

    Lujan syndrome is an X-linked condition that includes mild-to-moderate mental retardation, poor social integration, normal secondary sexual development with normal testicular size, generalized hypotonia, hypernasal voice and dolichostenomelia. Major cardiac complications and lens dislocation have not been reported although severe myopia may occur. All reported cases have had negative cytogenetic screening for fra(X) syndrome but establishing this constellation of findings as a distinctive entity has been difficult. We report 4 males in two sibships with clinical findings consistent with Lujan syndrome, normal karyotypes, negative cytogenetic screening for fra(X) syndrome and a normal number of CGG repeats in the FMR-1 gene. Dermal fibroblasts explanted from one of the affected males were used to study fibrillin synthesis secretion and extracellular matrix incorporation into microfibrils. Cells from the affected individual showed normal synthesis and secretion of fibrillin when compared to control cells, but the fibrillin was not incorporated into the extracellular matrix. These results suggest the presence of a gene on the X chromosome which may play a role in microfibril assembly and when deficient may disrupt the incorporation of fibrillin into microfibrils. This may be important not only in normal body morphogenesis but also in the development/function of the brain. More affected individuals are needed to investigate these findings further.

  19. MicroRNA-134在FMR1基因敲除鼠脑组织中的表达及意义%Expression and significance of microRNA-134 in mouse brain tissue with FMR1 gene knockout

    Institute of Scientific and Technical Information of China (English)

    曾志涌; 邸伟; 肖都; 孙逊沙; 王玉良; 欧阳梅; 易咏红

    2010-01-01

    Objective To observe the expression ofmicroRNA-134 (miR-134) in the mouse brain tissue with FMR1 gene knockout during the different development periods and its expression characteristic, and explore whether the deficiency of fragile X mental retardation protein (FMRP) can induce the changes of miR-134 transcription. Methods FVB strain male mice, including FMR1 gene knockout (KO, n=15) and their wild type (WT, n=15) counterparts were chosen in the experiment. The expressions of miR-134 in the brain tissues of these KO mice that were 0 d, 4 and 6 w old and the age-matched WT mice were detected by qRT-PCR. Results The transcriptional level of miR-134 in the brain tissue of KO mice had no significant difference as compared with that of age-matched WT mice (P>0.05). The transcriptional levels of miR-134 in 6-w-old KO and WT mice were significantly decreased as compared with the newbom and 4-w-old same genotype mice (P<0.05). Conclusion The absence of FMRP does not influence the transcription of miR-134 and the transcriptional level of miR-134 in the brain tissues maintains a high level during the developmental stage of the nervous system and gradually decreases to a low level after grow-up, demonstrating its important role in regulating the development of nervous system.%目的 观察脆性X综合征(FXS)模型小鼠不同发育时期脑组织中microRNA-134(miR-134)的表达,明确miR-134的表达特点及脆性X智力低下蛋白(FMRP)缺失是否导致miR-134转录的改变. 方法 应用荧光实时定量PCR检测FVB近交系雄性0 d、4、6周(W)龄FMR1基因敲除型(KO)(KO0d、KO4w、KO6w)和同龄野生型(WT)(WT0d、WT4w、WT6w)小鼠脑组织中miR-134的表达(n=5). 结果同龄KO与WT小鼠miR-134的转录表达量差异无统计学意义(P>0.05);KO6w小鼠脑组织miR-134的转录表达量低于KO0d和KO2w小鼠,WT6w小鼠脑组织miR-134的转录表达量也低于WT0d和WT2w小鼠,差异均有统计学意义(P<0.05). 结论 FMRp

  20. Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field [v1; ref status: indexed, http://f1000r.es/2mk

    Directory of Open Access Journals (Sweden)

    Michael R. Hunsaker

    2013-12-01

    Full Text Available It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the FMR1 gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the Fmr1 knock-out (KO mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS.

  1. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Lara eCosta

    2015-03-01

    Full Text Available Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD in wild-type (wt and in Fmr1 KO mice, a mouse model of Fragile X syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices.Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions.The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of

  2. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    Science.gov (United States)

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  3. Expressions of Drebrins and lcam-5 in mouse cerebral cortex with Fmr-1 gene knockout and their significance in fragile X syndrome%Drebrins和Icam-5在Fmr-1基因敲除鼠大脑皮层的表达和意义

    Institute of Scientific and Technical Information of China (English)

    徐琴; 竺智伟; 赵正言

    2012-01-01

    [Objective]To investigate and compare the changes of Drebrin A,Drebrin E and lcam-5 mRNA levels in the cerebral cortex of Frr-1 gene knockout mouse during brain development periods.[Methods]Fmr-1 gene knockout (KO) male mice and their wild type (WT) counterparts were chosen in our experiment (4≤n≤ 10);the levels of target mRNAs were detected by real time quantitative PCR;check points were set on the 7th,14th,21th and 28rh postnatal d.[Results] The mRNA level of Drebrin A in the KO group was significantly lower than that in the WT group on the 14th postnatal d,while that of Drebrin E was significantly higher than that in the WT group (P<0.05).The mRNA level of lcam-5 in the KO group was significantly higher than that in the WT group on the 14th and 21th postnatal d (P<0.05).[Conclusion] The delayed shift of Drebrin A to Drebrin E and transitional over-expression of lcam-5 in developmental cerebral cortex are the reasons for mental retardation in Fragile X Syndrome.%目的 观察脆性X综合征(FXS)模型小鼠不同发育时期大脑皮层中Drebrin A、Drebrin E及Icam-5 mRNA水平变化情况及意义.方法 应用荧光实时定量PCR(RT-PCR)法检测FmrJ基因敲除KO小鼠及野生健康对照小鼠H出生后第7天、第14天、第21天和第28天大脑皮层Drebrin A、Drebrin E及Icam-5 mRNA的表达(4≤n≤10).结果 KO组小鼠出生后第14天Drebrin A mRNA水平较健康对照组小鼠明显降低,而同时间Drebrin E mRNA水平较健康对照组小鼠明显增高,差异均有统计学意义(P<0.05);KO组小鼠Icam-5 mRNA水平在出生后第14和21天均明显高于健康对照组,差异均有统计学意义(P<0.05).结论 Drebrin A和Drebrin E在大脑皮层发育期的表达交替延迟及Icam-5的一过性过度表达是FXS智力低下的原因之一.

  4. Linear Microbolometric Array Based on VOx Thin Film

    Science.gov (United States)

    Chen, Xi-Qu

    2010-05-01

    In this paper, a linear microbolometric array based on VOx thin film is proposed. The linear microbolometric array is fabricated by using micromachining technology, and its thermo-sensitive VOx thin film has excellent infrared response spectrum and TCR characteristics. Integrated with CMOS circuit, an experimentally prototypical monolithic linear microbolometric array is designed and fabricated. The testing results of the experimental linear array show that the responsivity of linear array can approach 18KV/W and is potential for infrared image systems.

  5. Array-based approaches to bacterial transcriptome analysis

    OpenAIRE

    Mäder, Ulrike; Nicolas, Pierre

    2012-01-01

    Microarray technology has been extensively used to compare or quantify genome-wide mRNA levels, a key factor in the adaptive response of bacteria to the environment. Classical gene expression arrays based on an existing genome annotation with relatively few probes for each gene, are well suited to assess the expression levels of all annotated transcripts under many different conditions. Newer genomic tiling arrays that cover both strands of a genome by overlapping probes and, more recently, R...

  6. Low Power Systolic Array Based Digital Filter for DSP Applications

    Directory of Open Access Journals (Sweden)

    S. Karthick

    2015-01-01

    Full Text Available Main concepts in DSP include filtering, averaging, modulating, and correlating the signals in digital form to estimate characteristic parameter of a signal into a desirable form. This paper presents a brief concept of low power datapath impact for Digital Signal Processing (DSP based biomedical application. Systolic array based digital filter used in signal processing of electrocardiogram analysis is presented with datapath architectural innovations in low power consumption perspective. Implementation was done with ASIC design methodology using TSMC 65 nm technological library node. The proposed systolic array filter has reduced leakage power up to 8.5% than the existing filter architectures.

  7. Small Area Array-Based LED Luminaire Design

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Yuan

    2008-01-09

    This report contains a summary of technical achievements during a three-year project to demonstrate high efficiency LED luminaire designs based on small area array-based gallium nitride diodes. Novel GaN-based LED array designs are described, specifically addressing the thermal, optical, electrical and mechanical requirements for the incorporation of such arrays into viable solid-state LED luminaires. This work resulted in the demonstration of an integrated luminaire prototype of 1000 lumens cool white light output with reflector shaped beams and efficacy of 89.4 lm/W at CCT of 6000oK and CRI of 73; and performance of 903 lumens warm white light output with reflector shaped beams and efficacy of 63.0 lm/W at CCT of 2800oK and CRI of 82. In addition, up to 1275 lumens cool white light output at 114.2 lm/W and 1156 lumens warm white light output at 76.5 lm/W were achieved if the reflector was not used. The success to integrate small area array-based LED designs and address thermal, optical, electrical and mechanical requirements was clearly achieved in these luminaire prototypes with outstanding performance and high efficiency.

  8. Tin Oxide Nanorod Array-Based Electrochemical Hydrogen Peroxide Biosensor

    Directory of Open Access Journals (Sweden)

    Liu Jinping

    2010-01-01

    Full Text Available Abstract SnO2 nanorod array grown directly on alloy substrate has been employed as the working electrode of H2O2 biosensor. Single-crystalline SnO2 nanorods provide not only low isoelectric point and enough void spaces for facile horseradish peroxidase (HRP immobilization but also numerous conductive channels for electron transport to and from current collector; thus, leading to direct electrochemistry of HRP. The nanorod array-based biosensor demonstrates high H2O2 sensing performance in terms of excellent sensitivity (379 μA mM−1 cm−2, low detection limit (0.2 μM and high selectivity with the apparent Michaelis–Menten constant estimated to be as small as 33.9 μM. Our work further demonstrates the advantages of ordered array architecture in electrochemical device application and sheds light on the construction of other high-performance enzymatic biosensors.

  9. Planar patterned stretchable electrode arrays based on flexible printed circuits

    International Nuclear Information System (INIS)

    For stretchable electronics to achieve broad industrial application, they must be reliable to manufacture and must perform robustly while undergoing large deformations. We present a new strategy for creating planar stretchable electronics and demonstrate one such device, a stretchable microelectrode array based on flex circuit technology. Stretchability is achieved through novel, rationally designed perforations that provide islands of low strain and continuous low-strain pathways for conductive traces. This approach enables the device to maintain constant electrical properties and planarity while undergoing applied strains up to 15%. Materials selection is not limited to polyimide composite devices and can potentially be implemented with either soft or hard substrates and can incorporate standard metals or new nano-engineered conductors. By using standard flex circuit technology, our planar microelectrode device achieved constant resistances for strains up to 20% with less than a 4% resistance offset over 120 000 cycles at 10% strain. (paper)

  10. Fiber-array based optogenetic prosthetic system for stimulation therapy

    Science.gov (United States)

    Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

    2012-02-01

    Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

  11. Array-based detection of genetic alterations associated with disease

    Science.gov (United States)

    Pinkel, Daniel; Albertson, Donna G.; Gray, Joe W.

    2007-09-11

    The present invention relates to DNA sequences from regions of copy number change on chromosome 20. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases.

  12. Array-based GNSS Ionospheric Sensing: Estimability and Precision Analyses

    Science.gov (United States)

    Teunissen, Peter

    2016-04-01

    Array-based GNSS Ionospheric Sensing: Estimability and Precision Analyses PJG Teunissen1,2, A Khodabandeh1 and B Zhang1 1GNSS Research Centre, Curtin University, Perth, Australia 2Geoscience and Remote Sensing, Delft University of Technology, The Netherlands Introduction: The Global Navigation Satellite Systems (GNSS) have proved to be an effective means of measuring the Earth's ionosphere. The well-known geometry-free linear combinations of the GNSS data serve as the input of an external ionospheric model to capture both the spatial and temporal characteristics of the ionosphere. Next to the slant ionospheric delays experienced by the GNSS antennas, the geometry-free combinations also contain additional unknown delays that are caused by the presence of the carrier-phase ambiguous cycles and/or the code instrumental delays. That the geometry-free combinations, without an external ionospheric model, cannot unbiasedly determine the slant ionospheric delays reveals the lack of information content in the GNSS data. Motivation and objectives: With the advent of modernized multi-frequency signals, one is confronted with many different combinations of the GNSS data that are capable of sensing the ionosphere. Owing to such diversity and the lack of information content in the GNSS data, various estimable ionospheric delays of different interpretations (and of different precision) can therefore be formed. How such estimable ionospheric delays should be interpreted and the extent to which they contribute to the precision of the unbiased slant ionosphere are the topics of this contribution. Approach and results: In this contribution, we apply S-system theory to study the estimability and precision of the estimable slant ionospheric delays that are measured by the multi-frequency GNSS data. Two different S-systems are presented, leading to two different estimable parameters of different precision: 1) the phase-driven ionospheric delays and 2) the code-driven ionospheric delays

  13. 75 FR 32484 - Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and...

    Science.gov (United States)

    2010-06-08

    ... Performance Evaluation, Result Reporting and Interpretation. The purpose of the public meeting is to seek input on challenges related to performance evaluation, determination of clinical significance, result... HUMAN SERVICES Food and Drug Administration Array-Based Cytogenetic Tests: Questions on...

  14. Expression of calcium/calAulin kinaseⅡα in fragile X mental retardation 1 gene knockout brain tissues in mice%CaMKⅡα在FMR1基因敲除小鼠脑组织中的表达

    Institute of Scientific and Technical Information of China (English)

    韦朝霞; 陈盛强; 陈希; 戴丽军

    2013-01-01

    目的 观察FMRI基因敲除型(KO)小鼠脑组织中钙/钙调素依赖蛋白激酶Ⅱα(CaMKⅡα)表达的改变,探讨CaMKⅡα是否为脆性X综合征相关蛋白(FMRP)的下调蛋白. 方法 PCR鉴定FVB近交系小鼠的基因型,按基因型的不同分为KO组和野生型(WT)组,每组10只.免疫组化染色检测KO及WT小鼠脑组织CaMKⅡα的表达与分布,用图像分析仪分别采集不同脑区免疫信号的吸光度(A)值进行比较. 结果 免疫组化染色检测显示KO与WT小鼠各个脑区普遍存在阳性信号;神经元胞浆尤其是靠近胞体的近端突起上信号呈强阳性,树突中亦有阳性信号,轴突上信号较弱;KO小鼠各脑区CaMKⅡα阳性信号的A值均较WT小鼠显著增高,差异有统计学意义(P<0.05). 结论 CaMKⅡα在成年KO小鼠各脑区的表达均显著增多,提示FMRP负性调节CaMKⅡα的表达.%Objective To observe the expression of calcium/calAulin kinaseⅡα (CaMKⅡα) in the brain tissues of fragile X mental retardation 1 (FMR1) gene knockout (KO) mice to investigate whether CaMKⅡα is regulated by fragile X mental retardation protein (FMRP).Methods According to the gene types of the FVB inbred mice identified by PCR,20 mice were divided into KO group and WT (wide type) group (n=10).The subcellular distribution and expression of CaMKⅡα were observed by immunohistochemical staining; the mean optical density (A) values of immunostaining signal of CaMKⅡα in various brain regions,including the motor cortex,temporal cortex,amygdala,hypothalamus and hippocampus,were determined by IBAS 2.0 image-analyzed system.Results CaMKⅡα immunoreactive cells were abundantly found in all brain subregions of KO and WT mice; especial positive signal was noted in the proximal processes of neurons,so as to those in the dendrite; week signcal was observed in the axon.No distributional difference was found between KO and WT mice.As compared with those in the WT mice,the A values were

  15. Microlens array-based high-gain screen design for direct projection head-up displays

    OpenAIRE

    Hedili, M. Kıvanç; Ürey, Hakan; Freeman, Mark O.

    2013-01-01

    Microlens array-based high-gain screen design for direct projection head-up displays M. Kivanc Hedili,1 Mark O. Freeman,2 and Hakan Urey1,* 1Optical Microsystems Laboratory, Koc University, Rumelifeneri Yolu, Sarıyer, İstanbul 34450, Turkey 2Lost Lake Technology LLC, 21623 W. Lost Lake Rd., Snohomish, Washington 98296, USA *Corresponding author: Received 2 October 2012; revised 28 December 2012; accepted 29 December 2012; posted 18 January 2013 (Doc. ID 17...

  16. Analysis of unstable DNA sequence in FRM1 gene in Polish families with fragile X syndrome

    International Nuclear Information System (INIS)

    The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGC repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted. (author). 19 refs., 4 figs, 1 tab

  17. Determination of pork spoilage by colorimetric gas sensor array based on natural pigments.

    Science.gov (United States)

    Huang, Xiao-wei; Zou, Xiao-bo; Shi, Ji-yong; Guo, Yanin; Zhao, Jie-wen; Zhang, Jianchun; Hao, Limin

    2014-02-15

    A new colorimetric gas-sensor array based on four natural pigments, that were extracted from spinach (Spinacia oleracea), red radish (Raphanus sativus L.), winter jasmine (Jasminum nudiflorum), and black rice (Oryza sativa L. indica), was developed for pork freshness evaluation. A colour change profile for each sample was obtained by differentiating the images of the sensor array before and after exposure to the odour of sample. The total viable count (TVC) per gram of pork was obtained by classical microbiological plating methods, and the biogenic amines were measured by HPLC. Biogenic amine index (BAI) for the determination of meat freshness was developed from the sum of putrescine and cadaverine. The colour change profiles were analysed using principal component analysis and correlated with conventional methods (BAI, TVC). A partial least squares (PLS) prediction model was obtained with r=0.854 and 0.933 for BAI and TVC, respectively. PMID:24128513

  18. 1-Mb resolution array-based comparative genomic hybridization using a BAC clone set optimized for cancer gene analysis

    NARCIS (Netherlands)

    Greshock, J; Naylor, TL; Margolin, A; Diskin, S; Cleaver, SH; Futreal, PA; deJong, PJ; Zhao, SY; Liebman, M; Weber, BL

    2004-01-01

    Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide determination of DNA copy number alterations. This technology has tremendous potential for disease-gene discovery in cancer and developmental disorders as well as numerous other applications. However, w

  19. Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing

    Science.gov (United States)

    Lu, Yichen; Lyu, Hongming; Richardson, Andrew G.; Lucas, Timothy H.; Kuzum, Duygu

    2016-01-01

    Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial. PMID:27642117

  20. An LED-array-based range imaging system used for enhancing three-dimensional imaging

    Science.gov (United States)

    Wang, Huanqin; Xu, Jun; He, Deyong; Zhao, Tianpeng; Wang, Anting; Ming, Hai; Kong, Deyi

    2010-11-01

    An LED-array-based range imaging system is proposed for three-dimensional (3-D) shape measurement. The range image is obtained by time-division electronic scanning of the LED Time-of-Flight (TOF) range finders in array, and no complex mechanical scanning is needed. By combining with a low cost CCD/CMOS sensor for capturing the twodimensional (2-D) image, the proposed range imaging system can be used to accomplish a high quality 3-D imaging. A sophisticated co-lens optical path is designed to assure the natural registration between the range image and 2-D image. Experimental tests for evaluation of the imaging system performance are described. It was found that the 3-D images can be acquired at a rate of 10 frames per second with a depth resolution better than 5mm in the range of 50 - 1000mm, which is sufficient for many practical applications, including the obstacle detection in robotics, machine automation, 3-D vision, virtual reality games and 3-D video.

  1. Wireless Remote Monitoring of Glucose Using a Functionalized ZnO Nanowire Arrays Based Sensor

    Directory of Open Access Journals (Sweden)

    Magnus Willander

    2011-08-01

    Full Text Available This paper presents a prototype wireless remote glucose monitoring system interfaced with a ZnO nanowire arrays-based glucose sensor, glucose oxidase enzyme immobilized onto ZnO nanowires in conjunction with a Nafion® membrane coating, which can be effectively applied for the monitoring of glucose levels in diabetics. Global System for Mobile Communications (GSM services like General Packet Radio Service (GPRS and Short Message Service (SMS have been proven to be logical and cost effective methods for gathering data from remote locations. A communication protocol that facilitates remote data collection using SMS has been utilized for monitoring a patient’s sugar levels. In this study, we demonstrate the remote monitoring of the glucose levels with existing GPRS/GSM network infra-structures using our proposed functionalized ZnO nanowire arrays sensors integrated with standard readily available mobile phones. The data can be used for centralized monitoring and other purposes. Such applications can reduce health care costs and allow caregivers to monitor and support to their patients remotely, especially those located in rural areas.

  2. ZnO nano-array-based EGFET biosensor for glucose detection

    Science.gov (United States)

    Qi, Junjie; Zhang, Huihui; Ji, Zhaoxia; Xu, Minxuan; Zhang, Yue

    2015-06-01

    Electrochemical biosensors are normally based on enzymatic catalysis of a reaction that produces or consumes electrons and the sensing membranes dominate the performance. In this work, ZnO nano-array-based EGFETs were fabricated for pH and glucose detection. The ZnO nano-arrays prepared via low-temperature hydrothermal method were well-aligned, with an average length of 2 μm and diameter of 100-150 nm, and have a typical hexagonal wurtzite structure. The sensor performed with a sensitivity of 45 mV/pH and response time of about 6-7 s from pH = 4-12. UV irradiation can improve the Vref response as a result of the formation of a depletion region at the surface of ZnO nanomaterials. Due to its high specific surface area, the ZnO nano-array EGFET sensor showed a sensitivity of -0.395 mV/μM to the glucose detection in a concentration range between 20 and 100 μM. These EGFET glucose biosensors demonstrate a low detectable concentration (20 μM) with good linearity, therefore may be used to detect glucose in saliva and tears at much lower concentrations than that in blood.

  3. High-resolution dynamic pressure sensor array based on piezo-phototronic effect tuned photoluminescence imaging.

    Science.gov (United States)

    Peng, Mingzeng; Li, Zhou; Liu, Caihong; Zheng, Qiang; Shi, Xieqing; Song, Ming; Zhang, Yang; Du, Shiyu; Zhai, Junyi; Wang, Zhong Lin

    2015-03-24

    A high-resolution dynamic tactile/pressure display is indispensable to the comprehensive perception of force/mechanical stimulations such as electronic skin, biomechanical imaging/analysis, or personalized signatures. Here, we present a dynamic pressure sensor array based on pressure/strain tuned photoluminescence imaging without the need for electricity. Each sensor is a nanopillar that consists of InGaN/GaN multiple quantum wells. Its photoluminescence intensity can be modulated dramatically and linearly by small strain (0-0.15%) owing to the piezo-phototronic effect. The sensor array has a high pixel density of 6350 dpi and exceptional small standard deviation of photoluminescence. High-quality tactile/pressure sensing distribution can be real-time recorded by parallel photoluminescence imaging without any cross-talk. The sensor array can be inexpensively fabricated over large areas by semiconductor product lines. The proposed dynamic all-optical pressure imaging with excellent resolution, high sensitivity, good uniformity, and ultrafast response time offers a suitable way for smart sensing, micro/nano-opto-electromechanical systems.

  4. Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

  5. Genomic profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization.

    Directory of Open Access Journals (Sweden)

    Shunichi Yoshioka

    Full Text Available We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC and their lymph node metastases, and to identify genomic copy number aberrations (CNAs related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs with their paired lymph node metastases (LNMs, and also those of LNMs with non-metastatic primary tumors (NMPTs. Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.

  6. Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins

    Directory of Open Access Journals (Sweden)

    Kahlem Pascal

    2006-06-01

    Full Text Available Abstract Background Trisomy of human chromosome 21 (Chr21 results in Down's syndrome, a complex developmental and neurodegenerative disease. Molecular analysis of Down's syndrome, however, poses a particular challenge, because the aneuploid region of Chr21 contains many genes of unknown function. Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. Following this idea, we used a transfected-cell array technique to perform a rapid and cost-effective analysis of the intracellular distribution of Chr 21 proteins. Results We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb to MCM3AP (46.6 Mb, with part of them expressed aberrantly in the Down's syndrome mouse model. Open reading frames of these genes were cloned into a mammalian expression vector with an amino-terminal His6 tag. All of the constructs were arrayed on glass slides and reverse transfected into HEK293T cells for protein expression. Co-localization detection using a set of organelle markers was carried out for each Chr21 protein. Here, we report the subcellular localization properties of 52 proteins. For 34 of these proteins, their localization is described for the first time. Furthermore, the alteration in cell morphology and growth as a result of protein over-expression for claudin-8 and claudin-14 genes has been characterized. Conclusion The cell array-based protein expression and detection approach is a cost-effective platform for large-scale functional analyses, including protein subcellular localization and cell phenotype screening. The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome.

  7. Array-based satellite phase bias sensing: theory and GPS/BeiDou/QZSS results

    International Nuclear Information System (INIS)

    Single-receiver integer ambiguity resolution (IAR) is a measurement concept that makes use of network-derived non-integer satellite phase biases (SPBs), among other corrections, to recover and resolve the integer ambiguities of the carrier-phase data of a single GNSS receiver. If it is realized, the very precise integer ambiguity-resolved carrier-phase data would then contribute to the estimation of the receiver’s position, thus making (near) real-time precise point positioning feasible. Proper definition and determination of the SPBs take a leading part in developing the idea of single-receiver IAR. In this contribution, the concept of array-based between-satellite single-differenced (SD) SPB determination is introduced, which is aimed to reduce the code-dominated precision of the SD-SPB corrections. The underlying model is realized by giving the role of the local reference network to an array of antennas, mounted on rigid platforms, that are separated by short distances so that the same ionospheric delay is assumed to be experienced by all the antennas. To that end, a closed-form expression of the array-aided SD-SPB corrections is presented, thereby proposing a simple strategy to compute the SD-SPBs. After resolving double-differenced ambiguities of the array’s data, the variance of the SD-SPB corrections is shown to be reduced by a factor equal to the number of antennas. This improvement in precision is also affirmed by numerical results of the three GNSSs GPS, BeiDou and QZSS. Experimental results demonstrate that the integer-recovered ambiguities converge to integers faster, upon increasing the number of antennas aiding the SD-SPB corrections. (paper)

  8. Replication fidelity improvement of PMMA microlens array based on weight evaluation and optimization

    Science.gov (United States)

    Jiang, Bing-yan; Shen, Long-jiang; Peng, Hua-jiang; Yin, Xiang-lin

    2007-12-01

    High replication fidelity is a prerequisite of high quality plastic microlens array in injection molding. But, there's not an economical and practical method to evaluate and improve the replication fidelity until now. Based on part weight evaluation and optimization, this paper presents a new method of replication fidelity improvement. Firstly, a simplified analysis model of PMMA micro columns arrays (5×16) with 200μm diameter was set up. And then, Flow (3D) module of Moldflow MPI6.0 based on Navier-Stokes equations was used to calculate the weight of the micro columns arrays in injection molding. The effects of processing parameters (melt temperature, mold temperature, injection time, packing pressure and packing time) on the part weight were investigated in the simulations. The simulation results showed that the mold temperature and the injection time have important effects on the filling of micro columns; the optimal mold temperature and injection time for better replication fidelity could be determined by the curves of mold temperature vs part weight and injection time vs part weight. At last, the effects of processing parameters on part weight of micro columns array were studied experimentally. The experimental results showed that the increase of melt temperature and mold temperature can make the packing pressure transfer to micro cavity more effectively through runner system, and increase the part weight. From the observation results of the image measuring apparatus, it was discovered that the higher the part weight, the better the filling of the microstructures. In conclusion, part weight can be used to evaluate the replication fidelity of micro-feature structured parts primarily; which is an economical and practical method to improve the replication fidelity of microlens arrays based on weight evaluation and optimization.

  9. Association between chromosomal aberration of COX8C and tethered spinal cord syndrome: array-based comparative genomic hybridization analysis.

    Science.gov (United States)

    Zhao, Qiu-Jiong; Bai, Shao-Cong; Cheng, Cheng; Tao, Ben-Zhang; Wang, Le-Kai; Liang, Shuang; Yin, Ling; Hang, Xing-Yi; Shang, Ai-Jia

    2016-08-01

    Copy number variations have been found in patients with neural tube abnormalities. In this study, we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents. Of eight copy number variations, four were non-polymorphic. These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes, and microcephaly. Gene function enrichment analysis revealed that COX8C, a gene associated with metabolic disorders of the nervous system, was located in the copy number variation region of Patient 1. Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome. Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease. PMID:27651783

  10. Association between chromosomal aberration of COX8C and tethered spinal cord syndrome: array-based comparative genomic hybridization analysis

    Directory of Open Access Journals (Sweden)

    Qiu-jiong Zhao

    2016-01-01

    Full Text Available Copy number variations have been found in patients with neural tube abnormalities. In this study, we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents. Of eight copy number variations, four were non-polymorphic. These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes, and microcephaly. Gene function enrichment analysis revealed that COX8C, a gene associated with metabolic disorders of the nervous system, was located in the copy number variation region of Patient 1. Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome. Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.

  11. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

    Science.gov (United States)

    Choi, Y-W; Bae, S M; Kim, Y-W; Lee, H N; Kim, Y W; Park, T C; Ro, D Y; Shin, J C; Shin, S J; Seo, J-S; Ahn, W S

    2007-01-01

    Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

  12. Normalization and centering of array-based heterologous genome hybridization based on divergent control probes

    Directory of Open Access Journals (Sweden)

    Wheeler David

    2011-05-01

    Full Text Available Abstract Background Hybridization of heterologous (non-specific nucleic acids onto arrays designed for model-organisms has been proposed as a viable genomic resource for estimating sequence variation and gene expression in non-model organisms. However, conventional methods of normalization that assume equivalent distributions (such as quantile normalization are inappropriate when applied to non-specific (heterologous hybridization. We propose an algorithm for normalizing and centering intensity data from heterologous hybridization that makes no prior assumptions of distribution, reduces the false appearance of homology, and provides a way for researchers to confirm whether heterologous hybridization is suitable. Results Data are normalized by adjusting for Gibbs free energy binding, and centered by adjusting for the median of a common set of control probes assumed to be equivalently dissimilar for all species. This procedure was compared to existing approaches and found to be as successful as Loess normalization at detecting sequence variations (deletions and even more successful than quantile normalization at reducing the accumulation of false positive probe matches between two related nematode species, Caenorhabditis elegans and C. briggsae. Despite the improvements, we still found that probe fluorescence intensity was too poorly correlated with sequence similarity to result in reliable detection of matching probe sequence. Conclusions Cross-species hybridizations can be a way to adapt genome-enabled tools for closely related non-model organisms, but data must be appropriately normalized and centered in a way that accommodates hybridization of nucleic acids with diverged sequence. For short, 25-mer probes, hybridization intensity alone may be insufficiently correlated with sequence similarity to allow reliable inference of homology at the probe level.

  13. Advantages of Array-Based Technologies for Pre-Emptive Pharmacogenomics Testing

    Directory of Open Access Journals (Sweden)

    Al Shahandeh

    2016-05-01

    Full Text Available As recognised by the National Institutes of Health (NIH Precision Medicine Initiative (PMI, microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in many clinical genetic contexts, particularly where novel mutations are involved. While these methods can be valuable for screening a restricted set of genes for known or novel mutations, implementation of whole genome sequencing in clinical practice continues to present challenges. Even very accurate high-throughput methods with small error rates can generate large numbers of false negative or false positive errors due to the high numbers of simultaneous readings. Additional validation is likely to be required for safe use of any such methods in clinical settings. Custom-designed arrays can offer advantages for screening for common, known mutations and, in this context, may currently be better suited for accredited, quality-controlled clinical genetic screening services, as illustrated by their successful application in several large-scale pre-emptive pharmacogenomics programs now underway. Excessive, inappropriate use of next-generation sequencing may waste scarce research funds and other resources. Microarrays presently remain the technology of choice in applications that require fast, cost-effective genome-wide screening of variants of known importance, particularly for large sample sizes. This commentary considers some of the applications where microarrays continue to offer advantages over next-generation sequencing technologies.

  14. Advantages of Array-Based Technologies for Pre-Emptive Pharmacogenomics Testing.

    Science.gov (United States)

    Shahandeh, Al; Johnstone, Daniel M; Atkins, Joshua R; Sontag, Jean-Marie; Heidari, Moones; Daneshi, Nilofar; Freeman-Acquah, Elvis; Milward, Elizabeth A

    2016-01-01

    As recognised by the National Institutes of Health (NIH) Precision Medicine Initiative (PMI), microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in many clinical genetic contexts, particularly where novel mutations are involved. While these methods can be valuable for screening a restricted set of genes for known or novel mutations, implementation of whole genome sequencing in clinical practice continues to present challenges. Even very accurate high-throughput methods with small error rates can generate large numbers of false negative or false positive errors due to the high numbers of simultaneous readings. Additional validation is likely to be required for safe use of any such methods in clinical settings. Custom-designed arrays can offer advantages for screening for common, known mutations and, in this context, may currently be better suited for accredited, quality-controlled clinical genetic screening services, as illustrated by their successful application in several large-scale pre-emptive pharmacogenomics programs now underway. Excessive, inappropriate use of next-generation sequencing may waste scarce research funds and other resources. Microarrays presently remain the technology of choice in applications that require fast, cost-effective genome-wide screening of variants of known importance, particularly for large sample sizes. This commentary considers some of the applications where microarrays continue to offer advantages over next-generation sequencing technologies. PMID:27600079

  15. Advantages of Array-Based Technologies for Pre-Emptive Pharmacogenomics Testing

    OpenAIRE

    Al Shahandeh; Johnstone, Daniel M.; Joshua R. Atkins; Jean-Marie Sontag; Moones Heidari; Nilofar Daneshi; Elvis Freeman-Acquah; Milward, Elizabeth A.

    2016-01-01

    As recognised by the National Institutes of Health (NIH) Precision Medicine Initiative (PMI), microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in many clinical genetic contexts, particularly where novel mutations are involved. While these methods can be valuable for screening a restricted set ...

  16. Whole genome sequencing in drug discovery research: a one fits all solution?

    OpenAIRE

    Marc Sultan

    2015-01-01

    With the recent availability of Illumina's HiSeq X ten sequencing platform, the cost of whole genome sequencing (WGS) has dropped to nearly $1,000 per genome. The affordability of WGS has now the potential of replacing other genotyping platforms such as whole exome sequencing (WES) and array based genotyping for (smaller) clinical study cohorts. In a recent pilot study, we compared the performance and genotyping quality of the HiSeq X WGS approach against WES and array based genotyping with r...

  17. Global mass spectrometry and transcriptomics array based drug profiling provides novel insight into glucosamine induced endoplasmic reticulum stress

    DEFF Research Database (Denmark)

    Carvalho, Ana Sofia; Ribeiro, Helena; Voabil, Paula;

    2014-01-01

    We investigated the molecular effects of glucosamine supplements, a popular and safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain, inflammation, and maintaining healthy joints. Numerous studies have reported an array of molecular effects after glucosamine treatment. We...... questioned whether the differences in the effects observed in previous studies were associated with the focus on a specific subproteome or with the use of specific cell lines or tissues. To address this question, global mass spectrometry- and transcription array-based glucosamine drug profiling was performed...... mainly observed glucosamine induced O-GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global and local changes in acetylation, methylation, and phosphorylation. For example, our data provides two additional examples of "yin-yang" between phosphorylation and O...

  18. Association between chromosomal aberration of COX8C and tethered spinal cord syndrome:array-based comparative genomic hybridization analysis

    Institute of Scientific and Technical Information of China (English)

    Qiu-jiong Zhao; Shao-cong Bai; Cheng Cheng; Ben-zhang Tao; Le-kai Wang; Shuang Liang; Ling Yin; Xing-yi Hang; Ai-jia Shang

    2016-01-01

    Copy number variations have been found in patients with neural tube abnormalities. In this study, we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents. Of eight copy number variations, four were non-polymorphic. These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes, and microcephaly. Gene function enrichment analysis revealed that COX8C, a gene associated with metabolic disorders of the nervous system, was located in the copy number variation region of Patient 1. Our results indicate that ar-ray-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome. Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.

  19. A genome-wide analysis of array-based comparative genomic hybridization (CGH) data to detect intra-species variations and evolutionary relationships.

    Science.gov (United States)

    Array-based comparative genomics hybridization (CGH) has gained prevalence as a technique of choice for the detection of structural variations in the genome. In this study, we propose a novel genome-wide method of classification using CGH data, in order to reveal putative phylogenetic relationships ...

  20. Design of thin-film filters for resolution improvements in filter-array based spectrometers using DSP

    Science.gov (United States)

    Lee, Woong-Bi; Kim, Cheolsun; Ju, Gun Wu; Lee, Yong Tak; Lee, Heung-No

    2016-05-01

    Miniature spectrometers have been widely developed in various academic and industrial applications such as bio-medical, chemical and environmental engineering. As a family of spectrometers, optical filter-array based spectrometers fabricated using CMOS or Nano technology provide miniaturization, superior portability and cost effectiveness. In filterarray based spectrometers, the resolution which represents the ability how closely resolve two neighboring spectra, depends on the number of filters and the characteristics of the transmission functions (TFs) of the filters. In practice, due to the small-size and low-cost fabrication, the number of filters is limited and the shape of the TF of each filter is nonideal. As a development of modern digital signal processing (DSP), the spectrometers are equipped with DSP algorithms not only to alleviate distortions due to unexpected noise or interferences among filters but also reconstruct the original signal spectrum. For a high-resolution spectrum reconstruction by the DSP, the TFs of the filters need to be sufficiently uncorrelated with each other. In this paper, we present a design of optical thin-film filters which have the uncorrelated TFs. Each filter consists of multiple layers of high- and low-refractive index materials deposited on a substrate. The proposed design helps the DSP algorithm to improve resolution with a small number of filters. We demonstrate that a resolution of 5 nm within a range from 500 nm to 1100 nm can be achieved with only 64 filters.

  1. Two Dimensional Array Based Overlay Network for Balancing Load of Peer-to-Peer Live Video Streaming

    International Nuclear Information System (INIS)

    The live video data is streaming usually in a tree-based overlay network or in a mesh-based overlay network. In case of departure of a peer with additional upload bandwidth, the overlay network becomes very vulnerable to churn. In this paper, a two dimensional array-based overlay network is proposed for streaming the live video stream data. As there is always a peer or a live video streaming server to upload the live video stream data, so the overlay network is very stable and very robust to churn. Peers are placed according to their upload and download bandwidth, which enhances the balance of load and performance. The overlay network utilizes the additional upload bandwidth of peers to minimize chunk delivery delay and to maximize balance of load. The procedure, which is used for distributing the additional upload bandwidth of the peers, distributes the additional upload bandwidth to the heterogeneous strength peers in a fair treat distribution approach and to the homogeneous strength peers in a uniform distribution approach. The proposed overlay network has been simulated by Qualnet from Scalable Network Technologies and results are presented in this paper

  2. Controlling system for smart hyper-spectral imaging array based on liquid-crystal Fabry-Perot device

    Science.gov (United States)

    Jiang, Xue; Chen, Xin; Rong, Xin; Liu, Kan; Zhang, Xinyu; Ji, An; Xie, Changsheng

    2011-11-01

    A research for developing a kind of smart spectral imaging detection technique based on the electrically tunable liquidcrystal (LC) FP structure is launched. It has some advantages of low cost, highly compact integration, perfuming wavelength selection without moving any micro-mirror of FP device, and the higher reliability and stability. The controlling system for hyper-spectral imaging array based on LC-FP device includes mainly a MSP430F5438 as its core. Considering the characteristics of LC-FP device, the controlling system can provide a driving signal of 1-10 kHz and 0- 30Vrms for the device in a static driving mode. This paper introduces the hardware designing of the control system in detail. It presents an overall hardware solutions including: (1) the MSP430 controlling circuit, and (2) the operational amplifier circuit, and (3) the power supply circuit, and (4) the AD conversion circuit. The techniques for the realization of special high speed digital circuits, which is necessary for the PCB employed, is also discussed.

  3. Design of Smart Ion-Selective Electrode Arrays Based on Source Separation through Nonlinear Independent Component Analysis

    Directory of Open Access Journals (Sweden)

    Duarte L.T.

    2014-03-01

    Full Text Available The development of chemical sensor arrays based on Blind Source Separation (BSS provides a promising solution to overcome the interference problem associated with Ion-Selective Electrodes (ISE. The main motivation behind this new approach is to ease the time-demanding calibration stage. While the first works on this problem only considered the case in which the ions under analysis have equal valences, the present work aims at developing a BSS technique that works when the ions have different charges. In this situation, the resulting mixing model belongs to a particular class of nonlinear systems that have never been studied in the BSS literature. In order to tackle this sort of mixing process, we adopted a recurrent network as separating system. Moreover, concerning the BSS learning strategy, we develop a mutual information minimization approach based on the notion of the differential of the mutual information. The method works requires a batch operation, and, thus, can be used to perform off-line analysis. The validity of our approach is supported by experiments where the mixing model parameters were extracted from actual data.

