Showing papers on "Genomics published in 2001"
TL;DR: This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis.
Abstract: The early notion that cancer is caused by mutations in genes critical for the control of cell growth implied that genome stability is important for preventing oncogenesis. During the past decade, knowledge about the mechanisms by which genes erode and the molecular machinery designed to counteract this time-dependent genetic degeneration has increased markedly. At the same time, it has become apparent that inherited or acquired deficiencies in genome maintenance systems contribute significantly to the onset of cancer. This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis.
3,898 citations
TL;DR: It is becoming clear that alternative splicing has an extremely important role in expanding protein diversity and might therefore partially underlie the apparent discrepancy between gene number and organismal complexity.
1,184 citations
TL;DR: It is demonstrated how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation, and this approach to functional analysis, using comparative metabolomics, is called FANCY—an abbreviation for functional analysis by co-responses in yeast.
Abstract: A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent," that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY—an abbreviation for functional analysis by co-responses in yeast.
1,014 citations
01 Jan 2001
TL;DR: Genetical genomics as discussed by the authors combines the power of genomics and genetics in a way that is likely to become instrumental in the further unravelling of metabolic, regulatory and developmental pathways.
Abstract: The recent successes of genome-wide expression profiling in biology tend to overlook the power of genetics. We here propose a merger of genomics and genetics into ‘genetical genomics’. This involves expression profiling and marker-based fingerprinting of each individual of a segregating population, and exploits all the statistical tools used in the analysis of quantitative trait loci. Genetical genomics will combine the power of two different worlds in a way that is likely to become instrumental in the further unravelling of metabolic, regulatory and developmental pathways.
952 citations
TL;DR: This work proposes a merger of genomics and genetics into 'genetical genomics', which involves expression profiling and marker-based fingerprinting of each individual of a segregating population, and exploits all the statistical tools used in the analysis of quantitative trait loci.
924 citations
TL;DR: In the analysis of the genome, a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted are identified and there may be new targets for vaccine and antibiotic development.
Abstract: Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.
809 citations
01 Jan 2001
631 citations
TL;DR: Adaptations of the targeting induced local lesions in genomes are reported, which help to understand gene function and effective reverse genetic strategies are increasingly in demand.
Abstract: With the completion of genome sequencing projects, emphasis in genomics has shifted from analyzing sequences to understanding gene function, and effective reverse genetic strategies are increasingly in demand. Here we report adaptations of the targeting induced local lesions in genomes (TILLING)
575 citations
TL;DR: It is estimated that the unlinked duplicated zebrafish genes are between 300 and 450 Myr, which means that genome duplication could have provided the genetic raw material for teleost radiation and the loss of different duplicates in different populations may have promoted speciation in ancient teleost populations.
Abstract: There are approximately 25 000 species in the division Teleostei and most are believed to have arisen during a relatively short period of time ca. 200 Myr ago. The discovery of 'extra' Hox gene clusters in zebrafish (Danio rerio), medaka (Oryzias latipes), and pufferfish (Fugu rubripes), has led to the hypothesis that genome duplication provided the genetic raw material necessary for the teleost radiation. We identified 27 groups of orthologous genes which included one gene from man, mouse and chicken, one or two genes from tetraploid Xenopus and two genes from zebrafish. A genome duplication in the ancestor of teleost fishes is the most parsimonious explanation for the observations that for 15 of these genes, the two zebrafish orthologues are sister sequences in phylogenies that otherwise match the expected organismal tree, the zebrafish gene pairs appear to have been formed at approximately the same time, and are unlinked. Phylogenies of nine genes differ a little from the tree predicted by the fish-specific genome duplication hypothesis: one tree shows a sister sequence relationship for the zebrafish genes but differs slightly from the expected organismal tree and in eight trees, one zebrafish gene is the sister sequence to a clade which includes the second zebrafish gene and orthologues from Xenopus, chicken, mouse and man. For these nine gene trees, deviations from the predictions of the fish-specific genome duplication hypothesis are poorly supported. The two zebrafish orthologues for each of the three remaining genes are tightly linked and are, therefore, unlikely to have been formed during a genome duplication event. We estimated that the unlinked duplicated zebrafish genes are between 300 and 450 Myr. Thus, genome duplication could have provided the genetic raw material for teleost radiation. Alternatively, the loss of different duplicates in different populations (i.e. 'divergent resolution') may have promoted speciation in ancient teleost populations.
497 citations
TL;DR: Using ‘exon’ and ‘tiling’ arrays fabricated by ink-jet oligonucleotide synthesis, an experimental approach is devised to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons.
