Showing papers on "Genomics published in 1998"
TL;DR: The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve the understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions.
Abstract: Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
7,779 citations
TL;DR: The complete genome sequence of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus, is described, which contains 834 protein-coding genes and is more closely related to mitochondria than is any other microbe studied so far.
Abstract: We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 p ...
1,599 citations
TL;DR: The advances of the human genome project and the completion of total genome sequences for yeast and many bacterial species, have enabled investigators to view genetic information in the context of the entire genome and recognize that the mechanisms for some genetic diseases are best understood at a genomic level.
870 citations
TL;DR: Advances in microarray technology enable massive parallel mining of biological data, with biological chips providing hybridization-based expression monitoring, polymorphism detection and genotyping on a genomic scale.
863 citations
TL;DR: It is suggested that functional predictions can be greatly improved by focusing on how the genes became similar in sequence (i.e., evolution) rather than on the sequence similarity itself.
Abstract: The ability to accurately predict gene function based on gene sequence is an important tool in many areas of biological research. Such predictions have become particularly important in the genomics age in which numerous gene sequences are generated with little or no accompanying experimentally determined functional information. Almost all functional prediction methods rely on the identification, characterization, and quantification of sequence similarity between the gene of interest and genes for which functional information is available. Because sequence is the prime determining factor of function, sequence similarity is taken to imply similarity of function. There is no doubt that this assumption is valid in most cases. However, sequence similarity does not ensure identical functions, and it is common for groups of genes that are similar in sequence to have diverse (although usually related) functions. Therefore, the identification of sequence similarity is frequently not enough to assign a predicted function to an uncharacterized gene; one must have a method of choosing among similar genes with different functions. In such cases, most functional prediction methods assign likely functions by quantifying the levels of similarity among genes. I suggest that functional predictions can be greatly improved by focusing on how the genes became similar in sequence (i.e., evolution) rather than on the sequence similarity itself. It is well established that many aspects of comparative biology can benefit from evolutionary studies (Felsenstein 1985), and comparative molecular biology is no exception (e.g., Altschul et al. 1989; Goldman et al. 1996). In this commentary, I discuss the use of evolutionary information in the prediction of gene function. To appreciate the potential of a phylogenomic approach to the prediction of gene function, it is necessary to first discuss how gene sequence is commonly used to predict gene function and some general features about gene evolution.
608 citations
TL;DR: In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE).
Abstract: Elucidation of the changes in gene expression associated with biological processes is a central problem in biology. Advances in molecular and computational biology have led to the development of powerful, high-thoughput methods for the analysis of differential gene expression. These tools have opened up new opportunities in disciplines ranging from cell and developmental biology to drug development and pharmacogenomics. In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE). The application of EST sequencing and microarray hybridization is illustrated by the discovery of novel genes associated with osteoblast differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax-6. These and other examples illustrate the power of genomics for discovering novel genes that are important in biology and which also represent new targets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, and that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success. J. Cell. Biochem. Suppls. 30/31:286-296, 1998. © 1998 Wiley-Liss, Inc.
252 citations
TL;DR: This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting and is validated by four repeated, blind experiments.
Abstract: Medical DNA diagnostics will increasingly rely on an accurate and inexpensive identification of mutations that affect the function of a gene. To validate diagnostic sequencing by hybridization (SBH), a number of p53 samples were analyzed with the complete set of 8192 noncomplementary 7-mer oligonu-cleotides. In four repeated, blind experiments we accurately sequenced 1.1 kb per each of 12 homozygote and heterozygote samples possessing base substitutions, insertions, and deletions. This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting.
242 citations
Book•
01 Dec 1998
TL;DR: Genetics and the organism the structure of genes and genomes gene function the inheritance of genes recombination genes gene interaction gene mutations chromosome mutations the genetics of bacteria and phages and the applications of recombinant DNA technology.
Abstract: Genetics and the organism the structure of genes and genomes gene function the inheritance of genes recombination genes gene interaction gene mutations chromosome mutations the genetics of bacteria and phages recombinant DNA technology applications of recombinant DNA technology genomics transposable genetic elements regulation of gene transcription cancer as a genetic disease pathways of differentiation population genetics quantitative genetics.
193 citations
TL;DR: The infection genomics approach toward the TB epidemic has been to isolate and characterize a mouse gene, Bcg (Nramp1), which controls natural susceptibility to infection with Mycobacteria, as well as Salmonella and Leishmania.