  4. Simultaneous determination of pH, urea, acetylcholine and heavy metals using array-based enzymatic optical biosensor.

    Science.gov (United States)

    Tsai, Hsiao-chung; Doong, Ruey-an

    2005-03-15

    An array-based optical biosensor for the simultaneous analysis of multiple samples in the presence of unrelated multi-analytes was fabricated. Urease and acetylcholinesterase (AChE) were used as model enzymes and were co-entrapped with the sensing probe, FITC-dextran, in the sol-gel matrix to measure pH, urea, acetylcholine (ACh) and heavy metals (enzyme inhibitors). Environmental and biological samples spiked with metal ions were also used to evaluate the application of the array biosensor to real samples. The biosensor exhibited high specificity in identifying multiple analytes. No obvious cross-interference was observed when a 50-spot array biosensor was used for simultaneous analysis of multiple samples in the presence of multiple analytes. The sensing system can determine pH over a dynamic range from 4 to 8.5. The limits of detection (LODs) of 2.5-50 microM with a dynamic range of 2-3 orders of magnitude for urea and ACh measurements were obtained. Moreover, the urease-encapsulated array biosensor was used to detect heavy metals. The analytical ranges of Cd(II), Cu(II), and Hg(II) were between 10 nM and 100 mM. When real samples were spiked with heavy metals, the array biosensor also exhibited potential effectiveness in screening enzyme inhibitors.

  5. Use Array-basedCGH technology for fetal chromosomal anomalies syndrome diagnosis%运用Array-basedCGH技术进行胎儿染色体异常综合征的诊断研究

    Institute of Scientific and Technical Information of China (English)

    易广才; 童华

    2011-01-01

    Objective: To use high - resolution Array - basedCCH (aCCH) technology for chromosomes of the small mutation (missing or amplified) to cause fetal malformation syndrome, and its formation mechanism. Method:use of a Agilent4 × 44K CGH chip to detect the normal samples and specimens from the three malformation of Fetal DNA ( M1:normalfetal; M2:abdominal wall defect fetal; M3: single umbilical artery with congenital heart disease, double outlet right ventricle, Ventricular septal defect and mitral atresia pulmonary artery stenosis; M4: karyorype 47, +21, congenital heart disease, Ventricular septal defect, fetus side lateral ventricle broadening, the fetus is small) by the comparative genomic hybridization. Results: M2/MI; high copy (amplification) 560 of fragments of DNA (genes), low copy or missing 1504 of DNA (genes) of the fragment; M3/M1: high copy 511 fragments of DNA (genes) , low copy or missing 1142 articles DNA (genes) of the fragment; M4/M1: section 3034 high copy DNA (genes) of the fragment, low copy or missing section 3571 DNA (genes) fragment. Conclusion; the small mutation of chromosome fragments is one of the main causes which lead to fetal malformation syndrome, the high - resolution aCCH technology is able to be used for quickly and accurately on its testing and prenatal diagnosis.%目的,运用高分辨率的Array-basedCGH(aCGH)技术研究染色体的微小变异(缺失或扩增)引起的胎儿畸形综合征,及其形成机理.方法 采用Agilent4×44K CGH,芯片对一个正常标本和三个畸形胎儿标本DNA(MI 正常胎儿;M2腹壁缺损;M3单脐动脉合并先天性心脏病,右室双出口,空间隔缺损,肺动脉狭窄,二尖瓣闭锁;M4染色体核型47,+21,先天性心脏病,室间隔缺损,胎儿一侧脑室增宽,胎儿偏小)进行比较基因组杂交捡洲.结果 M2/Ml:高拷贝(扩增)560条DNA(基因)片段,低拷贝或缺失1504条DNA(基因)片断;M3/M1:高拷贝511条DNA(基因)片段,低拷贝或缺失1142

  6. ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing.

    Science.gov (United States)

    Moncini, S; Bedeschi, M F; Castronovo, P; Crippa, M; Calvello, M; Garghentino, R R; Scuvera, G; Finelli, P; Venturin, M

    2013-12-01

    In this report, we describe two adult brothers affected by moderate non-specific intellectual disability (ID). They showed minor facial anomalies, not clearly ascribable to any specific syndromic patterns, microcephaly, brachydactyly and broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1 analysis were normal in both cases. We performed array-CGH analysis that revealed no copy-number variations potentially associated with ID. Subsequent exome sequence analysis allowed the identification of the ATRX c.109C>T (p.R37X) mutation in both the affected brothers. Sanger sequencing confirmed the presence of the mutation in the brothers and showed that the mother is a healthy carrier. Mutations in the ATRX gene cause the X-linked alpha thalassemia/mental retardation (ATR-X) syndrome (MIM #301040), a severe clinical condition usually associated with profound ID, facial dysmorphism and alpha thalassemia. However, the syndrome is clinically heterogeneous and some mutations, including the c.109C>T, are associated with a broad phenotypic spectrum, with patients displaying a less severe phenotype with only mild-moderate ID. In the case presented here, exome sequencing provided an effective strategy to achieve the molecular diagnosis of ATR-X syndrome, which otherwise would have been difficult to consider due to the mild non-specific phenotype and the absence of a family history with typical severe cases. PMID:25606380

  7. An expandable crosstalk reduction method for inline fiber Fabry–Pérot sensor array based on fiber Bragg gratings

    Science.gov (United States)

    Jiang, Peng; Ma, Lina; Hu, Zhengliang; Hu, Yongming

    2016-07-01

    The inline time division multiplexing (TDM) fiber Fabry–Pérot (FFP) sensor array based on fiber Bragg gratings (FBGs) is attractive for many applications. But the intrinsic multi-reflection (MR) induced crosstalk limits applications especially those needing high resolution. In this paper we proposed an expandable method for MR-induced crosstalk reduction. The method is based on complexing-exponent synthesis using the phase-generated carrier (PGC) scheme and the special common character of the impulse responses. The method could promote demodulation stability simultaneously with the reduction of MR-induced crosstalk. A polarization-maintaining 3-TDM experimental system with an FBG reflectivity of about 5 % was set up to validate the method. The experimental results showed that crosstalk reduction of 13 dB and 15 dB was achieved for sensor 2 and sensor 3 respectively when a signal was applied to the first sensor and crosstalk reduction of 8 dB was achieved for sensor 3 when a signal was applied to sensor 2. The demodulation stability of the applied signal was promoted as well. The standard deviations of the amplitude distributions of the demodulated signals were reduced from 0.0046 to 0.0021 for sensor 2 and from 0.0114 to 0.0044 for sensor 3. Because of the convenience of the linear operation of the complexing-exponent and according to the common character of the impulse response we found, the method can be effectively extended to the array with more TDM channels if the impulse response of the inline FFP sensor array with more TDM channels is derived. It offers potential to develop a low-crosstalk inline FFP sensor array using the PGC interrogation technique with relatively high reflectivity FBGs which can guarantee enough light power received by the photo-detector.

  8. Multi-view Hilbert transformation in full-ring-transducer-array based photoacoustic computed tomography (Conference Presentation)

    Science.gov (United States)

    Li, Lei; Li, Guo; Zhu, Liren; Xia, Jun; Wang, Lihong V.

    2016-03-01

    Photoacoustic tomography (PAT) exploits optical contrast and ultrasonic detection principles to form images of absorbed optical energy density within tissue. Based on the photoacoustic effect, PAT directly and quantitatively measures specific optical absorption. A full-ring ultrasonic transducer array based photoacoustic computed tomography (PACT) system was recently developed for small animal whole-body imaging with a full-view detection angle and high in-plane resolution (100 µm). However, due to the band-pass frequency response of the piezoelectric transducer elements, the reconstructed images present bipolar (both positive and negative) pixel values, which is artificial and counterintuitive for physicians and biologists seeking to interpret the image. Moreover, bipolar pixel values hinder quantification of physiological parameters, such as oxygen saturation and blood flow speed. Unipolar images can be obtained by deconvolving the raw channel data with the transducer's electrical impulse response and applying non-negativity during iteration, but this process requires complex transducer modeling and time-consuming computation. Here, we present a multi-view Hilbert transformation method to recover the unipolar initial pressure for full-ring PACT. Multi-view Hilbert transformation along the acoustic wave propagation direction minimizes reconstruction artifacts during envelope extraction and maintains the signal-to-noise ratio of the reconstructed images. The in-plane isotropic spatial resolution of this method was quantified to 168 μm within a 20 × 20 mm2 field of view. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with ex-vivo mouse brain structural imaging and in-vivo mouse wholebody imaging.

  9. A PMT array based diagnostics to measure spatial and temporal behavior of Hα emission from Aditya Tokamak

    International Nuclear Information System (INIS)

    The detailed information on fast changing plasma behavior during the breakdown and start-up phase of a tokamak plasma is very essential for achieving good plasma current flat-top region. A Photo multiplier tube (PMT) array based spectroscopic diagnostics has been designed and developed to measure the spatial profile of Hα, Hβ and C III radiation from Aditya tokamak plasma with very fast time response ∼100 μs and also with a good spatial resolution ∼ 3.5 cm at plasma mid plane. The system has been installed on Aditya tokamak to study the breakdown location by monitoring the Hα emission during the plasma formation stage. Two 8 channels linear multi anode PMT arrays with high gains, wide dynamic range and low noise are used as detector. The module comes with built-in high voltage power supply and built-in amplifier. Collimated light has been collected from the plasma along 16 line-of-sights passing through the entire plasma poloidal cross section from the top port of Aditya tokamak and transferred to the PMT array using 1 mm core diameter optical fibers. The Hα spectra is obtained using 8 miniature interference filters (IF) centered at 656.3 nm placed in front of the PMT array. For the 2nd PMT array, another arrangement for wavelength selection is developed using bigger 2.5” IF, where lights from multiple fibers can be passed through for wavelength selection simultaneously. The spatial and temporal profiles of Hα emissions have been studied during the formation phase of Aditya tokamak plasma by changing the vertical field and delay of its application with respect to loop voltage. It was found that the plasma initiates in the high field side of tokamak most of the times. The details on experimental set-up and the results of the experiments will be discussed in this presentation. (author)

  10. Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas

    Directory of Open Access Journals (Sweden)

    Berg Marianne

    2006-09-01

    Full Text Available Abstract Background In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches. Results Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss. Conclusion We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation

  11. Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

    1996-08-09

    Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

  12. Fmr1 KO and Fenobam Treatment Differentially Impact Distinct Synapse Populations of Mouse Neocortex

    OpenAIRE

    Wang, Gordon X.; Smith, Stephen J.; MOURRAIN, PHILIPPE

    2014-01-01

    Cognitive deficits in fragile X syndrome (FXS) are attributed to molecular abnormalities of the brain’s vast and heterogeneous synapse populations. Unfortunately, the density of synapses coupled with their molecular heterogeneity presents formidable challenges in understanding the specific contribution of synapse changes in FXS. We demonstrate powerful new methods for the large-scale molecular analysis of individual synapses that allow quantification of numerous specific changes in synapse po...

  13. Fmr1 KO Mice as a Possible Model of Autistic Features

    OpenAIRE

    Maude Bernardet; Crusio, Wim E.

    2006-01-01

    Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level ...

  14. Convergence of hippocampal pathophysiology in Syngap+/- and Fmr1-/y mice

    OpenAIRE

    Barnes, Stephanie; Wijetunge, Lasani; Jackson, Adam D.; Katsanevaki, Danai; Osterweil, Emily; Komiyama, Noboru H.; Grant, Seth; Bear, Mark F.; Nägerl, U. Valentin; Kind, Peter; Wyllie, David

    2015-01-01

    Previous studies have hypothesized that diverse genetic causes of intellectual disability (ID) and autism spectrum disorders (ASDs) converge on common cellular pathways. Testing this hypothesis requires detailed phenotypic analyses of animal models with genetic mutations that accurately reflect those seen in the human condition (i.e., have structural validity) and which produce phenotypes that mirror ID/ASDs (i.e., have face validity). We show that SynGAP haploinsufficiency, which causes ID w...

  15. Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors

    Directory of Open Access Journals (Sweden)

    Kanamori Masahiko

    2012-11-01

    Full Text Available Abstract Background The genetic pathways of aggressive changes of bone tumors are still poorly understood. It is very important to analyze DNA copy number alterations (DCNAs, to identify the molecular events in the step of progression to the aggressive change of bone tissue. Methods Genome-wide array-based comparative genomic hybridization (array CGH was used to investigate DCNAs of 14 samples from 13 aggressive bone tumors, such as giant cell tumors (GCTs and osteosarcoma (OS, etc. Results Primary aggressive bone tumors had copy number gains of 17.8±12.7% in the genome, and losses of 17.3±11.4% in 287 target clones (threshold for each DCNA: ≦085, 1.15≦. Genetic unstable cases, which were defined by the total DCNAs aberration ≧30%, were identified in 9 of 13 patients (3 of 7 GCTs and all malignant tumors. High-level amplification of TGFβ2, CCND3, WI-6509, SHGC-5557, TCL1A, CREBBP, HIC1, THRA, AFM217YD10, LAMA3, RUNX1 and D22S543, were commonly observed in aggressive bone tumors. On the other hand, NRAS, D2S447, RAF1, ROBO1, MYB, MOS, FGFR2, HRAS, D13S319, D13S327, D18S552, YES1 and DCC, were commonly low. We compared genetic instability between a primary OS and its metastatic site in Case #13. Metastatic lesion showed increased 9 DCNAs of remarkable change (m/p ratio ≧1.3 folds, compared to a primary lesion. D1S214, D1S1635, EXT1, AFM137XA11, 8 M16/SP6, CCND2, IGH, 282 M15/SP6, HIC1 and LAMA3, were overexpressed. We gave attention to HIC1 (17p13.3, which was common high amplification in this series. Conclusion Our results may provide several entry points for the identification of candidate genes associated with aggressive change of bone tumors. Especially, the locus 17p11-13 including HIC1 close to p53 was common high amplification in this series and review of the literature.

  16. Automatic sequences

    CERN Document Server

    Haeseler, Friedrich

    2003-01-01

    Automatic sequences are sequences which are produced by a finite automaton. Although they are not random they may look as being random. They are complicated, in the sense of not being not ultimately periodic, they may look rather complicated, in the sense that it may not be easy to name the rule by which the sequence is generated, however there exists a rule which generates the sequence. The concept automatic sequences has special applications in algebra, number theory, finite automata and formal languages, combinatorics on words. The text deals with different aspects of automatic sequences, in particular:· a general introduction to automatic sequences· the basic (combinatorial) properties of automatic sequences· the algebraic approach to automatic sequences· geometric objects related to automatic sequences.

  17. Field programmable gate array-based real-time optical Doppler tomography system for in vivo imaging of cardiac dynamics in the chick embryo

    DEFF Research Database (Denmark)

    Thrane, Lars; Larsen, Henning Engelbrecht; Norozi, Kambiz;

    2009-01-01

    We demonstrate a field programmable gate-array-based real-time optical Doppler tomography system. A complex-valued bandpass filter is used for the first time in optical coherence tomography signal processing to create the analytic signal. This method simplifies the filter design, and allows...... digital computer (CORDIC) algorithm, which is an efficient algorithm that maps well to the field programmable gate array. Flow phantom experiments, and the use of this system for in vivo imaging of cardiac dynamics in the chick embryo, are presented. We demonstrate the visualization of blood flow...

  18. Control of Metal Arrays Based on Heterometallics Masquerading in Heterochiral Aggregations of Chiral Clothespin-Shaped Complexes.

    Science.gov (United States)

    Naito, Masaya; Inoue, Ryo; Iida, Masayuki; Kuwajima, Yuuki; Kawamorita, Soichiro; Komiya, Naruyoshi; Naota, Takeshi

    2015-09-01

    Heterometal arrays in molecular aggregations were obtained by the spontaneous and ultrasound-induced gelation of organic liquids containing the chiral, clothespin-shaped trans-bis(salicylaldiminato) d8 transition-metal complexes 1. Heterometallic mixtures of complexes 1 a (Pd) and 1 b (Pt) underwent strict heterochiral aggregation entirely due to the organic shell structure of the clothespin shape, with no effect of the metal cores. This phenomenon provides an unprecedented means of generating highly controlled heterometallic arrangements such as alternating sequences [(+)-Pd(-)-Pt(+)-Pd(-)-Pt⋅⋅⋅] as well as a variety of single metal-enriched arrays (e.g., [(+)-Pt(-)-Pd(+)-Pd(-)-Pd(+)-Pd(-)-Pd⋅⋅⋅] and [(+)-Pd(-)-Pt(+)-Pt(-)-Pt(+)-Pt(-)-Pt⋅⋅⋅]) upon the introduction of an optically active masquerading unit with a different metal core in the heterochiral single-metal sequence. The present method can be applied to form various new aggregates with optically active Pd and Pt units, to allow 1) tuning of the gelation ultrasound sensitivity based on the different hearing abilities of the metal units; 2) aggregation-induced chirality transfer between heterometallic species; and 3) aggregation-induced chirality enhancement. A mechanistic rationale is proposed for these molecular aggregations based on the molecular structures of the units and the morphologies of the aggregates. PMID:26212577

  19. A Mismatch EndoNuclease Array-Based Methodology (MENA for Identifying Known SNPs or Novel Point Mutations

    Directory of Open Access Journals (Sweden)

    Josep M. Comeron

    2016-04-01

    Full Text Available Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs, point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1 genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2 identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3 screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation.

  20. Array-based comparative genomic hybridization facilitates identification of breakpoints of a novel der(1)t(1;18)(p36.3;q23)dn in a child presenting with mental retardation.

    Science.gov (United States)

    Lennon, P A; Cooper, M L; Curtis, M A; Lim, C; Ou, Z; Patel, A; Cheung, S W; Bacino, C A

    2006-06-01

    Monosomy of distal 1p36 represents the most common terminal deletion in humans and results in one of the most frequently diagnosed mental retardation syndromes. This deletion is considered a contiguous gene deletion syndrome, and has been shown to vary in deletion sizes that contribute to the spectrum of phenotypic anomalies seen in patients with monosomy 1p36. We report on an 8-year-old female with characteristics of the monosomy 1p36 syndrome who demonstrated a novel der(1)t(1;18)(p36.3;q23). Initial G-banded karyotype analysis revealed a deleted chromosome 1, with a breakpoint within 1p36.3. Subsequent FISH and array-based comparative genomic hybridization not only confirmed and partially characterized the deletion of chromosome 1p36.3, but also uncovered distal trisomy for 18q23. In this patient, the duplicated 18q23 is translocated onto the deleted 1p36.3 region, suggesting telomere capture. Molecular characterization of this novel der(1)t(1;18)(p36.3;q23), guided by our clinical array-comparative genomic hybridization, demonstrated a 3.2 Mb terminal deletion of chromosome 1p36.3 and a 200 kb duplication of 18q23 onto the deleted 1p36.3, presumably stabilizing the deleted chromosome 1. DNA sequence analysis around the breakpoints demonstrated no homology, and therefore this telomere capture of distal 18q is apparently the result of a non-homologous recombination. Partial trisomy for 18q23 has not been previously reported. The importance of mapping the breakpoints of all balanced and unbalanced translocations found in the clinical laboratory, when phenotypic abnormalities are found, is discussed.

  1. Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity

    Directory of Open Access Journals (Sweden)

    Zadeh Soheila

    2010-07-01

    Full Text Available Abstract Background HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin, remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC and fluorescence in situ hybridization (FISH are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. Methods In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. Results Array-based comparative genomic hybridization (array CGH analysis of chromosome 17 resolved HER2 gene status in [20/20] (100% of cases and revealed additional chromosome 17 copy number changes in [18/20] (90% of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. Conclusions These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17

  2. Genome Sequencing

    DEFF Research Database (Denmark)

    Sato, Shusei; Andersen, Stig Uggerhøj

    2014-01-01

    The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based on transcr......The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...

  3. Evaluation of an array-based method for human papillomavirus detection and genotyping in comparison with conventional methods used in cervical cancer screening.

    Science.gov (United States)

    García-Sierra, Nerea; Martró, Elisa; Castellà, Eva; Llatjós, Mariona; Tarrats, Antoni; Bascuñana, Elisabet; Díaz, Rosana; Carrasco, María; Sirera, Guillem; Matas, Lurdes; Ausina, Vicente

    2009-07-01

    Cervical cancer is the second-most prevalent cancer in young women around the world. Infection with human papillomavirus (HPV), especially high-risk HPV types (HR-HPV), is necessary for the development of this cancer. HPV-DNA detection is increasingly being used in cervical cancer screening programs, together with the Papanicolau smear test. We evaluated the usefulness of introducing this new array-based HPV genotyping method (i.e., Clinical Arrays Papillomavirus Humano) in the cervical cancer screening algorithm in our center. The results obtained using this method were compared to those obtained by the hybrid capture II high-risk HPV DNA test (HC-II) and Papanicolau in a selected group of 408 women. The array-based assay was performed in women that were HC-II positive or presented cytological alterations. Among 246 array-positive patients, 123 (50%) presented infection with >or=2 types, and HR-HPV types were detected in 206 (83.7%), mainly HPV-16 (24.0%). Up to 132 (33.2%) specimens were classified as ASCUS (for atypical squamous cells of undetermined significance), and only 48 (36.4%) of them were HPV-DNA positive by either assay; however, 78.7% of these cases were caused by HR-HPV types. The agreement between both HPV-DNA detection techniques was fairly good (n = 367). Screening with Papanicolau smear and HC-II tests, followed by HPV detection and genotyping, provided an optimal identification of women at risk for the development of cervical cancer. Furthermore, with the identification of specific genotypes, either in single or multiple infections, a better prediction of disease progression was achieved. The array method also made allowed us to determine the possible contribution of the available vaccines in our setting.

  4. Sequence assembly

    DEFF Research Database (Denmark)

    Scheibye-Alsing, Karsten; Hoffmann, S.; Frankel, Annett Maria;

    2009-01-01

    and plays an important role in processing the information generated by these methods. Here, we provide a comprehensive overview of the current publicly available sequence assembly programs. We describe the basic principles of computational assembly along with the main concerns, such as repetitive sequences...

  5. Research on group analogy state evaluation method of photovoltaic array based on the vertical and horizontal dimensions%基于纵横维度的光伏阵列群体类比状态评估方法研究

    Institute of Scientific and Technical Information of China (English)

    王景丹; 龚晓伟; 霍富强; 牛高远; 葛琪; 王留送; 苏战辉

    2016-01-01

    In photovoltaic array state estimation, the dimensionality of indicator selected is narrow and will lead to big error in the judgment of abnormal state and reason, therefore, this paper proposes one kind of state evaluation method for PV arrays based on the vertical and horizontal dimensions. The method divides the characteristics parameters of PV array in accordance with hierarchy structure and defines time sequence nodes and monitoring points of PV array. From the horizontal angle, it constructs evaluation model of running status of PV array based on the evaluation scheme of positive and negative ideal point, and then obtains the best distance degrees of an indicator in different PV array unit. Afterwards, it uses the Gauss curve fitting to structure the function relations of time between the best distance degrees and evaluation index from the vertical angle, and then acquires the group of running state curve of PV arrays. Thereby, it effectively identifies the abnormal array and relevant indicators, gives warning timely, and provides decision basis for operation and maintenance of PV array. It verifies the assessment method combined with solar data of practical engineering, experimental results show that the method can accurately reflect the actual running condition of PV array, and has a certain application value.%针对光伏阵列状态评估中指标选取维度较窄,异常状态及原因判定误差较大的问题,提出一种基于纵横维度的光伏阵列群体类比状态评估方法。将光伏阵列状态评估特征参量按照递阶层次结构划分,定义时间序列节点和光伏阵列监测点。从横向角度构造基于正负理想点评估法的光伏阵列运行状态评估模型,得出某项评估指标在不同光伏阵列单元中的最佳距离度。从纵向角度利用高斯曲线拟合法构造最佳距离度与评估指标的时间函数关系,得出光伏阵列群体运行状态曲线。从而准确识别异常阵列

  6. Dna Sequencing

    Science.gov (United States)

    Tabor, Stanley; Richardson, Charles C.

    1995-04-25

    A method for sequencing a strand of DNA, including the steps off: providing the strand of DNA; annealing the strand with a primer able to hybridize to the strand to give an annealed mixture; incubating the mixture with four deoxyribonucleoside triphosphates, a DNA polymerase, and at least three deoxyribonucleoside triphosphates in different amounts, under conditions in favoring primer extension to form nucleic acid fragments complementory to the DNA to be sequenced; labelling the nucleic and fragments; separating them and determining the position of the deoxyribonucleoside triphosphates by differences in the intensity of the labels, thereby to determine the DNA sequence.

  7. Time-dependent c-Myc transactomes mapped by Array-based nuclear run-on reveal transcriptional modules in human B cells.

    Directory of Open Access Journals (Sweden)

    Jinshui Fan

    Full Text Available BACKGROUND: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome". METHODOLOGY/PRINCIPAL FINDINGS: We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs. CONCLUSIONS/SIGNIFICANCE: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

  8. Main: Sequences [KOME

    Lifescience Database Archive (English)

    Full Text Available Sequences Nucleotide Sequence Nucleotide sequence of full length cDNA (trimmed sequence) kome_ine_full_seque...nce_db.fasta.zip kome_ine_full_sequence_db.zip kome_ine_full_sequence_db ...

  9. Array-based photoacoustic spectroscopy

    Science.gov (United States)

    Autrey, S. Thomas; Posakony, Gerald J.; Chen, Yu

    2005-03-22

    Methods and apparatus for simultaneous or sequential, rapid analysis of multiple samples by photoacoustic spectroscopy are disclosed. A photoacoustic spectroscopy sample array including a body having at least three recesses or affinity masses connected thereto is used in conjunction with a photoacoustic spectroscopy system. At least one acoustic detector is positioned near the recesses or affinity masses for detection of acoustic waves emitted from species of interest within the recesses or affinity masses.

  10. [Sequencing babies?].

    Science.gov (United States)

    Jordan, Bertrand

    2015-10-01

    An extension of newborn screening to genome sequencing is now feasible but raises a number of scientific, organisational and ethical issues. This is being explored in discussions and in several funded trials, in order to maximize benefits and avoid some identified risks. As some companies are already offering such a service, this is quite an urgent matter. PMID:26481033

  11. Self-aligned tip deinsulation of atomic layer deposited Al2O3 and parylene C coated Utah electrode array based neural interfaces

    International Nuclear Information System (INIS)

    The recently developed alumina and parylene C bilayer encapsulation improved the lifetime of neural interfaces. Tip deinsulation of Utah electrode array based neural interfaces is challenging due to the complex 3D geometries and high aspect ratios of the devices. A three-step self-aligned process was developed for tip deinsulation of bilayer encapsulated arrays. The deinsulation process utilizes laser ablation to remove parylene C, O2 reactive ion etching to remove carbon and parylene residues, and buffered oxide etch to remove alumina deposited by atomic layer deposition, and expose the IrOx tip metallization. The deinsulated iridium oxide area was characterized by scanning electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy to determine the morphology, surface morphology, composition, and electrical properties of the deposited layers and deinsulated tips. The alumina layer was found to prevent the formation of micro cracks on iridium oxide during the laser ablation process, which has been previously reported as a challenge for laser deinsulation of parylene films. The charge injection capacity, charge storage capacity, and impedance of deinsulated iridium oxide were characterized to determine the deinsulation efficacy compared to parylene-only insulation. Deinsulated iridium oxide with bilayer encapsulation had higher charge injection capacity (240 versus 320 nC) and similar electrochemical impedance (2.5 versus 2.5 kΩ) compared to deinsulated iridium oxide with only parylene coating for an area of 2 × 10−4 cm2. Tip impedances were in the range of 20–50 kΩ, with a median of 32 kΩ and a standard deviation of 30 kΩ, showing the effectiveness of the self-aligned deinsulation process for alumina and parylene C bilayer encapsulation. The relatively uniform tip impedance values demonstrated the consistency of tip exposures. (paper)

  12. Reduction in the amount of crosstalk with reduced number of focal spot rows in a grating array based zonal wavefront sensor

    Science.gov (United States)

    Pathak, Biswajit; Boruah, Bosanta R.

    2015-06-01

    The Shack Hartmann wavefront sensor (SHWS), named after Johannes Franz Hartmann and Roland Shack, is one of the most well-known and popularly used optical wavefront sensor that finds numerous applications in various optical technologies. SHWS samples the incident wavefront by means of a lenslet array to produce an array of regular 2D array of focal spots on the detector plane of a digital camera, in the case of an unaberrated plane wavefront. If the incident wavefront is aberrated or deviates from a plane wavefront, the respective focal spots get shifted from its reference positions corresponding to the regular grid. If the incident wavefront aberration increases or has a very large curvature, the focal spot of one lenslet may enter the detector sub-aperture of the nearby lenslet. Thus, the SHWS has a limited dynamic range that is restricted to aberrations which do not allow the sub-images to be displaced out from their own detector sub-array. It makes the SHWS sensitive to cross-talk when higher order aberrations are present thereby unavoidably a ecting the wavefront estimation process. The array of tiny lenses of the SHWS can be replaced by an array of gratings followed by a focusing lens, generating an array of focal spots which is similar to that as in the case of a SHWS. In this paper, the spatial frequency of such a grating array based zonal wavefront sensor is configured to produce lesser number of rows of focal spots. The reduction in the number of focal spot rows reduces the amount of cross talk in the vertical direction. In this paper we present preliminary experimental results to demonstrate the above stated reduction in crosstalk.

  13. Genomic Variance Estimation Based on Genotyping-by-Sequencing with Different Coverage in Perennial Ryegrass

    DEFF Research Database (Denmark)

    Ashraf, Bilal; Fé, Dario; Jensen, Just;

    2014-01-01

    Advancement in next generation sequencing (NGS) technologies has significantly decreased the cost of DNA sequencing enabling increased use of genotyping by sequencing (GBS) in several plant species. In contrast to array-based genotyping GBS also allows for easy estimation of allele frequencies...... at each SNP in family pools or polyploids. There are, however, several statistical challenges associated with this method, including low sequencing depth and missing values. Low sequencing depth results in inaccuracies in estimates of allele frequencies for each SNP. In this work we have focused...... on optimizing methods and models utilizing F2 family phenotype records and NGS information from F2 family pools in perennial ryegrass. Genomic variance was estimated using genomic relationship matrices based on different coverage depths to verify effects of coverage depth. Example traits were seed yield, rust...

  14. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing

    Science.gov (United States)

    Redin, Claire; Gérard, Bénédicte; Lauer, Julia; Herenger, Yvan; Muller, Jean; Quartier, Angélique; Masurel-Paulet, Alice; Willems, Marjolaine; Lesca, Gaétan; El-Chehadeh, Salima; Le Gras, Stéphanie; Vicaire, Serge; Philipps, Muriel; Dumas, Michaël; Geoffroy, Véronique; Feger, Claire; Haumesser, Nicolas; Alembik, Yves; Barth, Magalie; Bonneau, Dominique; Colin, Estelle; Dollfus, Hélène; Doray, Bérénice; Delrue, Marie-Ange; Drouin-Garraud, Valérie; Flori, Elisabeth; Fradin, Mélanie; Francannet, Christine; Goldenberg, Alice; Lumbroso, Serge; Mathieu-Dramard, Michèle; Martin-Coignard, Dominique; Lacombe, Didier; Morin, Gilles; Polge, Anne; Sukno, Sylvie; Thauvin-Robinet, Christel; Thevenon, Julien; Doco-Fenzy, Martine; Genevieve, David; Sarda, Pierre; Edery, Patrick; Isidor, Bertrand; Jost, Bernard; Olivier-Faivre, Laurence; Mandel, Jean-Louis; Piton, Amélie

    2014-01-01

    Background Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. Methods We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases. Results We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients’ clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders. Conclusions With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes

  15. Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism

    NARCIS (Netherlands)

    Haberl, M.G.; Zerbi, V.; Veltien, A.A.; Ginger, M.; Heerschap, A.; Frick, A.

    2015-01-01

    Fragile X syndrome (FXS), the most common inherited form of intellectual disability disorder and a frequent cause of autism spectrum disorder (ASD), is characterized by a high prevalence of sensory symptoms. Perturbations in the anatomical connectivity of neocortical circuits resulting in their func

  16. GENERAL OVERGROWTH IN THE FRAGILE-X SYNDROME - VARIABILITY IN THE PHENOTYPIC-EXPRESSION OF THE FMR1 GENE MUTATION

    NARCIS (Netherlands)

    DEVRIES, BBA; ROBINSON, H; STOLTEDIJKSTRA, [No Value; GI, CVTP; DIJKSTRA, PF; VANDOOM, J; HALLEY, DJJ; OOSTRA, BA; TURNER, G; NIERMEIJER, MF

    1995-01-01

    The fragile X syndrome, which often presents in childhood with overgrowth, may in some cases show some diagnostic overlap with classical Sotos syndrome. We describe four fragile X patients with general overgrowth, all of whom are from families with other affected relatives who show the classic Marti

  17. Study of collimator array based on single collimating lens%基于单准直透镜的阵列准直器研究

    Institute of Scientific and Technical Information of China (English)

    袁志林; 杨睿; 杨柳; 宋丽丹; 孙莉萍; 马雨虹; 王猛; 陈定康; 郭金平; 唐丽红

    2012-01-01

    提出了一种基于单准直透镜和光纤阵列的阵列准直器,深入研究了此种方案的光路无胶和光路有胶的两种实现方式:并基于高斯光束传输矩阵和q参数相关理论,从理论上详细地计算、推导了各变量之间的关系,并进行了模拟仿真及实验验证,得到了理论和实验一致的结果.对两种实现方式的结构及封装设计也进行了初步的摸索和实验,并制作出了性能良好的阵列准直器.理论和实验表明,该方案具有易加工、低成本、易封装、性能优等特点,也易于扩展成多维阵列准直器,可为可重构光分插复用器系统和光交叉连接系统的发展提供强有力的器件支撑.%A new collimator array based on single collimating lens and fiber array is proposed in the paper. An in-depth study is conducted on the two realizing methods, one is with glue in the optical path and the other is without glue in the optical path. Based on Gauss optics transmission matrix and q parameter theory, the relationship among the variables is deduced and computed theoretically, simulated virtually and confirmed experimentally. Good agreement between theoretical results and simulation, experimental results is obtained. The mechanical and packaging designs of the two realizing methods are first studied, then the proposed collimator arrays, with good performance are made. Both the theoretical and experimental results show that the scheme has the merits of easy-to-make, low cost, easy-to-package, good performance, good scalability, etc., which can strongly support the development of reconfigurable optical add- drop multiplexer system and optical cross-connect system.

  18. Evaluation of SNP calling using single and multiple-sample calling algorithms by validation against array base genotyping and Mendelian inheritance

    OpenAIRE

    Kumar, Pankaj; Al-Shafai, Mashael; Al Muftah, Wadha Ahmed; Chalhoub, Nader; Elsaid, Mahmoud F; Aleem, Alice Abdel; Suhre, Karsten

    2014-01-01

    Background With diminishing costs of next generation sequencing (NGS), whole genome analysis becomes a standard tool for identifying genetic causes of inherited diseases. Commercial NGS service providers in general not only provide raw genomic reads, but further deliver SNP calls to their clients. However, the question for the user arises whether to use the SNP data as is, or process the raw sequencing data further through more sophisticated SNP calling pipelines with more advanced algorithms...

  19. Identification of sequence variants in genetic disease-causing genes using targeted next-generation sequencing.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wei

    Full Text Available BACKGROUND: Identification of gene variants plays an important role in research on and diagnosis of genetic diseases. A combination of enrichment of targeted genes and next-generation sequencing (targeted DNA-HiSeq results in both high efficiency and low cost for targeted sequencing of genes of interest. METHODOLOGY/PRINCIPAL FINDINGS: To identify mutations associated with genetic diseases, we designed an array-based gene chip to capture all of the exons of 193 genes involved in 103 genetic diseases. To evaluate this technology, we selected 7 samples from seven patients with six different genetic diseases resulting from six disease-causing genes and 100 samples from normal human adults as controls. The data obtained showed that on average, 99.14% of 3,382 exons with more than 30-fold coverage were successfully detected using Targeted DNA-HiSeq technology, and we found six known variants in four disease-causing genes and two novel mutations in two other disease-causing genes (the STS gene for XLI and the FBN1 gene for MFS as well as one exon deletion mutation in the DMD gene. These results were confirmed in their entirety using either the Sanger sequencing method or real-time PCR. CONCLUSIONS/SIGNIFICANCE: Targeted DNA-HiSeq combines next-generation sequencing with the capture of sequences from a relevant subset of high-interest genes. This method was tested by capturing sequences from a DNA library through hybridization to oligonucleotide probes specific for genetic disorder-related genes and was found to show high selectivity, improve the detection of mutations, enabling the discovery of novel variants, and provide additional indel data. Thus, targeted DNA-HiSeq can be used to analyze the gene variant profiles of monogenic diseases with high sensitivity, fidelity, throughput and speed.

  20. Main: Sequences [KOME

    Lifescience Database Archive (English)

    Full Text Available Sequences Amino Acid Sequence Amino Acid sequence of full length cDNA (Longest ORF) kome_ine_full_sequence..._amino_db.fasta.zip kome_ine_full_sequence_amino_db.zip kome_ine_full_sequence_amino_db ...

  1. Classifying Genomic Sequences by Sequence Feature Analysis

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Liu; Dian Jiao; Xiao Sun

    2005-01-01

    Traditional sequence analysis depends on sequence alignment. In this study, we analyzed various functional regions of the human genome based on sequence features, including word frequency, dinucleotide relative abundance, and base-base correlation. We analyzed the human chromosome 22 and classified the upstream,exon, intron, downstream, and intergenic regions by principal component analysis and discriminant analysis of these features. The results show that we could classify the functional regions of genome based on sequence feature and discriminant analysis.

  2. Multi-task Sequence to Sequence Learning

    OpenAIRE

    Luong, Minh-Thang; Le, Quoc V.; Sutskever, Ilya; Vinyals, Oriol; Kaiser, Lukasz

    2015-01-01

    Sequence to sequence learning has recently emerged as a new paradigm in supervised learning. To date, most of its applications focused on only one task and not much work explored this framework for multiple tasks. This paper examines three multi-task learning (MTL) settings for sequence to sequence models: (a) the oneto-many setting - where the encoder is shared between several tasks such as machine translation and syntactic parsing, (b) the many-to-one setting - useful when only the decoder ...

  3. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

    2009-06-01

    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  4. Fibonacci-Like Sequence

    OpenAIRE

    Shikha Bhatnagar; Bijendra Singh; Omprakash Sikhwal

    2013-01-01

    The Fibonacci and Lucas sequences are well-known examples of second order recurrence sequences, which belong to particular class of recursive sequences. In this article, Fibonacci-Like sequence is introduced and defined by The Binet’s formula and generating function of Fibonacci-Like sequence are presented with some identities and connection formulae.

  5. Whole Genome Sequencing

    Science.gov (United States)

    ... you want to learn. Search form Search Whole Genome Sequencing You are here Home Testing & Services Testing ... the full story, click here . What is whole genome sequencing? Whole genome sequencing is the mapping out ...

  6. Multimodal sequence learning.

    Science.gov (United States)

    Kemény, Ferenc; Meier, Beat

    2016-02-01

    While sequence learning research models complex phenomena, previous studies have mostly focused on unimodal sequences. The goal of the current experiment is to put implicit sequence learning into a multimodal context: to test whether it can operate across different modalities. We used the Task Sequence Learning paradigm to test whether sequence learning varies across modalities, and whether participants are able to learn multimodal sequences. Our results show that implicit sequence learning is very similar regardless of the source modality. However, the presence of correlated task and response sequences was required for learning to take place. The experiment provides new evidence for implicit sequence learning of abstract conceptual representations. In general, the results suggest that correlated sequences are necessary for implicit sequence learning to occur. Moreover, they show that elements from different modalities can be automatically integrated into one unitary multimodal sequence.

  7. Sequence Read Archive (SRA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Sequence Read Archive (SRA) stores raw sequencing data from the next generation of sequencing platforms including Roche 454 GS System®, Illumina Genome...

  8. Consensus Sequence Zen

    OpenAIRE

    Schneider, Thomas D.

    2002-01-01

    Consensus sequences are widely used in molecular biology but they have many flaws. As a result, binding sites of proteins and other molecules are missed during studies of genetic sequences and important biological effects cannot be seen. Information theory provides a mathematically robust way to avoid consensus sequences. Instead of using consensus sequences, sequence conservation can be quantitatively presented in bits of information by using sequence logo graphics to repre...

  9. Identification of the bovine Arachnomelia mutation by massively parallel sequencing implicates sulfite oxidase (SUOX in bone development.

    Directory of Open Access Journals (Sweden)

    Cord Drögemüller

    2010-08-01

    Full Text Available Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a ∼7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development.

  10. The generalized quaternion sequence

    Science.gov (United States)

    Deveci, Ömür

    2016-04-01

    In this work, we define the recurrence sequence by using the relation matrix of the generalized quaternion group and then, we obtain miscellaneous properties of this sequence. Also, we obtain the cyclic groups and the semigroups which are produced by generating matrix of the sequence defined when read modulo m. Furthermore, we study this sequence modulo m, and then we derive the relationship among the order the cyclic groups obtained and the periods of the sequence defined.

