Functional analysis of the human genome
著者
書誌事項
Functional analysis of the human genome
（The Human molecular genetics series / series advisors, D.N. Cooper, S.E. Humphries, T. Strachan）
BIOS, 1995
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注記
Includes bibliographies and index
内容説明・目次
内容説明
An excellent review of the relationship between structure and function in the human genome, and a detailed description of some of the important methodologies for unravelling the function of genes and genomic structures.
目次
Contributors -- Abbreviations -- Preface -- Foreword /V.A. McKusick -- 1 Structure and function in the human genome /D.N. Cooper -- Introduction -- Chromatin structure and transcription -- Chromatin structure -- Nucleosome positioning -- Transcriptional domains -- Chiasmata, recombination and recombination hotspots -- Scaffold attachment regions -- Centromeres -- Telomeres -- Origins of DNA replication -- Genes -- Gene structure and organization -- seudogenes -- Functional organization of human genes -- Repetitive sequence elements -- Tandem repeats -- Alu sequences -- LINE elements -- Endogenous retroviral sequences -- Transcriptional regulation -- Promoter elements -- Enhancers -- Negative regulatory elements -- Locus control regions -- Boundary elements -- Trans-acting protein factors -- Sequences involved in transcriptional termination -- mRNA splicing and processing -- Sequences involved in determining mRNA stability -- Role of sequences in 5' untranslated regions -- DNA methylation -- Distribution of 5-methylcytosine -- Replication of the methylation pattern and de novo methylation -- Role of DNA methylation in the regulation of transcription -- Role of DNA methylation in X-inactivation -- Changes in DNA methylation during embryogenesis -- DNA methylation and imprinting -- References -- 2 Mapping the human genome /D.N. Cooper -- Introduction -- Markers -- Gene sequences -- DNA polymorphisms -- D-segments -- Sequence-tagged sites -- Inter-Alu PCR probes -- Allele-specific oligonucleotides -- Cytogenetic mapping -- Somatic cell hybrid analysis -- Radiation hybrid mapping -- Fluorescence in situ hybridization -- In situ PCR -- High-resolution physical mapping -- Yeast artificial chromosome cloning -- Contig assembly -- Pulsed-field gel electrophoresis and CpG island mapping -- Chromosome jumping /linking libraries -- DNA sequencing -- Progress in physical mapping -- Genetic mapping -- Transcription map of the human genome -- Comparative gene mapping -- References -- 3 Cloning the transcribed portion of the genome /P. Towner -- Introduction -- Gene detection -- Preparation of target material -- Isolation of total RNA -- Isolation of mRNA -- Preparation of cDNA -- Selection of specific genes -- Library-based cDNA cloning strategies -- Construction of a cDNA library -- Screening cDNA libraries -- Manipulation of identified cDNA sequences -- PCR-based isolation of genes from cDNA -- Primer design -- Mixed-pool or redundant oligonucleotide primers -- Primary PCR reaction -- Isolation of the 3' end of a cDNA -- Isolation of the 5' end of a cDNA -- Gene identification by differential display -- Expression systems -- Expression using E. coli -- Eukaryotic expression systems -- References -- 4 Retroviral insertional mutagenesis. F. Farzaneh, J. Gaken -- andS.-U. Gan -- Introduction -- The retroviral life cycle -- Host range -- Replication-defective retroviral vectors -- Packaging cell lines -- Conditions required for efficient mutagenesis -- Mechanisms involved in retroviral insertional mutagenesis -- Mutation frequency -- Multiplicity of infection -- Mutant selection procedures -- Cloning of the sites of pro virus integration -- Construction of genomic libraries -- PCR-mediated amplification -- Identification of the gene of interest -- Identification of common sites of provirus integration -- Library screening by nuclear run-on probes -- References -- 5 Gene entrapment. H. von Melchner and H.E. Ruley -- Introduction -- Gene trap vectors -- Cloning and analysis of flanking sequences -- Isolation and use of promoter-tagged sites -- Insertional mutagenesis in cultured cells -- Insertional mutagenesis in mice -- Identification of regulated genes -- References -- 6 Gene transfer studies. D. Darling and M. Kuiper -- Introduction -- What is transfection? -- What form should the DNA be in? -- Generalized requirements for eukaryotic gene transcription -- Eukaryotic gene transcription -- SV-based plasmids -- Specialized eukaryotic host cells -- Specialized plasmids -- Double insert plasmids -- Inducible expression -- Epstein-Barr virus-based plasmids -- Shuttle vectors -- Multifunctional plasmids -- Transfection procedures -- Calcium phosphate co-precipitation -- DEAE-dextran -- Electroporation -- Liposomes and lipid-based transfection -- Adenovirus and poly-L-lysine-conjugated complexes -- Alternative transfection procedures -- Assays for new protein synthesis -- Dominant selectable marker genes -- Reporter genes -- Analysis of cloned genes -- Identification of ligands for novel receptors -- Identification of transcription factors -- References -- 7 Foreign DNA integration and DNA methylation patterns /W. Doerfler -- Introduction -- The adenovirus system as a model -- Site selection in the integration of adenovirus DNA -- Modes of adenovirus DNA integration - a synopsis of data -- On the mechanism of integrative recombination -- Insertion of foreign DNA by a versatile mechanism -- Studies on the mechanism of integrative recombination in a cell-free system -- De novo DNA methylation of integrated foreign DNA -- De novo methylation of integrated foreign DNA: a cellular defence mechanism? -- Initiation of de novo methylation in mammalian cells is not predominantly dependent upon the nucleotide sequence of foreign DNA -- Methylation of triplet repeat amplifications in the human genome: manifestation of the cellular defence mechanism -- Alterations in patterns of cellular DNA methylation and gene expression as consequences of foreign DNA insertions into mammalian genomes -- DNA methylation and gene activity -- A fully 5'-CG-3' but not a 5'-CCGG-3' methylated late FV3 promoter retains activity -- Topology of the promoter of RNA polymerase II- and Ill-transcribed genes is modified by the methylation of 5'-CG-3' dinucleotides -- Impact of 5'-CG-3' methylation on the activity of different eukaryotic promoters: a comparison -- Uptake of foreign DNA through the gastrointestinal tract -- A concept of oncogenesis - implications for gene therapy and research on transgenic organisms -- References -- 8 Transgenic animals in human gene analysis /F. Theuring -- Introduction -- Methodology -- Transgenes to study gene regulation -- Transgenes to study gene function -- Functional analysis: gain-of-function -- Functional analysis: loss-of-function -- Conclusions -- References -- 9 Homologous recombination /A. Mansouri -- Introduction -- Embryonic stem cells -- Principles of homologous recombination in mammalian cells -- Targeting vectors -- Promoterless constructs -- Positive-negative selection procedure -- Hit-and-run and in-out targeting strategies -- Potential of homologous recombination in embryonic stem cells -- Developmental biology -- Animal models of human disease -- Homologous recombination and gene therapy -- Future perspectives: Cre-LoxP mediated gene targeting -- References -- 10 Complementation analysis /A. Patel -- Introduction -- Principles of somatic cell hybridization -- De novo and salvage pathways of nucleotide synthesis -- Purine nucleotide synthesis -- The HPRT gene -- HPRT variants -- Pyrimidine nucleotide synthesis -- Metabolic cooperation -- The HAT selection system -- Selection procedures for the isolation of hybrid cells -- Identification of complementation groups and topological relationships -- Extinction and activation -- Assignment of complementation groups in clinical diseases -- Assignment of complementation groups in senescence -- Assignment of complementation groups in biochemical pathways -- Assignment of complementation groups in cytokine activity -- Identification of the dominant /recessive nature of genetic lesions -- Chromosome segregation -- Dominant and recessive genetic changes involved in senescence -- Dominant and recessive nature of viral genes -- Dominant and recessive events in tumour progression -- Dominant nature of multi-drug resistance genes -- Dominant and recessive events involved in the immunological process -- Dominant and recessive developmentally regulated genes -- Microcell fusion: principles and application to the chromosomal localization of genes -- Introduction to microcell fusion -- General principles for microcell-mediated transfer -- Pinpointing chromosomes involved in specific disease processes -- Identification of tumour suppressor genes -- Identification of genes involved in cellular senescence -- References -- 11 Antisense oligonucleotides: a survey of recent literature, possible mechanisms of action and therapeutic progress /D. Pollock andj. Gaken -- Introduction -- Some examples of antisense action in different systems -- Targeting and design -- Uptake of antisense oligonucleotides -- Toxicity of antisense oligonucleotides -- Modifications to the structure of antisense oligonucleotides -- Possible mechanisms of action -- Steric inhibition -- RNase H-like cleavage of target RNA -- Triplex DNA formation -- Double-stranded oligonucleotides -- Circular oligonucleotides Ribozymes -- Non-specific cleavage of host RNA -- Therapeutic applications -- References -- Index.
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