Abstract: The scope of the tuberculosis (TB) epidemic in the world today is enormous, with about 30 million active cases. Current research into preventing the spread of TB is focused on development of new drugs to inactivate Mycobacterium tuberculosis, the causative agent of TB, as well as on identifying the critical steps of host defense to infection with Mycobacteria, which might also yield therapeutic targets. Our infection genomics approach toward the latter strategy has been to isolate and characterize a mouse gene, Bcg (Nramp1), which controls natural susceptibility to infection with Mycobacteria, as well as Salmonella and Leishmania. Through comparative genomics, we have identified the homologous human NRAMP1 gene, alleles of which are now being used for tests of linkage with TB and leprosy.
149 citations
TL;DR: The future goals of genomic analysis of HC21 will be the determination of its complete nucleotide sequence and the identification and functional analysis of all of its genes, to provide a molecular explanation of the pathophysiology of Down syndrome.
140 citations
TL;DR: This review focuses on the potential of cDNA microarrays to define gene expression in lymphoid cells, a field which is in its infancy and should provide essential new insights into lymphocyte differentiation and activation, the pathogenesis of immune disorders, and the molecular abnormalities in lymphoids malignancies.
Abstract: The identity and abundance of mRNA species within a cell dictate, to a large extent, the biological potential of that cell. Although posttranscriptional mechanisms modify protein expression in critical ways, cellular differentiation requires key changes in gene transcription, as evidenced by the potent phenotypes that result from disruption of transcription factor genes in mice. It is now possible to assess the mRNA profile of a cell globally using recently developed genomics techniques. This review focuses on the potential of cDNA microarrays to define gene expression in lymphoid cells, a field which is in its infancy. Examples of cellular activation genes and cytokine inducible genes discovered using this technology are presented but these represent only a taste of the fruit that this new technology will ultimately bear. Gene expression profiles should provide essential new insights into lymphocyte differentiation and activation, the pathogenesis of immune disorders, and the molecular abnormalities in lymphoid malignancies.
Book•
01 Jan 1998
TL;DR: Part One: Genome Structure, Stability, and Evolution; Part Two: Strategies for Genome Analysis; Part Three: Physical Maps of Bacteria and Their Methods for Construction.
Abstract: Part One: Genome Structure, Stability, and Evolution. Genome structure. Genome stability. Genome evolution. Part Two: Strategies for Genome Analysis. Physical mapping strategies. Genomic fingerprinting methods. Genomic sequencing projects. Part Three: Physical Maps of Bacteria and Their Methods for Construction. Index.
TL;DR: The application of ENU mutagenesis is reviewed and discussed in the context of a new era of functional genomics, which will have at its core the functional analysis of genes.
Abstract: The worldwide effort to completely sequence the human and mouse genome will be accomplished within the next years The focus of current activities within the framework of human genome research is mainly on the assembly of high resolution genetic and physical maps and genomic sequencing Cloning of new genes is getting more easy using those maps Nevertheless, it is necessary to work on a systematic analysis of gene function Results obtained from these efforts will be of enormous value for future biological and biomedical research However, even the complete sequence will not in all cases reveal the molecular and cellular role of the different genes Therefore, the next phase of the Human Genome Project will have at its core the functional analysis of genes Those genes relevant for the diagnosis, prevention and therapy of human diseases are of particular interest Looking at the history of life sciences, mutants have been the most important tool to obtain insight into the biological function of genes The mouse is the model of choice for the study of inherited diseases in man In order to meet the requirements for functional human genome analysis, we need a large number of mouse mutants similar to the collection of mutants available for other model organisms such as flys and worms To fully apply the power of genetics, multiple alleles of the same gene such as hypomorphs or hypermorphs are required Efficient production of mouse mutants showing specific phenotypes can be achieved by the use of ethylnitrosourea (ENU) ENU is the most powerful mutagen known and we currently see a renaissance of ENU mutagenesis The application of ENU mutagenesis is reviewed and discussed in the context of a new era of functional genomics
01 Jan 1998
TL;DR: The powerful combination of genomics and bioinformatics is providing a wealth of information about Mycobacterium tuberculosis, the aetiological agent of human tuberculosis, that will facilitate the conception and development of new therapies.
Abstract: The powerful combination of genomics and bioinformatics is providing a wealth of information about Mycobacterium tuberculosis, the aetiological agent of human tuberculosis, that will facilitate the conception and development of new therapies. The starting point for genome sequencing was the integrated map of the 4.4 Mb circular chromosome of the widely used, virulent reference strain, M. tuberculosis H37Rv. Cosmids and bacterial artificial chromosomes were selected from ordered libraries and subjected to systematic shotgun sequence analysis. This approach simplified sequence assembly as the genome is rich in repetitive DNA. In common with most bacteria, > 90% of the potential coding capacity is used, and probable or tentative functions could be attributed to > 70% of the genes. The potential biological roles of two of the principal driving forces in genome dynamics, insertion sequence elements and polymorphic multigene families are discussed.