  11. Diagnosis and Prognostication of Ductal Adenocarcinomas of the Pancreas Based on Genome-Wide DNA Methylation Profiling by Bacterial Artificial Chromosome Array-Based Methylated CpG Island Amplification

    Directory of Open Access Journals (Sweden)

    Masahiro Gotoh

    2011-01-01

    Full Text Available To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs, bacterial artificial chromosome (BAC array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.

  12. Polynomially Bounded Sequences and Polynomial Sequences

    Directory of Open Access Journals (Sweden)

    Okazaki Hiroyuki

    2015-09-01

    Full Text Available In this article, we formalize polynomially bounded sequences that plays an important role in computational complexity theory. Class P is a fundamental computational complexity class that contains all polynomial-time decision problems [11], [12]. It takes polynomially bounded amount of computation time to solve polynomial-time decision problems by the deterministic Turing machine. Moreover we formalize polynomial sequences [5].

  13. Genome Sequence Databases (Overview): Sequencing and Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Lapidus, Alla L.

    2009-01-01

    From the date its role in heredity was discovered, DNA has been generating interest among scientists from different fields of knowledge: physicists have studied the three dimensional structure of the DNA molecule, biologists tried to decode the secrets of life hidden within these long molecules, and technologists invent and improve methods of DNA analysis. The analysis of the nucleotide sequence of DNA occupies a special place among the methods developed. Thanks to the variety of sequencing technologies available, the process of decoding the sequence of genomic DNA (or whole genome sequencing) has become robust and inexpensive. Meanwhile the assembly of whole genome sequences remains a challenging task. In addition to the need to assemble millions of DNA fragments of different length (from 35 bp (Solexa) to 800 bp (Sanger)), great interest in analysis of microbial communities (metagenomes) of different complexities raises new problems and pushes some new requirements for sequence assembly tools to the forefront. The genome assembly process can be divided into two steps: draft assembly and assembly improvement (finishing). Despite the fact that automatically performed assembly (or draft assembly) is capable of covering up to 98% of the genome, in most cases, it still contains incorrectly assembled reads. The error rate of the consensus sequence produced at this stage is about 1/2000 bp. A finished genome represents the genome assembly of much higher accuracy (with no gaps or incorrectly assembled areas) and quality ({approx}1 error/10,000 bp), validated through a number of computer and laboratory experiments.

  14. Contamination of sequence databases with adaptor sequences

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Takeo; Sanders, A.R.; Detera-Wadleigh, S.D. [National Institute of Mental Health, Bethesda, MD (United States)

    1997-02-01

    Because of the exponential increase in the amount of DNA sequences being added to the public databases on a daily basis, it has become imperative to identify sources of contamination rapidly. Previously, contaminations of sequence databases have been reported to alert the scientific community to the problem. These contaminations can be divided into two categories. The first category comprises host sequences that have been difficult for submitters to manage or control. Examples include anomalous sequences derived from Escherichia coli, which are inserted into the chromosomes (and plasmids) of the bacterial hosts. Insertion sequences are highly mobile and are capable of transposing themselves into plasmids during cloning manipulation. Another example of the first category is the infection with yeast genomic DNA or with bacterial DNA of some commercially available cDNA libraries from Clontech. The second category of database contamination is due to the inadvertent inclusion of nonhost sequences. This category includes incorporation of cloning-vector sequences and multicloning sites in the database submission. M13-derived artifacts have been common, since M13-based vectors have been widely used for subcloning DNA fragments. Recognizing this problem, the National Center for Biotechnology Information (NCBI) started to screen, in April 1994, all sequences directly submitted to GenBank, against a set of vector data retrieved from GenBank by use of key-word searches, such as {open_quotes}vector.{close_quotes} In this report, we present evidence for another sequence artifact that is widespread but that, to our knowledge, has not yet been reported. 11 refs., 1 tab.

  15. Anomaly Detection in Sequences

    Data.gov (United States)

    National Aeronautics and Space Administration — We present a set of novel algorithms which we call sequenceMiner, that detect and characterize anomalies in large sets of high-dimensional symbol sequences that...

  16. DNA sequencing conference, 2

    Energy Technology Data Exchange (ETDEWEB)

    Cook-Deegan, R.M. [Georgetown Univ., Kennedy Inst. of Ethics, Washington, DC (United States); Venter, J.C. [National Inst. of Neurological Disorders and Strokes, Bethesda, MD (United States); Gilbert, W. [Harvard Univ., Cambridge, MA (United States); Mulligan, J. [Stanford Univ., CA (United States); Mansfield, B.K. [Oak Ridge National Lab., TN (United States)

    1991-06-19

    This conference focused on DNA sequencing, genetic linkage mapping, physical mapping, informatics and bioethics. Several were used to study this sequencing and mapping. This article also discusses computer hardware and software aiding in the mapping of genes.

  17. sequenceMiner algorithm

    Data.gov (United States)

    National Aeronautics and Space Administration — Detecting and describing anomalies in large repositories of discrete symbol sequences. sequenceMiner has been open-sourced! Download the file below to try it out....

  18. Sequence information signal processor

    Science.gov (United States)

    Peterson, John C.; Chow, Edward T.; Waterman, Michael S.; Hunkapillar, Timothy J.

    1999-01-01

    An electronic circuit is used to compare two sequences, such as genetic sequences, to determine which alignment of the sequences produces the greatest similarity. The circuit includes a linear array of series-connected processors, each of which stores a single element from one of the sequences and compares that element with each successive element in the other sequence. For each comparison, the processor generates a scoring parameter that indicates which segment ending at those two elements produces the greatest degree of similarity between the sequences. The processor uses the scoring parameter to generate a similar scoring parameter for a comparison between the stored element and the next successive element from the other sequence. The processor also delivers the scoring parameter to the next processor in the array for use in generating a similar scoring parameter for another pair of elements. The electronic circuit determines which processor and alignment of the sequences produce the scoring parameter with the highest value.

  19. Roles of repetitive sequences

    Energy Technology Data Exchange (ETDEWEB)

    Bell, G.I.

    1991-12-31

    The DNA of higher eukaryotes contains many repetitive sequences. The study of repetitive sequences is important, not only because many have important biological function, but also because they provide information on genome organization, evolution and dynamics. In this paper, I will first discuss some generic effects that repetitive sequences will have upon genome dynamics and evolution. In particular, it will be shown that repetitive sequences foster recombination among, and turnover of, the elements of a genome. I will then consider some examples of repetitive sequences, notably minisatellite sequences and telomere sequences as examples of tandem repeats, without and with respectively known function, and Alu sequences as an example of interspersed repeats. Some other examples will also be considered in less detail.

  20. DNA sequences encoding erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Lin, F.K.

    1987-10-27

    A purified and isolated DNA sequence is described consisting essentially of a DNA sequence encoding a polypeptide having an amino acid sequence sufficiently duplicative of that of erythropoietin to allow possession of the biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells, and to increase hemoglobin synthesis or iron uptake.

  1. On Asymptotically Orthonormal Sequences

    OpenAIRE

    Fricain, Emmanuel; Rupam, Rishika

    2016-01-01

    An asymptotically orthonormal sequence is a sequence which is 'nearly' orthonormal in the sense that it satisfies the Parseval equality up to two constants close to one. In this paper, we explore such sequences formed by normalized reproducing kernels of model spaces and de Branges Rovnyak spaces.

  2. Low autocorrelation binary sequences

    Science.gov (United States)

    Packebusch, Tom; Mertens, Stephan

    2016-04-01

    Binary sequences with minimal autocorrelations have applications in communication engineering, mathematics and computer science. In statistical physics they appear as groundstates of the Bernasconi model. Finding these sequences is a notoriously hard problem, that so far can be solved only by exhaustive search. We review recent algorithms and present a new algorithm that finds optimal sequences of length N in time O(N {1.73}N). We computed all optimal sequences for N≤slant 66 and all optimal skewsymmetric sequences for N≤slant 119.

  3. Repdigits in -Lucas Sequences

    Indian Academy of Sciences (India)

    Jhon J J Bravo; Florian Luca

    2014-05-01

    For an integer ≥ 2, let $(L_n^{(k)})_n$ be the -Lucas sequence which starts with $0,\\ldots,0,2,1$ ( terms) and each term afterwards is the sum of the preceding terms. In 2000, Luca (Port. Math. 57(2) 2000 243-254) proved that 11 is the largest number with only one distinct digit (the so-called repdigit) in the sequence $(L_n^{(2)})_n$. In this paper, we address a similar problem in the family of -Lucas sequences. We also show that the -Lucas sequences have similar properties to those of -Fibonacci sequences and occur in formulae simultaneously with the latter.

  4. A novel fragile X syndrome mutation reveals a conserved role for the carboxy-terminus in FMRP localization and function.

    Science.gov (United States)

    Okray, Zeynep; de Esch, Celine E F; Van Esch, Hilde; Devriendt, Koen; Claeys, Annelies; Yan, Jiekun; Verbeeck, Jelle; Froyen, Guy; Willemsen, Rob; de Vrij, Femke M S; Hassan, Bassem A

    2015-02-17

    Loss of function of the FMR1 gene leads to fragile X syndrome (FXS), the most common form of intellectual disability. The loss of FMR1 function is usually caused by epigenetic silencing of the FMR1 promoter leading to expansion and subsequent methylation of a CGG repeat in the 5' untranslated region. Very few coding sequence variations have been experimentally characterized and shown to be causal to the disease. Here, we describe a novel FMR1 mutation and reveal an unexpected nuclear export function for the C-terminus of FMRP. We screened a cohort of patients with typical FXS symptoms who tested negative for CGG repeat expansion in the FMR1 locus. In one patient, we identified a guanine insertion in FMR1 exon 15. This mutation alters the open reading frame creating a short novel C-terminal sequence, followed by a stop codon. We find that this novel peptide encodes a functional nuclear localization signal (NLS) targeting the patient FMRP to the nucleolus in human cells. We also reveal an evolutionarily conserved nuclear export function associated with the endogenous C-terminus of FMRP. In vivo analyses in Drosophila demonstrate that a patient-mimetic mutation alters the localization and function of Dfmrp in neurons, leading to neomorphic neuronal phenotypes.

  5. Sequences of commutator operations

    CERN Document Server

    Aichinger, Erhard

    2012-01-01

    Given the congruence lattice L of a finite algebra A with a Mal'cev term, we look for those sequences of operations on L that are sequences of higher commutator operations of expansions of A. The properties of higher commutators proved so far delimit the number of such sequences: the number is always at most countably infinite; if it is infinite, then L is the union of two proper subintervals with nonempty intersection.

  6. Next-generation sequencing

    DEFF Research Database (Denmark)

    Rieneck, Klaus; Bak, Mads; Jønson, Lars;

    2013-01-01

    the feasibility of predicting the fetal KEL1 phenotype using next-generation sequencing (NGS) technology. STUDY DESIGN AND METHODS: The KEL1/2 single-nucleotide polymorphism was polymerase chain reaction (PCR) amplified with one adjoining base, and the PCR product was sequenced using a genome analyzer (GAIIx......, Illumina); several millions of PCR sequences were analyzed. RESULTS: The results demonstrated the feasibility of diagnosing the fetal KEL1 or KEL2 blood group from cell-free DNA purified from maternal plasma. CONCLUSION: This method requires only one primer pair, and the large amount of sequence...

  7. Genomic Methods Take the Plunge: Recent Advances in High-Throughput Sequencing of Marine Mammals.

    Science.gov (United States)

    Cammen, Kristina M; Andrews, Kimberly R; Carroll, Emma L; Foote, Andrew D; Humble, Emily; Khudyakov, Jane I; Louis, Marie; McGowen, Michael R; Olsen, Morten Tange; Van Cise, Amy M

    2016-11-01

    The dramatic increase in the application of genomic techniques to non-model organisms (NMOs) over the past decade has yielded numerous valuable contributions to evolutionary biology and ecology, many of which would not have been possible with traditional genetic markers. We review this recent progression with a particular focus on genomic studies of marine mammals, a group of taxa that represent key macroevolutionary transitions from terrestrial to marine environments and for which available genomic resources have recently undergone notable rapid growth. Genomic studies of NMOs utilize an expanding range of approaches, including whole genome sequencing, restriction site-associated DNA sequencing, array-based sequencing of single nucleotide polymorphisms and target sequence probes (e.g., exomes), and transcriptome sequencing. These approaches generate different types and quantities of data, and many can be applied with limited or no prior genomic resources, thus overcoming one traditional limitation of research on NMOs. Within marine mammals, such studies have thus far yielded significant contributions to the fields of phylogenomics and comparative genomics, as well as enabled investigations of fitness, demography, and population structure. Here we review the primary options for generating genomic data, introduce several emerging techniques, and discuss the suitability of each approach for different applications in the study of NMOs. PMID:27511190

  8. Microfluidic System for Solution Array Based Bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Dougherty, G M; Tok, J B; Pannu, S S; Rose, K A

    2006-02-10

    The objective of this project is to demonstrate new enabling technology for multiplex biodetection systems that are flexible, miniaturizable, highly automated, low cost, and high performance. It builds on prior successes at LLNL with particle-based solution arrays, such as those used in the Autonomous Pathogen Detection System (APDS) successfully field deployed to multiple locations nationwide. We report the development of a multiplex solution array immunoassay based upon engineered metallic nanorod particles. Nanobarcodes{reg_sign} particles are fabricated by sequential electrodeposition of dissimilar metals within porous alumina templates, yielding optically encoded striping patterns that can be read using standard laboratory microscope optics and PC-based image processing software. The addition of self-assembled monolayer (SAM) coatings and target-specific antibodies allows each encoded class of nanorod particles to be directed against a different antigen target. A prototype assay panel directed against bacterial, viral, and soluble protein targets demonstrates simultaneous detection at sensitivities comparable to state of the art immunoassays, with minimal cross-reactivity. Studies have been performed to characterize the colloidal properties (zeta potential) of the suspended nanorod particles as a function of pH, the ionic strength of the suspending solution, and surface functionalization state. Additional studies have produced means for the non-contact manipulation of the particles, including the insertion of magnetic nickel stripes within the encoding pattern, and control via externally applied electromagnetic fields. Using the results of these studies, the novel Nanobarcodes{reg_sign} based assay was implemented in a prototype automated system with the sample processing functions and optical readout performed on a microfluidic card. The unique physical properties of the nanorod particles enable the development of integrated microfluidic systems for biodefense, protein expression studies, and other applications.

  9. Cosmetology: Scope and Sequence.

    Science.gov (United States)

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for a cosmetology vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and the…

  10. HIV Sequence Compendium 2015

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas Kenneth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Cristian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Pennsylvania, Philadelphia, PA (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-05

    This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  11. Mapping sequences by parts

    Directory of Open Access Journals (Sweden)

    Guziolowski Carito

    2007-09-01

    Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.

  12. Evolution of DNA Sequencing

    International Nuclear Information System (INIS)

    Sanger and coworkers introduced DNA sequencing in 1970s for the first time. It principally relied on termination of growing nucleotide chain when a dideoxythymidine triphosphate (ddTTP) was inserted in it. Detection of terminated sequences was done radiographically on Polyacrylamide Gel Electrophoresis (PAGE). Improvements that have evolved over time in original Sanger sequencing include replacement of radiography with fluorescence, use of separate fluorescent markers for each nucleotide, use of capillary electrophoresis instead of polyacrylamide gel electrophoresis and then introduction of capillary array electrophoresis. However, this technique suffered from few inherent limitations like decreased sensitivity for low level mutant alleles, complexities in analyzing highly polymorphic regions like Major Histocompatibility Complex (MHC) and high DNA concentrations required. Several Next Generation Sequencing (NGS) technologies have been introduced by Roche, Illumina and other commercial manufacturers that tend to overcome Sanger sequencing limitations and have been reviewed. Introduction of NGS in clinical research and medical diagnostics is expected to change entire diagnostic approach. These include study of cancer variants, detection of minimal residual disease, exome sequencing, detection of Single Nucleotide Polymorphisms (SNPs) and their disease association, epigenetic regulation of gene expression and sequencing of microorganisms genome. (author)

  13. Fabrication of high density silicon nanodot array based on soft imprinting theory%低压压印制备硅点阵结构的工艺研究

    Institute of Scientific and Technical Information of China (English)

    刘玉东; 陶伟; 王时飞; 李鑫; 王旭迪

    2013-01-01

    高密度、图形规则的硅点阵结构由于其独特的光电性能具有广泛的应用前景.本文介绍了一种以低压压印结合反应离子刻蚀制备硅点阵的方法,即利用PDMS模板通过压印复制获得PMMA掩模结构,用反应离子刻蚀在硅片表面制得高度有序的硅纳米点阵结构.实验和有限元模拟结果表明,低压压印因为毛细作用下光刻胶在模板内的充分填充可以获得良好的图形复制精度和较小的残余胶厚度,因此适于大面积高密度光刻胶结构的均匀复制.%High density and regular silicon nanodot array patterns have been widely researched in many front fields,but the fabrication still remain many problems.In this paper,we present a new method to fabricate silicon nanodot array based on soft imprinting theory.Firstly,according to soft imprinting,we got the PMMA mask by PDMS mould,after that,highly ordered silicon array patterns were obtained combining with reactive ion etching.Experimental and finite element analysis results show that,soft imprinting has a better graphic reproduction accuracy and smaller residual photoresist thickness due to the capillary force,which can lead to better filling of polymer,so it is suitable for large area uniform replication of high density photoresist structure.

  14. Next generation sequencing in research and diagnostics of ocular birth defects.

    Science.gov (United States)

    Raca, Gordana; Jackson, Craig; Warman, Berta; Bair, Tom; Schimmenti, Lisa A

    2010-06-01

    Sequence capture enrichment (SCE) strategies and massively parallel next generation sequencing (NGS) are expected to increase the rate of gene discovery for genetically heterogeneous hereditary diseases, but at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. Our study assessed whether array based target enrichment followed by re-sequencing on the Roche Genome Sequencer FLX (GS FLX) system could be used for novel mutation identification in more than 1000 exons representing 100 candidate genes for ocular birth defects, and as a control, whether these methods could detect two known mutations in the PAX2 gene. We assayed two samples with heterozygous sequence changes in PAX2 that were previously identified by conventional Sanger sequencing. These changes were a c.527G>C (S176T) substitution and a single basepair deletion c.77delG. The nucleotide substitution c.527G>C was easily identified by NGS. A deletion of one base in a long polyG stretch (c.77delG) was not registered initially by the GS Reference Mapper, but was detected in repeated analysis using two different software packages. Different approaches were evaluated for distinguishing false positives (sequencing errors) and benign polymorphisms from potentially pathogenic sequence changes that require further follow-up. Although improvements will be necessary in accuracy, speed, ease of data analysis and cost, our study confirms that NGS can be used in research and diagnostic settings to screen for mutations in hundreds of loci in genetically heterogeneous human diseases. PMID:20359920

  15. Classification of base sequences

    CERN Document Server

    Djokovic, Dragomir Z

    2010-01-01

    Base sequences BS(n+1,n) are quadruples of {1,-1}-sequences (A;B;C;D), with A and B of length n+1 and C and D of length n, such that the sum of their nonperiodic autocorrelation functions is a delta-function. The base sequence conjecture, asserting that BS(n+1,n) exist for all n, is stronger than the famous Hadamard matrix conjecture. We introduce a new definition of equivalence for base sequences BS(n+1,n) and construct a canonical form. By using this canonical form, we have enumerated the equivalence classes of BS(n+1,n) for n <= 30. Due to excessive size of the equivalence classes, the tables in the paper cover only the cases n <= 12.

  16. Pierre Robin sequence

    Science.gov (United States)

    Pierre Robin syndrome; Pierre Robin complex; Pierre Robin anomaly ... The exact causes of Pierre Robin sequence are unknown. It may be part of many genetic syndromes. The lower jaw develops slowly before birth, but ...

  17. Scope and Sequence.

    Science.gov (United States)

    Callison, Daniel

    2002-01-01

    Discusses scope and sequence plans for curriculum coordination in elementary and secondary education related to school libraries. Highlights include library skills; levels of learning objectives; technology skills; media literacy skills; and information inquiry skills across disciplines by grade level. (LRW)

  18. Yeast genome sequencing:

    DEFF Research Database (Denmark)

    Piskur, Jure; Langkjær, Rikke Breinhold

    2004-01-01

    For decades, unicellular yeasts have been general models to help understand the eukaryotic cell and also our own biology. Recently, over a dozen yeast genomes have been sequenced, providing the basis to resolve several complex biological questions. Analysis of the novel sequence data has shown...... of closely related species helps in gene annotation and to answer how many genes there really are within the genomes. Analysis of non-coding regions among closely related species has provided an example of how to determine novel gene regulatory sequences, which were previously difficult to analyse because...... they are short and degenerate and occupy different positions. Comparative genomics helps to understand the origin of yeasts and points out crucial molecular events in yeast evolutionary history, such as whole-genome duplication and horizontal gene transfer(s). In addition, the accumulating sequence data provide...

  19. Biological sequence analysis

    DEFF Research Database (Denmark)

    Durbin, Richard; Eddy, Sean; Krogh, Anders Stærmose;

    This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis, and phylogene......This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis...

  20. HIV Sequence Compendium 2010

    Energy Technology Data Exchange (ETDEWEB)

    Kuiken, Carla [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Foley, Brian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Christian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Alabama, Tuscaloosa, AL (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2010-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  1. Text Mining: (Asynchronous Sequences

    Directory of Open Access Journals (Sweden)

    Sheema Khan

    2014-12-01

    Full Text Available In this paper we tried to correlate text sequences those provides common topics for semantic clues. We propose a two step method for asynchronous text mining. Step one check for the common topics in the sequences and isolates these with their timestamps. Step two takes the topic and tries to give the timestamp of the text document. After multiple repetitions of step two, we could give optimum result.

  2. Nanapore Sequencing with MSPA

    Science.gov (United States)

    Gundlach, Jens H.

    2011-10-01

    Nanopore sequencing is the simplest concept of converting the sequence of a single DNA molecule directly into an electronic signal. We introduced the protein pore MspA. derived from Mycobacterium smegmatis, to nanpore sequencing [1]. MspA has a single, narrow (-1.2nm) and short (MspA is reproducible with sub-nanometer precision and is engineerable using genetic mutations. DNA moves through the pore at rates exceeding 1nt/microsec. too fast to observe the passage of each nucleotide. However, when DNA is held with double stranded DNA sections or an avidin anchor, single nucleotides resident in MspA's constriction can be identified with highly resolved current differences. We have provided proof of principle of a nanopore sequencing method [2] in which we use DNA modified by inserting double stranded DNA-sections between every nucleotide. The double stranded sections are designed to halt translocation for long enough to sequentially read the sequence of the original DNA molecule. Prospects and developments to sequence unmodified native DNA using MspA will be discussed.[4pt] [1] T.Z. Butler, et al, PNAS 105 20647 (2008)[0pt] [2] I.M. Derrington, et al, PNAS 107 16060 (2010).

  3. DNA copy number, including telomeres and mitochondria, assayed using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Jackson Stuart

    2010-04-01

    Full Text Available Abstract Background DNA copy number variations occur within populations and aberrations can cause disease. We sought to develop an improved lab-automatable, cost-efficient, accurate platform to profile DNA copy number. Results We developed a sequencing-based assay of nuclear, mitochondrial, and telomeric DNA copy number that draws on the unbiased nature of next-generation sequencing and incorporates techniques developed for RNA expression profiling. To demonstrate this platform, we assayed UMC-11 cells using 5 million 33 nt reads and found tremendous copy number variation, including regions of single and homogeneous deletions and amplifications to 29 copies; 5 times more mitochondria and 4 times less telomeric sequence than a pool of non-diseased, blood-derived DNA; and that UMC-11 was derived from a male individual. Conclusion The described assay outputs absolute copy number, outputs an error estimate (p-value, and is more accurate than array-based platforms at high copy number. The platform enables profiling of mitochondrial levels and telomeric length. The assay is lab-automatable and has a genomic resolution and cost that are tunable based on the number of sequence reads.

  4. Detection of chromosomal aneuploidy in human preimplantation embryos by next-generation sequencing.

    Science.gov (United States)

    Wang, Li; Wang, Xiaohong; Zhang, Jianguang; Song, Zhuo; Wang, Shufang; Gao, Yang; Wang, Jun; Luo, Yaning; Niu, Ziru; Yue, Xiaojing; Xu, Genming; Cram, David S; Yao, Yuanqing

    2014-05-01

    Embryos produced by assisted reproductive technologies are commonly associated with a high level of aneuploidy. Currently, 24-chromosome profiling of embryo biopsy samples by array-based methods is available to identify euploid embryos for transfer that have a higher potential for implantation and development to term. From a laboratory and patient perspective, there is a need to explore the feasibility of developing an alternative method for routine aneuploidy assessment of embryos that would be more comprehensive, cost-effective, and efficient. We speculated that aneuploidy could be readily assessed in test single-cell biopsy samples by first performing whole genome amplification followed by library generation, massively parallel shot-gun sequencing, and finally bioinformatics analysis to quantitatively compare the ratio of uniquely mapped reads to reference cells. Using Down syndrome as an example, the copy number change for chromosome 21 was consistently 1.5-fold higher in multiple cell and single-cell samples with a 47,XX,+21 karyotype. Applying the validated sequencing strategy to 10 sister blastomeres from a single human embryo, we showed that the aneuploidy status called by sequencing was consistent with short tandem repeat allelic profiling. These validation studies indicate that aneuploidy detection using sequencing-based methodology is feasible for further improving the practice of preimplantation genetic diagnosis. PMID:24648399

  5. Lack of expansion of triplet repeats in the FMR1, FRAXE, and FRAXF loci in male multiplex families with autism and pervasive developmental disorders

    Energy Technology Data Exchange (ETDEWEB)

    Holden, J.J.A.; Julien-Inalsingh, C. [Queen`s Univ., Kingston (Canada); Wing, M. [Ongwanada Resource Centre, Kingston (Canada)] [and others

    1996-08-09

    Sib, twin, and family studies have shown that a genetic cause exists in many cases of autism, with a portion of cases associated with a fragile X chromosome. Three folate-sensitive fragile sites in the Xq27{r_arrow}Xq28 region have been cloned and found to have polymorphic trinucleotide repeats at the respective sites; these repeats are amplified and methylated in individuals who are positive for the different fragile sites. We have tested affected boys and their mothers from 19 families with two autistic/PDD boys for amplification and/or instability of the triplet repeats at these loci and concordance of inheritance of alleles by affected brothers. In all cases, the triplet repeat numbers were within the normal range, with no individuals having expanded or premutation-size alleles. For each locus, there was no evidence for an increased frequency of concordance, indicating that mutations within these genes are unlikely to be responsible for the autistic/PDD phenotypes in the affected boys. Thus, we think it is important to retest those autistic individuals who were cytogenetically positive for a fragile X chromosome, particularly cases where there is no family history of the fragile X syndrome, using the more accurate DNA-based testing procedures. 29 refs., 1 fig., 1 tab.

  6. The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice

    NARCIS (Netherlands)

    M.F. Vinueza Veloz (Maria); R.A.M. Buijsen (Ronald); R. Willemsen (Rob); A. Cupido (Alexander); L.W.J. Bosman (Laurens); S.K.E. Koekkoek (Bas); J.W. Potters (Jan Willem); B.A. Oostra (Ben); C.I. de Zeeuw (Chris)

    2012-01-01

    textabstractFragile X syndrome (FXS) is the most common inherited form of intellectual disability. Patients with FXS do not only suffer from cognitive problems, but also from abnormalities/deficits in procedural memory formation. It has been proposed that a lack of fragile X mental retardation prote

  7. Cortisol Response to Behavior Problems in FMR1 Premutation Mothers of Adolescents and Adults with Fragile X Syndrome: A Diathesis-Stress Model

    Science.gov (United States)

    Hartley, Sigan L.; Seltzer, Marsha Mailick; Hong, Jinkuk; Greenberg, Jan S.; Smith, Leann; Almeida, David; Coe, Chris; Abbeduto, Leonard

    2012-01-01

    Mothers of adolescents and adults with fragile X syndrome (FXS) are faced with high levels of parenting stress. The extent to which mothers are negatively impacted by this stress, however, may be influenced by their own genetic status. The present study uses a diathesis-stress model to examine the ways in which a genetic vulnerability in mothers…

  8. Adaptive Processing for Sequence Alignment

    KAUST Repository

    Zidan, Mohammed Affan

    2012-01-26

    Disclosed are various embodiments for adaptive processing for sequence alignment. In one embodiment, among others, a method includes obtaining a query sequence and a plurality of database sequences. A first portion of the plurality of database sequences is distributed to a central processing unit (CPU) and a second portion of the plurality of database sequences is distributed to a graphical processing unit (GPU) based upon a predetermined splitting ratio associated with the plurality of database sequences, where the database sequences of the first portion are shorter than the database sequences of the second portion. A first alignment score for the query sequence is determined with the CPU based upon the first portion of the plurality of database sequences and a second alignment score for the query sequence is determined with the GPU based upon the second portion of the plurality of database sequences.

  9. Program Synthesizes UML Sequence Diagrams

    Science.gov (United States)

    Barry, Matthew R.; Osborne, Richard N.

    2006-01-01

    A computer program called "Rational Sequence" generates Universal Modeling Language (UML) sequence diagrams of a target Java program running on a Java virtual machine (JVM). Rational Sequence thereby performs a reverse engineering function that aids in the design documentation of the target Java program. Whereas previously, the construction of sequence diagrams was a tedious manual process, Rational Sequence generates UML sequence diagrams automatically from the running Java code.

  10. What is next generation sequencing?

    OpenAIRE

    Behjati, Sam; Tarpey, Patrick S.

    2013-01-01

    Next generation sequencing (NGS), massively parallel or deep sequencing are related terms that describe a DNA sequencing technology which has revolutionised genomic research. Using NGS an entire human genome can be sequenced within a single day. In contrast, the previous Sanger sequencing technology, used to decipher the human genome, required over a decade to deliver the final draft. Although in genome research NGS has mostly superseded conventional Sanger sequencing, it has not yet translat...

  11. Controlled processing during sequencing.

    Science.gov (United States)

    Thothathiri, Malathi; Rattinger, Michelle

    2015-01-01

    Longstanding evidence has identified a role for the frontal cortex in sequencing within both linguistic and non-linguistic domains. More recently, neuropsychological studies have suggested a specific role for the left premotor-prefrontal junction (BA 44/6) in selection between competing alternatives during sequencing. In this study, we used neuroimaging with healthy adults to confirm and extend knowledge about the neural correlates of sequencing. Participants reproduced visually presented sequences of syllables and words using manual button presses. Items in the sequence were presented either consecutively or concurrently. Concurrent presentation is known to trigger the planning of multiple responses, which might compete with one another. Therefore, we hypothesized that regions involved in controlled processing would show greater recruitment during the concurrent than the consecutive condition. Whole-brain analysis showed concurrent > consecutive activation in sensory, motor and somatosensory cortices and notably also in rostral-dorsal anterior cingulate cortex. Region of interest analyses showed increased activation within left BA 44/6 and correlation between this region's activation and behavioral response times. Functional connectivity analysis revealed increased connectivity between left BA 44/6 and the posterior lobe of the cerebellum during the concurrent than the consecutive condition. These results corroborate recent evidence and demonstrate the involvement of BA 44/6 and other control regions when ordering co-activated representations.

  12. Controlled processing during sequencing

    Directory of Open Access Journals (Sweden)

    Malathi eThothathiri

    2015-10-01

    Full Text Available Longstanding evidence has identified a role for the frontal cortex in sequencing within both linguistic and non-linguistic domains. More recently, neuropsychological studies have suggested a specific role for the left premotor-prefrontal junction (BA 44/6 in selection between competing alternatives during sequencing. In this study, we used neuroimaging with healthy adults to confirm and extend knowledge about the neural correlates of sequencing. Participants reproduced visually presented sequences of syllables and words using manual button presses. Items in the sequence were presented either consecutively or concurrently. Concurrent presentation is known to trigger the planning of multiple responses, which might compete with one another. Therefore, we hypothesized that regions involved in controlled processing would show greater recruitment during the concurrent than the consecutive condition. Whole-brain analysis showed concurrent > consecutive activation in sensory, motor and somatosensory cortices and notably also in rostral-dorsal anterior cingulate cortex (ACC. Region of interest analyses showed increased activation within left BA 44/6 and correlation between this region’s activation and behavioral response times. Functional connectivity analysis revealed increased connectivity between left BA 44/6 and the posterior lobe of the cerebellum during the concurrent than the consecutive condition. These results corroborate recent evidence and demonstrate the involvement of BA 44/6 and other control regions when ordering co-activated representations.

  13. Ternary Chaotic Pulse Compression Sequences

    Directory of Open Access Journals (Sweden)

    J. B. Seventline

    2010-09-01

    Full Text Available In this paper method available for generating ternary sequences is discussed. These sequences are useful in many applications but specifically in synchronization of block codes and pulse compression in radar. The ternary sequences are derived from chaotic maps. It is feasible to achieve simultaneously superior performances in detection range and range resolution using the proposed ternary sequences. The properties of these sequences like autocorrelation function, Peak Side Lobe Ratio (PSLR, ambiguity diagram and performance under AWGN noise background has been studied. The generation of these sequences is much simpler, and the available number of sequences is virtually infinite and not limited by the length of the sequence.

  14. MPPT control system of photovoltaic array based on PSO-BPNN estimation%基于PSO优化BPNN估计光伏阵列MPPT控制系统研究

    Institute of Scientific and Technical Information of China (English)

    周习祥; 李加升

    2013-01-01

    In order to make full use of PV to transform energy and improve the generating efficiency of photovoltaic array,a modeling method based on PSO-BPNN was raised based on the analysis of photovoltaic array's volt-ampere characteristics and maximum power point tracking (MPPT).Consequently,the dynamic model of the photovoltaic array was constructed with the improved neural network and the maximum power point tracking for the photovoltaic array was realized through PSO-BPNN model fitting the nonlinear relation between output power and output voltage of PV array.Matlab/Simulink simulation and on-line test results indicate that the photovoltaic array MPPT control system based PSO-BPNN can track photovoltaic array's maximum power point rapidly and accurately,which makes BP neural network's convergence speed quicker and fall into the local extremum easily.Above all,the modeling precision,system stability and energy conversion efficiency can be improved.So,MPPT control system of the photovoltaic array based PSO-BPNN is a feasible way of studying photovoltaic power generation.%为了充分利用光伏阵列转换能量,提高光伏阵列的发电效率,在分析光伏阵列的伏安特性及最大功率点跟踪(MPPT)原理的基础上,提出了一种基于粒子群算法优化BP神经网络(PSO-BPNN)的建模方法,并用这种改进的神经网络构建了光伏阵列的动态模型.通过PSO-BPNN模型拟合光伏阵列输出功率与输出电压的非线性关系,实现了对光伏阵列的最大功率点跟踪.Matlab/Simulink仿真及在线测试结果表明:基于PSO-BPNN估计的光伏阵列MPPT控制系统能快速、精确地跟踪光伏阵列的最大功率点,改善了BP神经网络收敛速度慢,易陷入局部极值,建模精度不高的缺点,提高了系统的稳定性和能量转换效率,是研究光伏发电这个复杂非线性系统的一个可行办法.

  15. Sequencing BPS Spectra

    CERN Document Server

    Gukov, Sergei; Saberi, Ingmar; Stosic, Marko; Sulkowski, Piotr

    2015-01-01

    This paper provides both a detailed study of color-dependence of link homologies, as realized in physics as certain spaces of BPS states, and a broad study of the behavior of BPS states in general. We consider how the spectrum of BPS states varies as continuous parameters of a theory are perturbed. This question can be posed in a wide variety of physical contexts, and we answer it by proposing that the relationship between unperturbed and perturbed BPS spectra is described by a spectral sequence. These general considerations unify previous applications of spectral sequence techniques to physics, and explain from a physical standpoint the appearance of many spectral sequences relating various link homology theories to one another. We also study structural properties of colored HOMFLY homology for links and evaluate Poincar\\'e polynomials in numerous examples. Among these structural properties is a novel "sliding" property, which can be explained by using (refined) modular $S$-matrix. This leads to the identifi...

  16. Instruction sequence processing operators

    NARCIS (Netherlands)

    J.A. Bergstra; C.A. Middelburg

    2009-01-01

    This paper concerns instruction sequences whose execution involves the processing of instructions by an execution environment that offers a family of services and may yield a Boolean value at termination. We introduce a composition operator for families of services and three operators that have a di

  17. THE RHIC SEQUENCER.

    Energy Technology Data Exchange (ETDEWEB)

    VAN ZEIJTS,J.; DOTTAVIO,T.; FRAK,B.; MICHNOFF,R.

    2001-06-18

    The Relativistic Heavy Ion Collider (RHIC) has a high level asynchronous time-line driven by a controlling program called the ''Sequencer''. Most high-level magnet and beam related issues are orchestrated by this system. The system also plays an important task in coordinated data acquisition and saving. We present the program, operator interface, operational impact and experience.

  18. Twin anemia polycythemia sequence

    NARCIS (Netherlands)

    Slaghekke, Femke

    2014-01-01

    In this thesis we describe that Twin Anemia Polycythemia Sequence (TAPS) is a form of chronic feto-fetal transfusion in monochorionic (identical) twins based on a small amount of blood transfusion through very small anastomoses. For the antenatal diagnosis of TAPS, Middle Cerebral Artery – Peak Syst

  19. Properties of Semijoin Sequences

    Institute of Scientific and Technical Information of China (English)

    BengC.Ooi; B.Srinivasan

    1989-01-01

    The problem of finding optimum semijoin sequ4ence of an arbitrary query under linear cost function for the transmission cost is NP.hard.Hence heuristic algorithms with desirable properties are explored.In this paper four properties of semijoin programs for distributed query processing are identified,The use of these properties in constructing semijoin sequence is justified.An existing algorithm is modified incorporating these properties.Empirical comparison with existing algorithms shows the superiority of the proposed algorithm.

  20. Learning Sequence Neighbourhood Metrics

    CERN Document Server

    Bayer, Justin; van der Smagt, Patrick

    2011-01-01

    Recurrent neural networks (RNNs) in combination with a pooling operator and the neighbourhood components analysis (NCA) objective function are able to detect the characterizing dynamics of sequences and embed them into a fixed-length vector space of arbitrary dimensionality. Subsequently, the resulting features are meaningful and can be used for visualization or nearest neighbour classification in linear time. This kind of metric learning for sequential data enables the use of algorithms tailored towards fixed length vector spaces such as R^n.

  1. Sequence Classification: 885394 [

    Lifescience Database Archive (English)

    Full Text Available 703); The expression pattern of this gene is described in PMID:12000842; possible frameshift detected when compared...Non-TMB TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|23619146|ref|NP_705108.1| Slight difference exist when compa...red to the published sequence of EBL-1 from Dd2 strain of P. falciparum (PMID:10613

  2. Image sequence analysis

    CERN Document Server

    1981-01-01

    The processing of image sequences has a broad spectrum of important applica­ tions including target tracking, robot navigation, bandwidth compression of TV conferencing video signals, studying the motion of biological cells using microcinematography, cloud tracking, and highway traffic monitoring. Image sequence processing involves a large amount of data. However, because of the progress in computer, LSI, and VLSI technologies, we have now reached a stage when many useful processing tasks can be done in a reasonable amount of time. As a result, research and development activities in image sequence analysis have recently been growing at a rapid pace. An IEEE Computer Society Workshop on Computer Analysis of Time-Varying Imagery was held in Philadelphia, April 5-6, 1979. A related special issue of the IEEE Transactions on Pattern Anal­ ysis and Machine Intelligence was published in November 1980. The IEEE Com­ puter magazine has also published a special issue on the subject in 1981. The purpose of this book ...

  3. Information Theory of DNA Sequencing

    CERN Document Server

    Motahari, Abolfazl; Tse, David

    2012-01-01

    DNA sequencing is the basic workhorse of modern day biology and medicine. Shotgun sequencing is the dominant technique used: many randomly located short fragments called reads are extracted from the DNA sequence, and these reads are assembled to reconstruct the original sequence. By drawing an analogy between the DNA sequencing problem and the classic communication problem, we define an information theoretic notion of sequencing capacity. This is the maximum number of DNA base pairs that can be resolved reliably per read, and provides a fundamental limit to the performance that can be achieved by any assembly algorithm. We compute the sequencing capacity explicitly for a simple statistical model of the DNA sequence and the read process. Using this framework, we also study the impact of noise in the read process on the sequencing capacity.

  4. Psychoacoustic Properties of Fibonacci Sequences

    Directory of Open Access Journals (Sweden)

    J. Sokoll

    2008-01-01

    Full Text Available 1202, Fibonacci set up one of the most interesting sequences in number theory. This sequence can be represented by so-called Fibonacci Numbers, and by a binary sequence of zeros and ones. If such a binary Fibonacci Sequence is played back as an audio file, a very dissonant sound results. This is caused by the “almost-periodic”, “self-similar” property of the binary sequence. The ratio of zeros and ones converges to the golden ratio, as do the primary and secondary spectral components intheir frequencies and amplitudes. These Fibonacci Sequences will be characterized using listening tests and psychoacoustic analyses. 