Abstract: The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using ‘exon’ and ‘tiling’ arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.
480 citations
TL;DR: It is led to conclude that recombination between common families, as compared to the invention of new families and recombination among these, has also been a major contribution to the evolution of kingdom-specific and species-specific functions in organisms in all three kingdoms.
TL;DR: A definition for this new field of bioinformatics is proposed and some of the research that is being pursued is reviewed, particularly in relation to transcriptional regulatory systems.
Abstract: Summary Background: The recent flood of data from genome sequences and functional genomics has given rise to new field, bioinformatics, which combines elements of biology and computer science. Objectives: Here we propose a definition for this new field and review some of the research that is being pursued, particularly in relation to transcriptional regulatory systems. Methods: Our definition is as follows: Bioinformatics is conceptualizing biology in terms of macromolecules (in the sense of physical-chemistry) and then applying “informatics” techniques (derived from disciplines such as applied maths, computer science, and statistics) to understand and organize the information associated with these molecules, on a large-scale. Results and Conclusions: Analyses in bioinformatics predominantly focus on three types of large datasets available in molecular biology: macromolecular structures, genome sequences, and the results of functional genomics experiments (eg expression data).
TL;DR: Computational analyses of the human genome will reveal the number of genes and repetitive elements, the extent of gene duplication and compositional heterogeneity in thehuman genome, andThe extent of domain shuffling and domain sharing among proteins.
Abstract: The completion of the human genome will greatly accelerate the development of a new branch of science—evolutionary genomics We can now directly address important questions about the evolutionary history of human genes and their regulatory sequences Computational analyses of the human genome will reveal the number of genes and repetitive elements, the extent of gene duplication and compositional heterogeneity in the human genome, and the extent of domain shuffling and domain sharing among proteins Here we present some first glimpses of these features
TL;DR: How the human genome sequence and the completed genome sequences of other organisms will expand the authors' understanding of human diseases, both those caused by mutations in a single gene and those where many genes and multiple factors are involved is discussed.
Abstract: The genomics era has provided great opportunities for deciphering the genes that are mutated in human diseases. In their Future Directions9 article,
Peltonen and McKusick
discuss how the human genome sequence and the completed genome sequences of other organisms will expand our understanding of human diseases, both those caused by mutations in a single gene and those where many genes and multiple factors are involved. From SNP maps to individual drug response profiling, the human genome sequence will lead to improved diagnostic testing for disease susceptibility genes and individually tailored treatment regimens for those who have already developed disease symptoms.
TL;DR: The enigma of genomic and phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975 as mentioned in this paper.
Abstract: The genomic era revolutionized evolutionary biology. The enigma of
genotypic-phenotypic diversity and biodiversity evolution of genes,
genomes, phenomes, and biomes, reviewed here, was central in the
research program of the Institute of Evolution, University of Haifa,
since 1975. We explored the following questions. ( i ) How
much of the genomic and phenomic diversity in nature is adaptive and
processed by natural selection? ( ii ) What is the origin
and evolution of adaptation and speciation processes under
spatiotemporal variables and stressful macrogeographic and
microgeographic environments? We advanced ecological genetics into
ecological genomics and analyzed globally ecological, demographic, and
life history variables in 1,200 diverse species across life, thousands
of populations, and tens of thousands of individuals tested mostly for
allozyme and partly for DNA diversity. Likewise, we tested thermal,
chemical, climatic, and biotic stresses in several model organisms.
Recently, we introduced genetic maps and quantitative trait loci to
elucidate the genetic basis of adaptation and speciation. The
genome–phenome holistic model was deciphered by the global regressive,
progressive, and convergent evolution of subterranean mammals. Our
results indicate abundant genotypic and phenotypic diversity in nature.
The organization and evolution of molecular and organismal diversity in
nature at global, regional, and local scales are nonrandom and
structured; display regularities across life; and are positively
correlated with, and partly predictable by, abiotic and biotic
environmental heterogeneity and stress. Biodiversity evolution, even in
small isolated populations, is primarily driven by natural selection,
including diversifying, balancing, cyclical, and purifying selective
regimes, interacting with, but ultimately overriding, the effects of
mutation, migration, and stochasticity.
[...]
TL;DR: This work has determined functional categories for nearly 1,000 documented disease genes, and found striking correlations between the function of the gene product and features of disease, such as age of onset and mode of inheritance.
