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High order intra-strand partial symmetry increases with organismal complexity in animal evolution

SCIENTIFIC REPORTS 2014年第1期4卷 6400-6400页

作者： Wang, Shengqin Tu, Jing Jia, Zhongwei Lu, Zuhong Southeast Univ Sch Biol Sci & Med Engn State Key Lab Bioelect Nanjing 210096 Jiangsu Peoples R China Peking Univ Coll Engn Dept Biomed Engn Beijing 100781 Peoples R China Peking Univ Natl Inst Drug Dependence Beijing 100191 Peoples R China

For sufficiently long genomic sequence, the frequency of any short nucleotide fragment on one strand is approximately equal to the frequency of its reverse complement on the same strand. Despite being studied over two decades, the precise mechanism involved has not yet been made clear. In this study, we calculated the high order intra-strand partial symmetry (IPS) for 14 animal species by using a fixed sliding window method to scan each genome sequence. The study showed that the IPS was positive associated with organismal complexity measured by the number of distinct cell types. The results indicated that the IPS might be resulted from the increasing of functional non-coding dnas, and plays an important role in the evolution process of complex body plans.

关键词： EVOLUTION (Biology) OLIGONUCLEOTIDES non-coding dna GENOMES HAIRPIN (Genetics) ANIMAL genetics

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Identification of candidate intergenic risk loci in autism spectrum disorder

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BMC GENOMICS 2013年第1期14卷 1-6页

作者： Walker, Susan Scherer, Stephen W. Hosp Sick Children Program Genet & Genome Biol Ctr Appl Genom Toronto ON M5G 1L7 Canada Univ Toronto McLaughlin Ctr Toronto ON M5S 1A1 Canada

Background: Copy number variations (CNVs) and dna sequence alterations affecting specific neuronal genes are established risk factors for Autism Spectrum Disorder (ASD). In what is largely considered a genetic condition, so far, these mutations account for similar to 20% of individuals having an ASD diagnosis. However, non-coding genomic sequence also contains functional elements introducing additional disease risk loci for investigation. Results: We have performed genome-wide analyses and identified rare inherited CNVs affecting non-genic intervals in 41 of 1491 (3%) of ASD cases examined. Examples of such intergenic CNV regions include 16q21 and 2p16.3 near known ASD risk genes CDH8 and NRXN1 respectively, as well as novel loci contiguous with ZHX2, MOCS1, LRRC4C, SEMA3C, and other genes. Conclusions: Rare variants in intergenic regions may implicate new risk loci and genes in ASD and also present useful data for comparison with coming whole genome sequence datasets.

关键词： Autism spectrum disorder Copy number variation non-coding dna

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A meta-analysis of the genomic and transcriptomic composition of complex life

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CELL CYCLE 2013年第13期12卷 2061-2072页

作者： Liu, Ganqiang Mattick, John S. Taft, Ryan J. Univ Queensland Inst Mol Biosci Brisbane Qld Australia St Vincents Hosp Garvan Inst Med Res Darlinghurst NSW 2010 Australia

It is now clear that animal genomes are predominantly non-protein-coding, and that these sequences encode a wide array of RNA transcripts and other regulatory elements that are fundamental to the development of complex life. We have previously argued that the proportion of an animal genome that is non-protein-coding dna (ncdna) correlates well with its apparent biological complexity. Here we extend on that work and, using data from a total of 1,627 prokaryotic and 153 eukaryotic complete and annotated genomes, show that the proportion of ncdna per haploid genome is significantly positively correlated with a previously published proxy of biological complexity, the number of distinct cell types. This is in contrast to the amount of the genome that encodes proteins, which we show is essentially unchanged across Metazoa. Furthermore, using a total of 179 RNA-seq data sets from nematode (47), fruit fly (72), zebrafish (20) and human (42), we show, consistent with other recent reports, that the vast majority of ncdna in animals is transcribed. This includes more than 60 human loci previously considered "gene deserts," many of which are expressed tissue-specifically and associated with previously reported GWAS SNPs. These results suggest that ncdna, and the ncRNAs encoded within it, may be intimately involved in the evolution, maintenance and development of complex life.