  5. Protocols for 16S rDNA Array Analyses of Microbial Communities by Sequence-Specific Labeling of DNA Probes

    Directory of Open Access Journals (Sweden)

    Knut Rudi

    2003-01-01

    Full Text Available Analyses of complex microbial communities are becoming increasingly important. Bottlenecks in these analyses, however, are the tools to actually describe the biodiversity. Novel protocols for DNA array-based analyses of microbial communities are presented. In these protocols, the specificity obtained by sequence-specific labeling of DNA probes is combined with the possibility of detecting several different probes simultaneously by DNA array hybridization. The gene encoding 16S ribosomal RNA was chosen as the target in these analyses. This gene contains both universally conserved regions and regions with relatively high variability. The universally conserved regions are used for PCR amplification primers, while the variable regions are used for the specific probes. Protocols are presented for DNA purification, probe construction, probe labeling, and DNA array hybridizations.

  6. Allele Re-sequencing Technologies

    DEFF Research Database (Denmark)

    Byrne, Stephen; Farrell, Jacqueline Danielle; Asp, Torben

    2013-01-01

    The development of next-generation sequencing technologies has made sequencing an affordable approach for detection of genetic variations associated with various traits. However, the cost of whole genome re-sequencing still remains too high to be feasible for many plant species with large and com...... alternative to whole genome re-sequencing to identify causative genetic variations in plants. One challenge, however, will be efficient bioinformatics strategies for data handling and analysis from the increasing amount of sequence information.......The development of next-generation sequencing technologies has made sequencing an affordable approach for detection of genetic variations associated with various traits. However, the cost of whole genome re-sequencing still remains too high to be feasible for many plant species with large...

  7. Spaces of Ideal Convergent Sequences

    Directory of Open Access Journals (Sweden)

    M. Mursaleen

    2014-01-01

    Full Text Available In the present paper, we introduce some sequence spaces using ideal convergence and Musielak-Orlicz function ℳ=Mk. We also examine some topological properties of the resulting sequence spaces.

  8. Novel sequences propel familiar folds.

    Science.gov (United States)

    Jawad, Zahra; Paoli, Massimo

    2002-04-01

    Recent structure determinations have made new additions to a set of strikingly different sequences that give rise to the same topology. Proteins with a beta propeller fold are characterized by extreme sequence diversity despite the similarity in their three-dimensional structures. Several fold predictions, based in part on sequence repeats thought to match modular beta sheets, have been proved correct.

  9. Sequencing Games with Repeated Players

    NARCIS (Netherlands)

    Estevez Fernandez, M.A.; Borm, P.E.M.; Calleja, P.; Hamers, H.J.M.

    2004-01-01

    Two classes of one machine sequencing situations are considered in which each job corresponds to exactly one player but a player may have more than one job to be processed, so called RP(repeated player) sequencing situations.In max-RP sequencing situations it is assumed that each player's cost funct

  10. Rapid Polymer Sequencer

    Science.gov (United States)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  11. The Galaxy End Sequence

    CERN Document Server

    Eales, Stephen; Smith, Matthew; Appah, Kiran; Ciesla, Laure; Duffield, Chris; Schofield, Simon

    2016-01-01

    A common assumption is that galaxies fall in two distinct regions on a plot of specific star-formation rate (SSFR) versus galaxy stellar mass: a star-forming Galaxy Main Sequence (GMS) and a separate region of `passive' or `red and dead galaxies'. Starting from a volume-limited sample of nearby galaxies designed to contain most of the stellar mass in this volume, and thus being a fair representation of the Universe at the end of 12 billion years of galaxy evolution, we investigate the distribution of galaxies in this diagram today. We show that galaxies follow a strongly curved extended GMS with a steep negative slope at high galaxy stellar masses. There is a gradual change in the morphologies of the galaxies along this distribution, but there is no clear break between early-type and late-type galaxies. Examining the other evidence that there are two distinct populations, we argue that the `red sequence' is the result of the colours of galaxies changing very little below a critical value of the SSFR, rather t...

  12. Complete Convergence of Exchangeable Sequences

    Directory of Open Access Journals (Sweden)

    George Stoica

    2011-01-01

    Full Text Available We prove that exchangeable sequences converge completely in the Baum-Katz sense under the same conditions as i.i.d. sequences do. Problem statement: The research was needed as the rate of convergence in the law of large numbers for exchangeable sequences was previously obtained under restricted hypotheses. Approach: We applied powerful techniques involving inequalities for independent sequences of random variables. Results: We obtained the maximal rate of convergence and provided an example to show that our findings are sharp. Conclusion/Recommendations: The technique used in the paper may be adapted in the similar study for identically distributed sequences.

  13. Review of alignment and SNP calling algorithms for next-generation sequencing data.

    Science.gov (United States)

    Mielczarek, M; Szyda, J

    2016-02-01

    Application of the massive parallel sequencing technology has become one of the most important issues in life sciences. Therefore, it was crucial to develop bioinformatics tools for next-generation sequencing (NGS) data processing. Currently, two of the most significant tasks include alignment to a reference genome and detection of single nucleotide polymorphisms (SNPs). In many types of genomic analyses, great numbers of reads need to be mapped to the reference genome; therefore, selection of the aligner is an essential step in NGS pipelines. Two main algorithms-suffix tries and hash tables-have been introduced for this purpose. Suffix array-based aligners are memory-efficient and work faster than hash-based aligners, but they are less accurate. In contrast, hash table algorithms tend to be slower, but more sensitive. SNP and genotype callers may also be divided into two main different approaches: heuristic and probabilistic methods. A variety of software has been subsequently developed over the past several years. In this paper, we briefly review the current development of NGS data processing algorithms and present the available software.

  14. Solid phase sequencing of biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles (Del Mar, CA); Koster, Hubert (La Jolla, CA)

    2010-09-28

    This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

  15. The Evolution of Nanopore Sequencing

    Directory of Open Access Journals (Sweden)

    Yue eWang

    2015-01-01

    Full Text Available The $1,000 Genome project has been drawing increasing attention since its launch a decade ago. Nanopore sequencing, the third-generation, is believed to be one of the most promising sequencing technologies to reach four gold standards set for the $1,000 Genome while the second-generation sequencing technologies are bringing about a revolution in life sciences, particularly in genome sequencing-based personalized medicine. Both of protein and solid-state nanopores have been extensively investigated for a series of issues, from detection of ionic current blockage to field-effect-transistor (FET sensors. A newly released protein nanopore sequencer has shown encouraging potential that nanopore sequencing will ultimately fulfill the gold standards. In this review, we address advances, challenges, and possible solutions of nanopore sequencing according to these standards.

  16. Universal sequence map (USM of arbitrary discrete sequences

    Directory of Open Access Journals (Sweden)

    Almeida Jonas S

    2002-02-01

    Full Text Available Abstract Background For over a decade the idea of representing biological sequences in a continuous coordinate space has maintained its appeal but not been fully realized. The basic idea is that any sequence of symbols may define trajectories in the continuous space conserving all its statistical properties. Ideally, such a representation would allow scale independent sequence analysis – without the context of fixed memory length. A simple example would consist on being able to infer the homology between two sequences solely by comparing the coordinates of any two homologous units. Results We have successfully identified such an iterative function for bijective mappingψ of discrete sequences into objects of continuous state space that enable scale-independent sequence analysis. The technique, named Universal Sequence Mapping (USM, is applicable to sequences with an arbitrary length and arbitrary number of unique units and generates a representation where map distance estimates sequence similarity. The novel USM procedure is based on earlier work by these and other authors on the properties of Chaos Game Representation (CGR. The latter enables the representation of 4 unit type sequences (like DNA as an order free Markov Chain transition table. The properties of USM are illustrated with test data and can be verified for other data by using the accompanying web-based tool:http://bioinformatics.musc.edu/~jonas/usm/. Conclusions USM is shown to enable a statistical mechanics approach to sequence analysis. The scale independent representation frees sequence analysis from the need to assume a memory length in the investigation of syntactic rules.

  17. Solid phase sequencing of biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles R.; Hubert, Koster

    2014-06-24

    This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Probes may be affixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

  18. Turtle Graphics of Morphic Sequences

    Science.gov (United States)

    Zantema, Hans

    2016-02-01

    The simplest infinite sequences that are not ultimately periodic are pure morphic sequences: fixed points of particular morphisms mapping single symbols to strings of symbols. A basic way to visualize a sequence is by a turtle curve: for every alphabet symbol fix an angle, and then consecutively for all sequence elements draw a unit segment and turn the drawing direction by the corresponding angle. This paper investigates turtle curves of pure morphic sequences. In particular, criteria are given for turtle curves being finite (consisting of finitely many segments), and for being fractal or self-similar: it contains an up-scaled copy of itself. Also space-filling turtle curves are considered, and a turtle curve that is dense in the plane. As a particular result we give an exact relationship between the Koch curve and a turtle curve for the Thue-Morse sequence, where until now for such a result only approximations were known.

  19. Graphene nanodevices for DNA sequencing

    Science.gov (United States)

    Heerema, Stephanie J.; Dekker, Cees

    2016-02-01

    Fast, cheap, and reliable DNA sequencing could be one of the most disruptive innovations of this decade, as it will pave the way for personalized medicine. In pursuit of such technology, a variety of nanotechnology-based approaches have been explored and established, including sequencing with nanopores. Owing to its unique structure and properties, graphene provides interesting opportunities for the development of a new sequencing technology. In recent years, a wide range of creative ideas for graphene sequencers have been theoretically proposed and the first experimental demonstrations have begun to appear. Here, we review the different approaches to using graphene nanodevices for DNA sequencing, which involve DNA passing through graphene nanopores, nanogaps, and nanoribbons, and the physisorption of DNA on graphene nanostructures. We discuss the advantages and problems of each of these key techniques, and provide a perspective on the use of graphene in future DNA sequencing technology.

  20. Short sequence motifs, overrepresented in mammalian conservednon-coding sequences

    Energy Technology Data Exchange (ETDEWEB)

    Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

    2007-02-21

    Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by

  1. Application of difference sequences theory

    OpenAIRE

    Khantarzhiev, Georgii

    2013-01-01

    The results of difference sequences theory are applied to analytic function theory and Diophantine equations. As a result we have the equation which connects the $n$-th derivative of a function with the difference sequence for the values of this function. Also the results of difference sequences theory helps to discover some features of the whole kind of Diophantine equations. The method presented allows to find limits where Diophantine equation does not have integer solutions. The higher pow...

  2. Nonlinear analysis of biological sequences

    Energy Technology Data Exchange (ETDEWEB)

    Torney, D.C.; Bruno, W.; Detours, V. [and others

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The main objectives of this project involved deriving new capabilities for analyzing biological sequences. The authors focused on tabulating the statistical properties exhibited by Human coding DNA sequences and on techniques of inferring the phylogenetic relationships among protein sequences related by descent.

  3. Blazar Sequence in Fermi Era

    Indian Academy of Sciences (India)

    Liang Chen

    2014-09-01

    In this paper, we review the latest research results on the topic of blazar sequence. It seems that the blazar sequence is phenomenally ruled out, while the theoretical blazar sequence still holds. We point out that black hole mass is a dominated parameter accounting for high-power-high-synchrotron-peaked and low-power-low-sychrotron-peaked blazars. Because most blazars have similar size of emission region, theoretical blazar sequence implies that the break of Spectral Energy Distribution (SED) is a cooling break in nature.

  4. SNMR pulse sequence phase cycling

    Science.gov (United States)

    Walsh, David O; Grunewald, Elliot D

    2013-11-12

    Technologies applicable to SNMR pulse sequence phase cycling are disclosed, including SNMR acquisition apparatus and methods, SNMR processing apparatus and methods, and combinations thereof. SNMR acquisition may include transmitting two or more SNMR pulse sequences and applying a phase shift to a pulse in at least one of the pulse sequences, according to any of a variety cycling techniques. SNMR processing may include combining SNMR from a plurality of pulse sequences comprising pulses of different phases, so that desired signals are preserved and indesired signals are canceled.

  5. Assembly sequencing with toleranced parts

    Energy Technology Data Exchange (ETDEWEB)

    Latombe, J.C. [Stanford Univ., CA (United States). Robotics Lab.; Wilson, R.H. [Sandia National Labs., Albuquerque, NM (United States). Intelligent Systems and Robotics Center

    1995-02-21

    The goal of assembly sequencing is to plan a feasible series of operations to construct a product from its individual parts. Previous research has thoroughly investigated assembly sequencing under the assumption that parts have nominal geometry. This paper considers the case where parts have toleranced geometry. Its main contribution is an efficient procedure that decides if a product admits an assembly sequence with infinite translations that is feasible for all possible instances of the components within the specified tolerances. If the product admits one such sequence, the procedure can also generate it. For the cases where there exists no such assembly sequence, another procedure is proposed which generates assembly sequences that are feasible only for some values of the toleranced dimensions. If this procedure produces no such sequence, then no instance of the product is assemblable. Finally, this paper analyzes the relation between assembly and disassembly sequences in the presence of toleranced parts. This work assumes a simple, but non-trivial tolerance language that falls short of capturing all imperfections of a manufacturing process. Hence, it is only one step toward assembly sequencing with toleranced parts.

  6. The ontology of biological sequences

    Directory of Open Access Journals (Sweden)

    Kelso Janet

    2009-11-01

    Full Text Available Abstract Background Biological sequences play a major role in molecular and computational biology. They are studied as information-bearing entities that make up DNA, RNA or proteins. The Sequence Ontology, which is part of the OBO Foundry, contains descriptions and definitions of sequences and their properties. Yet the most basic question about sequences remains unanswered: what kind of entity is a biological sequence? An answer to this question benefits formal ontologies that use the notion of biological sequences and analyses in computational biology alike. Results We provide both an ontological analysis of biological sequences and a formal representation that can be used in knowledge-based applications and other ontologies. We distinguish three distinct kinds of entities that can be referred to as "biological sequence": chains of molecules, syntactic representations such as those in biological databases, and the abstract information-bearing entities. For use in knowledge-based applications and inclusion in biomedical ontologies, we implemented the developed axiom system for use in automated theorem proving. Conclusion Axioms are necessary to achieve the main goal of ontologies: to formally specify the meaning of terms used within a domain. The axiom system for the ontology of biological sequences is the first elaborate axiom system for an OBO Foundry ontology and can serve as starting point for the development of more formal ontologies and ultimately of knowledge-based applications.

  7. ABS: Sequence alignment by scanning

    KAUST Repository

    Bonny, Mohamed Talal

    2011-08-01

    Sequence alignment is an essential tool in almost any computational biology research. It processes large database sequences and considered to be high consumers of computation time. Heuristic algorithms are used to get approximate but fast results. We introduce fast alignment algorithm, called Alignment By Scanning (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the well-known alignment algorithms, the FASTA (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 76% enhancement in alignment score when it is compared with the FASTA Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  8. Fast global sequence alignment technique

    KAUST Repository

    Bonny, Mohamed Talal

    2011-11-01

    Bioinformatics database is growing exponentially in size. Processing these large amount of data may take hours of time even if super computers are used. One of the most important processing tool in Bioinformatics is sequence alignment. We introduce fast alignment algorithm, called \\'Alignment By Scanning\\' (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the wellknown sequence alignment algorithms, the \\'GAP\\' (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 51% enhancement in alignment score when it is compared with the GAP Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  9. Multilocus Sequence Typing of Total-Genome-Sequenced Bacteria

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Cosentino, Salvatore; Rasmussen, Simon;

    2012-01-01

    Accurate strain identification is essential for anyone working with bacteria. For many species, multilocus sequence typing (MLST) is considered the "gold standard" of typing, but it is traditionally performed in an expensive and time-consuming manner. As the costs of whole-genome sequencing (WGS)...

  10. Finite extensions of Bessel sequences

    OpenAIRE

    Bakić, Damir; Berić, Tomislav

    2015-01-01

    The paper studies finite extensions of Bessel sequences in infinite-dimensional Hilbert spaces. We provide a characterization of Bessel sequences that can be extended to frames by adding finitely many vectors. We also characterize frames that can be converted to Parseval frames by finite-dimensional perturbations. Finally, some results on excesses of frames and near-Riesz bases are derived.

  11. Sequence conserved for subcellular localization

    Science.gov (United States)

    Nair, Rajesh; Rost, Burkhard

    2002-01-01

    The more proteins diverged in sequence, the more difficult it becomes for bioinformatics to infer similarities of protein function and structure from sequence. The precise thresholds used in automated genome annotations depend on the particular aspect of protein function transferred by homology. Here, we presented the first large-scale analysis of the relation between sequence similarity and identity in subcellular localization. Three results stood out: (1) The subcellular compartment is generally more conserved than what might have been expected given that short sequence motifs like nuclear localization signals can alter the native compartment; (2) the sequence conservation of localization is similar between different compartments; and (3) it is similar to the conservation of structure and enzymatic activity. In particular, we found the transition between the regions of conserved and nonconserved localization to be very sharp, although the thresholds for conservation were less well defined than for structure and enzymatic activity. We found that a simple measure for sequence similarity accounting for pairwise sequence identity and alignment length, the HSSP distance, distinguished accurately between protein pairs of identical and different localizations. In fact, BLAST expectation values outperformed the HSSP distance only for alignments in the subtwilight zone. We succeeded in slightly improving the accuracy of inferring localization through homology by fine tuning the thresholds. Finally, we applied our results to the entire SWISS-PROT database and five entirely sequenced eukaryotes. PMID:12441382

  12. PERIODIC COMPLEMENTARY BINARY SEQUENCE PAIRS

    Institute of Scientific and Technical Information of China (English)

    XuChengqian; ZhaoXiaoqun

    2002-01-01

    A new set of binary sequences-Periodic Complementary Binary Sequence Pair (PCSP)is proposed .A new class of block design-Difference Family Pair (DFP)is also proposed .The relationship between PCSP and DFP,the properties and exising conditions of PCSP and the recursive constructions for PCSP are given.

  13. PERIODIC COMPLEMENTARY BINARY SEQUENCE PAIRS

    Institute of Scientific and Technical Information of China (English)

    Xu Chengqian; Zhao Xiaoqun

    2002-01-01

    A new set of binary sequences-Periodic Complementary Binary Sequence Pair (PCSP) is proposed. A new class of block design-Difference Family Pair (DFP) is also proposed.The relationship between PCSP and DFP, the properties and existing conditions of PCSP and the recursive constructions for PCSP are given.

  14. Rapid Diagnostics of Onboard Sequences

    Science.gov (United States)

    Starbird, Thomas W.; Morris, John R.; Shams, Khawaja S.; Maimone, Mark W.

    2012-01-01

    Keeping track of sequences onboard a spacecraft is challenging. When reviewing Event Verification Records (EVRs) of sequence executions on the Mars Exploration Rover (MER), operators often found themselves wondering which version of a named sequence the EVR corresponded to. The lack of this information drastically impacts the operators diagnostic capabilities as well as their situational awareness with respect to the commands the spacecraft has executed, since the EVRs do not provide argument values or explanatory comments. Having this information immediately available can be instrumental in diagnosing critical events and can significantly enhance the overall safety of the spacecraft. This software provides auditing capability that can eliminate that uncertainty while diagnosing critical conditions. Furthermore, the Restful interface provides a simple way for sequencing tools to automatically retrieve binary compiled sequence SCMFs (Space Command Message Files) on demand. It also enables developers to change the underlying database, while maintaining the same interface to the existing applications. The logging capabilities are also beneficial to operators when they are trying to recall how they solved a similar problem many days ago: this software enables automatic recovery of SCMF and RML (Robot Markup Language) sequence files directly from the command EVRs, eliminating the need for people to find and validate the corresponding sequences. To address the lack of auditing capability for sequences onboard a spacecraft during earlier missions, extensive logging support was added on the Mars Science Laboratory (MSL) sequencing server. This server is responsible for generating all MSL binary SCMFs from RML input sequences. The sequencing server logs every SCMF it generates into a MySQL database, as well as the high-level RML file and dictionary name inputs used to create the SCMF. The SCMF is then indexed by a hash value that is automatically included in all command

  15. Spatiotemporal correlations of aftershock sequences

    CERN Document Server

    Peixoto, Tiago P; Davidsen, Jörn

    2010-01-01

    Aftershock sequences are of particular interest in seismic research since they may condition seismic activity in a given region over long time spans. While they are typically identified with periods of enhanced seismic activity after a large earthquake as characterized by the Omori law, our knowledge of the spatiotemporal correlations between events in an aftershock sequence is limited. Here, we study the spatiotemporal correlations of two aftershock sequences form California (Parkfield and Hector Mine) using the recently introduced concept of "recurrent" events. We find that both sequences have very similar properties and that most of them are captured by the space-time epidemic-type aftershock sequence (ETAS) model if one takes into account catalog incompleteness. However, the stochastic model does not capture the spatiotemporal correlations leading to the observed structure of seismicity on small spatial scales.

  16. Multilocus sequence typing of total-genome-sequenced bacteria.

    Science.gov (United States)

    Larsen, Mette V; Cosentino, Salvatore; Rasmussen, Simon; Friis, Carsten; Hasman, Henrik; Marvig, Rasmus Lykke; Jelsbak, Lars; Sicheritz-Pontén, Thomas; Ussery, David W; Aarestrup, Frank M; Lund, Ole

    2012-04-01

    Accurate strain identification is essential for anyone working with bacteria. For many species, multilocus sequence typing (MLST) is considered the "gold standard" of typing, but it is traditionally performed in an expensive and time-consuming manner. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available to scientists and routine diagnostic laboratories. Currently, the cost is below that of traditional MLST. The new challenges will be how to extract the relevant information from the large amount of data so as to allow for comparison over time and between laboratories. Ideally, this information should also allow for comparison to historical data. We developed a Web-based method for MLST of 66 bacterial species based on WGS data. As input, the method uses short sequence reads from four sequencing platforms or preassembled genomes. Updates from the MLST databases are downloaded monthly, and the best-matching MLST alleles of the specified MLST scheme are found using a BLAST-based ranking method. The sequence type is then determined by the combination of alleles identified. The method was tested on preassembled genomes from 336 isolates covering 56 MLST schemes, on short sequence reads from 387 isolates covering 10 schemes, and on a small test set of short sequence reads from 29 isolates for which the sequence type had been determined by traditional methods. The method presented here enables investigators to determine the sequence types of their isolates on the basis of WGS data. This method is publicly available at www.cbs.dtu.dk/services/MLST. PMID:22238442

  17. Generation and analysis of expressed sequence tags from the medicinal plant Salvia miltiorrhiza

    Institute of Scientific and Technical Information of China (English)

    SPENCER; David; F

    2010-01-01

    Salvia miltiorrhiza Bge.is a well-known traditional Chinese herb.Its roots have been formulated and used clinically for the treatment of various diseases.However,little genetic information has so far been available and this fact has become a major obstacle for molecular studies.To address this lack of genetic information,an Expressed Sequence Tag (EST) library from whole plantlets of S.miltiorrhiza was generated.From the 12959 cDNA clones that were randomly selected and subjected to single-pass sequencing from their 5′ ends,10288 ESTs (with sizes≥100 bp) were selected and assembled into 1288 contigs,leaving 2937 singletons,for a total of 4225 unigenes.These were analyzed using BLASTX (against protein databases),RPS-BLAST (against a conserved domain database) as well as the web-based KEGG Automatic Annotation Server for metabolic enzyme assignment.Based on the metabolic enzyme assignment,expression patterns of 14 secondary metabolic enzyme genes in different organs and under different treatments were verified using real-time PCR analysis.Additionally,a total of 122 microsatellites were identified from the ESTs,with 89 having sufficient flanking sequences for primer design.This set of ESTs represents a significant proportion of the S.miltiorrhiza transcriptome,and gives preliminary insights into the gene complement of S.miltiorrhiza.They will prove useful for uncovering secondary metabolic pathways,analyzing cDNA-array based gene expression,genetic manipulation to improve yield of desirable secondary products,and molecular marker identification.

  18. Ossification sequence heterochrony among amphibians.

    Science.gov (United States)

    Harrington, Sean M; Harrison, Luke B; Sheil, Christopher A

    2013-01-01

    Heterochrony is an important mechanism in the evolution of amphibians. Although studies have centered on the relationship between size and shape and the rates of development, ossification sequence heterochrony also may have been important. Rigorous, phylogenetic methods for assessing sequence heterochrony are relatively new, and a comprehensive study of the relative timing of ossification of skeletal elements has not been used to identify instances of sequence heterochrony across Amphibia. In this study, a new version of the program Parsimov-based genetic inference (PGi) was used to identify shifts in ossification sequences across all extant orders of amphibians, for all major structural units of the skeleton. PGi identified a number of heterochronic sequence shifts in all analyses, the most interesting of which seem to be tied to differences in metamorphic patterns among major clades. Early ossification of the vomer, premaxilla, and dentary is retained by Apateon caducus and members of Gymnophiona and Urodela, which lack the strongly biphasic development seen in anurans. In contrast, bones associated with the jaws and face were identified as shifting late in the ancestor of Anura. The bones that do not shift late, and thereby occupy the earliest positions in the anuran cranial sequence, are those in regions of the skull that undergo the least restructuring throughout anuran metamorphosis. Additionally, within Anura, bones of the hind limb and pelvic girdle were also identified as shifting early in the sequence of ossification, which may be a result of functional constraints imposed by the drastic metamorphosis of most anurans.

  19. Variational Sequences, Representation Sequences and Applications in Physics

    OpenAIRE

    Palese, Marcella; Rossi, Olga; Winterroth, Ekkehart; Musilová, Jana

    2015-01-01

    This paper is a review containing new original results on the finite order variational sequence and its different representations with emphasis on applications in the theory of variational symmetries and conservation laws in physics.

  20. A Criterion for Regular Sequences

    Indian Academy of Sciences (India)

    D P Patil; U Storch; J Stückrad

    2004-05-01

    Let be a commutative noetherian ring and $f_1,\\ldots,f_r \\in R$. In this article we give (cf. the Theorem in $\\mathcal{x}$2) a criterion for $f_1,\\ldots,f_r$ to be regular sequence for a finitely generated module over which strengthens and generalises a result in [2]. As an immediate consequence we deduce that if $V(g_1,\\ldots,g_r) \\subseteq V(f_1,\\ldots,f_r)$ in Spec and if $f_1,\\ldots,f_r$ is a regular sequence in , then $g_1,\\ldots,g_r$ is also a regular sequence in .

  1. New Orthogonal Small Set Kasami Code Sequence

    OpenAIRE

    I Nyoman Pramaita; I G.A.G.K. Diafari; DNKP Negara; Agus Dharma

    2015-01-01

    In this paper, the authors propose the design of a new orthogonal small set Kasami code sequence generated using combination of non-orthogonal m-sequence and small set Kasami code sequence. The authors demonstrate that the proposed code sequence has comparable auto-correlation function (ACF), cross- correlation function (CCF), peak cross-correlation values with that of the existing orthogonal small set Kasami code sequence. Though the proposed code sequence has less code sequence sets than th...

  2. Using comparative genomic hybridization to survey genomic sequence divergence across species: a proof-of-concept from Drosophila

    Directory of Open Access Journals (Sweden)

    Kulathinal Rob J

    2010-04-01

    Full Text Available Abstract Background Genome-wide analysis of sequence divergence among species offers profound insights into the evolutionary processes that shape lineages. When full-genome sequencing is not feasible for a broad comparative study, we propose the use of array-based comparative genomic hybridization (aCGH in order to identify orthologous genes with high sequence divergence. Here we discuss experimental design, statistical power, success rate, sources of variation and potential confounding factors. We used a spotted PCR product microarray platform from Drosophila melanogaster to assess sequence divergence on a gene-by-gene basis in three fully sequenced heterologous species (D. sechellia, D. simulans, and D. yakuba. Because complete genome assemblies are available for these species this study presents a powerful test for the use of aCGH as a tool to measure sequence divergence. Results We found a consistent and linear relationship between hybridization ratio and sequence divergence of the sample to the platform species. At higher levels of sequence divergence (D. melanogaster ~84% of features had significantly less hybridization to the array in the heterologous species than the platform species, and thus could be identified as "diverged". At lower levels of divergence (≥ 97% identity, only 13% of genes were identified as diverged. While ~40% of the variation in hybridization ratio can be accounted for by variation in sequence identity of the heterologous sample relative to D. melanogaster, other individual characteristics of the DNA sequences, such as GC content, also contribute to variation in hybridization ratio, as does technical variation. Conclusions Here we demonstrate that aCGH can accurately be used as a proxy to estimate genome-wide divergence, thus providing an efficient way to evaluate how evolutionary processes and genomic architecture can shape species diversity in non-model systems. Given the increased number of species for which

  3. ISIS Individualized Support In Sequencing

    NARCIS (Netherlands)

    Drachsler, Hendrik; Hummel, Hans

    2007-01-01

    Drachsler, H., & Hummel, H. G. K. (2007). ISIS Individualized Support In Sequencing. Presentation given during the PIP meeting on March 22, 2007. Open University of the Netherlands: Heerlen, The Netherlands.

  4. DNA Sequencing Using capillary Electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Barry Karger

    2011-05-09

    The overall goal of this program was to develop capillary electrophoresis as the tool to be used to sequence for the first time the Human Genome. Our program was part of the Human Genome Project. In this work, we were highly successful and the replaceable polymer we developed, linear polyacrylamide, was used by the DOE sequencing lab in California to sequence a significant portion of the human genome using the MegaBase multiple capillary array electrophoresis instrument. In this final report, we summarize our efforts and success. We began our work by separating by capillary electrophoresis double strand oligonucleotides using cross-linked polyacrylamide gels in fused silica capillaries. This work showed the potential of the methodology. However, preparation of such cross-linked gel capillaries was difficult with poor reproducibility, and even more important, the columns were not very stable. We improved stability by using non-cross linked linear polyacrylamide. Here, the entangled linear chains could move when osmotic pressure (e.g. sample injection) was imposed on the polymer matrix. This relaxation of the polymer dissipated the stress in the column. Our next advance was to use significantly lower concentrations of the linear polyacrylamide that the polymer could be automatically blown out after each run and replaced with fresh linear polymer solution. In this way, a new column was available for each analytical run. Finally, while testing many linear polymers, we selected linear polyacrylamide as the best matrix as it was the most hydrophilic polymer available. Under our DOE program, we demonstrated initially the success of the linear polyacrylamide to separate double strand DNA. We note that the method is used even today to assay purity of double stranded DNA fragments. Our focus, of course, was on the separation of single stranded DNA for sequencing purposes. In one paper, we demonstrated the success of our approach in sequencing up to 500 bases. Other

  5. Guitars, Violins, and Geometric Sequences

    Science.gov (United States)

    Barger, Rita; Haehl, Martha

    2007-01-01

    This article describes middle school mathematics activities that relate measurement, ratios, and geometric sequences to finger positions or the placement of frets on stringed musical instruments. (Contains 2 figures and 2 tables.)

  6. Pythagorean Triples from Harmonic Sequences.

    Science.gov (United States)

    DiDomenico, Angelo S.; Tanner, Randy J.

    2001-01-01

    Shows how all primitive Pythagorean triples can be generated from harmonic sequences. Use inductive and deductive reasoning to explore how Pythagorean triples are connected with another area of mathematics. (KHR)

  7. Classification of Base Sequences (+1,

    Directory of Open Access Journals (Sweden)

    Dragomir Ž. Ðoković

    2010-01-01

    Full Text Available Base sequences BS(+1, are quadruples of {±1}-sequences (;;;, with A and B of length +1 and C and D of length n, such that the sum of their nonperiodic autocor-relation functions is a -function. The base sequence conjecture, asserting that BS(+1, exist for all n, is stronger than the famous Hadamard matrix conjecture. We introduce a new definition of equivalence for base sequences BS(+1, and construct a canonical form. By using this canonical form, we have enumerated the equivalence classes of BS(+1, for ≤30. As the number of equivalence classes grows rapidly (but not monotonically with n, the tables in the paper cover only the cases ≤13.

  8. The Conditional Sequence Information Function

    Directory of Open Access Journals (Sweden)

    Osman Guzide

    2010-01-01

    Full Text Available Problem statement: A great deal of attention has been given to the theory of information. It has found its applications in science especially in the area of Biothecnology. Previous studies on the subject has been limited to either conditional or sequence problem solving. This study combines both conditional and sequence properties of the information function. By doing this, researchers can find solutions to more problems that are applicable in real life. Approach: First, properties of the dynamical systems and the information function defined by Shannon has been provided, Then, the conditional sequence information function of a dynamical system together with its proof was presented. Result: This new function now exists now and ready for the use in many real life problems such as finding solutions to DNA sequence with conditional sickness. Conclusion: This new function created opens a new avenue to researches in solving more complex problems by using its developed properties.

  9. Mining protein sequences for motifs.

    Science.gov (United States)

    Narasimhan, Giri; Bu, Changsong; Gao, Yuan; Wang, Xuning; Xu, Ning; Mathee, Kalai

    2002-01-01

    We use methods from Data Mining and Knowledge Discovery to design an algorithm for detecting motifs in protein sequences. The algorithm assumes that a motif is constituted by the presence of a "good" combination of residues in appropriate locations of the motif. The algorithm attempts to compile such good combinations into a "pattern dictionary" by processing an aligned training set of protein sequences. The dictionary is subsequently used to detect motifs in new protein sequences. Statistical significance of the detection results are ensured by statistically determining the various parameters of the algorithm. Based on this approach, we have implemented a program called GYM. The Helix-Turn-Helix motif was used as a model system on which to test our program. The program was also extended to detect Homeodomain motifs. The detection results for the two motifs compare favorably with existing programs. In addition, the GYM program provides a lot of useful information about a given protein sequence. PMID:12487759

  10. Modified Genetic Algorithm for DNA Sequence Assembly by Shotgun and Hybridization Sequencing Techniques

    OpenAIRE

    Prof.Narayan Kumar Sahu; Prof.Somesh Dewangan; Prof.Akash Wanjari

    2012-01-01

    Since the advent of rapid DNA sequencing methods in 1976, scientists have had the problem of inferring DNA sequences from sequenced fragments. Shotgun sequencing is a well-established biological and computational method used in practice. Many conventional algorithms for shotgun sequencing are based on the notion of pair wise fragment overlap. While shotgun sequencing infers a DNA sequence given the sequences of overlapping fragments, a recent and complementary method, called sequencing by hy...

  11. Sequence diversity and functional conformity

    OpenAIRE

    de Lange, Orlando

    2015-01-01

    At least four phylogenetically distinct groups of bacteria encode repeat proteins with the common ability to bind specific DNA sequences with a unique but conserved code. Each repeat binds a single DNA base, and specificity is determined by the amino acid residue at position 13 of each repeat. Repeats are typically 33-35 amino acids long. Comparing repeat sequences across all groups reveals that only three positions are hyper-conserved. Repeats are in most cases functionally compatible such t...

  12. On train track splitting sequences

    CERN Document Server

    Masur, Howard; Schleimer, Saul

    2010-01-01

    We show that the subsurface projection of a train track splitting sequence is an unparameterized quasi-geodesic in the curve complex of the subsurface. For the proof we introduce induced tracks, efficient position, and wide curves. This result is an important step in the proof that the disk complex is Gromov hyperbolic. As another application we show that train track sliding and splitting sequences give quasi-geodesics in the train track graph, generalizing a result of Hamenstaedt [Invent. Math.].

  13. Integrated sequence analysis. Final report

    International Nuclear Information System (INIS)

    The NKS/RAK subprojet 3 'integrated sequence analysis' (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term 'methodology' denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  14. Structural complexity of DNA sequence.

    Science.gov (United States)

    Liou, Cheng-Yuan; Tseng, Shen-Han; Cheng, Wei-Chen; Tsai, Huai-Ying

    2013-01-01

    In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results. PMID:23662161

  15. Structural Complexity of DNA Sequence

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Liou

    2013-01-01

    Full Text Available In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results.

  16. Optimization of sequence alignment for simple sequence repeat regions

    Directory of Open Access Journals (Sweden)

    Ogbonnaya Francis C

    2011-07-01

    Full Text Available Abstract Background Microsatellites, or simple sequence repeats (SSRs, are tandemly repeated DNA sequences, including tandem copies of specific sequences no longer than six bases, that are distributed in the genome. SSR has been used as a molecular marker because it is easy to detect and is used in a range of applications, including genetic diversity, genome mapping, and marker assisted selection. It is also very mutable because of slipping in the DNA polymerase during DNA replication. This unique mutation increases the insertion/deletion (INDELs mutation frequency to a high ratio - more than other types of molecular markers such as single nucleotide polymorphism (SNPs. SNPs are more frequent than INDELs. Therefore, all designed algorithms for sequence alignment fit the vast majority of the genomic sequence without considering microsatellite regions, as unique sequences that require special consideration. The old algorithm is limited in its application because there are many overlaps between different repeat units which result in false evolutionary relationships. Findings To overcome the limitation of the aligning algorithm when dealing with SSR loci, a new algorithm was developed using PERL script with a Tk graphical interface. This program is based on aligning sequences after determining the repeated units first, and the last SSR nucleotides positions. This results in a shifting process according to the inserted repeated unit type. When studying the phylogenic relations before and after applying the new algorithm, many differences in the trees were obtained by increasing the SSR length and complexity. However, less distance between different linage had been observed after applying the new algorithm. Conclusions The new algorithm produces better estimates for aligning SSR loci because it reflects more reliable evolutionary relations between different linages. It reduces overlapping during SSR alignment, which results in a more realistic

  17. Genome Sequence of Canine Herpesvirus.

    Directory of Open Access Journals (Sweden)

    Konstantinos V Papageorgiou

    Full Text Available Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154 isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp and a unique short sequence (7.7 kbp that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively. The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease.

  18. Long-range barcode labeling-sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Feng; Zhang, Tao; Singh, Kanwar K.; Pennacchio, Len A.; Froula, Jeff L.; Eng, Kevin S.

    2016-10-18

    Methods for sequencing single large DNA molecules by clonal multiple displacement amplification using barcoded primers. Sequences are binned based on barcode sequences and sequenced using a microdroplet-based method for sequencing large polynucleotide templates to enable assembly of haplotype-resolved complex genomes and metagenomes.

  19. Pig genome sequence - analysis and publication strategy

    NARCIS (Netherlands)

    Archibald, A.L.; Bolund, L.; Churcher, C.; Fredholm, M.; Groenen, M.A.M.; Harlizius, B.

    2010-01-01

    Background - The pig genome is being sequenced and characterised under the auspices of the Swine Genome Sequencing Consortium. The sequencing strategy followed a hybrid approach combining hierarchical shotgun sequencing of BAC clones and whole genome shotgun sequencing. Results - Assemblies of the B

  20. Thread extraction for polyadic instruction sequences

    NARCIS (Netherlands)

    J.A. Bergstra; C.A. Middelburg

    2009-01-01

    Instruction sequences are often fragmented. An important reason for instruction sequence fragmentation is that the execution architecture at hand to execute instruction sequences sets bounds to the size of instruction sequences. In this paper, we study instruction sequences that have been split into

  1. A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX.

    Science.gov (United States)

    Ansari, Morad; Rainger, Jacqueline K; Murray, Jennie E; Hanson, Isabel; Firth, Helen V; Mehendale, Felicity; Amiel, Jeanne; Gordon, Christopher T; Percesepe, Antonio; Mazzanti, Laura; Fryer, Alan; Ferrari, Paola; Devriendt, Koenraad; Temple, I Karen; FitzPatrick, David R

    2014-10-01

    Pierre Robin sequence (PRS) is an aetiologically distinct subgroup of cleft palate. We aimed to define the critical genomic interval from five different 5q22-5q31 deletions associated with PRS or PRS-associated features and assess each gene within the region as a candidate for the PRS component of the phenotype. Clinical array-based comparative genome hybridisation (aCGH) data were used to define a 2.08 Mb minimum region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of PRS. Commonly associated anomalies were talipes equinovarus (TEV), finger contractures and crumpled ear helices. Expression analysis of the orthologous genes within the PRS critical region in embryonic mice showed that the strongest candidate genes were FBN2 and PHAX. Targeted aCGH of the critical region and sequencing of these genes in a cohort of 25 PRS patients revealed no plausible disease-causing mutations. In conclusion, deletion of ∼2 Mb on 5q23 region causes a clinically recognisable subtype of PRS. Haploinsufficiency for FBN2 accounts for the digital and auricular features. A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism.

  2. ARC Code TI: sequenceMiner

    Data.gov (United States)

    National Aeronautics and Space Administration — The sequenceMiner was developed to address the problem of detecting and describing anomalies in large sets of high-dimensional symbol sequences. sequenceMiner works...

  3. Sequencing Needs for Viral Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  4. Sequence Patterns of Identity Authentication Protocols

    Institute of Scientific and Technical Information of China (English)

    Tao Hongcai; He Dake

    2006-01-01

    From the viewpoint of protocol sequence, analyses are made of the sequence patterns of possible identity authentication protocol under two cases: with or without the trusted third party (TTP). Ten feasible sequence patterns of authentication protocol with TTP and 5 sequence patterns without TTP are gained. These gained sequence patterns meet the requirements for identity authentication,and basically cover almost all the authentication protocols with TTP and without TTP at present. All of the sequence patterns gained are classified into unilateral or bilateral authentication. Then , according to the sequence symmetry, several good sequence patterns with TTP are evaluated. The accompolished results can provide a reference to design of new identity authentication protocols.