Abstract: The complete human genome sequence will facilitate the identification of all genes that contribute to disease. We propose that the functional classification of disease genes and their products will reveal general principles of human disease. We have determined functional categories for nearly 1,000 documented disease genes, and found striking correlations between the function of the gene product and features of disease, such as age of onset and mode of inheritance. As knowledge of disease genes grows, including those contributing to complex traits, more sophisticated analyses will be possible; their results will yield a deeper understanding of disease and an enhanced integration of medicine with biology.
TL;DR: Extension of phylogenetic analysis to the genome scale has the potential of uncovering deep evolutionary relationships between prokaryotic lineages, and put into question the sister-group relationship between the two major archaeal groups, Euryarchaeota and CrenarchAEota, and suggest instead that Eury Archaeota might be a paraphyletic group with respect to Cren archaeota.
Abstract: The availability of multiple complete genome sequences from diverse taxa prompts the development of new phylogenetic approaches, which attempt to incorporate information derived from comparative analysis of complete gene sets or large subsets thereof. Such attempts are particularly relevant because of the major role of horizontal gene transfer and lineage-specific gene loss, at least in the evolution of prokaryotes. Five largely independent approaches were employed to construct trees for completely sequenced bacterial and archaeal genomes: i) presence-absence of genomes in clusters of orthologous genes; ii) conservation of local gene order (gene pairs) among prokaryotic genomes; iii) parameters of identity distribution for probable orthologs; iv) analysis of concatenated alignments of ribosomal proteins; v) comparison of trees constructed for multiple protein families. All constructed trees support the separation of the two primary prokaryotic domains, bacteria and archaea, as well as some terminal bifurcations within the bacterial and archaeal domains. Beyond these obvious groupings, the trees made with different methods appeared to differ substantially in terms of the relative contributions of phylogenetic relationships and similarities in gene repertoires caused by similar life styles and horizontal gene transfer to the tree topology. The trees based on presence-absence of genomes in orthologous clusters and the trees based on conserved gene pairs appear to be strongly affected by gene loss and horizontal gene transfer. The trees based on identity distributions for orthologs and particularly the tree made of concatenated ribosomal protein sequences seemed to carry a stronger phylogenetic signal. The latter tree supported three potential high-level bacterial clades,: i) Chlamydia-Spirochetes, ii) Thermotogales-Aquificales (bacterial hyperthermophiles), and ii) Actinomycetes-Deinococcales-Cyanobacteria. The latter group also appeared to join the low-GC Gram-positive bacteria at a deeper tree node. These new groupings of bacteria were supported by the analysis of alternative topologies in the concatenated ribosomal protein tree using the Kishino-Hasegawa test and by a census of the topologies of 132 individual groups of orthologous proteins. Additionally, the results of this analysis put into question the sister-group relationship between the two major archaeal groups, Euryarchaeota and Crenarchaeota,and suggest instead that Euryarchaeota might be a paraphyletic group with respect to Crenarchaeota. We conclude that, the extensive horizontal gene flow and lineage-specific gene loss notwithstanding, extension of phylogenetic analysis to the genome scale has the potential of uncovering deep evolutionary relationships between prokaryotic lineages.
TL;DR: The complete assembly of the entire human genome sequence by Venter et al. confirms recent estimates that the total number of human protein coding genes might be less than 30,000--a mere one-third increase over the nematode Caenorhabditis elegans.
Abstract: The complete assembly of the entire human genome sequence by
Venter
et al.
confirms recent estimates that the total number of human protein coding genes might be less than 30,000--a mere one-third increase over the nematode
Caenorhabditis elegans. Such a low gene number constitutes a paradigm change, which could drastically modify our understanding of organism complexity and evolution, as well as our current interpretation of transcriptome analyses. It may also have severe consequences on the long-term sustainability of the biomedical industry in the postgenomic era.
TL;DR: Empithelial β-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells that cluster to all known defensin genes in the human genome.
TL;DR: The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes.
Abstract: The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes. Can the draft human genome sequences help us to define the role of these elements more closely?
TL;DR: The next important challenge will be to construct saturation mutant lines for the functional analysis of all of the genes revealed by the Rice Genomic Sequencing Project in the context of the rice plant as a whole.
TL;DR: The editors of the new Annual Review of Genomics and Human Genetics aim to cover these fields in the broadest sense and this means that while few will read this book from cover to cover, there certainly is something to savour here for everybody.