关键词： noncoding RNA non-coding dna evolution complexity lincRNA small RNA

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ChroMoS: an integrated web tool for SNP classification, prioritization and functional interpretation

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BIOINFORMATICS 2013年第17期29卷 2197-2198页

作者： Barenboim, Maxim Manke, Thomas Max Planck Inst Immunobiol & Epigenet Bioinformat & Deep Sequencing Unit D-79108 Freiburg Germany

Genome-wide association studies and re-sequencing projects are revealing an increasing number of disease-associated SNPs, a large fraction of which are non-coding. Although they could have relevance for disease susceptibility and progression, the lack of information about regulatory regions impedes the assessment of their functionality. Here we present a web server, ChroMoS (Chromatin Modified SNPs), which combines genetic and epigenetic data with the goal of facilitating SNPs' classification, prioritization and prediction of their functional consequences. ChroMoS uses a large database of SNPs and chromatin states, but allows a user to provide his/her own genetic information. Based on the SNP classification and interactive prioritization, a user can compute the functional impact of multiple SNPs using two prediction tools, one for differential analysis of transcription factor binding (sTRAP) and another for SNPs with potential impact on binding of miRNAs (MicroSNiPer).

关键词： SINGLE nucleotide polymorphisms GENOMES non-coding dna GENETIC regulation BIOINFORMATICS CHROMATIN

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The Challenges of Statistical Patterns of Language: The Case of Menzerath's Law in Genomes

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COMPLEXITY 2013年第3期18卷 11-17页

作者： Ferrer-I-Cancho, Ramon Forns, Nuria Hernandez-Fernandez, Antoni Bel-enguix, Gemma Baixeries, Jaume Univ Politecn Cataluna TALP Res Ctr LARCA Complex & Quantitat Linguist Lab Dept Llenguatges & Sistemes Informat Barcelona Catalonia Spain Univ Barcelona Fac Biol Dept Microbiol Barcelona Catalonia Spain Univ Barcelona Dept Linguist Gen Barcelona Catalonia Spain Univ Aix Marseille Lab Informat Fondamentale Marseille France CNRS Marseille France

The importance of statistical patterns of language has been debated over decades. Although Zipf's law is perhaps the most popular case, recently, Menzerath's law has begun to be involved. Menzerath's law manifests in language, music and genomes as a tendency of the mean size of the parts to decrease as the number of parts increases in many situations. This statistical regularity emerges also in the context of genomes, for instance, as a tendency of species with more chromosomes to have a smaller mean chromosome size. It has been argued that the instantiation of this law in genomes is not indicative of any parallel between language and genomes because (a) the law is inevitable and (b) noncoding dna dominates genomes. Here mathematical, statistical, and conceptual challenges of these criticisms are discussed. Two major conclusions are drawn: the law is not inevitable and languages also have a correlate of noncoding dna. However, the wide range of manifestations of the law in and outside genomes suggests that the striking similarities between noncoding dna and certain linguistics units could be anecdotal for understanding the recurrence of that statistical law. (c) 2012 Wiley Periodicals, Inc. Complexity, 2012

关键词： statistical laws language genomes music non-coding dna Menzerath's law

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Genetics Driving Epigenetics

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SCIENCE 2013年第6159期342卷 705-706页

作者： Furey, Terrence S. Sethupathy, Praveen Univ N Carolina Dept Biol Chapel Hill NC 27599 USA Univ N Carolina Dept Genet Chapel Hill NC 27599 USA Univ N Carolina Carolina Ctr Genome Sci Chapel Hill NC 27599 USA Univ N Carolina Lineberger Comprehens Canc Ctr Chapel Hill NC 27599 USA

Humans vary according to a plethora of traits, such as height, hair color, behavior, and susceptibility to disease. Both genetics (nature) and environment (nurture) contribute to this variation. Recent large-scale genetic studies have identified thousands of specific dna variations in the human population that are associated with different traits. However, these studies do not answer a key question: By what means do most dna variants alter cellular behavior and contribute to differences in specific traits, such as height? A trio of papers in this issue by Kasowski et al. on page 750 (1), Kilpinen et al. on page 744 (2), and McVicker et al. on page 747 (3) provide a framework for exploring the mechanistic link between genetic and trait variation in the human population. Specifically, they find that dna variants influence a layer of gene regulation called epigenetics through the sequence-specific activity of transcription factors.