  5. Transgressive Surface as Sequence Boundary

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Analysis of the four cases of the sequence boundary (SB)-transgressive surface (TS) relation in nature shows that applying transgressive surfaces as sequence boundaries has the following merits: it improves the methodology of stratigraphic subdivision; the position of transgressive surface in a sea level curve is relatively fixed; the transgressive surface is a transforming surface of the stratal structure; in platforms or ramps, the transgressive surface is the only choice for determining the sequence boundary; the transgressive surface is a readily recognized physical surface reflected by seismic records in seismostratigraphy. The paper reaches a conclusion that to delineate a SB in terms of the TS is theoretically and practically better than to delineate it between highstand and lowstand sediments as has been done traditionally.

  6. On the base sequence conjecture

    CERN Document Server

    Djokovic, Dragomir Z

    2010-01-01

    Let BS(m,n) denote the set of base sequences (A;B;C;D), with A and B of length m and C and D of length n. The base sequence conjecture (BSC) asserts that BS(n+1,n) exist (i.e., are non-empty) for all n. This is known to be true for n <= 36 and when n is a Golay number. We show that it is also true for n=37 and n=38. It is worth pointing out that BSC is stronger than the famous Hadamard matrix conjecture. In order to demonstrate the abundance of base sequences, we have previously attached to BS(n+1,n) a graph Gamma_n and computed the Gamma_n for n <= 27. We now extend these computations and determine the Gamma_n for n=28,...,35. We also propose a conjecture describing these graphs in general.

  7. Vector sequences - Budding yeast cDNA sequencing project | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Budding yeast cDNA sequencing project Vector sequences Data detail Data name Vector sequences Description of data contents Vector seq...wnload License Update History of This Database Site Policy | Contact Us Vector sequences - Budding yeast cDNA sequencing project | LSDB Archive ... ...uences used for sequencing. Multi FASTA format. 7 entries. Data file File name: vec

  8. KERNEL WORDS AND GAP SEQUENCE OF THE TRIBONACCI SEQUENCE

    Institute of Scientific and Technical Information of China (English)

    Yuke HUANG; Zhiying WEN

    2016-01-01

    In this paper, we investigate the factor properties and gap sequence of the Tri-bonacci sequence, the fixed point of the substitution σ(a, b, c) = (ab, ac, a). Let ωp be the p-th occurrence of ω and Gp(ω) be the gap between ωp and ωp+1. We introduce a notion of kernel for each factor ω, and then give the decomposition of the factor ω with respect to its kernel. Using the kernel and the decomposition, we prove the main result of this paper:for each factorω, the gap sequence{Gp(ω)}p≥1 is the Tribonacci sequence over the alphabet{G1(ω), G2(ω), G4(ω)}, and the expressions of gaps are determined completely. As an appli-cation, for each factorω and p∈N, we determine the position ofωp. Finally we introduce a notion of spectrum for studying some typical combinatorial properties, such as power, overlap and separate of factors.

  9. A repetitive sequence assembler based on next-generation sequencing.

    Science.gov (United States)

    Lian, S; Tu, Y; Wang, Y; Chen, X; Wang, L

    2016-01-01

    Repetitive sequences of variable length are common in almost all eukaryotic genomes, and most of them are presumed to have important biomedical functions and can cause genomic instability. Next-generation sequencing (NGS) technologies provide the possibility of identifying capturing these repetitive sequences directly from the NGS data. In this study, we assessed the performances in identifying capturing repeats of leading assemblers, such as Velvet, SOAPdenovo, SGA, MSR-CA, Bambus2, ALLPATHS-LG, and AByss using three real NGS datasets. Our results indicated that most of them performed poorly in capturing the repeats. Consequently, we proposed a repetitive sequence assembler, named NGSReper, for capturing repeats from NGS data. Simulated datasets were used to validate the feasibility of NGSReper. The results indicate that the completeness of capturing repeat is up to 99%. Cross validation was performed in three real NGS datasets, and extensive comparisons indicate that NGSReper performed best in terms of completeness and accuracy in capturing repeats. In conclusion, NGSReper is an appropriate and suitable tool for capturing repeats directly from NGS data. PMID:27525861

  10. Sequences and series involving the sequence of composite numbers

    Directory of Open Access Journals (Sweden)

    Panayiotis Vlamos

    2002-01-01

    Full Text Available Denoting by pn and cn the nth prime number and the nth composite number, respectively, we prove that both the sequence (xnn≥1, defined by xn=∑k=1n (ck+1−ck / k−pn / n, and the series ∑n=1∞ (pcn−cpn / npn are convergent.

  11. Integrated sequence analysis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, K.; Pyy, P

    1998-02-01

    The NKS/RAK subprojet 3 `integrated sequence analysis` (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term `methodology` denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  12. $delta$-Quasi Cauchy Sequences

    OpenAIRE

    Cakalli, Huseyin

    2010-01-01

    Recently, a concept of forward continuity and a concept of forward compactness are introduced in the senses that a function $f$ is forward continuous if $\\lim_{n\\to\\infty} \\Delta f(x_{n})=0$ whenever $\\lim_{n\\to\\infty} \\Delta x_{n}=0$,\\; and a subset $E$ of $\\textbf{R}$ is forward compact if any sequence $\\textbf{x}=(x_{n})$ of points in $E$ has a subsequence $\\textbf{z}=(z_{k})=(x_{n_{k}})$ of the sequence $\\textbf{x}$ such that $\\lim_{k\\to \\infty} \\Delta z_{k}=0$ where $\\Delta z_{k}=z_{k+1}...

  13. The origin of biased sequence depth in sequence-independent nucleic acid amplification and optimization for efficient massive parallel sequencing.

    Directory of Open Access Journals (Sweden)

    Toon Rosseel

    Full Text Available Sequence Independent Single Primer Amplification is one of the most widely used random amplification approaches in virology for sequencing template preparation. This technique relies on oligonucleotides consisting of a 3' random part used to prime complementary DNA synthesis and a 5' defined tag sequence for subsequent amplification. Recently, this amplification method was combined with next generation sequencing to obtain viral sequences. However, these studies showed a biased distribution of the resulting sequence reads over the analyzed genomes. The aim of this study was to elucidate the mechanisms that lead to biased sequence depth when using random amplification. Avian paramyxovirus type 8 was used as a model RNA virus to investigate these mechanisms. We showed, based on in silico analysis of the sequence depth in relation to GC-content, predicted RNA secondary structure and sequence complementarity to the 3' part of the tag sequence, that the tag sequence has the main contribution to the observed bias in sequence depth. We confirmed this finding experimentally using both fragmented and non-fragmented viral RNAs as well as primers differing in random oligomer length (6 or 12 nucleotides and in the sequence of the amplification tag. The observed oligonucleotide annealing bias can be reduced by extending the random oligomer sequence and by in silico combining sequence data from SISPA experiments using different 5' defined tag sequences. These findings contribute to the optimization of random nucleic acid amplification protocols that are currently required for downstream applications such as viral metagenomics and microarray analysis.

  14. Sequences in language and text

    CERN Document Server

    Mikros, George K

    2015-01-01

    The aim of this volume is to present the diverse but highly interesting area of the quantitative analysis of the sequence of various linguistic structures. The collected articles present a wide spectrum of quantitative analyses of linguistic syntagmatic structures and explore novel sequential linguistic entities. This volume will be interesting to all researchers studying linguistics using quantitative methods.

  15. Single-primer fluorescent sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Ruth, J.L.; Morgan, C.A.; Middendorf, L.R.; Grone, D.L.; Brumbaugh, J.A.

    1987-05-01

    Modified linker arm oligonucleotides complementary to standard M13 priming sites were synthesized, labelled with either one, two, or three fluoresceins, and purified by reverse-phase HPLC. When used as primers in standard dideoxy M13 sequencing with /sup 32/P-dNTPs, normal autoradiographic patterns were obtained. To eliminate the radioactivity, direct on-line fluorescence detection was achieved by the use of a scanning 10 mW Argon laser emitting 488 nm light. Fluorescent bands were detected directly in standard 0.2 or 0.35 mm thick polyacrylamide gels at a distance of 24 cm from the loading wells by a photomultiplier tube filtered at 520 nm. Horizontal and temporal location of each band was displayed by computer as a band in real time, providing visual appearance similar to normal 4-lane autoradiograms. Using a single primer labelled with two fluoresceins, sequences of between 500 and 600 bases have been read in a single loading with better than 98% accuracy; up to 400 bases can be read reproducibly with no errors. More than 50 sequences have been determined by this method. This approach requires only 1-2 ug of cloned template, and produces continuous sequence data at about one band per minute.

  16. Single-cell semiconductor sequencing.

    Science.gov (United States)

    Kohn, Andrea B; Moroz, Tatiana P; Barnes, Jeffrey P; Netherton, Mandy; Moroz, Leonid L

    2013-01-01

    RNA-seq or transcriptome analysis of individual cells and small-cell populations is essential for virtually any biomedical field. It is especially critical for developmental, aging, and cancer biology as well as neuroscience where the enormous heterogeneity of cells present a significant methodological and conceptual challenge. Here we present two methods that allow for fast and cost-efficient transcriptome sequencing from ultra-small amounts of tissue or even from individual cells using semiconductor sequencing technology (Ion Torrent, Life Technologies). The first method is a reduced representation sequencing which maximizes capture of RNAs and preserves transcripts' directionality. The second, a template-switch protocol, is designed for small mammalian neurons. Both protocols, from cell/tissue isolation to final sequence data, take up to 4 days. The efficiency of these protocols has been validated with single hippocampal neurons and various invertebrate tissues including individually identified neurons within a simpler memory-forming circuit of Aplysia californica and early (1-, 2-, 4-, 8-cells) embryonic and developmental stages from basal metazoans.

  17. Farey Sequences and Resistor Networks

    Indian Academy of Sciences (India)

    Sameen Ahmed Khan

    2012-05-01

    In this article, we employ the Farey sequence and Fibonacci numbers to establish strict upper and lower bounds for the order of the set of equivalent resistances for a circuit constructed from equal resistors combined in series and in parallel. The method is applicable for networks involving bridge and non-planar circuits.

  18. Instruction Sequences for Computer Science

    NARCIS (Netherlands)

    J.A. Bergstra; C.A. Middelburg

    2012-01-01

    This book demonstrates that the concept of an instruction sequence offers a novel and useful viewpoint on issues relating to diverse subjects in computer science. Selected issues relating to well-known subjects from the theory of computation and the area of computer architecture are rigorously inves

  19. Fractals in DNA sequence analysis

    Institute of Scientific and Technical Information of China (English)

    Yu Zu-Guo(喻祖国); Vo Anh; Gong Zhi-Min(龚志民); Long Shun-Chao(龙顺潮)

    2002-01-01

    Fractal methods have been successfully used to study many problems in physics, mathematics, engineering, finance,and even in biology. There has been an increasing interest in unravelling the mysteries of DNA; for example, how can we distinguish coding and noncoding sequences, and the problems of classification and evolution relationship of organisms are key problems in bioinformatics. Although much research has been carried out by taking into consideration the long-range correlations in DNA sequences, and the global fractal dimension has been used in these works by other people, the models and methods are somewhat rough and the results are not satisfactory. In recent years, our group has introduced a time series model (statistical point of view) and a visual representation (geometrical point of view)to DNA sequence analysis. We have also used fractal dimension, correlation dimension, the Hurst exponent and the dimension spectrum (multifractal analysis) to discuss problems in this field. In this paper, we introduce these fractal models and methods and the results of DNA sequence analysis.

  20. Pig genome sequence - analysis and publication strategy

    DEFF Research Database (Denmark)

    Archibald, Alan L.; Bolund, Lars; Churcher, Carol;

    2010-01-01

    BACKGROUND: The pig genome is being sequenced and characterised under the auspices of the Swine Genome Sequencing Consortium. The sequencing strategy followed a hybrid approach combining hierarchical shotgun sequencing of BAC clones and whole genome shotgun sequencing. RESULTS: Assemblies......) is under construction and will incorporate whole genome shotgun sequence (WGS) data providing > 30x genome coverage. The WGS sequence, most of which comprise short Illumina/Solexa reads, were generated from DNA from the same single Duroc sow as the source of the BAC library from which clones were...

  1. Stream cipher based on GSS sequences

    Institute of Scientific and Technical Information of China (English)

    HU Yupu; XIAO Guozhen

    2004-01-01

    Generalized self-shrinking sequences, simply named the GSS sequences,are novel periodic sequences that have many advantages in cryptography. In this paper,we give several results about GSS sequence's application to cryptography. First, we give a simple method for selecting those GSS sequences whose least periods reach the maximum. Second, we give a method for describing and computing the auto-correlation coefficients of GSS sequences. Finally, we point out that some GSS sequences, when used as stream ciphers, have a security weakness.

  2. The Toothpick Sequence and Other Sequences from Cellular Automata

    CERN Document Server

    Applegate, David; Sloane, N J A

    2010-01-01

    A two-dimensional arrangement of toothpicks is constructed by the following iterative procedure. At stage 1, place a single toothpick of length 1 on a square grid, aligned with the y-axis. At each subsequent stage, for every exposed toothpick end, place an orthogonal toothpick centered at that end. The resulting structure has a fractal-like appearance. We will analyze the toothpick sequence, which gives the total number of toothpicks after n steps. We also study several related sequences that arise from enumerating active cells in cellular automata. Some unusual recurrences appear: a typical example is that instead of the Fibonacci recurrence, which we may write as a(2+i) = a(i) + a(i+1), we set n = 2^k+i (0 = 0} (1+x^{2^k-1}+2x^{2^k}) and variations thereof.

  3. Identification of PKD2 mutations in human preimplantation embryos in vitro using a combination of targeted next-generation sequencing and targeted haplotyping.

    Science.gov (United States)

    Chen, Song-Chang; Xu, Xiao-Li; Zhang, Jun-Yu; Ding, Guo-Lian; Jin, Li; Liu, Bei; Sun, Dong-Mei; Mei, Chang-Lin; Yang, Xiao-Nan; Huang, He-Feng; Xu, Chen-Ming

    2016-01-01

    Here, we evaluate the applicability of a new method that combines targeted next-generation sequencing (NGS) with targeted haplotyping in identifying PKD2 gene mutations in human preimplantation embryos in vitro. To achieve this goal, a proband family with a heterozygous deletion of c.595_595 + 14delGGTAAGAGCGCGCGA in exon 1 of the PKD2 gene was studied. A total of 10 samples were analyzed, including 7 embryos. An array-based gene chip was designed to capture all of the exons of 21 disease-related genes, including PKD2. We performed Sanger sequencing combined with targeted haplotyping to evaluate the feasibility of this new method. A total of 7.09 G of data were obtained from 10 samples by NGS. In addition, 24,142 informative single-nucleotide polymorphisms (SNPs) were identified. Haplotyping analysis of several informative SNPs of PKD2 that we selected revealed that embryos 3, 5, and 6 did not inherit the mutation haplotypes of the PKD2 gene, a finding that was 100% accurate and was consistent with Sanger sequencing. Our results demonstrate that targeted NGS combined with targeted haplotyping can be used to identify PKD2 gene mutations in human preimplantation embryos in vitro with high sensitivity, fidelity, throughput and speed. PMID:27150309

  4. Sequence-structure relations of biopolymers

    CERN Document Server

    Barrett, Christopher; Reidys, Christian M

    2015-01-01

    Motivation: DNA data is transcribed into single-stranded RNA, which folds into specific molecular structures. In this paper we pose the question to what extent sequence- and structure-information correlate. We view this correlation as structural semantics of sequence data that allows for a different interpretation than conventional sequence alignment. Structural semantics could enable us to identify more general embedded "patterns" in DNA and RNA sequences. Results: We compute the partition function of sequences with respect to a fixed structure and connect this computation to the mutual information of a sequence-structure pair for RNA secondary structures. We present a Boltzmann sampler and obtain the a priori probability of specific sequence patterns. We present a detailed analysis for the three PDB-structures, 2JXV (hairpin), 2N3R (3-branch multi-loop) and 1EHZ (tRNA). We localize specific sequence patterns, contrast the energy spectrum of the Boltzmann sampled sequences versus those sequences that refold ...

  5. Orthogonal Basis Spreading Sequence for Optimal CDMA

    OpenAIRE

    Tsuda, Hirofumi; Umeno, Ken

    2016-01-01

    Recently, new spreading sequences have been proposed to multiplex the capacity of users. In particular, Weyl spreading sequences have the larger capacity of users than Gold code. This paper shows that Weyl spreading sequences appear in bit restoring model and they are orthogonal basis in the particular situation. This result shows the reason why they have the large capacity and that any spreading sequence are expressed as the sum of Weyl spreading sequences.

  6. Hardware Acceleration of Bioinformatics Sequence Alignment Applications

    OpenAIRE

    Hasan, L.

    2011-01-01

    Biological sequence alignment is an important and challenging task in bioinformatics. Alignment may be defined as an arrangement of two or more DNA or protein sequences to highlight the regions of their similarity. Sequence alignment is used to infer the evolutionary relationship between a set of protein or DNA sequences. An accurate alignment can provide valuable information for experimentation on the newly found sequences. It is indispensable in basic research as well as in practical applic...

  7. Hardware Accelerated Sequence Alignment with Traceback

    OpenAIRE

    Scott Lloyd; Snell, Quinn O

    2009-01-01

    Biological sequence alignment is an essential tool used in molecular biology and biomedical applications. The growing volume of genetic data and the complexity of sequence alignment present a challenge in obtaining alignment results in a timely manner. Known methods to accelerate alignment on reconfigurable hardware only address sequence comparison, limit the sequence length, or exhibit memory and I/O bottlenecks. A space-efficient, global sequence alignment algorithm and architecture is pres...

  8. Nonparametric Inference for Periodic Sequences

    KAUST Repository

    Sun, Ying

    2012-02-01

    This article proposes a nonparametric method for estimating the period and values of a periodic sequence when the data are evenly spaced in time. The period is estimated by a "leave-out-one-cycle" version of cross-validation (CV) and complements the periodogram, a widely used tool for period estimation. The CV method is computationally simple and implicitly penalizes multiples of the smallest period, leading to a "virtually" consistent estimator of integer periods. This estimator is investigated both theoretically and by simulation.We also propose a nonparametric test of the null hypothesis that the data have constantmean against the alternative that the sequence of means is periodic. Finally, our methodology is demonstrated on three well-known time series: the sunspots and lynx trapping data, and the El Niño series of sea surface temperatures. © 2012 American Statistical Association and the American Society for Quality.

  9. Cassini Mission Sequence Subsystem (MSS)

    Science.gov (United States)

    Alland, Robert

    2011-01-01

    This paper describes my work with the Cassini Mission Sequence Subsystem (MSS) team during the summer of 2011. It gives some background on the motivation for this project and describes the expected benefit to the Cassini program. It then introduces the two tasks that I worked on - an automatic system auditing tool and a series of corrections to the Cassini Sequence Generator (SEQ_GEN) - and the specific objectives these tasks were to accomplish. Next, it details the approach I took to meet these objectives and the results of this approach, followed by a discussion of how the outcome of the project compares with my initial expectations. The paper concludes with a summary of my experience working on this project, lists what the next steps are, and acknowledges the help of my Cassini colleagues.

  10. Genome Sequence of Mycobacteriophage Momo.

    Science.gov (United States)

    Pope, Welkin H; Bina, Elizabeth A; Brahme, Indraneel S; Hill, Amy B; Himmelstein, Philip H; Hunsicker, Sara M; Ish, Amanda R; Le, Tinh S; Martin, Mary M; Moscinski, Catherine N; Shetty, Sameer A; Swierzewski, Tomasz; Iyengar, Varun B; Kim, Hannah; Schafer, Claire E; Grubb, Sarah R; Warner, Marcie H; Bowman, Charles A; Russell, Daniel A; Hatfull, Graham F

    2015-06-18

    Momo is a newly discovered phage of Mycobacterium smegmatis mc(2)155. Momo has a double-stranded DNA genome 154,553 bp in length, with 233 predicted protein-encoding genes, 34 tRNA genes, and one transfer-messenger RNA (tmRNA) gene. Momo has a myoviral morphology and shares extensive nucleotide sequence similarity with subcluster C1 mycobacteriophages.

  11. Sequencing Trade and Monetary Integration

    OpenAIRE

    Richard Pomfret

    2005-01-01

    Regional integration for at least the last sixty years has focused on trade integration. Balassa’s canonical taxonomy of regional trading arrangements is often interpreted as a sequence from free trade area through customs union and common market to economic union. In the 1980s the concept of deep integration went beyond trade with its focus on policy harmonization, which came to include monetary integration, but it presupposed trade integration as the first step in the regional integration s...

  12. Interdigitated electrode array based sensors for environmental monitoring of caesium

    Energy Technology Data Exchange (ETDEWEB)

    Nickson, I D [John Tyndall Nuclear Research Institute and Centre for Materials Science, University of Central Lancashire, Preston PR1 2HE (United Kingdom); Boxall, C [Engineering Department, Lancaster University, Lancaster LA1 4YR (United Kingdom); Port, S N, E-mail: c.boxall@lancaster.ac.uk [DSTL, Salisbury, Wiltshire SP4 0JQ (United Kingdom)

    2010-03-15

    The requirement for on-line and in-situ monitoring of analytes in process and effluent streams and in ground waters has become increasingly more important in recent years. We therefore describe the development of the transduction element for a fully automated online instrument for the detection of caesium. The sensor layer for this instrument employs an Ion Selective Conductimetric Microsensor (ISCOM) as the detector. This is based upon a plasticized polymeric membrane incorporating a selective ionophore, overlaying two interdigitated microelectrode arrays. A direct relationship has been observed between the bulk conductance (as determined by the microelectrodes) of the ionophore loaded membrane and the concentration of the primary ions in solution. Caesium selective ISCOMs were prepared using an ion selective membrane containing the commercially available ionophore Calix [6]arene-hexaacetic acid hexaethyl ester, polyvinylchloride (PVC) and plasticiser Nitrophenylether (NPOE). The relative levels of membrane components have also been varied in order to further enhance the ISCOM response. We also present preliminary data concerning the caesium selectivity with respect to a range of possible interferents, including rubidium.

  13. Interdigitated electrode array based sensors for environmental monitoring of caesium

    Science.gov (United States)

    Nickson, I. D.; Boxall, C.; Port, S. N.

    2010-03-01

    The requirement for on-line and in-situ monitoring of analytes in process and effluent streams and in ground waters has become increasingly more important in recent years. We therefore describe the development of the transduction element for a fully automated online instrument for the detection of caesium. The sensor layer for this instrument employs an Ion Selective Conductimetric Microsensor (ISCOM) as the detector. This is based upon a plasticized polymeric membrane incorporating a selective ionophore, overlaying two interdigitated microelectrode arrays. A direct relationship has been observed between the bulk conductance (as determined by the microelectrodes) of the ionophore loaded membrane and the concentration of the primary ions in solution. Caesium selective ISCOMs were prepared using an ion selective membrane containing the commercially available ionophore Calix [6]arene-hexaacetic acid hexaethyl ester, polyvinylchloride (PVC) and plasticiser Nitrophenylether (NPOE). The relative levels of membrane components have also been varied in order to further enhance the ISCOM response. We also present preliminary data concerning the caesium selectivity with respect to a range of possible interferents, including rubidium.

  14. GNSS array-based acquisition: theory and implementation

    OpenAIRE

    Arribas Lázaro, Javier

    2012-01-01

    This Dissertation addresses the signal acquisition problem using antenna arrays in the general framework of Global Navigation Satellite Systems (GNSS) receivers. The term GNSS classi es those navigation systems based on a constellation of satellites, which emit ranging signals useful for positioning. Although the American GPS is already available, which coexists with the renewed Russian Glonass, the forthcoming European contribution (Galileo) along with the Chinese Compass will be operative s...

  15. Deployable aerospace PV array based on amorphous silicon alloys

    Science.gov (United States)

    Hanak, Joseph J.; Walter, Lee; Dobias, David; Flaisher, Harvey

    1989-01-01

    The development of the first commercial, ultralight, flexible, deployable, PV array for aerospace applications is discussed. It is based on thin-film, amorphous silicon alloy, multijunction, solar cells deposited on a thin metal or polymer by a proprietary, roll-to-roll process. The array generates over 200 W at AM0 and is made of 20 giant cells, each 54 cm x 29 cm (1566 sq cm in area). Each cell is protected with bypass diodes. Fully encapsulated array blanket and the deployment mechanism weigh about 800 and 500 g, respectively. These data yield power per area ratio of over 60 W/sq m specific power of over 250 W/kg (4 kg/kW) for the blanket and 154 W/kg (6.5 kg/kW) for the power system. When stowed, the array is rolled up to a diameter of 7 cm and a length of 1.11 m. It is deployed quickly to its full area of 2.92 m x 1.11 m, for instant power. Potential applications include power for lightweight space vehicles, high altitude balloons, remotely piloted and tethered vehicles. These developments signal the dawning of a new age of lightweight, deployable, low-cost space arrays in the range from tens to tens of thousands of watts for near-term applications and the feasibility of multi-100 kW to MW arrays for future needs.

  16. Field Programmable Gate Arrays Based Realization of Truncated Multipliers

    OpenAIRE

    Muhammad H. Rais; Mohammed H. Mijalli

    2011-01-01

    Problem statement: Due to high cost and non reconfiguration of Application Specific Integrated Circuits (ASICs) in image processing applications, for example MPEG video compression used in CT scan frames requires real time conditions and the algorithms should be verified and optimized before implementation. Approach: Field Programmable Gate Array (FPGA) provides reconfiguration and implementation at the same time. Results: The implementation results of truncated multi...

  17. Medical x-ray-sensitive array based on CCD

    Science.gov (United States)

    Gnedenko, Valeri G.; Krasnjuk, Andrey A.; Larionov, Sergei V.; Phainberg, Evgeni M.; Shilin, Victor A.; Skrylev, Alexander S.; Stenin, Vladimir J.

    1996-04-01

    The achievements of CCD technology allow to design X-ray sensitive solid-state images for various medicine applications. The first medical systems have been created for using in dental practice and diagnosis. This radiovisiographic method allows to reduce X-ray exposure by 80%, except any films and provide paralleled diagnosis capacities which revolutionize every day practice. In the future a mosaic scanner with CCD chips will be used for detecting breast cancer.

  18. Fluorescence array-based sensing of nitroaromatics using conjugated polyelectrolytes.

    Science.gov (United States)

    Wu, Jiatao; Tan, Chunyan; Chen, Zhifang; Chen, Yu Zong; Tan, Ying; Jiang, Yuyang

    2016-05-23

    A sensor array consisting of six cationic fluorescent conjugated polyelectrolytes (CPEs) is reported, which could readily differentiate between nine closely related hydrophilic nitroaromatics (NACs) in separate aqueous solutions by fluorescence pattern recognition and linear discrimination analysis (LDA). PMID:27169808

  19. Field programmable gate array based data digitisation with commercial elements

    International Nuclear Information System (INIS)

    One of the most important aspects of particle identification experiments is the digitisation of time, amplitude and charge data from detectors. These conversions are done mostly with Application Specific ICs (ASICs). However, the recent developments in Field Programmable Gate Array (FPGA) technology allow us to use commercial electronic components for the required Front-End Electronics (FEE) and do the digitisation in the FPGA. It is possible to do Time-of-Flight (ToF), Time-over-Threshold (ToT), amplitude and charge measurements with converters implemented in FPGA. We call this principle COME and KISS: Use COMplex COMmercial Elements and Keep It Small and Simple.

  20. Wide band scanning arrays based on leaky wave radiation

    NARCIS (Netherlands)

    Bruni, S.; Neto, A.; Maci, S.; Gerini, G.

    2005-01-01

    A novel type of broadband integrated array scanning in one plane is proposed. Such arrays could be used for next generation airborne Synthetic Aperture Radars, or even UWB scanning arrays for automotive applications. The array is composed by broad-band leaky-wave slot elements radiating by means of

  1. Sequencing technologies to maximize recovery

    Energy Technology Data Exchange (ETDEWEB)

    Dusseault, M.B. [Waterloo Univ., ON (Canada)

    2006-07-01

    The deliberate sequencing of extraction technologies for viscous oil may optimize financial returns. Sequencing is based on an understanding that some technologies improve reservoir transport parameters through phenomena such as shear dilation; fracturing of shales through high pressure injection; thermal consolidation; shear rupture of clay dustings and shale laminae; and the dislodging of pore blocking agents. Cold heavy oil production with sand (CHOPS) increases reservoir permeability, porosity and compressibility, and can alter stress fields and flow paths, which can in turn lead to more effective subsequent thermal or gravity methods of extraction. High pressure thermal extraction processes such as steam flood (SF) and cyclic steam stimulation (CSS) generate reservoir dilation and viscosity reduction which mean that subsequent gravity methods such as VAPEX will achieve increased extraction efficiency. Massive dilation during cyclic injection phases means that recompaction drive mechanisms will improve recovery rates and recovery factors. Successful planning means that the physics and impacts on the reservoir of all commercial technologies must be understood, and initial systems of exploitation should be designed to minimize future well needs. It was concluded that if implemented correctly, the impact of sequencing on technically recoverable reserves estimates in heavy oil will be considerable. Recoverable reserves increases exceeding a trillion barrels are anticipated. 12 refs., 8 figs.

  2. Sequencing technologies to maximize recovery

    International Nuclear Information System (INIS)

    The deliberate sequencing of extraction technologies for viscous oil may optimize financial returns. Sequencing is based on an understanding that some technologies improve reservoir transport parameters through phenomena such as shear dilation; fracturing of shales through high pressure injection; thermal consolidation; shear rupture of clay dustings and shale laminae; and the dislodging of pore blocking agents. Cold heavy oil production with sand (CHOPS) increases reservoir permeability, porosity and compressibility, and can alter stress fields and flow paths, which can in turn lead to more effective subsequent thermal or gravity methods of extraction. High pressure thermal extraction processes such as steam flood (SF) and cyclic steam stimulation (CSS) generate reservoir dilation and viscosity reduction which mean that subsequent gravity methods such as VAPEX will achieve increased extraction efficiency. Massive dilation during cyclic injection phases means that recompaction drive mechanisms will improve recovery rates and recovery factors. Successful planning means that the physics and impacts on the reservoir of all commercial technologies must be understood, and initial systems of exploitation should be designed to minimize future well needs. It was concluded that if implemented correctly, the impact of sequencing on technically recoverable reserves estimates in heavy oil will be considerable. Recoverable reserves increases exceeding a trillion barrels are anticipated. 12 refs., 8 figs

  3. Detection of copy number variation from array intensity and sequencing read depth using a stepwise Bayesian model

    Directory of Open Access Journals (Sweden)

    Gerstein Mark B

    2010-10-01

    Full Text Available Abstract Background Copy number variants (CNVs have been demonstrated to occur at a high frequency and are now widely believed to make a significant contribution to the phenotypic variation in human populations. Array-based comparative genomic hybridization (array-CGH and newly developed read-depth approach through ultrahigh throughput genomic sequencing both provide rapid, robust, and comprehensive methods to identify CNVs on a whole-genome scale. Results We developed a Bayesian statistical analysis algorithm for the detection of CNVs from both types of genomic data. The algorithm can analyze such data obtained from PCR-based bacterial artificial chromosome arrays, high-density oligonucleotide arrays, and more recently developed high-throughput DNA sequencing. Treating parameters--e.g., the number of CNVs, the position of each CNV, and the data noise level--that define the underlying data generating process as random variables, our approach derives the posterior distribution of the genomic CNV structure given the observed data. Sampling from the posterior distribution using a Markov chain Monte Carlo method, we get not only best estimates for these unknown parameters but also Bayesian credible intervals for the estimates. We illustrate the characteristics of our algorithm by applying it to both synthetic and experimental data sets in comparison to other segmentation algorithms. Conclusions In particular, the synthetic data comparison shows that our method is more sensitive than other approaches at low false positive rates. Furthermore, given its Bayesian origin, our method can also be seen as a technique to refine CNVs identified by fast point-estimate methods and also as a framework to integrate array-CGH and sequencing data with other CNV-related biological knowledge, all through informative priors.

  4. Bernoulli measure of complex admissible kneading sequences

    CERN Document Server

    Bruin, Henk

    2012-01-01

    Iterated quadratic polynomials give rise to a rich collection of different dynamical systems that are parametrized by a simple complex parameter $c$. The different dynamical features are encoded by the \\emph{kneading sequence} which is an infinite sequence over $\\{0,\\1\\}$. Not every such sequence actually occurs in complex dynamics. The set of admissible kneading sequences was described by Milnor and Thurston for real quadratic polynomials, and by the authors in the complex case. We prove that the set of admissible kneading sequences has positive Bernoulli measure within the set of sequences over $\\{0,\\1\\}$.

  5. Static multiplicities in heterogeneous azeotropic distillation sequences

    DEFF Research Database (Denmark)

    Esbjerg, Klavs; Andersen, Torben Ravn; Jørgensen, Sten Bay;

    1998-01-01

    In this paper the results of a bifurcation analysis on heterogeneous azeotropic distillation sequences are given. Two sequences suitable for ethanol dehydration are compared: The 'direct' and the 'indirect' sequence. It is shown, that the two sequences, despite their similarities, exhibit very...... performances are compared for minimal impurities in both products, where the direct sequence exhibits output multiplicity, while the indirect sequence exhibits state multiplicity. The latter multiplicity may be avoided by accepting a slightly increased impurity in the ethanol product. Copyright (C) 1998 IFAC....

  6. Modified Genetic Algorithm for DNA Sequence Assembly by Shotgun and Hybridization Sequencing Techniques

    Directory of Open Access Journals (Sweden)

    Prof.Narayan Kumar Sahu

    2012-09-01

    Full Text Available Since the advent of rapid DNA sequencing methods in 1976, scientists have had the problem of inferring DNA sequences from sequenced fragments. Shotgun sequencing is a well-established biological and computational method used in practice. Many conventional algorithms for shotgun sequencing are based on the notion of pair wise fragment overlap. While shotgun sequencing infers a DNA sequence given the sequences of overlapping fragments, a recent and complementary method, called sequencing by hybridization (SBH, infers a DNA sequence given the set of oligomers that represents all sub words of some fixed length, k. In this paper, we propose a new computer algorithm for DNA sequence assembly that combines in a novel way the techniques of both shotgun and SBH methods. Based on our preliminary investigations, the algorithm promises- to be very fast and practical for DNA sequence assembly [1].

  7. Direct Chloroplast Sequencing: Comparison of Sequencing Platforms and Analysis Tools for Whole Chloroplast Barcoding

    OpenAIRE

    Marta Brozynska; Agnelo Furtado; Robert James Henry

    2014-01-01

    Direct sequencing of total plant DNA using next generation sequencing technologies generates a whole chloroplast genome sequence that has the potential to provide a barcode for use in plant and food identification. Advances in DNA sequencing platforms may make this an attractive approach for routine plant identification. The HiSeq (Illumina) and Ion Torrent (Life Technology) sequencing platforms were used to sequence total DNA from rice to identify polymorphisms in the whole chloroplast genom...

  8. Integration of retinal image sequences

    Science.gov (United States)

    Ballerini, Lucia

    1998-10-01

    In this paper a method for noise reduction in ocular fundus image sequences is described. The eye is the only part of the human body where the capillary network can be observed along with the arterial and venous circulation using a non invasive technique. The study of the retinal vessels is very important both for the study of the local pathology (retinal disease) and for the large amount of information it offers on systematic haemodynamics, such as hypertension, arteriosclerosis, and diabetes. In this paper a method for image integration of ocular fundus image sequences is described. The procedure can be divided in two step: registration and fusion. First we describe an automatic alignment algorithm for registration of ocular fundus images. In order to enhance vessel structures, we used a spatially oriented bank of filters designed to match the properties of the objects of interest. To evaluate interframe misalignment we adopted a fast cross-correlation algorithm. The performances of the alignment method have been estimated by simulating shifts between image pairs and by using a cross-validation approach. Then we propose a temporal integration technique of image sequences so as to compute enhanced pictures of the overall capillary network. Image registration is combined with image enhancement by fusing subsequent frames of a same region. To evaluate the attainable results, the signal-to-noise ratio was estimated before and after integration. Experimental results on synthetic images of vessel-like structures with different kind of Gaussian additive noise as well as on real fundus images are reported.

  9. Infinite matrices and sequence spaces

    CERN Document Server

    Cooke, Richard G

    2014-01-01

    This clear and correct summation of basic results from a specialized field focuses on the behavior of infinite matrices in general, rather than on properties of special matrices. Three introductory chapters guide students to the manipulation of infinite matrices, covering definitions and preliminary ideas, reciprocals of infinite matrices, and linear equations involving infinite matrices.From the fourth chapter onward, the author treats the application of infinite matrices to the summability of divergent sequences and series from various points of view. Topics include consistency, mutual consi

  10. Instruction Sequences with Indirect Jumps

    Directory of Open Access Journals (Sweden)

    C.A. Middelburg

    2007-01-01

    Full Text Available We study sequential programs that are instruction sequences with direct and indirect jump instructions. The intuition is that indirect jump instructions are jump instructions where the position of the instruction to jump to is the content of some memory cell.We consider several kinds of indirect jump instructions. For each kind, we define the meaning of programs with indirect jump instructions of that kind by means of a translation into programs without indirect jump instructions. For each kind, the intended behaviour of a program with indirect jump instructions of that kind under execution is the behaviour of the translated program under execution on interaction with some memory device.

  11. Arithmetic Self-Similarity of Infinite Sequences

    CERN Document Server

    Hendriks, Dimitri; Endrullis, Joerg; Dow, Mark; Klop, Jan Willem

    2012-01-01

    We define the arithmetic self-similarity (AS) of a one-sided infinite sequence sigma to be the set of arithmetic progressions through sigma which are a vertical shift of sigma. We classify the AS of several well-known sequences, such as the Thue-Morse sequence, the period doubling sequence, and the regular paperfolding sequence. The latter two are examples of (completely) additive sequences as well as of Toeplitz words. We investigate the intersection of these families. We give a complete characterization of single-gap patterns that yield additive Toeplitz words, and classify their AS. Moreover, we show that every arithmetic progression through a Toeplitz word generated by a one-gap pattern is again a Toeplitz word. Finally, we establish that generalized Morse sequences are specific sum-of-digits sequences, and show that their first difference is a Toeplitz word.

  12. An Assignment Sequence for Underprepared Writers.

    Science.gov (United States)

    Nimmo, Kristi

    2000-01-01

    Presents a sequenced writing assignment on shopping to aid basic writers. Describes a writing assignment focused around online and mail-order shopping. Notes steps in preparing for the assignment, the sequence, and discusses responses to the assignments. (SC)

  13. On Paranorm Zweier -Convergent Sequence Spaces

    Directory of Open Access Journals (Sweden)

    Vakeel A. Khan

    2013-01-01

    Full Text Available In this paper, we introduce the paranorm Zweier -convergent sequence spaces , , and , a sequence of positive real numbers. We study some topological properties, prove the decomposition theorem, and study some inclusion relations on these spaces.

  14. Prenatal diagnosis of a fetus with partial trisomy 8p resulting from a balanced maternal translocation by array-based comparative genomic hybridization%微阵列比较基因组杂交技术产前诊断母源性8p部分三体胎儿一例

    Institute of Scientific and Technical Information of China (English)

    郭彩琴; 王峻峰; 赵丽; 刘俊; 王俊; 肖建平

    2015-01-01

    Objective To determine the karyotype of a fetus with transverse aortic arch hypoplasia,and to investigate the feasibility of array-based comparative genomic hybridization (array-CGH) for molecular genetic diagnosis.Methods G-banding was performed to analyze the karyotypes of the fetus and its parents,and array CGH was applied to identify the chromosomal abnormality of the fetus.Results G-banding analysis revealed that the pregnant woman has carried a balanced translocation 46,XX,t(8;16) (p21;q24),while the fetus has carried an unbalanced translocation 46,XX,der(16)t(8;16)(p21;q24)mat.Array-CGH analysis suggested that the derivative chromosomal fragment has originated from 8p with breakpoints in 8p23.3 p21.3.Conclusion Trisomy 8p23.3-p21.3 may have predisposed to transverse aortic arch hypoplasia in the fetus.Parental karyotype analysis could help to characterize the translocation and evaluate the recurrent risk.Compared with routine karyotype analysis,aCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations.%目的 确定1例主动脉横弓发育不良胎儿的染色体核型,探讨微阵列比较基因组杂交(array based comparative genomic hybridization,array-CGH)技术在分子遗传学及产前诊断中的应用及优越性.方法 应用G显带分析胎儿及其父母的染色体核型,用array-CGH技术明确胎儿衍生染色体片段的来源和区域.结果 G显带染色体分析显示孕妇为46,XX,t(8;16)(p21;q24)平衡易位携带者,胎儿携带46,XX,der(16)t(8;16) (p21;q24)mat的非平衡易位.array-CGH检测证实胎儿衍生染色体片段源自8号染色体短臂,患儿为8p23.3 p21.3三体患儿.结论 胎儿的异常表型(主动脉横弓发育不良)与8p23.3p21.3三体密切相关,父母染色体分析可帮助明确易位性质及来源,从而有利于评估再发风险.array-CGH在染色体异常分析中具有更高的分辨率和准确性.