Book•
01 Jan 1998
TL;DR: Genetics: Analysis and Principles emphasizes the scientific method to give students the insight needed to develop scientific reasoning skills.
Abstract: PART I INTRODUCTION 1 Overview of Genetics PART II PATTERNS OF INHERITANCE 2 Mendelian Inheritance 3 Reproduction and Chromosome Transmission 4 Extensions of Mendelian Inheritance 5 Non-Mendelian Inheritance 6 Genetic Linkage and Mapping in Eukaryotes 7 Genetic Transfer and Mapping in Bacteria and Bacteriophages 8 Variation in Chromosome Structure and Number PART III MOLECULAR STRUCTURE AND REPLICATION OF THE GENETIC MATERIAL 9 Molecular Structure of DNA and RNA 10 Chromosome Organization and Molecular Structure 11 DNA Replication PART IV MOLECULAR PROPERTIES OF GENES 12 Gene Transcription and RNA Modification 13 Translation of mRNA 14 Gene Regulation in Bacteria and Bacteriophages 15 Gene Regulation in Eukaryotes 16 Gene Mutation and DNA Repair 17 Recombination and Transposition at the Molecular Level PART V GENETIC TECHNOLOGIES 18 Recombinant DNA Technology 19 Biotechnology 20 Genomics I: Analysis of DNA 21 Genomics II: Functional Genomics, Proteomics, and Bioinformatics PART VI GENETIC ANALYSIS OF INDIVIDUALS AND POPULATIONS 22 Medical Genetics and Cancer 23 Developmental Genetics 24 Population Genetics 25 Quantitative Genetics 26 Evolutionary Genetics
TL;DR: As ubiquitous decomposers, symbionts and parasites, fungi build populations not easily accommodated by population genetic theory, making them ideal subjects for tracking mutation and expression in genes of adaptive importance in experimental populations.
Abstract: As ubiquitous decomposers, symbionts and parasites, fungi build populations not easily accommodated by population genetic theory. Identifying and delineating individuals and populations is often difficult, and recombination can occur in complex and variable ways. Genotyping and gene genealogies provide the framework for identifying and delineating individuals and for detecting recombination in natural populations. Expanding genomic databases now make fungi ideal subjects for tracking mutation and expression in genes of adaptive importance in experimental populations.
TL;DR: A third complete archaeal genome sequence, replete with eukaryote-like genes for replication, transcription and translation, has appeared and shows bacteria-like features.
TL;DR: This work states that large-scale genome sequencing is filling up the catalogue of natural proteins at a breathtaking speed, and the relationship between structure determination and genomics is being investigated.
TL;DR: Less than two yeras after the sequence of its genome was completed, the baker's yeast, Saccharomyces cerevisiae, is a leading organism in the rapidly growing field of functional genomics.
Abstract: Less than two yeras after the sequence of its genome was completed, the baker's yeast, Saccharomyces cerevisiae, is a leading organism in the rapidly growing field of functional genomics. Two thousands novel protein coding genes, nearly all of them "orphans", have already been disrupted by the coordinated efforts of a large consortium of European laboratories, EUROFAN, and other initiatives. The mutants are submitted to many specialized functional assays, and studies are performed in parallel at the transcriptome and the proteome levels. With a central repository of mutant yeast strains, and a centralized database, EUROFAN lays the foundations for the future of genomics with yeast serving both as a model and a tool.
TL;DR: It is argued that a more complete map of the genome should seek to embody the richness of information that the authors expect of the maps they use to navigate their way around the outside world.
TL;DR: Comparison of the two genome sequences is mutually enriching and indicates that the M. leprae genome appears to have undergone shrinkage and large-scale gene inactivation, which may account for the exceptionally slow growth of this organism.
TL;DR: The Rice Genome Research Program in Japan has carried out rice genomics, such as large-scale cDNA analysis, construction of a fine-scale restriction fragment length (RFL) polymorphism map, and physical mapping of the rice genome with yeast and artificial chromosome clones as discussed by the authors.