关键词： TRAIT intercorrelations dna RESEARCH GENOMES non-coding dna GENE expression

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Cellular Senescence in Yeast Is Regulated by rdna noncoding Transcription

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CURRENT BIOLOGY 2013年第18期23卷 1794-1798页

作者： Saka, Kimiko Ide, Satoru Ganley, Austen R. D. Kobayashi, Takehiko Grad Univ Adv Studies Natl Inst Genet Cytogenet Div Mishima Shizuoka 4118540 Japan Grad Univ Adv Studies Dept Genet Mishima Shizuoka 4118540 Japan Massey Univ Inst Nat & Math Sci Auckland 0632 New Zealand

Genomic instability is a conserved factor in lifespan reduction, although the molecular mechanism is not known [1]. Studies in the yeast Saccharomyces cerevisiae over the past 20 years have found a connection between the ribosomal RNA gene cluster (rdna) and lifespan [2]. The highly repetitive rdna exhibits genomic instability, and the anti-aging histone deacetylase gene SIR2 regulates this instability. We previously proposed that SIR2 governs lifespan by repressing rdna noncoding transcription and rdna instability, but the extent to which lifespan is affected by SIR2 acting at the rdna versus other genomic regions, and the relationship between rdna noncoding transcription/rdna stability and lifespan have remained controversial. To control rdna noncoding transcription and rdna instability, we use a strain in which the rdna noncoding promoter is replaced with an inducible promoter. Here, we show that repression of noncoding transcription extends lifespan and makes SIR2 dispensable for lifespan extension. These results indicate that Sir2 maintains lifespan through repression of E-pro noncoding transcription in the rdna cluster, rather than pleiotropically at other loci. The observation of rdna instability in other organisms, including humans, suggests that this may be a conserved aging pathway.

关键词： CELL physiology YEAST PHYSIOLOGY RECOMBINANT dna non-coding dna HISTONE deacetylase GENOMICS

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Searching for functional genetic variants in non-coding dna

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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 2008年第4期35卷 372-375页

作者： Cobb, Joanna Busst, Cara Petrou, Steven Harrap, Stephen Ellis, Justine Univ Melbourne Dept Physiol Melbourne Vic 30101 Australia Howard Florey Inst Melbourne Vic Australia Murdoch Childerns Res Inst Melbourne Vic Australia

1. The search for dna sequence variants for complex human polygenic conditions has been a strong focus of recent genetic research. While gene loci have been identified, few variants in the coding sequences of these genes have been found, suggesting that non-coding sequence variation may underlie many complex conditions. 2. non-coding dna harbours regulatory elements capable of making changes to gene expression. However, regulatory dna sequences are currently difficult to recognize and their function is poorly understood, complicating the task of assigning potential functional significance to non-coding variation. 3. Comparative genomics, the study of evolutionary dna conservation, has enabled the emergent field of non-coding dna identification in human disease analysis. 4. This brief review will focus on the potential of a relatively high throughput technique based on comparative genomics, that may aid in the identification of functionally important non-coding sequence variation in complex diseases.

关键词： comparative genomics enhancer screening non-coding dna

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Phylogenetics of early branching eudicots: Comparing phylogenetic signal across plastid introns, spacers, and genes