  15. Goldbach conjecture sequences in quantum mechanics

    OpenAIRE

    Prudencio, Thiago; Silva, Edilberto O.

    2013-01-01

    We show that there is a correspondence between Goldbach conjecture sequences (GCS) and expectation values of the number operator in Fock states. We demonstrate that depending on the normalization or not of Fock state superpositions, we have sequences that are equivalent and sequences that are not equivalent to GCS. We propose an algorithm where sequences equivalent to GCS can be derived in terms of expectation values with normalized states. Defining states whose projections generate GCS, we r...

  16. Mappings of Type Special Space of Sequences

    Directory of Open Access Journals (Sweden)

    Awad A. Bakery

    2016-01-01

    Full Text Available We give sufficient conditions on a special space of sequences defined by Mohamed and Bakery (2013 such that the finite rank operators are dense in the complete space of operators whose approximation numbers belong to this sequence space. Hence, under a few conditions, every compact operator would be approximated by finite rank operators. We apply it on the sequence space defined by Tripathy and Mahanta (2003. Our results match those known for p-absolutely summable sequences of reals.

  17. Approximate word matches between two random sequences

    OpenAIRE

    Burden, Conrad J.; Kantorovitz, Miriam R; Wilson, Susan R

    2008-01-01

    Given two sequences over a finite alphabet $\\mathcal{L}$ , the D2 statistic is the number of m-letter word matches between the two sequences. This statistic is used in bioinformatics for expressed sequence tag database searches. Here we study a generalization of the D2 statistic in the context of DNA sequences, under the assumption of strand symmetric Bernoulli text. For k

  18. Discovering motifs that induce sequencing errors

    OpenAIRE

    Allhoff, Manuel; Schoenhuth, Alexander; Martin, M.(Deutsches Elektronen-Synchrotron, Hamburg, Germany); Costa, I.G.; Rahmann, S.; Marschall, Tobias

    2013-01-01

    Background Elevated sequencing error rates are the most predominant obstacle in single-nucleotide polymorphism (SNP) detection, which is a major goal in the bulk of current studies using next-generation sequencing (NGS). Beyond routinely handled generic sources of errors, certain base calling errors relate to specific sequence patterns. Statistically principled ways to associate sequence patterns with base calling errors have not been previously described. Extant approaches either incur decis...

  19. Nanopore DNA sequencing with MspA

    OpenAIRE

    Derrington, Ian M.; Butler, Tom Z.; Collins, Marcus D.; Manrao, Elizabeth; Pavlenok, Mikhail; Niederweis, Michael; Gundlach, Jens H.

    2010-01-01

    Nanopore sequencing has the potential to become a direct, fast, and inexpensive DNA sequencing technology. The simplest form of nanopore DNA sequencing utilizes the hypothesis that individual nucleotides of single-stranded DNA passing through a nanopore will uniquely modulate an ionic current flowing through the pore, allowing the record of the current to yield the DNA sequence. We demonstrate that the ionic current through the engineered Mycobacterium smegmatis porin A, MspA, has the ability...

  20. Quantitative phenotyping via deep barcode sequencing

    OpenAIRE

    SMITH, ANDREW M.; Heisler, Lawrence E.; Mellor, Joseph; Kaper, Fiona; Thompson, Michael J.; Chee, Mark; Roth, Frederick P.; Giaever, Guri; Nislow, Corey

    2009-01-01

    Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep sequencing to genome-scale fitness profiling to evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or “Bar-seq,” outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied...

  1. Evaluating Imputation Algorithms for Low-Depth Genotyping-By-Sequencing (GBS) Data.

    Science.gov (United States)

    Chan, Ariel W; Hamblin, Martha T; Jannink, Jean-Luc

    2016-01-01

    Well-powered genomic studies require genome-wide marker coverage across many individuals. For non-model species with few genomic resources, high-throughput sequencing (HTS) methods, such as Genotyping-By-Sequencing (GBS), offer an inexpensive alternative to array-based genotyping. Although affordable, datasets derived from HTS methods suffer from sequencing error, alignment errors, and missing data, all of which introduce noise and uncertainty to variant discovery and genotype calling. Under such circumstances, meaningful analysis of the data is difficult. Our primary interest lies in the issue of how one can accurately infer or impute missing genotypes in HTS-derived datasets. Many of the existing genotype imputation algorithms and software packages were primarily developed by and optimized for the human genetics community, a field where a complete and accurate reference genome has been constructed and SNP arrays have, in large part, been the common genotyping platform. We set out to answer two questions: 1) can we use existing imputation methods developed by the human genetics community to impute missing genotypes in datasets derived from non-human species and 2) are these methods, which were developed and optimized to impute ascertained variants, amenable for imputation of missing genotypes at HTS-derived variants? We selected Beagle v.4, a widely used algorithm within the human genetics community with reportedly high accuracy, to serve as our imputation contender. We performed a series of cross-validation experiments, using GBS data collected from the species Manihot esculenta by the Next Generation (NEXTGEN) Cassava Breeding Project. NEXTGEN currently imputes missing genotypes in their datasets using a LASSO-penalized, linear regression method (denoted 'glmnet'). We selected glmnet to serve as a benchmark imputation method for this reason. We obtained estimates of imputation accuracy by masking a subset of observed genotypes, imputing, and calculating the

  2. PacBio Sequencing and Its Applications

    Institute of Scientific and Technical Information of China (English)

    Anthony Rhoads; Kin Fai Au

    2015-01-01

    Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing (SGS) technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation (SV) in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with dis-eases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Addition-ally, PacBio’s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone.

  3. Incidental Sequence Learning across the Lifespan

    Science.gov (United States)

    Weiermann, Brigitte; Meier, Beat

    2012-01-01

    The purpose of the present study was to investigate incidental sequence learning across the lifespan. We tested 50 children (aged 7-16), 50 young adults (aged 20-30), and 50 older adults (aged >65) with a sequence learning paradigm that involved both a task and a response sequence. After several blocks of practice, all age groups slowed down…

  4. RNAome sequencing delineates the complete RNA landscape

    NARCIS (Netherlands)

    K.W.J. Derks (Kasper); J. Pothof (Joris)

    2015-01-01

    textabstractStandard RNA expression profiling methods rely on enrichment steps for specific RNA classes, thereby not detecting all RNA species. For example, small and large RNAs from the same sample cannot be sequenced in a single sequence run. We designed RNAome sequencing, which is a strand-specif

  5. Hardware Acceleration of Bioinformatics Sequence Alignment Applications

    NARCIS (Netherlands)

    Hasan, L.

    2011-01-01

    Biological sequence alignment is an important and challenging task in bioinformatics. Alignment may be defined as an arrangement of two or more DNA or protein sequences to highlight the regions of their similarity. Sequence alignment is used to infer the evolutionary relationship between a set of pr

  6. The recurrence sequence via the Fibonacci groups

    Science.gov (United States)

    Aküzüm, Yeşim; Deveci, Ömür

    2016-04-01

    This work develops properties of the recurrence sequence defined by the aid of the relation matrix of the Fibonacci groups. The study of this sequence modulo m yields cyclic groups and semigroups from generating matrix. Finally, we extend the sequence defined to groups and then, we obtain its period in the Fibonacci groups.

  7. Sequence Analysis in Demographic Research

    Directory of Open Access Journals (Sweden)

    Billari, Francesco C.

    2001-01-01

    Full Text Available EnglishThis paper examines the salient features of sequence analysis in demogrpahicresearch. The new approach allows a holistic perspective on life course analysis and is based on arepresentation of lives as sequences of states. Some of the methods for analyzing such data aresketched, from complex description to optimal matching ot monoethetic divisive algorithms. Afer ashort ilustration of a demographically-relevant example, the needs in terms of data collection and theopportunities of applying the same aproach to synthetic data are discussed.FrenchOn examine ici les principaux éléments de l’analyse par séquence endémographie. Cette nouvelle technique permet une perspective unifiée del’analyse du cours de la vie, en représentant la vie comme une série d’états.Certaines des méthodes pour de telles analyses sont décrites, en commençant parla description complexe, pour considérer ensuite les alignements optimales, etles algorithmes de division. Après un court exemple en démographie, onconsidère les besoins en données et les possibilités d’application aux donnéessynthétique.

  8. Artificial sequences and complexity measures

    Science.gov (United States)

    Baronchelli, Andrea; Caglioti, Emanuele; Loreto, Vittorio

    2005-04-01

    In this paper we exploit concepts of information theory to address the fundamental problem of identifying and defining the most suitable tools for extracting, in a automatic and agnostic way, information from a generic string of characters. We introduce in particular a class of methods which use in a crucial way data compression techniques in order to define a measure of remoteness and distance between pairs of sequences of characters (e.g. texts) based on their relative information content. We also discuss in detail how specific features of data compression techniques could be used to introduce the notion of dictionary of a given sequence and of artificial text and we show how these new tools can be used for information extraction purposes. We point out the versatility and generality of our method that applies to any kind of corpora of character strings independently of the type of coding behind them. We consider as a case study linguistic motivated problems and we present results for automatic language recognition, authorship attribution and self-consistent classification.

  9. Tidying up international nucleotide sequence databases: ecological, geographical and sequence quality annotation of its sequences of mycorrhizal fungi.

    Directory of Open Access Journals (Sweden)

    Leho Tedersoo

    Full Text Available Sequence analysis of the ribosomal RNA operon, particularly the internal transcribed spacer (ITS region, provides a powerful tool for identification of mycorrhizal fungi. The sequence data deposited in the International Nucleotide Sequence Databases (INSD are, however, unfiltered for quality and are often poorly annotated with metadata. To detect chimeric and low-quality sequences and assign the ectomycorrhizal fungi to phylogenetic lineages, fungal ITS sequences were downloaded from INSD, aligned within family-level groups, and examined through phylogenetic analyses and BLAST searches. By combining the fungal sequence database UNITE and the annotation and search tool PlutoF, we also added metadata from the literature to these accessions. Altogether 35,632 sequences belonged to mycorrhizal fungi or originated from ericoid and orchid mycorrhizal roots. Of these sequences, 677 were considered chimeric and 2,174 of low read quality. Information detailing country of collection, geographical coordinates, interacting taxon and isolation source were supplemented to cover 78.0%, 33.0%, 41.7% and 96.4% of the sequences, respectively. These annotated sequences are publicly available via UNITE (http://unite.ut.ee/ for downstream biogeographic, ecological and taxonomic analyses. In European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena/, the annotated sequences have a special link-out to UNITE. We intend to expand the data annotation to additional genes and all taxonomic groups and functional guilds of fungi.

  10. Exome sequencing: what clinicians need to know

    Directory of Open Access Journals (Sweden)

    Sastre L

    2014-03-01

    Full Text Available Leandro SastreInstituto de Investigaciones Biomédicas, CSIC/UAM, C/Arturo Duperier 4, Madrid, Spain; Terapias Experimentales y Biomarcadores en Cáncer, IdiPaz, Madrid, Spain; CIBER de Enfermedades Raras, CIBERER, Valencia, SpainAbstract: The recent development of high throughput methods of deoxyribonucleic acid (DNA sequencing has made it possible to determine individual genome sequences and their specific variations. A region of particular interest is the protein-coding part of the genome, or exome, which is composed of gene exons. The principles of exome purification and sequencing will be described in this review, as well as analyses of the data generated. Results will be discussed in terms of their possible functional and clinical significance. The advantages and limitations of exome sequencing will be compared to those of other massive sequencing approaches such as whole-genome sequencing, ribonucleic acid sequencing or selected DNA sequencing. Exome sequencing has been used recently in the study of various diseases. Monogenic diseases with Mendelian inheritance are among these, but studies have also been carried out on genetic variations that represent risk factors for complex diseases. Cancer is another intensive area for exome sequencing studies. Several examples of the use of exome sequencing in the diagnosis, prognosis, and treatment of these diseases will be described. Finally, remaining challenges and some practical and ethical considerations for the clinical application of exome sequencing will be discussed.Keywords: massively parallel sequencing, RNA sequencing, whole-genome sequencing, genetic variants, molecular diagnosis, pharmacogenomics, personalized medicine, NGS, SGS, SNP, SNV

  11. Problems of Sequence Stratigraphy in China

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A comprehensive study of outcrop sequence stratigraphy in China began in the early 1990s.The investigated strata range from Mesoproterozoic to Quaternary and the studied areas cover the three platforms and margins, the Southern Himalayas and the East China and South China seas.Problems of general concern in the sequence stratigraphy of China are discussed. These are: the hierarchy for sequence stratigraphy, the third-order Sequence and eustasy, the chronostratigraphic boundaries and GSSP, and the International Stratigraphic Chart and the sequence chronostratigraphy of China. The average time interval of Mesosequence (25-40 Ma) and of the Sequence (2-5 Ma) is suggested and the minor sequences below the Sequence are discussed. The time interval of the Sequence shows no evident decrease with time, but several epochs with remarkable short intervals occur in the Phanerozoic, which may represent a planetary behavior denoting the special development stages in earth's evolution. Sea level change curves are given separately for the three platforms and the different regions. The Global Stratotype Section and Point (GSSP) concept and practice are discussed, and a comparison between the first appearance point of biozone and the first flooding surface in the Sequence is made for designation of the chronostratigraphic boundary.It is suggested that the chronostratigraphic boundaries might be set at the first flooding surface in the Sequence for easy recognition. The idea of sequence chronostratigraphy is recommended, and a comparison between the International Stratigraphic Chart and the sequence chronostratigraphy of China is made. The close relation between chronostratigraphy and sequence stratigraphy makes it possible for sequence stratigraphy to improve chronostratigraphic research. It is pointed out that multidisciplinary study in chronostratigraphy is necessary and should be promising and profitable.

  12. Permutation Entropy for Random Binary Sequences

    Directory of Open Access Journals (Sweden)

    Lingfeng Liu

    2015-12-01

    Full Text Available In this paper, we generalize the permutation entropy (PE measure to binary sequences, which is based on Shannon’s entropy, and theoretically analyze this measure for random binary sequences. We deduce the theoretical value of PE for random binary sequences, which can be used to measure the randomness of binary sequences. We also reveal the relationship between this PE measure with other randomness measures, such as Shannon’s entropy and Lempel–Ziv complexity. The results show that PE is consistent with these two measures. Furthermore, we use PE as one of the randomness measures to evaluate the randomness of chaotic binary sequences.

  13. Chip-based sequencing nucleic acids

    Science.gov (United States)

    Beer, Neil Reginald

    2014-08-26

    A system for fast DNA sequencing by amplification of genetic material within microreactors, denaturing, demulsifying, and then sequencing the material, while retaining it in a PCR/sequencing zone by a magnetic field. One embodiment includes sequencing nucleic acids on a microchip that includes a microchannel flow channel in the microchip. The nucleic acids are isolated and hybridized to magnetic nanoparticles or to magnetic polystyrene-coated beads. Microreactor droplets are formed in the microchannel flow channel. The microreactor droplets containing the nucleic acids and the magnetic nanoparticles are retained in a magnetic trap in the microchannel flow channel and sequenced.

  14. MatrixPlot: visualizing sequence constraints

    DEFF Research Database (Denmark)

    Gorodkin, Jan; Stærfeldt, Hans Henrik; Lund, Ole;

    1999-01-01

    MatrixPlot: visualizing sequence constraints. Sub-title Abstract Summary : MatrixPlot is a program for making high-quality matrix plots, such as mutual information plots of sequence alignments and distance matrices of sequences with known three-dimensional coordinates. The user can add information...... about the sequences (e.g. a sequence logo profile) along the edges of the plot, as well as zoom in on any region in the plot. Availability : MatrixPlot can be obtained on request, and can also be accessed online at http://www. cbs.dtu.dk/services/MatrixPlot. Contact : gorodkin@cbs.dtu.dk...

  15. Design of Digital Hybrid Chaotic Sequence Generator

    Institute of Scientific and Technical Information of China (English)

    RAO Nini; ZENG Dong

    2004-01-01

    The feasibility of the hybrid chaotic sequences as the spreading codes in code divided multiple access(CDMA) system is analyzed.The design and realization of the digital hybrid chaotic sequence generator by very high speed integrated circuit hardware description language(VHDL) are described.A valid hazard canceledl method is presented.Computer simulations show that the stable digital sequence waveforms can be produced.The correlations of the digital hybrid chaotic sequences are compared with those of m-sequences.The results show that the correlations of the digital hybrid chaotic sequences are almost as good as those of m-sequences.The works in this paper explored a road for the practical applications of chaos.

  16. Nimble Protein Sequence Alignment in Grid (NPSAG

    Directory of Open Access Journals (Sweden)

    K. Somasundaram

    2008-01-01

    Full Text Available In Bio-Informatics application, the analysis of protein sequence is a kind of computation driven science which has rapidly and quickly growing biological data. Also databases used in these applications are heterogeneous in nature and alignment of protein sequence using physical techniques is expensive, slow and results are not always guaranteed/accurate. So this application requires cross-platform, cost-effective and more computing power algorithm for sequence matching and searching a sequence in database. Grid is one of the most emerging technologies of cost effective computing paradigm for large class of data and compute intensive application which enables large-scale aggregation and sharing of computational data and other resources across institutional boundaries. We proposed the Grid architecture for searching of distributed, heterogeneous genomic databases which contained protein sequences to speed up the analysis of large scale sequence data and performed sequence alignment for residues match.

  17. Computing with Hereditarily Finite Sequences

    CERN Document Server

    Tarau, Paul

    2011-01-01

    e use Prolog as a flexible meta-language to provide executable specifications of some fundamental mathematical objects and their transformations. In the process, isomorphisms are unraveled between natural numbers and combinatorial objects (rooted ordered trees representing hereditarily finite sequences and rooted ordered binary trees representing G\\"odel's System {\\bf T} types). This paper focuses on an application that can be seen as an unexpected "paradigm shift": we provide recursive definitions showing that the resulting representations are directly usable to perform symbolically arbitrary-length integer computations. Besides the theoretically interesting fact of "breaking the arithmetic/symbolic barrier", the arithmetic operations performed with symbolic objects like trees or types turn out to be genuinely efficient -- we derive implementations with asymptotic performance comparable to ordinary bitstring implementations of arbitrary-length integer arithmetic. The source code of the paper, organized as a ...

  18. Automatic Sequencing for Experimental Protocols

    Science.gov (United States)

    Hsieh, Paul F.; Stern, Ivan

    We present a paradigm and implementation of a system for the specification of the experimental protocols to be used for the calibration of AXAF mirrors. For the mirror calibration, several thousand individual measurements need to be defined. For each measurement, over one hundred parameters need to be tabulated for the facility test conductor and several hundred instrument parameters need to be set. We provide a high level protocol language which allows for a tractable representation of the measurement protocol. We present a procedure dispatcher which automatically sequences a protocol more accurately and more rapidly than is possible by an unassisted human operator. We also present back-end tools to generate printed procedure manuals and database tables required for review by the AXAF program. This paradigm has been tested and refined in the calibration of detectors to be used in mirror calibration.

  19. The RNA world, automatic sequences and oncogenetics

    International Nuclear Information System (INIS)

    We construct a model of the RNA world in terms of naturally evolving nucleotide sequences assuming only Crick-Watson base pairing and self-cleaving/splicing capability. These sequences have the following properties. 1) They are recognizable by an automation (or automata). That is, to each k-sequence, there exist a k-automation which accepts, recognizes or generates the k-sequence. These are known as automatic sequences. Fibonacci and Morse-Thue sequences are the most natural outcome of pre-biotic chemical conditions. 2) Infinite (resp. large) sequences are self-similar (resp. nearly self-similar) under certain rewrite rules and consequently give rise to fractal (resp.fractal-like) structures. Computationally, such sequences can also be generated by their corresponding deterministic parallel re-write system, known as a DOL system. The self-similar sequences are fixed points of their respective rewrite rules. Some of these automatic sequences have the capability that they can read or 'accept' other sequences while others can detect errors and trigger error-correcting mechanisms. They can be enlarged and have block and/or palindrome structure. Linear recurring sequences such as Fibonacci sequence are simply Feed-back Shift Registers, a well know model of information processing machines. We show that a mutation of any rewrite rule can cause a combinatorial explosion of error and relates this to oncogenetical behavior. On the other hand, a mutation of sequences that are not rewrite rules, leads to normal evolutionary change. Known experimental results support our hypothesis. (author). Refs

  20. An enhanced algorithm for multiple sequence alignment of protein sequences using genetic algorithm

    OpenAIRE

    Kumar, Manish

    2015-01-01

    One of the most fundamental operations in biological sequence analysis is multiple sequence alignment (MSA). The basic of multiple sequence alignment problems is to determine the most biologically plausible alignments of protein or DNA sequences. In this paper, an alignment method using genetic algorithm for multiple sequence alignment has been proposed. Two different genetic operators mainly crossover and mutation were defined and implemented with the proposed method in order to know the pop...

  1. Software for pre-processing Illumina next-generation sequencing short read sequences

    OpenAIRE

    Chen, Chuming; Khaleel, Sari S; Huang, Hongzhan; Cathy H Wu

    2014-01-01

    Background When compared to Sanger sequencing technology, next-generation sequencing (NGS) technologies are hindered by shorter sequence read length, higher base-call error rate, non-uniform coverage, and platform-specific sequencing artifacts. These characteristics lower the quality of their downstream analyses, e.g. de novo and reference-based assembly, by introducing sequencing artifacts and errors that may contribute to incorrect interpretation of data. Although many tools have been devel...

  2. Next-Generation Sequencing Techniques for Eukaryotic Microorganisms: Sequencing-Based Solutions to Biological Problems▿

    OpenAIRE

    Nowrousian, Minou

    2010-01-01

    Over the past 5 years, large-scale sequencing has been revolutionized by the development of several so-called next-generation sequencing (NGS) technologies. These have drastically increased the number of bases obtained per sequencing run while at the same time decreasing the costs per base. Compared to Sanger sequencing, NGS technologies yield shorter read lengths; however, despite this drawback, they have greatly facilitated genome sequencing, first for prokaryotic genomes and within the las...

  3. Assembly Sequence Planning for Mechanical Products

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    A method for assembly sequence planning is proposed in this paper. First, two methods for assembly sequence planning are compared, which are indirect method and direct method. Then, the limits of the previous assembly planning system are pointed out. On the basis of indirect method, an improved method for assembly sequence planning is put forward. This method is composed of four parts, which are assembly modeling for products, assembly sequence representing, assembly sequence planning, and evaluation and optimization. The assembly model is established by human machine interaction, and the assembly model contains components' information and the assembly relation among the components. The assembly sequence planning is based on the breaking up of the assembly model. And/or graph is used to represent assembly sequence set. Every component which satisfies the disassembly condition is recorded as a node of an and/or graph. After the disassembly sequence and/or graph is generated, heuristic algorithm - AO* algorithm is used to search the disassembly sequence and/or graph, and the optimum assembly sequence planning is realized. This method is proved to be effective in a prototype system which is a sub-project of a state 863/CIMS research project of China - ‘Concurrent Engineering’.

  4. Randomness in Sequence Evolution Increases over Time.

    Science.gov (United States)

    Wang, Guangyu; Sun, Shixiang; Zhang, Zhang

    2016-01-01

    The second law of thermodynamics states that entropy, as a measure of randomness in a system, increases over time. Although studies have investigated biological sequence randomness from different aspects, it remains unknown whether sequence randomness changes over time and whether this change consists with the second law of thermodynamics. To capture the dynamics of randomness in molecular sequence evolution, here we detect sequence randomness based on a collection of eight statistical random tests and investigate the randomness variation of coding sequences with an application to Escherichia coli. Given that core/essential genes are more ancient than specific/non-essential genes, our results clearly show that core/essential genes are more random than specific/non-essential genes and accordingly indicate that sequence randomness indeed increases over time, consistent well with the second law of thermodynamics. We further find that an increase in sequence randomness leads to increasing randomness of GC content and longer sequence length. Taken together, our study presents an important finding, for the first time, that sequence randomness increases over time, which may provide profound insights for unveiling the underlying mechanisms of molecular sequence evolution. PMID:27224236

  5. Predicting Contextual Sequences via Submodular Function Maximization

    CERN Document Server

    Dey, Debadeepta; Hebert, Martial; Bagnell, J Andrew

    2012-01-01

    Sequence optimization, where the items in a list are ordered to maximize some reward has many applications such as web advertisement placement, search, and control libraries in robotics. Previous work in sequence optimization produces a static ordering that does not take any features of the item or context of the problem into account. In this work, we propose a general approach to order the items within the sequence based on the context (e.g., perceptual information, environment description, and goals). We take a simple, efficient, reduction-based approach where the choice and order of the items is established by repeatedly learning simple classifiers or regressors for each "slot" in the sequence. Our approach leverages recent work on submodular function maximization to provide a formal regret reduction from submodular sequence optimization to simple cost-sensitive prediction. We apply our contextual sequence prediction algorithm to optimize control libraries and demonstrate results on two robotics problems: ...

  6. Evolutionarily conserved sequences on human chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Frazer, Kelly A.; Sheehan, John B.; Stokowski, Renee P.; Chen, Xiyin; Hosseini, Roya; Cheng, Jan-Fang; Fodor, Stephen P.A.; Cox, David R.; Patil, Nila

    2001-09-01

    Comparison of human sequences with the DNA of other mammals is an excellent means of identifying functional elements in the human genome. Here we describe the utility of high-density oligonucleotide arrays as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available. High-density arrays representing approximately 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized and then hybridized with mouse and dog DNA to identify sequences conserved between humans and mice (human-mouse elements) and between humans and dogs (human-dog elements). Our data show that sequence comparison of multiple species provides a powerful empiric method for identifying actively conserved elements in the human genome. A large fraction of these evolutionarily conserved elements are present in regions on chromosome 21 that do not encode known genes.

  7. Comparison of next-generation sequencing systems.

    Science.gov (United States)

    Liu, Lin; Li, Yinhu; Li, Siliang; Hu, Ni; He, Yimin; Pong, Ray; Lin, Danni; Lu, Lihua; Law, Maggie

    2012-01-01

    With fast development and wide applications of next-generation sequencing (NGS) technologies, genomic sequence information is within reach to aid the achievement of goals to decode life mysteries, make better crops, detect pathogens, and improve life qualities. NGS systems are typically represented by SOLiD/Ion Torrent PGM from Life Sciences, Genome Analyzer/HiSeq 2000/MiSeq from Illumina, and GS FLX Titanium/GS Junior from Roche. Beijing Genomics Institute (BGI), which possesses the world's biggest sequencing capacity, has multiple NGS systems including 137 HiSeq 2000, 27 SOLiD, one Ion Torrent PGM, one MiSeq, and one 454 sequencer. We have accumulated extensive experience in sample handling, sequencing, and bioinformatics analysis. In this paper, technologies of these systems are reviewed, and first-hand data from extensive experience is summarized and analyzed to discuss the advantages and specifics associated with each sequencing system. At last, applications of NGS are summarized.

  8. Sequencing intractable DNA to close microbial genomes.

    Directory of Open Access Journals (Sweden)

    Richard A Hurt

    Full Text Available Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled "intractable" resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such problematic regions in the "non-contiguous finished" Desulfovibrio desulfuricans ND132 genome (6 intractable gaps and the Desulfovibrio africanus genome (1 intractable gap. The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. The developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing.

  9. Nanopore DNA sequencing with MspA.

    Science.gov (United States)

    Derrington, Ian M; Butler, Tom Z; Collins, Marcus D; Manrao, Elizabeth; Pavlenok, Mikhail; Niederweis, Michael; Gundlach, Jens H

    2010-09-14

    Nanopore sequencing has the potential to become a direct, fast, and inexpensive DNA sequencing technology. The simplest form of nanopore DNA sequencing utilizes the hypothesis that individual nucleotides of single-stranded DNA passing through a nanopore will uniquely modulate an ionic current flowing through the pore, allowing the record of the current to yield the DNA sequence. We demonstrate that the ionic current through the engineered Mycobacterium smegmatis porin A, MspA, has the ability to distinguish all four DNA nucleotides and resolve single-nucleotides in single-stranded DNA when double-stranded DNA temporarily holds the nucleotides in the pore constriction. Passing DNA with a series of double-stranded sections through MspA provides proof of principle of a simple DNA sequencing method using a nanopore. These findings highlight the importance of MspA in the future of nanopore sequencing. PMID:20798343

  10. Pareto optimal pairwise sequence alignment.

    Science.gov (United States)

    DeRonne, Kevin W; Karypis, George

    2013-01-01

    Sequence alignment using evolutionary profiles is a commonly employed tool when investigating a protein. Many profile-profile scoring functions have been developed for use in such alignments, but there has not yet been a comprehensive study of Pareto optimal pairwise alignments for combining multiple such functions. We show that the problem of generating Pareto optimal pairwise alignments has an optimal substructure property, and develop an efficient algorithm for generating Pareto optimal frontiers of pairwise alignments. All possible sets of two, three, and four profile scoring functions are used from a pool of 11 functions and applied to 588 pairs of proteins in the ce_ref data set. The performance of the best objective combinations on ce_ref is also evaluated on an independent set of 913 protein pairs extracted from the BAliBASE RV11 data set. Our dynamic-programming-based heuristic approach produces approximated Pareto optimal frontiers of pairwise alignments that contain comparable alignments to those on the exact frontier, but on average in less than 1/58th the time in the case of four objectives. Our results show that the Pareto frontiers contain alignments whose quality is better than the alignments obtained by single objectives. However, the task of identifying a single high-quality alignment among those in the Pareto frontier remains challenging.

  11. On the Origin of Sequence

    Directory of Open Access Journals (Sweden)

    Peter T. S. van der Gulik

    2015-11-01

    Full Text Available Three aspects which make planet Earth special, and which must be taken in consideration with respect to the emergence of peptides, are the mineralogical composition, the Moon which is in the same size class, and the triple environment consisting of ocean, atmosphere, and continent. GlyGly is a remarkable peptide because it stimulates peptide bond formation in the Salt-Induced Peptide Formation reaction. The role glycine and aspartic acid play in the active site of RNA polymerase is remarkable too. GlyGly might have been the original product of coded peptide synthesis because of its importance in stimulating the production of oligopeptides with a high aspartic acid content, which protected small RNA molecules by binding Mg2+ ions. The feedback loop, which is closed by having RNA molecules producing GlyGly, is proposed as the essential element fundamental to life. Having this system running, longer sequences could evolve, gradually solving the problem of error catastrophe. The basic structure of the standard genetic code (8 fourfold degenerate codon boxes and 8 split codon boxes is an example of the way information concerning the emergence of life is frozen in the biological constitution of organisms: the structure of the code contains historical information.

  12. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags

    Science.gov (United States)

    de Souza, Sandro J.; Camargo, Anamaria A.; Briones, Marcelo R. S.; Costa, Fernando F.; Nagai, Maria Aparecida; Verjovski-Almeida, Sergio; Zago, Marco A.; Andrade, Luis Eduardo C.; Carrer, Helaine; El-Dorry, Hamza F. A.; Espreafico, Enilza M.; Habr-Gama, Angelita; Giannella-Neto, Daniel; Goldman, Gustavo H.; Gruber, Arthur; Hackel, Christine; Kimura, Edna T.; Maciel, Rui M. B.; Marie, Suely K. N.; Martins, Elizabeth A. L.; Nóbrega, Marina P.; Paçó-Larson, Maria Luisa; Pardini, Maria Inês M. C.; Pereira, Gonçalo G.; Pesquero, João Bosco; Rodrigues, Vanderlei; Rogatto, Silvia R.; da Silva, Ismael D. C. G.; Sogayar, Mari C.; de Fátima Sonati, Maria; Tajara, Eloiza H.; Valentini, Sandro R.; Acencio, Marcio; Alberto, Fernando L.; Amaral, Maria Elisabete J.; Aneas, Ivy; Bengtson, Mário Henrique; Carraro, Dirce M.; Carvalho, Alex F.; Carvalho, Lúcia Helena; Cerutti, Janete M.; Corrêa, Maria Lucia C.; Costa, Maria Cristina R.; Curcio, Cyntia; Gushiken, Tsieko; Ho, Paulo L.; Kimura, Elza; Leite, Luciana C. C.; Maia, Gustavo; Majumder, Paromita; Marins, Mozart; Matsukuma, Adriana; Melo, Analy S. A.; Mestriner, Carlos Alberto; Miracca, Elisabete C.; Miranda, Daniela C.; Nascimento, Ana Lucia T. O.; Nóbrega, Francisco G.; Ojopi, Élida P. B.; Pandolfi, José Rodrigo C.; Pessoa, Luciana Gilbert; Rahal, Paula; Rainho, Claudia A.; da Ro's, Nancy; de Sá, Renata G.; Sales, Magaly M.; da Silva, Neusa P.; Silva, Tereza C.; da Silva, Wilson; Simão, Daniel F.; Sousa, Josane F.; Stecconi, Daniella; Tsukumo, Fernando; Valente, Valéria; Zalcberg, Heloisa; Brentani, Ricardo R.; Reis, Luis F. L.; Dias-Neto, Emmanuel; Simpson, Andrew J. G.

    2000-01-01

    Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1,181 (1.45%) were found to match sequences in chromosome 22 with at least one ORESTES contig for 162 (65.6%) of the 247 known genes, for 67 (44.6%) of the 150 related genes, and for 45 of the 148 (30.4%) EST-predicted genes on this chromosome. Using a set of stringent criteria to validate our sequences, we identified a further 219 previously unannotated transcribed sequences on chromosome 22. Of these, 171 were in fact also defined by EST or full length cDNA sequences available in GenBank but not utilized in the initial annotation of the first human chromosome sequence. Thus despite representing less than 15% of all expressed human sequences in the public databases at the time of the present analysis, ORESTES sequences defined 48 transcribed sequences on chromosome 22 not defined by other sequences. All of the transcribed sequences defined by ORESTES coincided with DNA regions predicted as encoding exons by genscan. (http://genes.mit.edu/GENSCAN.html). PMID:11070084

  13. Predicting Contextual Sequences via Submodular Function Maximization

    OpenAIRE

    Dey, Debadeepta; Liu, Tian Yu; Hebert, Martial; Bagnell, J. Andrew

    2012-01-01

    Sequence optimization, where the items in a list are ordered to maximize some reward has many applications such as web advertisement placement, search, and control libraries in robotics. Previous work in sequence optimization produces a static ordering that does not take any features of the item or context of the problem into account. In this work, we propose a general approach to order the items within the sequence based on the context (e.g., perceptual information, environment description, ...

  14. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  15. Improving Recurrent Neural Networks For Sequence Labelling

    OpenAIRE

    Dinarelli, Marco; Tellier, Isabelle

    2016-01-01

    In this paper we study different types of Recurrent Neural Networks (RNN) for sequence labeling tasks. We propose two new variants of RNNs integrating improvements for sequence labeling, and we compare them to the more traditional Elman and Jordan RNNs. We compare all models, either traditional or new, on four distinct tasks of sequence labeling: two on Spoken Language Understanding (ATIS and MEDIA); and two of POS tagging for the French Treebank (FTB) and the Penn Treebank (PTB) corpora. The...

  16. A classification of periodic turtle sequences

    OpenAIRE

    J. Holdener; A. Wagaman

    2003-01-01

    A turtle sequence is a word constructed from an alphabet of two letters: F, which represents the forward motion of a turtle in the plane, and L, which represents a counterclockwise turn. In this paper, we investigate such sequences and establish links between the combinatoric properties of words and the geometric properties of the curves they generate. In particular, we classify periodic turtle sequences in terms of their closure (or lack thereof).

  17. WEAK CONVERGENCE OF HENSTOCK INTEGRABLE SEQUENCES

    Institute of Scientific and Technical Information of China (English)

    LuisaDiPiazza

    1994-01-01

    Some relationships between pointwise and weak convergence of a sequence of Henstock integrable functions are studied, In particular it is provided an example of a sequence of Henstock integrable functions whose pointwise limit is different from the weak one. By introducing an asymptotic version of the Henstock equiintegrability notion it is given a necessary and sufficient condition in order that a pointwisely convergent sequence of Henstock integrable functions is weakly convergent to its pointwise limit.

  18. Next-generation sequencing: applications beyond genomes

    OpenAIRE

    Marguerat, Samuel; Wilhelm, Brian T.; Bähler, Jürg

    2008-01-01

    The development of DNA sequencing more than 30 years ago has profoundly impacted biological research. In the last couple of years, remarkable technological innovations have emerged that allow the direct and cost-effective sequencing of complex samples at unprecedented scale and speed. These next-generation technologies make it feasible to sequence not only static genomes, but also entire transcriptomes expressed under different conditions. These and other powerful applications of next-generat...

  19. Repetitive sequence environment distinguishes housekeeping genes

    OpenAIRE

    Eller, C. Daniel; Regelson, Moira; Merriman, Barry; Nelson, Stan,; Horvath, Steve; Marahrens, York

    2006-01-01

    Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear E...

  20. A statistical study of aftershock sequences

    OpenAIRE

    Giorgio Ranalli

    2010-01-01

    A comprehensive statistical study of the phenomenology of aftershock sequences is made in this paper. The spatial distribution of aftershocks indicates that they are mainly crustal events; however, deeper sequences also take place. The analysis of the distribution of aftershocks in 15 sequences with respect to time and magnitude leads to the statistical confirmation of a set of phenomenological laws describing the process, namely, the time-frequency law of hyperbolic decay of aftershock activ...

  1. Scalable Transcriptome Preparation for Massive Parallel Sequencing

    OpenAIRE

    Stranneheim, Henrik; Werne, Beata; Sherwood, Ellen; Lundeberg, Joakim

    2011-01-01

    Background The tremendous output of massive parallel sequencing technologies requires automated robust and scalable sample preparation methods to fully exploit the new sequence capacity. Methodology In this study, a method for automated library preparation of RNA prior to massively parallel sequencing is presented. The automated protocol uses precipitation onto carboxylic acid paramagnetic beads for purification and size selection of both RNA and DNA. The automated sample preparation was comp...

  2. Scalable Transcriptome Preparation for Massive Parallel Sequencing

    OpenAIRE

    Henrik Stranneheim; Beata Werne; Ellen Sherwood; Joakim Lundeberg

    2011-01-01

    BACKGROUND: The tremendous output of massive parallel sequencing technologies requires automated robust and scalable sample preparation methods to fully exploit the new sequence capacity. METHODOLOGY: In this study, a method for automated library preparation of RNA prior to massively parallel sequencing is presented. The automated protocol uses precipitation onto carboxylic acid paramagnetic beads for purification and size selection of both RNA and DNA. The automated sample preparation was co...

  3. Accurate and comprehensive sequencing of personal genomes

    OpenAIRE

    Ajay, Subramanian S.; Parker, Stephen C.J.; Ozel Abaan, Hatice; Fuentes Fajardo, Karin V.; Margulies, Elliott H.

    2011-01-01

    As whole-genome sequencing becomes commoditized and we begin to sequence and analyze personal genomes for clinical and diagnostic purposes, it is necessary to understand what constitutes a complete sequencing experiment for determining genotypes and detecting single-nucleotide variants. Here, we show that the current recommendation of ∼30× coverage is not adequate to produce genotype calls across a large fraction of the genome with acceptably low error rates. Our results are based on analyses...

  4. Sequence and structural analysis of antibodies

    OpenAIRE

    Raghavan, A. K.

    2009-01-01

    The work presented in this thesis focusses on the sequence and structural analysis of antibodies and has fallen into three main areas. First I developed a method to assess how typical an antibody sequence is of the expressed human antibody repertoire. My hypothesis was that the more \\humanlike" an antibody sequence is (in other words how typical it is of the expressed human repertoire), the less likely it is to elicit an immune response when used in vivo in humans. In practi...

  5. Some properties of generalized Fibonacci sequence

    Science.gov (United States)

    Chong, Chin-Yoon; Ho, C. K.

    2015-12-01

    For all non-negative integer n and real constants a, b, p and q, the generalized Fibonacci sequence {U n } is defined by Un+2 = pUn+1 + qUn with the initial values U0 = a and U1 = b. Throughout the paper, we study some properties of the generalized Fibonacci sequence. Our results will motivate some new research problems concerning the contribution of the generalized sequence.

  6. Effects of Sequence Partitioning on Compression Rate

    OpenAIRE

    Alagoz, B. Baykant

    2010-01-01

    In the paper, a theoretical work is done for investigating effects of splitting data sequence into packs of data set. We proved that a partitioning of data sequence is possible to find such that the entropy rate at each subsequence is lower than entropy rate of the source. Effects of sequence partitioning on overall compression rate are argued on the bases of partitioning statistics, and then, an optimization problem for an optimal partition is defined to improve overall compression rate of a...