Abstract: Since 1991, the Rice Genome Research
Program in Japan has carried out rice genomics, such as large-scale
cDNA analysis, construction of a fine-scale restriction fragment length
polymorphism map, and physical mapping of the rice genome with yeast
artificial chromosome clones. These studies have made a great impact on
research into grass genomes and made rice a model plant for other
cereal crop research. Starting in 1998, the Rice Genome Research
Program will step into a new stage of genomics—that of genome
sequencing. This project eventually should reveal all of the genomic
sequence information in the rice plant and be an indispensable aid in
understanding the genomics of other grass species.
TL;DR: The offending fragments are sonicated heavily and recloned, as much smaller fragments, into pUC vector and the sequences obtained from the resulting library can be assembled, free from the effects of secondary structure, to produce high-quality, complete sequence.
Abstract: As the Human Genome Project moves into its sequencing phase, a serious problem has arisen. The same problem has been increasingly vexing in the closing phase of the Caenorhabditis elegans project. The difficulty lies in sequencing efficiently through certain regions in which the templates (DNA substrates for the sequencing process) form complex folded secondary structures that are inaccessible to the enzymes. The solution, however, is simply to break them up. Specifically, the offending fragments are sonicated heavily and recloned, as much smaller fragments, into pUC vector. The sequences obtained from the resulting library can subsequently be assembled, free from the effects of secondary structure, to produce high-quality, complete sequence. Because of the success and simplicity of this procedure, we have begun to use it for the sequencing of all regions in which standard primer walking has been at all difficult.
01 Jun 1998
TL;DR: The entire genome of Synechocystis sp. PCC6803 has been determined as mentioned in this paper, and the length of the circular genome was 3,573,480 bp, and a total of 3168 protein-coding genes were assigned to the genome by a computer assisted analysis.
Abstract: ▪ Abstract The nucleotide sequence of the entire genome of the unicellular cyanobacterium, Synechocystis sp. PCC6803, has been determined. The length of the circular genome was 3,573,480 bp, and a total of 3168 protein-coding genes were assigned to the genome by a computer-assisted analysis. The functions of approximately 45% of the genes were deduced based on sequence similarity to known genes. Here are distinctive features of genetic information carried by the cyanobacteria, which have a phylogenetic relationship to both bacteria and plants.
TL;DR: Positional cloning identifies novel resistance genes, even when the mechanisms are poorly understood, as with resistance to Bacillus thuringiensis toxins, and is described for Heliothis and Helicoverpa, two of the most destructive genera of pest moths worldwide.
Abstract: Genomics is the comparative study of the structure and function of entire genomes. Although the complete sequencing of the genome of any insect pest is far in the future, a genomic approach can be useful in the study of mechanisms of insecticide resistance. We describe this strategy for Heliothis and Helicoverpa, two of the most destructive genera of pest moths (Lepidoptera) worldwide. Genome-wide linkage mapping provides the location of major and minor resistance genes. Positional cloning identifies novel resistance genes, even when the mechanisms are poorly understood, as with resistance to Bacillus thuringiensis toxins. Anchor loci provide the reference points for comparing the genomes and the genetic architecture of resistance mechanisms among related species. Collectively, these tools enable the description of the evolutionary response of related, but independent, genomes to the common selective pressure of insecticides in the environment. They also provide information that is useful for targeted management of specific resistance genes, and may even speed the search for families of novel insecticidal targets in Lepidoptera.
TL;DR: The RS447 sequence is considered to consist of a new class of tandemly repeated satellite DNA elements in the mammalian genome, which may thus be called "megasatellite DNA."
TL;DR: The application of genomics to the study of crop species offers special opportunities for innovative approaches for combining sequence information with the vast reservoirs of historical information associated with crops and their evolution.
Abstract: Comparative genomics offers unparalleled opportunities to integrate historically distinct disciplines, to link disparate biological kingdoms, and to bridge basic and applied science. Cross-species, cross-genera, and cross-kingdom comparisons are proving key to understanding how genes are structured, how gene structure relates to gene function, and how changes in DNA have given rise to the biological diversity on the planet. The application of genomics to the study of crop species offers special opportunities for innovative approaches for combining sequence information with the vast reservoirs of historical information associated with crops and their evolution. The grasses provide a particularly well developed system for the development of tools to facilitate comparative genetic interpretation among members of a diverse and evolutionarily successful family. Rice provides advantages for genomic sequencing because of its small genome and its diploid nature, whereas each of the other grasses provides complementary genetic information that will help extract meaning from the sequence data. Because of the importance of the cereals to the human food chain, developments in this area can lead directly to opportunities for improving the health and productivity of our food systems and for promoting the sustainable use of natural resources.