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植物分类学报 2012年第2期50卷 85-108页

作者： Anna-Magdalena BARNISKE Thomas BORSCH Kai M(U)LLER Michael KRUG Andreas WORBERG Christoph NEINHUIS Dietmar QUANDT Institutfür Botanik Technische Universitüt Dresden 01217 Dresden Germany Botanischer Garten und Botanisches Museum Berlin-Dahlem und Institutfür Biologie/Botanik Dahlem Centre of Plant Sciences(DCPS)Freie Universit(a)t Berlin 14195 Berlin Germany Institute for Evolution and Biodiversity. Westf(ü)lische Wilhelms-Universit(a)t. 48149 Münster Germany Nees Institute for Biodiversity of Plants Rheinische Friedrich-Wilhelms-Universit(a)t Bonn 53115 Bonn Germany Institutfür Botanik Technische Universitüt Dresden 01217 Dresden Germany Nees Institute for Biodiversity of Plants Rheinische Friedrich-Wilhelms-Universit(a)t Bonn 53115 Bonn Germany

Recent phylogenetic analyses revealed a grade with Ranunculales,Sabiales,Proteales,Trochodendrales,and Buxales as first branching eudicots,with the respective positions of Proteales and Sabiales still lacking statistical *** previous analyses of conserved plastid genes remain inconclusive,we aimed to use and evaluate a representative set of plastid introns (group Ⅰ:trnL; group Ⅱ:petD,rpll6,trnK) and intergenic spacers (trnL-F,petB-petD,atpB-rbcL,rps3-rpll6) in comparison to the rapidly evolving matK and slowly evolving atpB and rbcL *** patterns of microstructural mutations converged across genomic regions,underscoring the existence of a general mutational pattern throughout the plastid *** signal differed strongly between functionally and structurally different genomic regions and was highest in matK,followed by spacers,then group Ⅱ and group Ⅰ *** more conserved atpB and rbcL coding regions showed distinctly lower phylogenetic information ***,maximum likelihood,and Bayesian phylogenetic analyses based on the combined dataset of non-coding and rapidly evolving regions (＞14 000 aligned characters) converged to a backbone topology ofeudicots with Ranunculales branching first,a Proteales-Sabiales clade second,followed by Trochodendrales and *** generally appeared as sister to all remaining core eudicots with maximum *** results show that a small number of intron and spacer sequences allow similar insights into phylogenetic relationships of eudicots compared to datasets of many combined *** non-coding proportion of the plastid genome thus can be considered an important information source for plastid phylogenomics.

关键词： backbone topology chloroplast phylogenomics early branching eudicots non-coding dna phylogenetic structure R

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Development of multilocus putatively neutral dna markers in the X-chromosome for population genetic studies in humans

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ANNALS OF HUMAN BIOLOGY 2012年第4期39卷 281-289页

作者： Khan, Naazneen Chittoria, Anita Pande, Veena Jaiswal, Yogesh Kumar Das, Aparup Natl Inst Malaria Res Evolutionary Genom & Bioinformat Lab Div Genom & Bioinformat New Delhi 110077 India Kumaun Univ Dept Biotechnol Naini Tal 263001 Uttarakhand India Jiwaji Univ Sch Studies Biotechnol Gwalior 474011 Madhya Pradesh India

Background: It has now been well documented that the type (coding, non-coding) and location (nuclear, mitochondrial etc.) of genetic markers heavily influence evolutionary inferences;realistic assumptions can be drawn if multiple putatively neutral dna fragments spread across the genome are used. Aim: To infer human population history, Single Nucleotide Polymorphisms (SNPs), located in the non-coding regions of different genes in the X-chromosome have been developed as 'putatively neutral markers'. Subjects and methods: A population sample consisting of 16 male individuals from the western part of India was utilized for sequencing eight dna fragments located in introns of three genes (Duchenne muscular dystrophy, Factor IX and Pyruvate dehydrogenase E1 sub-unit) on the human X-chromosome. PCR amplification and dna sequencing confirmed the polymorphic status of all the fragments. Results: Twenty nine SNPs were found to be segregating in the Western Indian population samples. Using these SNPs the nucleotide diversity and demographic parameters of the Western Indian population were estimated. Several tests of neutrality ascertained that all eight fragments evolve putatively neutrally. Further, linkage disequilibrium analyses confirmed this fact. Conclusion: All eight dna fragments seem to bear the characteristics to be considered as 'putatively neutral genetic markers' and thus, could be utilized for inference of human population and demographic histories.

关键词： Multilocus non-coding dna SNPs evolution India

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