  7. Nucleotide sequences encoding a thermostable alkaline protease

    Science.gov (United States)

    Wilson, David B.; Lao, Guifang

    1998-01-01

    Nucleotide sequences, derived from a thermophilic actinomycete microorganism, which encode a thermostable alkaline protease are disclosed. Also disclosed are variants of the nucleotide sequences which encode a polypeptide having thermostable alkaline proteolytic activity. Recombinant thermostable alkaline protease or recombinant polypeptide may be obtained by culturing in a medium a host cell genetically engineered to contain and express a nucleotide sequence according to the present invention, and recovering the recombinant thermostable alkaline protease or recombinant polypeptide from the culture medium.

  8. Detecting Emotions from Connected Action Sequences

    Science.gov (United States)

    Bernhardt, Daniel; Robinson, Peter

    In this paper we deal with the problem of detecting emotions from the body movements produced by naturally connected action sequences. Although action sequences are one of the most common forms of body motions in everyday scenarios their potential for emotion recognition has not been explored in the past. We show that there are fundamental differences between actions recorded in isolation and in natural sequences and demonstrate a number of techniques which allow us to correctly label action sequences with one of four emotions up to 86% of the time. Our results bring us an important step closer to recognizing emotions from body movements in natural scenarios.

  9. Genomic sequencing of Pleistocene cave bears

    Energy Technology Data Exchange (ETDEWEB)

    Noonan, James P.; Hofreiter, Michael; Smith, Doug; Priest, JamesR.; Rohland, Nadin; Rabeder, Gernot; Krause, Johannes; Detter, J. Chris; Paabo, Svante; Rubin, Edward M.

    2005-04-01

    Despite the information content of genomic DNA, ancient DNA studies to date have largely been limited to amplification of mitochondrial DNA due to technical hurdles such as contamination and degradation of ancient DNAs. In this study, we describe two metagenomic libraries constructed using unamplified DNA extracted from the bones of two 40,000-year-old extinct cave bears. Analysis of {approx}1 Mb of sequence from each library showed that, despite significant microbial contamination, 5.8 percent and 1.1 percent of clones in the libraries contain cave bear inserts, yielding 26,861 bp of cave bear genome sequence. Alignment of this sequence to the dog genome, the closest sequenced genome to cave bear in terms of evolutionary distance, revealed roughly the expected ratio of cave bear exons, repeats and conserved noncoding sequences. Only 0.04 percent of all clones sequenced were derived from contamination with modern human DNA. Comparison of cave bear with orthologous sequences from several modern bear species revealed the evolutionary relationship of these lineages. Using the metagenomic approach described here, we have recovered substantial quantities of mammalian genomic sequence more than twice as old as any previously reported, establishing the feasibility of ancient DNA genomic sequencing programs.

  10. Hardware Accelerated Sequence Alignment with Traceback

    Directory of Open Access Journals (Sweden)

    Scott Lloyd

    2009-01-01

    in a timely manner. Known methods to accelerate alignment on reconfigurable hardware only address sequence comparison, limit the sequence length, or exhibit memory and I/O bottlenecks. A space-efficient, global sequence alignment algorithm and architecture is presented that accelerates the forward scan and traceback in hardware without memory and I/O limitations. With 256 processing elements in FPGA technology, a performance gain over 300 times that of a desktop computer is demonstrated on sequence lengths of 16000. For greater performance, the architecture is scalable to more processing elements.

  11. Researches on Sequence of Plant Cystatin: Phytocystatin

    Institute of Scientific and Technical Information of China (English)

    QINQingfeng; HEWei; LIANGJun; ZHANGXingyao

    2005-01-01

    Plant cystatins or phytocystatins are cysteine proteinase inhibitors exist widely in different plant species. Because they can kill insects by inhibiting the digestive function of the cysteine proteinase in gut, they are believed to play an important role in plant's defense against pests. Phytocystatins contain the conserved QXVXG motif and show some features on their sequence different to animal cystatins.After sequencing the protein directly and the cDNA clone, a large number of plant cystatins have been characterized. A multialignment with BLAST software and a detail analysis of 38 phytocystatins show that phytocystatins possess a specific conserved amino acid sequence [LRVI]-[AGT]-[RQKE]-[FY]-[AS]-[VI]-X-[EGHDQV]-[HYFQ]-N different to the conserved sequence demonstrated by Margis in 1998. This conserved sequence can be enough to detect with exclusivity phytocystatin sequences on protein data banks. A classification of these phytocystatins is performed and they can be divided into 3 groups according to their features on amino acid sequence, and the group-I can be still divided into 3 subgroups based on the feature of their amino acid and genomic sequence. By the CLUSTALX software,the most conserved nucleotide sequences of phytocystatins were found, which could be used to design the degenerate premiers to search new phytocystatins with PCR reaction.

  12. Massively parallel sequencing of forensic STRs

    DEFF Research Database (Denmark)

    Parson, Walther; Ballard, David; Budowle, Bruce;

    2016-01-01

    The DNA Commission of the International Society for Forensic Genetics (ISFG) is reviewing factors that need to be considered ahead of the adoption by the forensic community of short tandem repeat (STR) genotyping by massively parallel sequencing (MPS) technologies. MPS produces sequence data...... accessible genome assembly, and in place before the uptake of MPS by the general forensic community starts to generate sequence data on a large scale. While the established nomenclature for CE-based STR analysis will remain unchanged in the future, the nomenclature of sequence-based STR genotypes will need...

  13. Visible periodicity of strong nucleosome DNA sequences.

    Science.gov (United States)

    Salih, Bilal; Tripathi, Vijay; Trifonov, Edward N

    2015-01-01

    Fifteen years ago, Lowary and Widom assembled nucleosomes on synthetic random sequence DNA molecules, selected the strongest nucleosomes and discovered that the TA dinucleotides in these strong nucleosome sequences often appear at 10-11 bases from one another or at distances which are multiples of this period. We repeated this experiment computationally, on large ensembles of natural genomic sequences, by selecting the strongest nucleosomes--i.e. those with such distances between like-named dinucleotides, multiples of 10.4 bases, the structural and sequence period of nucleosome DNA. The analysis confirmed the periodicity of TA dinucleotides in the strong nucleosomes, and revealed as well other periodic sequence elements, notably classical AA and TT dinucleotides. The matrices of DNA bendability and their simple linear forms--nucleosome positioning motifs--are calculated from the strong nucleosome DNA sequences. The motifs are in full accord with nucleosome positioning sequences derived earlier, thus confirming that the new technique, indeed, detects strong nucleosomes. Species- and isochore-specific variations of the matrices and of the positioning motifs are demonstrated. The strong nucleosome DNA sequences manifest the highest hitherto nucleosome positioning sequence signals, showing the dinucleotide periodicities in directly observable rather than in hidden form.

  14. A note on bifix-free sequences

    DEFF Research Database (Denmark)

    Nielsen, Peter Tolstrup

    1973-01-01

    A bifix of anL-aryn-tuple is a sequence which is both a prefix and a suffix of thatn-tuple. The practical importance of bifix-free patterns is emphasized, and we devise a systematic way of generating all such sequences and determine their number.......A bifix of anL-aryn-tuple is a sequence which is both a prefix and a suffix of thatn-tuple. The practical importance of bifix-free patterns is emphasized, and we devise a systematic way of generating all such sequences and determine their number....

  15. Recursive sequences in first-year calculus

    Science.gov (United States)

    Krainer, Thomas

    2016-02-01

    This article provides ready-to-use supplementary material on recursive sequences for a second-semester calculus class. It equips first-year calculus students with a basic methodical procedure based on which they can conduct a rigorous convergence or divergence analysis of many simple recursive sequences on their own without the need to invoke inductive arguments as is typically required in calculus textbooks. The sequences that are accessible to this kind of analysis are predominantly (eventually) monotonic, but also certain recursive sequences that alternate around their limit point as they converge can be considered.

  16. Representing objects, relations, and sequences.

    Science.gov (United States)

    Gallant, Stephen I; Okaywe, T Wendy

    2013-08-01

    Vector symbolic architectures (VSAs) are high-dimensional vector representations of objects (e.g., words, image parts), relations (e.g., sentence structures), and sequences for use with machine learning algorithms. They consist of a vector addition operator for representing a collection of unordered objects, a binding operator for associating groups of objects, and a methodology for encoding complex structures. We first develop constraints that machine learning imposes on VSAs; for example, similar structures must be represented by similar vectors. The constraints suggest that current VSAs should represent phrases ("The smart Brazilian girl") by binding sums of terms, in addition to simply binding the terms directly. We show that matrix multiplication can be used as the binding operator for a VSA, and that matrix elements can be chosen at random. A consequence for living systems is that binding is mathematically possible without the need to specify, in advance, precise neuron-to-neuron connection properties for large numbers of synapses. A VSA that incorporates these ideas, Matrix Binding of Additive Terms (MBAT), is described that satisfies all constraints. With respect to machine learning, for some types of problems appropriate VSA representations permit us to prove learnability rather than relying on simulations. We also propose dividing machine (and neural) learning and representation into three stages, with differing roles for learning in each stage. For neural modeling, we give representational reasons for nervous systems to have many recurrent connections, as well as for the importance of phrases in language processing. Sizing simulations and analyses suggest that VSAs in general, and MBAT in particular, are ready for real-world applications. PMID:23607563

  17. Direct chloroplast sequencing: comparison of sequencing platforms and analysis tools for whole chloroplast barcoding.

    Directory of Open Access Journals (Sweden)

    Marta Brozynska

    Full Text Available Direct sequencing of total plant DNA using next generation sequencing technologies generates a whole chloroplast genome sequence that has the potential to provide a barcode for use in plant and food identification. Advances in DNA sequencing platforms may make this an attractive approach for routine plant identification. The HiSeq (Illumina and Ion Torrent (Life Technology sequencing platforms were used to sequence total DNA from rice to identify polymorphisms in the whole chloroplast genome sequence of a wild rice plant relative to cultivated rice (cv. Nipponbare. Consensus chloroplast sequences were produced by mapping sequence reads to the reference rice chloroplast genome or by de novo assembly and mapping of the resulting contigs to the reference sequence. A total of 122 polymorphisms (SNPs and indels between the wild and cultivated rice chloroplasts were predicted by these different sequencing and analysis methods. Of these, a total of 102 polymorphisms including 90 SNPs were predicted by both platforms. Indels were more variable with different sequencing methods, with almost all discrepancies found in homopolymers. The Ion Torrent platform gave no apparent false SNP but was less reliable for indels. The methods should be suitable for routine barcoding using appropriate combinations of sequencing platform and data analysis.

  18. Timing-Sequence Testing of Parallel Programs

    Institute of Scientific and Technical Information of China (English)

    LIANG Yu; LI Shu; ZHANG Hui; HAN Chengde

    2000-01-01

    Testing of parallel programs involves two parts-testing of controlflow within the processes and testing of timing-sequence.This paper focuses on the latter, particularly on the timing-sequence of message-passing paradigms.Firstly the coarse-grained SYN-sequence model is built up to describe the execution of distributed programs. All of the topics discussed in this paper are based on it. The most direct way to test a program is to run it. A fault-free parallel program should be of both correct computing results and proper SYN-sequence. In order to analyze the validity of observed SYN-sequence, this paper presents the formal specification (Backus Normal Form) of the valid SYN-sequence. Till now there is little work about the testing coverage for distributed programs. Calculating the number of the valid SYN-sequences is the key to coverage problem, while the number of the valid SYN-sequences is terribly large and it is very hard to obtain the combination law among SYN-events. In order to resolve this problem, this paper proposes an efficient testing strategy-atomic SYN-event testing, which is to linearize the SYN-sequence (making it only consist of serial atomic SYN-events) first and then test each atomic SYN-event independently. This paper particularly provides the calculating formula about the number of the valid SYN-sequences for tree-topology atomic SYN-event (broadcast and combine). Furthermore,the number of valid SYN-sequences also,to some degree, mirrors the testability of parallel programs. Taking tree-topology atomic SYN-event as an example, this paper demonstrates the testability and communication speed of the tree-topology atomic SYN-event under different numbers of branches in order to achieve a more satisfactory tradeoff between testability and communication efficiency.

  19. Compressing DNA sequence databases with coil

    Directory of Open Access Journals (Sweden)

    Hendy Michael D

    2008-05-01

    Full Text Available Abstract Background Publicly available DNA sequence databases such as GenBank are large, and are growing at an exponential rate. The sheer volume of data being dealt with presents serious storage and data communications problems. Currently, sequence data is usually kept in large "flat files," which are then compressed using standard Lempel-Ziv (gzip compression – an approach which rarely achieves good compression ratios. While much research has been done on compressing individual DNA sequences, surprisingly little has focused on the compression of entire databases of such sequences. In this study we introduce the sequence database compression software coil. Results We have designed and implemented a portable software package, coil, for compressing and decompressing DNA sequence databases based on the idea of edit-tree coding. coil is geared towards achieving high compression ratios at the expense of execution time and memory usage during compression – the compression time represents a "one-off investment" whose cost is quickly amortised if the resulting compressed file is transmitted many times. Decompression requires little memory and is extremely fast. We demonstrate a 5% improvement in compression ratio over state-of-the-art general-purpose compression tools for a large GenBank database file containing Expressed Sequence Tag (EST data. Finally, coil can efficiently encode incremental additions to a sequence database. Conclusion coil presents a compelling alternative to conventional compression of flat files for the storage and distribution of DNA sequence databases having a narrow distribution of sequence lengths, such as EST data. Increasing compression levels for databases having a wide distribution of sequence lengths is a direction for future work.

  20. Generalized Identities of Companion Fibonacci-Like Sequences

    Directory of Open Access Journals (Sweden)

    Shikha Bhatnagar

    2013-06-01

    Full Text Available The Fibonacci sequence, Lucas sequence, Pell sequence, Pell-Lucas sequence, Jacobsthalsequence and Jacobsthal-Lucas sequence are most prominent examples of second order recursivesequences. In this paper, we deal with two companion Fibonacci- Like sequences which aregeneralization of Fibonacci-Like sequence. Further we obtain some generalized identities amongthe terms of companion Fibonacci-Like sequences, Jacobsthal and Jacobsthal-Lucas sequencesthrough Binet’s formulae.

  1. Generalized Identities of Companion Fibonacci-Like Sequences

    OpenAIRE

    Shikha Bhatnagar; Bijendra Singh; Omprakash Sikhwal

    2013-01-01

    The Fibonacci sequence, Lucas sequence, Pell sequence, Pell-Lucas sequence, Jacobsthalsequence and Jacobsthal-Lucas sequence are most prominent examples of second order recursivesequences. In this paper, we deal with two companion Fibonacci- Like sequences which aregeneralization of Fibonacci-Like sequence. Further we obtain some generalized identities amongthe terms of companion Fibonacci-Like sequences, Jacobsthal and Jacobsthal-Lucas sequencesthrough Binet’s formulae.

  2. Fibonacci-triple sequences and some fundamental properties

    Directory of Open Access Journals (Sweden)

    Bijendra Singh

    2010-12-01

    Full Text Available Fibonacci sequence stands as a kind of super sequence with fabulous properties. This note presents Fibonacci-Triple sequences that may also be called 3-F sequences. This is the explosive development in the region of Fibonacci sequence. Our purpose of this paper is to demonstrate fundamental properties of Fibonacci-Triple sequence.

  3. Genome Sequence of Pseudomonas chlororaphis Strain 189

    Science.gov (United States)

    Town, Jennifer; Audy, Patrice; Boyetchko, Susan M.

    2016-01-01

    Pseudomonas chlororaphis strain 189 is a potent inhibitor of the growth of the potato pathogen Phytophthora infestans. We determined the complete, finished sequence of the 6.8-Mbp genome of this strain, consisting of a single contiguous molecule. Strain 189 is closely related to previously sequenced strains of P. chlororaphis. PMID:27340063

  4. About a new family of sequences

    OpenAIRE

    Diniz, Felipe Bottega

    2016-01-01

    First we define a new kind of function over $\\mathbb{N}$. For each $i\\in\\mathbb{N}$ we have an associated function, which will be called $S_i$ . Then we define a new kind of sequence, to be made from the functions $S_i$ . Finally, we will see that some of these sequences has a self-similarity feature.

  5. Bonobos extract meaning from call sequences.

    Directory of Open Access Journals (Sweden)

    Zanna Clay

    Full Text Available Studies on language-trained bonobos have revealed their remarkable abilities in representational and communication tasks. Surprisingly, however, corresponding research into their natural communication has largely been neglected. We address this issue with a first playback study on the natural vocal behaviour of bonobos. Bonobos produce five acoustically distinct call types when finding food, which they regularly mix together into longer call sequences. We found that individual call types were relatively poor indicators of food quality, while context specificity was much greater at the call sequence level. We therefore investigated whether receivers could extract meaning about the quality of food encountered by the caller by integrating across different call sequences. We first trained four captive individuals to find two types of foods, kiwi (preferred and apples (less preferred at two different locations. We then conducted naturalistic playback experiments during which we broadcasted sequences of four calls, originally produced by a familiar individual responding to either kiwi or apples. All sequences contained the same number of calls but varied in the composition of call types. Following playbacks, we found that subjects devoted significantly more search effort to the field indicated by the call sequence. Rather than attending to individual calls, bonobos attended to the entire sequences to make inferences about the food encountered by a caller. These results provide the first empirical evidence that bonobos are able to extract information about external events by attending to vocal sequences of other individuals and highlight the importance of call combinations in their natural communication system.

  6. Molecular selection in a unified evolutionary sequence

    Science.gov (United States)

    Fox, S. W.

    1986-01-01

    With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

  7. Stochastic Modelling of Daily Rainfall sequences

    NARCIS (Netherlands)

    Buishand, T.A.

    1977-01-01

    Rainfall series of different climatic regions were analysed with the aim of generating daily rainfall sequences. A survey of the data is given in I, 1. When analysing daily rainfall sequences one must be aware of the following points:a. Seasonality. Because of seasonal variation of features of the r

  8. Novel algorithms for protein sequence analysis

    NARCIS (Netherlands)

    Ye, Kai

    2008-01-01

    Each protein is characterized by its unique sequential order of amino acids, the so-called protein sequence. Biology”s paradigm is that this order of amino acids determines the protein”s architecture and function. In this thesis, we introduce novel algorithms to analyze protein sequences. Chapter 1

  9. Complete Genome Sequence of Gordonia terrae 3612

    Science.gov (United States)

    Russell, Daniel A.; Guerrero Bustamante, Carlos A.; Garlena, Rebecca A.

    2016-01-01

    Here, we report the complete genome sequence of Gordonia terrae 3612, also known by the strain designations ATCC 25594, NRRL B-16283, and NBRC 100016. The genome sequence reveals it to be free of prophage and clustered regularly interspaced short palindromic repeats (CRISPRs), and it is an effective host for the isolation and characterization of Gordonia bacteriophages. PMID:27688316

  10. Project Report: Automatic Sequence Processor Software Analysis

    Science.gov (United States)

    Benjamin, Brandon

    2011-01-01

    The Mission Planning and Sequencing (MPS) element of Multi-Mission Ground System and Services (MGSS) provides space missions with multi-purpose software to plan spacecraft activities, sequence spacecraft commands, and then integrate these products and execute them on spacecraft. Jet Propulsion Laboratory (JPL) is currently is flying many missions. The processes for building, integrating, and testing the multi-mission uplink software need to be improved to meet the needs of the missions and the operations teams that command the spacecraft. The Multi-Mission Sequencing Team is responsible for collecting and processing the observations, experiments and engineering activities that are to be performed on a selected spacecraft. The collection of these activities is called a sequence and ultimately a sequence becomes a sequence of spacecraft commands. The operations teams check the sequence to make sure that no constraints are violated. The workflow process involves sending a program start command, which activates the Automatic Sequence Processor (ASP). The ASP is currently a file-based system that is comprised of scripts written in perl, c-shell and awk. Once this start process is complete, the system checks for errors and aborts if there are any; otherwise the system converts the commands to binary, and then sends the resultant information to be radiated to the spacecraft.

  11. Archaebacterial rhodopsin sequences: Implications for evolution

    Science.gov (United States)

    Lanyi, J. K.

    1991-01-01

    It was proposed over 10 years ago that the archaebacteria represent a separate kingdom which diverged very early from the eubacteria and eukaryotes. It follows that investigations of archaebacterial characteristics might reveal features of early evolution. So far, two genes, one for bacteriorhodopsin and another for halorhodopsin, both from Halobacterium halobium, have been sequenced. We cloned and sequenced the gene coding for the polypeptide of another one of these rhodopsins, a halorhodopsin in Natronobacterium pharaonis. Peptide sequencing of cyanogen bromide fragments, and immuno-reactions of the protein and synthetic peptides derived from the C-terminal gene sequence, confirmed that the open reading frame was the structural gene for the pharaonis halorhodopsin polypeptide. The flanking DNA sequences of this gene, as well as those of other bacterial rhodopsins, were compared to previously proposed archaebacterial consensus sequences. In pairwise comparisons of the open reading frame with DNA sequences for bacterio-opsin and halo-opsin from Halobacterium halobium, silent divergences were calculated. These indicate very considerable evolutionary distance between each pair of genes, even in the dame organism. In spite of this, three protein sequences show extensive similarities, indicating strong selective pressures.

  12. Complete Genome Sequence of Gordonia terrae 3612.

    Science.gov (United States)

    Russell, Daniel A; Guerrero Bustamante, Carlos A; Garlena, Rebecca A; Hatfull, Graham F

    2016-01-01

    Here, we report the complete genome sequence of Gordonia terrae 3612, also known by the strain designations ATCC 25594, NRRL B-16283, and NBRC 100016. The genome sequence reveals it to be free of prophage and clustered regularly interspaced short palindromic repeats (CRISPRs), and it is an effective host for the isolation and characterization of Gordonia bacteriophages. PMID:27688316

  13. From Arithmetic Sequences to Linear Equations

    Science.gov (United States)

    Matsuura, Ryota; Harless, Patrick

    2012-01-01

    The first part of the article focuses on deriving the essential properties of arithmetic sequences by appealing to students' sense making and reasoning. The second part describes how to guide students to translate their knowledge of arithmetic sequences into an understanding of linear equations. Ryota Matsuura originally wrote these lessons for…

  14. Multilocus Sequence Typing Tool for Cyclospora cayetanensis

    Science.gov (United States)

    Guo, Yaqiong; Roellig, Dawn M.; Li, Na; Tang, Kevin; Frace, Michael; Ortega, Ynes; Arrowood, Michael J.; Qvarnstrom, Yvonne; Wang, Lin; Moss, Delynn M.; Zhang, Longxian; Xiao, Lihua

    2016-01-01

    Because the lack of typing tools for Cyclospora cayetanensis has hampered outbreak investigations, we sequenced its genome and developed a genotyping tool. We observed 2 to 10 geographically segregated sequence types at each of 5 selected loci. This new tool could be useful for case linkage and infection/contamination source tracking. PMID:27433881

  15. Concept For Generation Of Long Pseudorandom Sequences

    Science.gov (United States)

    Wang, C. C.

    1990-01-01

    Conceptual very-large-scale integrated (VLSI) digital circuit performs exponentiation in finite field. Algorithm that generates unusually long sequences of pseudorandom numbers executed by digital processor that includes such circuits. Concepts particularly advantageous for such applications as spread-spectrum communications, cryptography, and generation of ranging codes, synthetic noise, and test data, where usually desirable to make pseudorandom sequences as long as possible.

  16. Acoustic Packaging of Action Sequences by Infants

    Science.gov (United States)

    Brand, Rebecca J.; Tapscott, Stephanie

    2007-01-01

    This study investigated whether acoustic input, in the form of infant-directed speech, influenced infants' segmenting of action sequences. Thirty-two 7.5- to 11.5-month-old infants were familiarized with video sequences made up of short action clips. Narration coincided with portions of the action stream to package certain pairs of clips together.…

  17. What's Next? Judging Sequences of Binary Events

    Science.gov (United States)

    Oskarsson, An T.; Van Boven, Leaf; McClelland, Gary H.; Hastie, Reid

    2009-01-01

    The authors review research on judgments of random and nonrandom sequences involving binary events with a focus on studies documenting gambler's fallacy and hot hand beliefs. The domains of judgment include random devices, births, lotteries, sports performances, stock prices, and others. After discussing existing theories of sequence judgments,…

  18. SPARSE SEQUENCE CONSTRUCTION OF LDPC CODES

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    This letter proposes a novel and simple construction of regular Low-Density Parity-Check (LDPC) codes using sparse binary sequences. It utilizes the cyclic cross correlation function of sparse sequences to generate codes with girth8. The new codes perform well using the sumproduct decoding. Low encodingcomplexity can also be achieved due to the inherent quasi-cyclic structure of the codes.

  19. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags

    OpenAIRE

    de Souza, Sandro J.; Anamaria A Camargo; Briones, Marcelo R. S.; Fernando F. Costa; NAGAI, MARIA APARECIDA; Verjovski-Almeida, Sergio; Zago, Marco A.; Andrade, Luis Eduardo C.; Carrer, Helaine; El-Dorry, Hamza F. A.; Espreafico, Enilza M.; Habr-Gama, Angelita; Giannella-Neto, Daniel; Goldman, Gustavo H.; Gruber, Arthur

    2000-01-01

    Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1,181 ...

  20. EXTENSION OF SEQUENCE STRATIGRAPHIC MODEL AND SEQUENCE STRATIGRAPHC ANALYSIS IN LIMNIC DEPOSITIONAL BASIN

    Institute of Scientific and Technical Information of China (English)

    李增学; 魏久传; 王民镇; 李守春; 李青山; 金秀昆; 兰恒星

    1996-01-01

    The architectural patterns of sedimentary succession are diverse in different depositionalbasins. The sedimentary architecture and geological condition of such basins asepicontinental sea, intraplate limnic basins, etc., differ clearly from those of continentalmargin basin. Extension, complement and perfection of sequence stratigraphic models are needed in the studies ofvarious depositional basins based on the classical sequence model. This paper, for this reason,expounds the thought, principles of sequence division, methodology and technology of the studyof sequence stratigraphy in epicontinental and limnic basins.

  1. NGS-based deep bisulfite sequencing.

    Science.gov (United States)

    Lee, Suman; Kim, Joomyeong

    2016-01-01

    We have developed an NGS-based deep bisulfite sequencing protocol for the DNA methylation analysis of genomes. This approach allows the rapid and efficient construction of NGS-ready libraries with a large number of PCR products that have been individually amplified from bisulfite-converted DNA. This approach also employs a bioinformatics strategy to sort the raw sequence reads generated from NGS platforms and subsequently to derive DNA methylation levels for individual loci. The results demonstrated that this NGS-based deep bisulfite sequencing approach provide not only DNA methylation levels but also informative DNA methylation patterns that have not been seen through other existing methods.•This protocol provides an efficient method generating NGS-ready libraries from individually amplified PCR products.•This protocol provides a bioinformatics strategy sorting NGS-derived raw sequence reads.•This protocol provides deep bisulfite sequencing results that can measure DNA methylation levels and patterns of individual loci.

  2. Aligning Sequences by Minimum Description Length

    Directory of Open Access Journals (Sweden)

    John S. Conery

    2008-01-01

    Full Text Available This paper presents a new information theoretic framework for aligning sequences in bioinformatics. A transmitter compresses a set of sequences by constructing a regular expression that describes the regions of similarity in the sequences. To retrieve the original set of sequences, a receiver generates all strings that match the expression. An alignment algorithm uses minimum description length to encode and explore alternative expressions; the expression with the shortest encoding provides the best overall alignment. When two substrings contain letters that are similar according to a substitution matrix, a code length function based on conditional probabilities defined by the matrix will encode the substrings with fewer bits. In one experiment, alignments produced with this new method were found to be comparable to alignments from CLUSTALW. A second experiment measured the accuracy of the new method on pairwise alignments of sequences from the BAliBASE alignment benchmark.

  3. Sequence Affects the Cyclization of DNA Minicircles.

    Science.gov (United States)

    Wang, Qian; Pettitt, B Montgomery

    2016-03-17

    Understanding how the sequence of a DNA molecule affects its dynamic properties is a central problem affecting biochemistry and biotechnology. The process of cyclizing short DNA, as a critical step in molecular cloning, lacks a comprehensive picture of the kinetic process containing sequence information. We have elucidated this process by using coarse-grained simulations, enhanced sampling methods, and recent theoretical advances. We are able to identify the types and positions of structural defects during the looping process at a base-pair level. Correlations along a DNA molecule dictate critical sequence positions that can affect the looping rate. Structural defects change the bending elasticity of the DNA molecule from a harmonic to subharmonic potential with respect to bending angles. We explore the subelastic chain as a possible model in loop formation kinetics. A sequence-dependent model is developed to qualitatively predict the relative loop formation time as a function of DNA sequence. PMID:26938490

  4. M-sequences in ophthalmic electrophysiology.

    Science.gov (United States)

    Müller, Philipp L; Meigen, Thomas

    2016-01-01

    The aim of this review is to use the multimedia aspects of a purely digital online publication to explain and illustrate the highly capable technique of m-sequences in multifocal ophthalmic electrophysiology. M-sequences have been successfully applied in clinical routines during the past 20 years. However, the underlying mathematical rationale is often daunting. These mathematical properties of m-sequences allow one not only to separate the responses from different fields but also to analyze adaptational effects and impacts of former events. By explaining the history, the formation, and the different aspects of application, a better comprehension of the technique is intended. With this review we aim to clarify the opportunities of m-sequences in order to motivate scientists to use m-sequences in their future research. PMID:26818968

  5. Genotyping-by-Sequencing in Plants

    Directory of Open Access Journals (Sweden)

    Gregory D. May

    2012-09-01

    Full Text Available The advent of next-generation DNA sequencing (NGS technologies has led to the development of rapid genome-wide Single Nucleotide Polymorphism (SNP detection applications in various plant species. Recent improvements in sequencing throughput combined with an overall decrease in costs per gigabase of sequence is allowing NGS to be applied to not only the evaluation of small subsets of parental inbred lines, but also the mapping and characterization of traits of interest in much larger populations. Such an approach, where sequences are used simultaneously to detect and score SNPs, therefore bypassing the entire marker assay development stage, is known as genotyping-by-sequencing (GBS. This review will summarize the current state of GBS in plants and the promises it holds as a genome-wide genotyping application.

  6. Transcriptome sequencing goals, assembly, and assessment.

    Science.gov (United States)

    Wheat, Christopher W; Vogel, Heiko

    2011-01-01

    Transcriptome sequencing provides quick, direct access to the mRNA. With this information, one can design primers for PCR of thousands of different genes, SNP markers, probes for microarrays and qPCR, or just use the sequence data itself in comparative studies. Transcriptome sequencing, while getting cheaper, is still an expensive endeavor, with an examination of data quality and its assembly infrequently performed in depth. Here, we outline many of the important issues we think need consideration when starting a transcriptome sequencing project. We also walk the reader through a detailed analysis of an example transcriptome dataset, highlighting the importance of both within-dataset analysis and comparative inferences. Our hope is that with greater attention focused upon assessing assembly performance, advances in transcriptome assembly will increase as prices continue to drop and new technologies, such as Illumina sequencing, start to be used. PMID:22065435

  7. Smgcd: metrics for biological sequence data

    International Nuclear Information System (INIS)

    In the realm of bioinformatics, the key challenges are to manage, store and retrieve the biological data efficiently. It can be classified in to structured, unstructured and semi-structured contents. Typically, the semi-structured biological data comprised of biological sequences. The complex biological sequences produce huge volume of biological data which further produce much more problems for its management, storage and retrieval. This paper proposed metrics; namely, symmetry measure, molecular weight measure, similarity or diversity measure, size base measure, size gap measure, complexity measure and size complexity diversity measure to manage the raised problems in biological data sequences. These metrics measure the sequence complexity, molecular weights, length with gaps and without gaps, its symmetry and similarity through mathematical formulations. The metrics are demonstrated and validated using the proposed hybrid technique which combines empirical evidence with theoretical formulation. This research opens new horizons for efficient management to measure the functionality and quality of metadata for single and multiple biological sequences. (author)

  8. The DNA sequence of human chromosome 7.

    Science.gov (United States)

    Hillier, Ladeana W; Fulton, Robert S; Fulton, Lucinda A; Graves, Tina A; Pepin, Kymberlie H; Wagner-McPherson, Caryn; Layman, Dan; Maas, Jason; Jaeger, Sara; Walker, Rebecca; Wylie, Kristine; Sekhon, Mandeep; Becker, Michael C; O'Laughlin, Michelle D; Schaller, Mark E; Fewell, Ginger A; Delehaunty, Kimberly D; Miner, Tracie L; Nash, William E; Cordes, Matt; Du, Hui; Sun, Hui; Edwards, Jennifer; Bradshaw-Cordum, Holland; Ali, Johar; Andrews, Stephanie; Isak, Amber; Vanbrunt, Andrew; Nguyen, Christine; Du, Feiyu; Lamar, Betty; Courtney, Laura; Kalicki, Joelle; Ozersky, Philip; Bielicki, Lauren; Scott, Kelsi; Holmes, Andrea; Harkins, Richard; Harris, Anthony; Strong, Cynthia Madsen; Hou, Shunfang; Tomlinson, Chad; Dauphin-Kohlberg, Sara; Kozlowicz-Reilly, Amy; Leonard, Shawn; Rohlfing, Theresa; Rock, Susan M; Tin-Wollam, Aye-Mon; Abbott, Amanda; Minx, Patrick; Maupin, Rachel; Strowmatt, Catrina; Latreille, Phil; Miller, Nancy; Johnson, Doug; Murray, Jennifer; Woessner, Jeffrey P; Wendl, Michael C; Yang, Shiaw-Pyng; Schultz, Brian R; Wallis, John W; Spieth, John; Bieri, Tamberlyn A; Nelson, Joanne O; Berkowicz, Nicolas; Wohldmann, Patricia E; Cook, Lisa L; Hickenbotham, Matthew T; Eldred, James; Williams, Donald; Bedell, Joseph A; Mardis, Elaine R; Clifton, Sandra W; Chissoe, Stephanie L; Marra, Marco A; Raymond, Christopher; Haugen, Eric; Gillett, Will; Zhou, Yang; James, Rose; Phelps, Karen; Iadanoto, Shawn; Bubb, Kerry; Simms, Elizabeth; Levy, Ruth; Clendenning, James; Kaul, Rajinder; Kent, W James; Furey, Terrence S; Baertsch, Robert A; Brent, Michael R; Keibler, Evan; Flicek, Paul; Bork, Peer; Suyama, Mikita; Bailey, Jeffrey A; Portnoy, Matthew E; Torrents, David; Chinwalla, Asif T; Gish, Warren R; Eddy, Sean R; McPherson, John D; Olson, Maynard V; Eichler, Evan E; Green, Eric D; Waterston, Robert H; Wilson, Richard K

    2003-07-10

    Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame. PMID:12853948

  9. Locomotor sequence learning in visually guided walking

    DEFF Research Database (Denmark)

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-01-01

    to modify step length from one trial to the next. Our sequence learning paradigm is derived from the serial reaction-time (SRT) task that has been used in upper limb studies. Both random and ordered sequences of step lengths were used to measure sequence-specific and sequence non-specific learning during......Voluntary limb modifications must be integrated with basic walking patterns during visually guided walking. Here we tested whether voluntary gait modifications can become more automatic with practice. We challenged walking control by presenting visual stepping targets that instructed subjects...... of step lengths over 300 training steps. Younger children (age 6-10 years, N = 8) have lower baseline performance, but their magnitude and rate of sequence learning was the same compared to older children (11-16 years, N = 10) and healthy adults. In addition, learning capacity may be more limited...

  10. Metagenomics using next-generation sequencing.

    Science.gov (United States)

    Bragg, Lauren; Tyson, Gene W

    2014-01-01

    Traditionally, microbial genome sequencing has been restricted to the small number of species that can be grown in pure culture. The progressive development of culture-independent methods over the last 15 years now allows researchers to sequence microbial communities directly from environmental samples. This approach is commonly referred to as "metagenomics" or "community genomics". However, the term metagenomics is applied liberally in the literature to describe any culture-independent analysis of microbial communities. Here, we define metagenomics as shotgun ("random") sequencing of the genomic DNA of a sample taken directly from the environment. The metagenome can be thought of as a sampling of the collective genome of the microbial community. We outline the considerations and analyses that should be undertaken to ensure the success of a metagenomic sequencing project, including the choice of sequencing platform and methods for assembly, binning, annotation, and comparative analysis.

  11. Sequencing and comparing whole mitochondrial genomes ofanimals

    Energy Technology Data Exchange (ETDEWEB)

    Boore, Jeffrey L.; Macey, J. Robert; Medina, Monica

    2005-04-22

    Comparing complete animal mitochondrial genome sequences is becoming increasingly common for phylogenetic reconstruction and as a model for genome evolution. Not only are they much more informative than shorter sequences of individual genes for inferring evolutionary relatedness, but these data also provide sets of genome-level characters, such as the relative arrangements of genes, that can be especially powerful. We describe here the protocols commonly used for physically isolating mtDNA, for amplifying these by PCR or RCA, for cloning,sequencing, assembly, validation, and gene annotation, and for comparing both sequences and gene arrangements. On several topics, we offer general observations based on our experiences to date with determining and comparing complete mtDNA sequences.

  12. Reading biological processes from nucleotide sequences

    Science.gov (United States)

    Murugan, Anand

    Cellular processes have traditionally been investigated by techniques of imaging and biochemical analysis of the molecules involved. The recent rapid progress in our ability to manipulate and read nucleic acid sequences gives us direct access to the genetic information that directs and constrains biological processes. While sequence data is being used widely to investigate genotype-phenotype relationships and population structure, here we use sequencing to understand biophysical mechanisms. We present work on two different systems. First, in chapter 2, we characterize the stochastic genetic editing mechanism that produces diverse T-cell receptors in the human immune system. We do this by inferring statistical distributions of the underlying biochemical events that generate T-cell receptor coding sequences from the statistics of the observed sequences. This inferred model quantitatively describes the potential repertoire of T-cell receptors that can be produced by an individual, providing insight into its potential diversity and the probability of generation of any specific T-cell receptor. Then in chapter 3, we present work on understanding the functioning of regulatory DNA sequences in both prokaryotes and eukaryotes. Here we use experiments that measure the transcriptional activity of large libraries of mutagenized promoters and enhancers and infer models of the sequence-function relationship from this data. For the bacterial promoter, we infer a physically motivated 'thermodynamic' model of the interaction of DNA-binding proteins and RNA polymerase determining the transcription rate of the downstream gene. For the eukaryotic enhancers, we infer heuristic models of the sequence-function relationship and use these models to find synthetic enhancer sequences that optimize inducibility of expression. Both projects demonstrate the utility of sequence information in conjunction with sophisticated statistical inference techniques for dissecting underlying biophysical

  13. Finding Common Sequence and Structure Motifs in a set of RNA sequences

    DEFF Research Database (Denmark)

    Gorodkin, Jan; Heyer, Laurie J.; Stormo, Gary D.

    1997-01-01

    We present a computational scheme to search for the most common motif, composed of a combination of sequence and structure constraints, among a collection of RNA sequences. The method uses a simplified version of the Sankoff algorithm for simultaneous folding and alignment of RNA sequences...

  14. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags

    DEFF Research Database (Denmark)

    de Souza, S J; Camargo, A A; Briones, M R;

    2000-01-01

    Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central ...

  15. Sequencing and Analysis of a Genomic Fragment Provide an Insight into the Dunaliella viridis Genomic Sequence

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ming SUN; Yuan-Ping TANG; Xiang-Zong MENG; Wen-Wen ZHANG; Shan LI; Zhi-Rui DENG; Zheng-Kai XU; Ren-Tao SONG

    2006-01-01

    Dunaliella is a genus of wall-less unicellular eukaryotic green alga. Its exceptional resistances to salt and various other stresses have made it an ideal model for stress tolerance study. However, very little is known about its genome and genomic sequences. In this study, we sequenced and analyzed a 29,268 bp genomic fragment from Dunaliella viridis. The fragment showed low sequence homology to the GenBank database. At the nucleotide level, only a segment with significant sequence homology to 18S rRNA was found. The fragment contained six putative genes, but only one gene showed significant homology at the protein level to GenBank database. The average GC content of this sequence was 51.1%, which was much lower than that of close related green algae Chlamydomonas (65.7%). Significant segmental duplications were found within this fragment. The duplicated sequences accounted for about 35.7% of the entire region. Large amounts of simple sequence repeats (microsatellites) were found, with strong bias towards (AC)n type (76%). Analysis of other Dunaliella genomic sequences in the GenBank database (total 25,749 bp) was in agreement with these findings. These sequence features made it difficult to sequence Dunaliella genomic sequences. Further investigation should be made to reveal the biological significance of these unique sequence features.

  16. SOME GEOMETRIC PROPERTIES OF A NEW DIFFERENCE SEQUENCE SPACE INVOLVING LACUNARY SEQUENCES

    Institute of Scientific and Technical Information of China (English)

    Murat KARAKAŞ; Mikail ET; Vatan KARAKAYA

    2013-01-01

    In this paper, we define a new generalized difference sequence space involving lacunary sequence. Then, we examine k-NUC property and property (β) for this space and also show that it is not rotund where p=(pr) is a bounded sequence of positive real numbers with pr ≥1 for all r∈N.

  17. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics

    NARCIS (Netherlands)

    Sikkema-Raddatz, B.; Johansson, L.F.; de Boer, E.N.; Almomani, R.; Boven, L.G.; van den Berg, M.P.; van Spaendonck-Zwarts, K.Y.; van Tintelen, J.P.; Sijmons, R.H.; Jongbloed, J.D.H.; Sinke, R.J.

    2013-01-01

    Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences of genes. However, it cannot yet replace Sanger sequencing (SS) in diagnostics because of incomplete representation and coverage of exons leading to missing clinically relevant mutations. Targeted next-g

  18. Sequencing and analysis of a genomic fragment provide an insight into the Dunaliella viridis genomic sequence.

    Science.gov (United States)

    Sun, Xiao-Ming; Tang, Yuan-Ping; Meng, Xiang-Zong; Zhang, Wen-Wen; Li, Shan; Deng, Zhi-Rui; Xu, Zheng-Kai; Song, Ren-Tao

    2006-11-01

    Dunaliella is a genus of wall-less unicellular eukaryotic green alga. Its exceptional resistances to salt and various other stresses have made it an ideal model for stress tolerance study. However, very little is known about its genome and genomic sequences. In this study, we sequenced and analyzed a 29,268 bp genomic fragment from Dunaliella viridis. The fragment showed low sequence homology to the GenBank database. At the nucleotide level, only a segment with significant sequence homology to 18S rRNA was found. The fragment contained six putative genes, but only one gene showed significant homology at the protein level to GenBank database. The average GC content of this sequence was 51.1%, which was much lower than that of close related green algae Chlamydomonas (65.7%). Significant segmental duplications were found within this fragment. The duplicated sequences accounted for about 35.7% of the entire region. Large amounts of simple sequence repeats (microsatellites) were found, with strong bias towards (AC)(n) type (76%). Analysis of other Dunaliella genomic sequences in the GenBank database (total 25,749 bp) was in agreement with these findings. These sequence features made it difficult to sequence Dunaliella genomic sequences. Further investigation should be made to reveal the biological significance of these unique sequence features. PMID:17091199

  19. Whole-Genome Shotgun Sequencing of a Colonizing Multilocus Sequence Type 17 Streptococcus agalactiae Strain

    OpenAIRE

    Singh, Pallavi; Springman, A. Cody; Davies, H Dele; Manning, Shannon D.

    2012-01-01

    This report highlights the whole-genome shotgun draft sequence for a Streptococcus agalactiae strain representing multilocus sequence type (ST) 17, isolated from a colonized woman at 8 weeks postpartum. This sequence represents an important addition to the published genomes and will promote comparative genomic studies of S. agalactiae recovered from diverse sources.

  20. Large Zero Autocorrelation Zone of Golay Sequences and $4^q$-QAM Golay Complementary Sequences

    CERN Document Server

    Gong, Guang; Yang, Yang

    2011-01-01

    Sequences with good correlation properties have been widely adopted in modern communications, radar and sonar applications. In this paper, we present our new findings on some constructions of single $H$-ary Golay sequence and $4^q$-QAM Golay complementary sequence with a large zero autocorrelation zone, where $H\\ge 2$ is an arbitrary even integer and $q\\ge 2$ is an arbitrary integer. Those new results on Golay sequences and QAM Golay complementary sequences can be explored during synchronization and detection at the receiver end and thus improve the performance of the communication system.

  1. Viewing multiple sequence alignments with the JavaScript Sequence Alignment Viewer (JSAV)

    OpenAIRE

    Martin, A. C. R.

    2014-01-01

    The JavaScript Sequence Alignment Viewer (JSAV) is designed as a simple-to-use JavaScript component for displaying sequence alignments on web pages. The display of sequences is highly configurable with options to allow alternative coloring schemes, sorting of sequences and ’dotifying’ repeated amino acids. An option is also available to submit selected sequences to another web site, or to other JavaScript code. JSAV is implemented purely in JavaScript making use of the JQuery and JQuery-UI li...

  2. Value of a newly sequenced bacterial genome.

    Science.gov (United States)

    Barbosa, Eudes Gv; Aburjaile, Flavia F; Ramos, Rommel Tj; Carneiro, Adriana R; Le Loir, Yves; Baumbach, Jan; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

    2014-05-26

    Next-generation sequencing (NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft (partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information. PMID:24921006

  3. Enhanced Dynamic Algorithm of Genome Sequence Alignments

    Directory of Open Access Journals (Sweden)

    Arabi E. keshk

    2014-05-01

    Full Text Available The merging of biology and computer science has created a new field called computational biology that explore the capacities of computers to gain knowledge from biological data, bioinformatics. Computational biology is rooted in life sciences as well as computers, information sciences, and technologies. The main problem in computational biology is sequence alignment that is a way of arranging the sequences of DNA, RNA or protein to identify the region of similarity and relationship between sequences. This paper introduces an enhancement of dynamic algorithm of genome sequence alignment, which called EDAGSA. It is filling the three main diagonals without filling the entire matrix by the unused data. It gets the optimal solution with decreasing the execution time and therefore the performance is increased. To illustrate the effectiveness of optimizing the performance of the proposed algorithm, it is compared with the traditional methods such as Needleman-Wunsch, Smith-Waterman and longest common subsequence algorithms. Also, database is implemented for using the algorithm in multi-sequence alignments for searching the optimal sequence that matches the given sequence.

  4. CATEGORIZATION OF EVENT SEQUENCES FOR LICENSE APPLICATION

    Energy Technology Data Exchange (ETDEWEB)

    G.E. Ragan; P. Mecheret; D. Dexheimer

    2005-04-14

    The purposes of this analysis are: (1) Categorize (as Category 1, Category 2, or Beyond Category 2) internal event sequences that may occur before permanent closure of the repository at Yucca Mountain. (2) Categorize external event sequences that may occur before permanent closure of the repository at Yucca Mountain. This includes examining DBGM-1 seismic classifications and upgrading to DBGM-2, if appropriate, to ensure Beyond Category 2 categorization. (3) State the design and operational requirements that are invoked to make the categorization assignments valid. (4) Indicate the amount of material put at risk by Category 1 and Category 2 event sequences. (5) Estimate frequencies of Category 1 event sequences at the maximum capacity and receipt rate of the repository. (6) Distinguish occurrences associated with normal operations from event sequences. It is beyond the scope of the analysis to propose design requirements that may be required to control radiological exposure associated with normal operations. (7) Provide a convenient compilation of the results of the analysis in tabular form. The results of this analysis are used as inputs to the consequence analyses in an iterative design process that is depicted in Figure 1. Categorization of event sequences for permanent retrieval of waste from the repository is beyond the scope of this analysis. Cleanup activities that take place after an event sequence and other responses to abnormal events are also beyond the scope of the analysis.

  5. Exploration of noncoding sequences in metagenomes.

    Directory of Open Access Journals (Sweden)

    Fabián Tobar-Tosse

    Full Text Available Environment-dependent genomic features have been defined for different metagenomes, whose genes and their associated processes are related to specific environments. Identification of ORFs and their functional categories are the most common methods for association between functional and environmental features. However, this analysis based on finding ORFs misses noncoding sequences and, therefore, some metagenome regulatory or structural information could be discarded. In this work we analyzed 23 whole metagenomes, including coding and noncoding sequences using the following sequence patterns: (G+C content, Codon Usage (Cd, Trinucleotide Usage (Tn, and functional assignments for ORF prediction. Herein, we present evidence of a high proportion of noncoding sequences discarded in common similarity-based methods in metagenomics, and the kind of relevant information present in those. We found a high density of trinucleotide repeat sequences (TRS in noncoding sequences, with a regulatory and adaptive function for metagenome communities. We present associations between trinucleotide values and gene function, where metagenome clustering correlate with microorganism adaptations and kinds of metagenomes. We propose here that noncoding sequences have relevant information to describe metagenomes that could be considered in a whole metagenome analysis in order to improve their organization, classification protocols, and their relation with the environment.

  6. Value of a newly sequenced bacterial genome

    Institute of Scientific and Technical Information of China (English)

    Eudes; GV; Barbosa; Flavia; F; Aburjaile; Rommel; TJ; Ramos; Adriana; R; Carneiro; Yves; Le; Loir; Jan; Baumbach; Anderson; Miyoshi; Artur; Silva; Vasco; Azevedo

    2014-01-01

    Next-generation sequencing(NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft(partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information.

  7. Fungal genome sequencing: basic biology to biotechnology.

    Science.gov (United States)

    Sharma, Krishna Kant

    2016-08-01

    The genome sequences provide a first glimpse into the genomic basis of the biological diversity of filamentous fungi and yeast. The genome sequence of the budding yeast, Saccharomyces cerevisiae, with a small genome size, unicellular growth, and rich history of genetic and molecular analyses was a milestone of early genomics in the 1990s. The subsequent completion of fission yeast, Schizosaccharomyces pombe and genetic model, Neurospora crassa initiated a revolution in the genomics of the fungal kingdom. In due course of time, a substantial number of fungal genomes have been sequenced and publicly released, representing the widest sampling of genomes from any eukaryotic kingdom. An ambitious genome-sequencing program provides a wealth of data on metabolic diversity within the fungal kingdom, thereby enhancing research into medical science, agriculture science, ecology, bioremediation, bioenergy, and the biotechnology industry. Fungal genomics have higher potential to positively affect human health, environmental health, and the planet's stored energy. With a significant increase in sequenced fungal genomes, the known diversity of genes encoding organic acids, antibiotics, enzymes, and their pathways has increased exponentially. Currently, over a hundred fungal genome sequences are publicly available; however, no inclusive review has been published. This review is an initiative to address the significance of the fungal genome-sequencing program and provides the road map for basic and applied research. PMID:25721271

  8. Fungal genome sequencing: basic biology to biotechnology.

    Science.gov (United States)

    Sharma, Krishna Kant

    2016-08-01

    The genome sequences provide a first glimpse into the genomic basis of the biological diversity of filamentous fungi and yeast. The genome sequence of the budding yeast, Saccharomyces cerevisiae, with a small genome size, unicellular growth, and rich history of genetic and molecular analyses was a milestone of early genomics in the 1990s. The subsequent completion of fission yeast, Schizosaccharomyces pombe and genetic model, Neurospora crassa initiated a revolution in the genomics of the fungal kingdom. In due course of time, a substantial number of fungal genomes have been sequenced and publicly released, representing the widest sampling of genomes from any eukaryotic kingdom. An ambitious genome-sequencing program provides a wealth of data on metabolic diversity within the fungal kingdom, thereby enhancing research into medical science, agriculture science, ecology, bioremediation, bioenergy, and the biotechnology industry. Fungal genomics have higher potential to positively affect human health, environmental health, and the planet's stored energy. With a significant increase in sequenced fungal genomes, the known diversity of genes encoding organic acids, antibiotics, enzymes, and their pathways has increased exponentially. Currently, over a hundred fungal genome sequences are publicly available; however, no inclusive review has been published. This review is an initiative to address the significance of the fungal genome-sequencing program and provides the road map for basic and applied research.

  9. PHASE TRANSITION IN SEQUENCE UNIQUE RECONSTRUCTION

    Institute of Scientific and Technical Information of China (English)

    Li XIA; Chan ZHOU

    2007-01-01

    In this paper,sequence unique reconstruction refers to the property that a sequence is uniquely reconstructable from all its K-tuples.We propose and study the phase transition behavior of the probability P(K)of unique reconstruction with regard to tuple size K in random sequences (iid model).Based on Monte Carlo experiments,artificial proteins generated from iid model exhibit a phase transition when P(K)abruptly jumps from a low value phase(e.g.<0.1)to a high value phase (e.g.>0.9).With a generalization to any alphabet,we prove that for a random sequence of length L,as L is large enough,P(K)undergoes a sharp phase transition when P≤0.1015 where p=P(two random letters match).Besides,formulas are derived to estimate the transition points,which may be of practical use in sequencing DNA by hybridization.Concluded from our study,most proteins do not deviate greatly from random sequences in the sense of sequence unique reconstruction,while there are some "stubborn" proteins which only become uniquely reconstructable at a very large K and probably have biological implications.

  10. Detection for chromosomal aberrations in 43 fetuses with spontaneous abortion and stillbirth by array-based comparative genomic hybridization%微阵列比较基因组杂交检测43例自然流产和死胎的染色体畸变

    Institute of Scientific and Technical Information of China (English)

    李颖; 龚亚飞; 刘寒艳; 宋艳琴; 何文茵; 魏君; 孙筱放; 陈欣洁

    2015-01-01

    目的 应用微阵列比较基因组杂交技术检测43例自然流产和死胎的全基因组拷贝数变异(copy number variations,CNV),探讨该技术的应用价值.方法 采用Agilent 4×44K定制芯片和Affymetrix Cytoscan 750K芯片对43例原因不明自然流产的绒毛和死胎的皮肤组织进行基因组CNV检测,用相应软件对检测结果进行分析,将发现的CNS与国际基因组拷贝数多态性数据库进行比对,剔除常见的多态性CNV,并结合国际病理性CNV数据库DECIPHER、ISCA、OMIM进行核查,同时与既往文献进行比对,分析其是否具有致病性.对其中2例CNS补充夫妻双方的基因芯片检测,以明确CNV的来源.结果 全部43例标本均成功获得芯片检测结果,成功率为100%.共检测出异常32例(74.4%),其中非整倍体26例(4例合并CNV),单纯性CNV 6例.结论 微阵列比较基因组杂交技术可用于检测流产、死胎的组织标本,为难以进行细胞培养及核型分析的流产绒毛及死胎标本提供了一种快速有效的检测方法,为不明原因的自然流产及死胎的病因学诊断提供一种更好的遗传学手段.%Objective To assess the value of array-based comparative genomic hybridization (arrayCGH) for analyzing tissues derived from spontaneous abortion and stillbirth.Methods Agilent Human Genome CGH Microarray 4 × 44K chip and Affymetrix Cytoscan 750K Array were utilized to detect genomewide copy number variations (CNV) in 43 fetuses with spontaneous abortion and stillbirth.All identified CNV were analyzed with references from Database of Genomic variants (DGV),database of DECIPHER,ISCA and OMIM,as well as comprehensive literature review to determine whether the identified CNV were pathogenic.Parental DNA of two cases was also analyzed with the same arrays for pathogenic or unknown significant CNVs.Results All of the 43 specimens were successfully analyzed.Clinically significant chromosomal aberrations were identified in 32 (74.4

  11. Robot Sequencing and Visualization Program (RSVP)

    Science.gov (United States)

    Cooper, Brian K.; Maxwell,Scott A.; Hartman, Frank R.; Wright, John R.; Yen, Jeng; Toole, Nicholas T.; Gorjian, Zareh; Morrison, Jack C

    2013-01-01

    The Robot Sequencing and Visualization Program (RSVP) is being used in the Mars Science Laboratory (MSL) mission for downlink data visualization and command sequence generation. RSVP reads and writes downlink data products from the operations data server (ODS) and writes uplink data products to the ODS. The primary users of RSVP are members of the Rover Planner team (part of the Integrated Planning and Execution Team (IPE)), who use it to perform traversability/articulation analyses, take activity plan input from the Science and Mission Planning teams, and create a set of rover sequences to be sent to the rover every sol. The primary inputs to RSVP are downlink data products and activity plans in the ODS database. The primary outputs are command sequences to be placed in the ODS for further processing prior to uplink to each rover. RSVP is composed of two main subsystems. The first, called the Robot Sequence Editor (RoSE), understands the MSL activity and command dictionaries and takes care of converting incoming activity level inputs into command sequences. The Rover Planners use the RoSE component of RSVP to put together command sequences and to view and manage command level resources like time, power, temperature, etc. (via a transparent realtime connection to SEQGEN). The second component of RSVP is called HyperDrive, a set of high-fidelity computer graphics displays of the Martian surface in 3D and in stereo. The Rover Planners can explore the environment around the rover, create commands related to motion of all kinds, and see the simulated result of those commands via its underlying tight coupling with flight navigation, motor, and arm software. This software is the evolutionary replacement for the Rover Sequencing and Visualization software used to create command sequences (and visualize the Martian surface) for the Mars Exploration Rover mission.

  12. Stem kernels for RNA sequence analyses.

    Science.gov (United States)

    Sakakibara, Yasubumi; Popendorf, Kris; Ogawa, Nana; Asai, Kiyoshi; Sato, Kengo

    2007-10-01

    Several computational methods based on stochastic context-free grammars have been developed for modeling and analyzing functional RNA sequences. These grammatical methods have succeeded in modeling typical secondary structures of RNA, and are used for structural alignment of RNA sequences. However, such stochastic models cannot sufficiently discriminate member sequences of an RNA family from nonmembers and hence detect noncoding RNA regions from genome sequences. A novel kernel function, stem kernel, for the discrimination and detection of functional RNA sequences using support vector machines (SVMs) is proposed. The stem kernel is a natural extension of the string kernel, specifically the all-subsequences kernel, and is tailored to measure the similarity of two RNA sequences from the viewpoint of secondary structures. The stem kernel examines all possible common base pairs and stem structures of arbitrary lengths, including pseudoknots between two RNA sequences, and calculates the inner product of common stem structure counts. An efficient algorithm is developed to calculate the stem kernels based on dynamic programming. The stem kernels are then applied to discriminate members of an RNA family from nonmembers using SVMs. The study indicates that the discrimination ability of the stem kernel is strong compared with conventional methods. Furthermore, the potential application of the stem kernel is demonstrated by the detection of remotely homologous RNA families in terms of secondary structures. This is because the string kernel is proven to work for the remote homology detection of protein sequences. These experimental results have convinced us to apply the stem kernel in order to find novel RNA families from genome sequences. PMID:17933013

  13. Sequencing, analysis, and annotation of expressed sequence tags for Camelus dromedarius.

    Directory of Open Access Journals (Sweden)

    Abdulaziz M Al-Swailem

    Full Text Available Despite its economical, cultural, and biological importance, there has not been a large scale sequencing project to date for Camelus dromedarius. With the goal of sequencing complete DNA of the organism, we first established and sequenced camel EST libraries, generating 70,272 reads. Following trimming, chimera check, repeat masking, cluster and assembly, we obtained 23,602 putative gene sequences, out of which over 4,500 potentially novel or fast evolving gene sequences do not carry any homology to other available genomes. Functional annotation of sequences with similarities in nucleotide and protein databases has been obtained using Gene Ontology classification. Comparison to available full length cDNA sequences and Open Reading Frame (ORF analysis of camel sequences that exhibit homology to known genes show more than 80% of the contigs with an ORF>300 bp and approximately 40% hits extending to the start codons of full length cDNAs suggesting successful characterization of camel genes. Similarity analyses are done separately for different organisms including human, mouse, bovine, and rat. Accompanying web portal, CAGBASE (http://camel.kacst.edu.sa/, hosts a relational database containing annotated EST sequences and analysis tools with possibility to add sequences from public domain. We anticipate our results to provide a home base for genomic studies of camel and other comparative studies enabling a starting point for whole genome sequencing of the organism.

  14. Sequencing of chloroplast genome using whole cellular DNA and Solexa sequencing technology

    Directory of Open Access Journals (Sweden)

    Jian eWu

    2012-11-01

    Full Text Available Sequencing of the chloroplast genome using traditional sequencing methods has been difficult because of its size (>120 kb and the complicated procedures required to prepare templates. To explore the feasibility of sequencing the chloroplast genome using DNA extracted from whole cells and Solexa sequencing technology, we sequenced whole cellular DNA isolated from leaves of three Brassica rapa accessions with one lane per accession. In total, 246 Mb, 362Mb, 361 Mb sequence data were generated for the three accessions Chiifu-401-42, Z16 and FT, respectively. Microreads were assembled by reference-guided assembly using the cpDNA sequences of B. rapa, Arabidopsis thaliana, and Nicotiana tabacum. We achieved coverage of more than 99.96% of the cp genome in the three tested accessions using the B. rapa sequence as the reference. When A. thaliana or N. tabacum sequences were used as references, 99.7–99.8% or 95.5–99.7% of the B. rapa chloroplast genome was covered, respectively. These results demonstrated that sequencing of whole cellular DNA isolated from young leaves using the Illumina Genome Analyzer is an efficient method for high-throughput sequencing of chloroplast genome.

  15. Effects of the Ion PGM™ Hi-Q™ sequencing chemistry on sequence data quality.

    Science.gov (United States)

    Churchill, Jennifer D; King, Jonathan L; Chakraborty, Ranajit; Budowle, Bruce

    2016-09-01

    Massively parallel sequencing (MPS) offers substantial improvements over current forensic DNA typing methodologies such as increased resolution, scalability, and throughput. The Ion PGM™ is a promising MPS platform for analysis of forensic biological evidence. The system employs a sequencing-by-synthesis chemistry on a semiconductor chip that measures a pH change due to the release of hydrogen ions as nucleotides are incorporated into the growing DNA strands. However, implementation of MPS into forensic laboratories requires a robust chemistry. Ion Torrent's Hi-Q™ Sequencing Chemistry was evaluated to determine if it could improve on the quality of the generated sequence data in association with selected genetic marker targets. The whole mitochondrial genome and the HID-Ion STR 10-plex panel were sequenced on the Ion PGM™ system with the Ion PGM™ Sequencing 400 Kit and the Ion PGM™ Hi-Q™ Sequencing Kit. Concordance, coverage, strand balance, noise, and deletion ratios were assessed in evaluating the performance of the Ion PGM™ Hi-Q™ Sequencing Kit. The results indicate that reliable, accurate data are generated and that sequencing through homopolymeric regions can be improved with the use of Ion Torrent's Hi-Q™ Sequencing Chemistry. Overall, the quality of the generated sequencing data supports the potential for use of the Ion PGM™ in forensic genetic laboratories.

  16. Effects of the Ion PGM™ Hi-Q™ sequencing chemistry on sequence data quality.

    Science.gov (United States)

    Churchill, Jennifer D; King, Jonathan L; Chakraborty, Ranajit; Budowle, Bruce

    2016-09-01

    Massively parallel sequencing (MPS) offers substantial improvements over current forensic DNA typing methodologies such as increased resolution, scalability, and throughput. The Ion PGM™ is a promising MPS platform for analysis of forensic biological evidence. The system employs a sequencing-by-synthesis chemistry on a semiconductor chip that measures a pH change due to the release of hydrogen ions as nucleotides are incorporated into the growing DNA strands. However, implementation of MPS into forensic laboratories requires a robust chemistry. Ion Torrent's Hi-Q™ Sequencing Chemistry was evaluated to determine if it could improve on the quality of the generated sequence data in association with selected genetic marker targets. The whole mitochondrial genome and the HID-Ion STR 10-plex panel were sequenced on the Ion PGM™ system with the Ion PGM™ Sequencing 400 Kit and the Ion PGM™ Hi-Q™ Sequencing Kit. Concordance, coverage, strand balance, noise, and deletion ratios were assessed in evaluating the performance of the Ion PGM™ Hi-Q™ Sequencing Kit. The results indicate that reliable, accurate data are generated and that sequencing through homopolymeric regions can be improved with the use of Ion Torrent's Hi-Q™ Sequencing Chemistry. Overall, the quality of the generated sequencing data supports the potential for use of the Ion PGM™ in forensic genetic laboratories. PMID:27025714

  17. Pittosporum cryptic virus 1: genome sequence completion using next-generation sequencing.

    Science.gov (United States)

    Elbeaino, Toufic; Kubaa, Raied Abou; Tuzlali, Hasan Tuna; Digiaro, Michele

    2016-07-01

    Next-generation sequencing (NGS) was applied to dsRNAs extracted from an Italian pittosporum plant infected with pittosporum cryptic virus 1 (PiCV1). NGS allowed assembly of the full genome sequence of PiCV1, comprising dsRNA1 (1.9 kbp) and dsRNA2 (1.5 kbp), which encode the RNA-dependent RNA polymerase and capsid protein genes, respectively. Phylogenetic and sequence analyses confirmed that PiCV1 is a new member of the genus Deltapartitivirus, family Partiviridae. From the same plant, NSG also permitted assembly of the complete genome sequence of eggplant mottled dwarf virus (EMDV), which shared 86 % to 98 % nucleotide sequence identity with complete and partial sequences (ca 6750 nt) of other known EMDV isolates with sequences available in the GenBank database. PMID:27087112

  18. Iterative Method for Generating Correlated Binary Sequences

    CERN Document Server

    Usatenko, O V; Apostolov, S S; Makarov, N M; Krokhin, A A

    2014-01-01

    We propose a new efficient iterative method for generating random correlated binary sequences with prescribed correlation function. The method is based on consecutive linear modulations of initially uncorrelated sequence into a correlated one. Each step of modulation increases the correlations until the desired level has been reached. Robustness and efficiency for the proposed algorithm are tested by generating sequences with inverse power-law correlations. The substantial increase in the strength of correlation in the iterative method with respect to the single-step filtering generation is shown for all studied correlation functions. Our results can be used for design of disordered superlattices, waveguides, and surfaces with selective transport properties.

  19. Generation of Goldbach sequences in quantum mechanics

    CERN Document Server

    Prudencio, Thiago

    2013-01-01

    This Letter reports for the first time the problem of generating Goldbach sequences in terms of Fock states and examine their equivalence with the corresponding Goldbach conjecture terms. We show that the expectation values of number operators in Fock states cannot generate these sequences without ambiguity due to normalization of superpositions of Fock states. Instead, we show that a complete correspondence between the Goldbach conjecture terms and the Goldbach sequences generated by Fock states can be achieved by means of projections involving number operator and superpositions of Fock states. Our proposal appears as a new alternative way to interpret measurements in fundamental quantum mechanics.

  20. Scale-PC shielding analysis sequences

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, S.M.

    1996-05-01

    The SCALE computational system is a modular code system for analyses of nuclear fuel facility and package designs. With the release of SCALE-PC Version 4.3, the radiation shielding analysis community now has the capability to execute the SCALE shielding analysis sequences contained in the control modules SAS1, SAS2, SAS3, and SAS4 on a MS- DOS personal computer (PC). In addition, SCALE-PC includes two new sequences, QADS and ORIGEN-ARP. The capabilities of each sequence are presented, along with example applications.

  1. Cloned endogenous retroviral sequences from human DNA.

    OpenAIRE

    Bonner, T I; O'Connell, C; Cohen, M.

    1982-01-01

    We have screened a human DNA library using as probe a chimpanzee sequence that contains homology to the polymerase gene of the endogenous baboon virus. One set of overlapping clones spans about 20 kilobases and contains regions of DNA sequence homology to the gag p30, gag p15, and polymerase genes of Moloney murine leukemia virus. Furthermore, the spacings are the same as in Moloney virus between these sequences and a 480-nucleotide region that has the structural characteristics of a 3' copy ...

  2. Sequence and structual analysis of antibodies.

    OpenAIRE

    Raghavan, A. K.

    2008-01-01

    The work presented in this thesis focuses on the sequence and structural analysis of antibodies and has fallen into three main areas. First I developed a method to assess how typical an antibody sequence is of the expressed human antibody repertoire. My hypothesis was that the more "human like" an antibody sequence is (in other words how typical it is of the expressed human repertoire), the less likely it is to elicit an immune response when used in vivo in humans. In practice, I found that, ...

  3. Initial retrieval sequence and blending strategy

    Energy Technology Data Exchange (ETDEWEB)

    Pemwell, D.L.; Grenard, C.E.

    1996-09-01

    This report documents the initial retrieval sequence and the methodology used to select it. Waste retrieval, storage, pretreatment and vitrification were modeled for candidate single-shell tank retrieval sequences. Performance of the sequences was measured by a set of metrics (for example,high-level waste glass volume, relative risk and schedule).Computer models were used to evaluate estimated glass volumes,process rates, retrieval dates, and blending strategy effects.The models were based on estimates of component inventories and concentrations, sludge wash factors and timing, retrieval annex limitations, etc.

  4. How Long is an Aftershock Sequence?

    Science.gov (United States)

    Godano, Cataldo; Tramelli, Anna

    2016-07-01

    The occurrence of a mainschok is always followed by aftershocks spatially distributed within the fault area. The aftershocks rate decay with time is described by the empirical Omori law which was inferred by catalogues analysis. The sequences discrimination within catalogues is not a straightforward operation, especially for low-magnitude mainshocks. Here, we describe the rate decay of the Omori law obtained using different sequence discrimination tools and we discover that, when the background seismicity is excluded, the sequences tend to last for the temporal extension of the catalogue.

  5. Deep sequencing increases hepatitis C virus phylogenetic cluster detection compared to Sanger sequencing.

    Science.gov (United States)

    Montoya, Vincent; Olmstead, Andrea; Tang, Patrick; Cook, Darrel; Janjua, Naveed; Grebely, Jason; Jacka, Brendan; Poon, Art F Y; Krajden, Mel

    2016-09-01

    Effective surveillance and treatment strategies are required to control the hepatitis C virus (HCV) epidemic. Phylogenetic analyses are powerful tools for reconstructing the evolutionary history of viral outbreaks and identifying transmission clusters. These studies often rely on Sanger sequencing which typically generates a single consensus sequence for each infected individual. For rapidly mutating viruses such as HCV, consensus sequencing underestimates the complexity of the viral quasispecies population and could therefore generate different phylogenetic tree topologies. Although deep sequencing provides a more detailed quasispecies characterization, in-depth phylogenetic analyses are challenging due to dataset complexity and computational limitations. Here, we apply deep sequencing to a characterized population to assess its ability to identify phylogenetic clusters compared with consensus Sanger sequencing. For deep sequencing, a sample specific threshold determined by the 50th percentile of the patristic distance distribution for all variants within each individual was used to identify clusters. Among seven patristic distance thresholds tested for the Sanger sequence phylogeny ranging from 0.005-0.06, a threshold of 0.03 was found to provide the maximum balance between positive agreement (samples in a cluster) and negative agreement (samples not in a cluster) relative to the deep sequencing dataset. From 77 HCV seroconverters, 10 individuals were identified in phylogenetic clusters using both methods. Deep sequencing analysis identified an additional 4 individuals and excluded 8 other individuals relative to Sanger sequencing. The application of this deep sequencing approach could be a more effective tool to understand onward HCV transmission dynamics compared with Sanger sequencing, since the incorporation of minority sequence variants improves the discrimination of phylogenetically linked clusters. PMID:27282472

  6. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    OpenAIRE

    Conroy, R. S.; Koretsky, A P; Moreland, J.

    2009-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and na...

  7. Identifying driver mutations in sequenced cancer genomes

    DEFF Research Database (Denmark)

    Raphael, Benjamin J; Dobson, Jason R; Oesper, Layla;

    2014-01-01

    High-throughput DNA sequencing is revolutionizing the study of cancer and enabling the measurement of the somatic mutations that drive cancer development. However, the resulting sequencing datasets are large and complex, obscuring the clinically important mutations in a background of errors, noise......, and random mutations. Here, we review computational approaches to identify somatic mutations in cancer genome sequences and to distinguish the driver mutations that are responsible for cancer from random, passenger mutations. First, we describe approaches to detect somatic mutations from high-throughput DNA...... sequencing data, particularly for tumor samples that comprise heterogeneous populations of cells. Next, we review computational approaches that aim to predict driver mutations according to their frequency of occurrence in a cohort of samples, or according to their predicted functional impact on protein...

  8. Using mobile sequencers in an academic classroom.

    Science.gov (United States)

    Zaaijer, Sophie; Erlich, Yaniv

    2016-01-01

    The advent of mobile DNA sequencers has made it possible to generate DNA sequencing data outside of laboratories and genome centers. Here, we report our experience of using the MinION, a mobile sequencer, in a 13-week academic course for undergraduate and graduate students. The course consisted of theoretical sessions that presented fundamental topics in genomics and several applied hackathon sessions. In these hackathons, the students used MinION sequencers to generate and analyze their own data and gain hands-on experience in the topics discussed in the theoretical classes. The manuscript describes the structure of our class, the educational material, and the lessons we learned in the process. We hope that the knowledge and material presented here will provide the community with useful tools to help educate future generations of genome scientists. PMID:27054412

  9. Sequencing Information Management System (SIMS). Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fields, C.

    1996-02-15

    A feasibility study to develop a requirements analysis and functional specification for a data management system for large-scale DNA sequencing laboratories resulted in a functional specification for a Sequencing Information Management System (SIMS). This document reports the results of this feasibility study, and includes a functional specification for a SIMS relational schema. The SIMS is an integrated information management system that supports data acquisition, management, analysis, and distribution for DNA sequencing laboratories. The SIMS provides ad hoc query access to information on the sequencing process and its results, and partially automates the transfer of data between laboratory instruments, analysis programs, technical personnel, and managers. The SIMS user interfaces are designed for use by laboratory technicians, laboratory managers, and scientists. The SIMS is designed to run in a heterogeneous, multiplatform environment in a client/server mode. The SIMS communicates with external computational and data resources via the internet.

  10. Viral detection by high-throughput sequencing.

    Science.gov (United States)

    Motooka, Daisuke; Nakamura, Shota; Hagiwara, Katsuro; Nakaya, Takaaki

    2015-01-01

    We applied a high-throughput sequencing platform, Ion PGM, for viral detection in fecal samples from adult cows collected in Hokkaido, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.25 ml of fecal specimens (N = 8), and more than 5 μg of cDNA was synthesized. Unbiased high-throughput sequencing using the 318 v2 semiconductor chip of these eight samples yielded 57-580 K (average: 270 K, after data analysis) reads in a single run. As a result, viral genome sequences were detected in each specimen. In addition to bacteriophage, mammal- and insect-derived viruses, partial genome sequences of plant, algal, and protozoal viruses were detected. Thus, this metagenomic analysis of fecal specimens could be useful to comprehensively understand viral populations of the intestine and food sources in animals. PMID:25287501

  11. Long range correlations in DNA sequences

    CERN Document Server

    Mohanty, A K

    2002-01-01

    The so called long range correlation properties of DNA sequences are studied using the variance analyses of the density distribution of a single or a group of nucleotides in a model independent way. This new method which was suggested earlier has been applied to extract slope parameters that characterize the correlation properties for several intron containing and intron less DNA sequences. An important aspect of all the DNA sequences is the properties of complimentarity by virtue of which any two complimentary distributions (like GA is complimentary to TC or G is complimentary to ATC) have identical fluctuations at all scales although their distribution functions need not be identical. Due to this complimentarity, the famous DNA walk representation whose statistical interpretation is still unresolved is shown to be a special case of the present formalism with a density distribution corresponding to a purine or a pyrimidine group. Another interesting aspect of most of the DNA sequences is that the factorial m...

  12. Algebraic structures of sequences of numbers

    Science.gov (United States)

    Huang, I.-Chiau

    2012-09-01

    For certain sequences of numbers, commutative rings with a module structure over a non-commutative ring are constructed. Identities of these numbers are considered as realizations of algebraic relations.

  13. New stopping criteria for segmenting DNA sequences

    CERN Document Server

    Li, W

    2001-01-01

    We propose a solution on the stopping criterion in segmenting inhomogeneous DNA sequences with complex statistical patterns. This new stopping criterion is based on Bayesian Information Criterion (BIC) in the model selection framework. When this stopping criterion is applied to a left telomere sequence of yeast Saccharomyces cerevisiae and the complete genome sequence of bacterium Escherichia coli, borders of biologically meaningful units were identified (e.g. subtelomeric units, replication origin, and replication terminus), and a more reasonable number of domains was obtained. We also introduce a measure called segmentation strength which can be used to control the delineation of large domains. The relationship between the average domain size and the threshold of segmentation strength is determined for several genome sequences.

  14. Viral detection by high-throughput sequencing.

    Science.gov (United States)

    Motooka, Daisuke; Nakamura, Shota; Hagiwara, Katsuro; Nakaya, Takaaki

    2015-01-01

    We applied a high-throughput sequencing platform, Ion PGM, for viral detection in fecal samples from adult cows collected in Hokkaido, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.25 ml of fecal specimens (N = 8), and more than 5 μg of cDNA was synthesized. Unbiased high-throughput sequencing using the 318 v2 semiconductor chip of these eight samples yielded 57-580 K (average: 270 K, after data analysis) reads in a single run. As a result, viral genome sequences were detected in each specimen. In addition to bacteriophage, mammal- and insect-derived viruses, partial genome sequences of plant, algal, and protozoal viruses were detected. Thus, this metagenomic analysis of fecal specimens could be useful to comprehensively understand viral populations of the intestine and food sources in animals.

  15. Extracting biological knowledge from DNA sequences

    Energy Technology Data Exchange (ETDEWEB)

    De La Vega, F.M. [CINVESTAV-IPN (Mexico); Thieffry, D. [Universite Libre de Bruxelles, Rhode-Saint-Genese (Belgium)]|[Universidad Nacional Autonoma de Mexico, Morelos (Mexico); Collado-Vides, J. [Universidad Nacional Autonoma de Mexico, Morelos (Mexico)

    1996-12-31

    This session describes the elucidation of information from dna sequences and what challenges computational biologists face in their task of summarizing and deciphering the human genome. Techniques discussed include methods from statistics, information theory, artificial intelligence and linguistics. 1 ref.

  16. Optimization of a sequence of reactors

    DEFF Research Database (Denmark)

    Vidal, Rene Victor Valqui

    1991-01-01

    Concerns the optimal production of sulphuric acid in a sequence of reactors. Using a suitable approximation to the objective function, this problem can easily be solved using the maximum principle. A numerical example documents the applicability of the suggested approach...

  17. Characterizing leader sequences of CRISPR loci

    DEFF Research Database (Denmark)

    Alkhnbashi, Omer; Shah, Shiraz Ali; Garrett, Roger Antony;

    2016-01-01

    The CRISPR-Cas system is an adaptive immune system in many archaea and bacteria, which provides resistance against invading genetic elements. The first phase of CRISPR-Cas immunity is called adaptation, in which small DNA fragments are excised from genetic elements and are inserted into a CRISPR...... array generally adjacent to its so called leader sequence at one end of the array. It has been shown that transcription initiation and adaptation signals of the CRISPR array are located within the leader. However, apart from promoters, there is very little knowledge of sequence or structural motifs...... sequences by focusing on the consensus repeat of the adjacent CRISPR array and weak upstream conservation signals. We applied our tool to the analysis of a comprehensive genomic database and identified several characteristic properties of leader sequences specific to archaea and bacteria, ranging from...

  18. Fibonacci Sequence and Supramolecular Structure of DNA.

    Science.gov (United States)

    Shabalkin, I P; Grigor'eva, E Yu; Gudkova, M V; Shabalkin, P I

    2016-05-01

    We proposed a new model of supramolecular DNA structure. Similar to the previously developed by us model of primary DNA structure [11-15], 3D structure of DNA molecule is assembled in accordance to a mathematic rule known as Fibonacci sequence. Unlike primary DNA structure, supramolecular 3D structure is assembled from complex moieties including a regular tetrahedron and a regular octahedron consisting of monomers, elements of the primary DNA structure. The moieties of the supramolecular DNA structure forming fragments of regular spatial lattice are bound via linker (joint) sequences of the DNA chain. The lattice perceives and transmits information signals over a considerable distance without acoustic aberrations. Linker sequences expand conformational space between lattice segments allowing their sliding relative to each other under the action of external forces. In this case, sliding is provided by stretching of the stacked linker sequences.

  19. Comparative genomics beyond sequence-based alignments

    DEFF Research Database (Denmark)

    Þórarinsson, Elfar; Yao, Zizhen; Wiklund, Eric D.;

    2008-01-01

    Recent computational scans for non-coding RNAs (ncRNAs) in multiple organisms have relied on existing multiple sequence alignments. However, as sequence similarity drops, a key signal of RNA structure--frequent compensating base changes--is increasingly likely to cause sequence-based alignment...... methods to misalign, or even refuse to align, homologous ncRNAs, consequently obscuring that structural signal. We have used CMfinder, a structure-oriented local alignment tool, to search the ENCODE regions of vertebrate multiple alignments. In agreement with other studies, we find a large number...... of potential RNA structures in the ENCODE regions. We report 6587 candidate regions with an estimated false-positive rate of 50%. More intriguingly, many of these candidates may be better represented by alignments taking the RNA secondary structure into account than those based on primary sequence alone, often...

  20. Network of tRNA Gene Sequences

    Institute of Scientific and Technical Information of China (English)

    WEI Fang-ping; LI Sheng; MA Hong-ru

    2008-01-01

    A network of 3719 tRNA gene sequences was constructed using simplest alignment. Its topology, degree distribution and clustering coefficient were studied. The behaviors of the network shift from fluctuated distribution to scale-free distribution when the similarity degree of the tRNA gene sequences increases. The tRNA gene sequences with the same anticodon identity are more self-organized than those with different anticodon identities and form local clusters in the network. Some vertices of the local cluster have a high connection with other local clusters, and the probable reason was given. Moreover, a network constructed by the same number of random tRNA sequences was used to make comparisons. The relationships between the properties of the tRNA similarity network and the characters of tRNA evolutionary history were discussed.