Abstract: Do we need another review series now we have Nature Review Genetics, Trends in Genetics, and all the current opinion journals? Does anybody have time to read them now? Must we have another high impact journal almost every month? The answer depends as much on the reader's taste as on the way the dish is served. In this regard the annual reviews series has always been unique because of its consistent high quality and broad scope. The editors of the new Annual Review of Genomics and Human Genetics aim to cover these fields in the broadest sense and this they do. This means that while few will read this book from cover to cover, there certainly is something to savour here for everybody. In this first issue for instance, there is a fascinating account by James Crow of his personal experience with human genetics as it developed from its early beginnings with the chromosome maps of the Sturtevant and Morgan labs working on Drosophila. Crow takes us back in time so that we can experience what great skills and determination it took to make those early important discoveries. It is enlightening to see cytogenetics described as `pitiful' in the first half of the last century. But what joy it is to read about discoveries that might have been made but weren't. As Crow says: `some were overlooked, others were simply regarded as uninteresting'. There is a lesson here for all of us. Surely there must be things out there even now to discover which are not recognized because we cannot see beyond our own fixed beliefs? There is much more in this 580-page first volume. Many chapters will appeal to clinical geneticists and those working in diagnostic settings. Scholarly accounts of the genetics of trinucleotide repeat diseases, disorders of iron metabolism, Williams syndrome, newborn screening, and public concern about genetics, are examples of this. On the other hand, fundamental aspects of genetics and genomics are included also, such as estimating allele age, gene family evolution, methods for large scale analysis of sequence variation, or bioinformatic tools. Clearly, this new genomics and human genetics volume is much more appealing to human geneticists than the annual review of genetics which has been on the shelves of many human genetics department's libraries. In short: there is something here for everybody. This new series of high quality reviews can compete with the best in the field.
TL;DR: It is shown, by phylogenetic and sequence analysis, that at least 16% of these elements have undergone apparent rearrangements that may have resulted in large-scale deletions, duplications and chromosome reshuffling during the evolution of the human genome.
Abstract: Human endogenous retroviruses (HERVs), which are remnants of past retroviral infections of the germline cells of our ancestors, make up as much as 8% of the human genome and may even outnumber genes. Most HERVs seem to have entered the genome between 10 and 50 million years ago, and they comprise over 200 distinct groups and subgroups. Although repeated sequence elements such as HERVs have the potential to lead to chromosomal rearrangement through homologous recombination between distant loci, evidence for the generality of this process is lacking. To gain insight into the expansion of these elements in the genome during the course of primate evolution, we have identified 23 new members of the HERV-K (HML-2) group, which is thought to contain the most recently active members. Here we show, by phylogenetic and sequence analysis, that at least 16% of these elements have undergone apparent rearrangements that may have resulted in large-scale deletions, duplications and chromosome reshuffling during the evolution of the human genome.
TL;DR: Various experimental approaches or in silico algorithms aim at clustering proteins into networks with biological significance, including yeast two-hybrid system, which is the technology of choice to detect protein-protein interactions on a proteomic scale.
Book•
01 Jan 2001
TL;DR: The goal of this book is to demonstrate the efforts towards in-situ applicability of the proteomics and Transgenics approaches to genomics and population genetics.
Abstract: Table of Contents Chapter 1 Genes, Genomes, and Genetic Analysis Chapter 2 DNA Structure and Genetic Variation Chapter 3 Transmission Genetics: The Principle of Segregation Chapter 4 Chromosomes and Sex-Chromosome Inheritance Chapter 5 Genetic Linkage and Chromosome Mapping Chapter 6 Molecular Biology of DNA Replication and Recombination Chapter 7 Molecular Organization of Chromosomes Chapter 8 Human Karyotypes and Chromosome Behavior Chapter 9 Genetics of Bacteria and Their Viruses Chapter 10 Molecular Biology of Gene Expression Chapter 11 Molecular Mechanisms of Gene Regulation Chapter 12 Genomics, Proteomics, and Transgenics Chapter 13 Genetic Control of Development Chapter 14 Molecular Mechanisms of Mutation and DNA Repair Chapter 15 Molecular Genetics of the Cell Cycle and Cancer Chapter 16 Mitochondrial DNA and Extranuclear Inheritance Chapter 17 Molecular Evolution and Population Genetics Chapter 18 The Genetic Basis of Complex Traits Chapter 19 Human Evolutionary Genetics
TL;DR: Comparative genomic analyses suggest that loss of genes is part of the ongoing evolution of the slow-growing mycobacterial pathogens and might also explain how the vaccine strain BCG became attenuated.
TL;DR: This work focuses on gene expression analysis following exposure of plants to high salinity, using salt-shock experiments to mimic stresses that affect hydration and ion homeostasis and generates insertional mutants that affect stress tolerance in several organisms.
TL;DR: The recent results of genome-wide approaches to studying the genetic diversity of pathogenic bacteria indicate that the acquisition of DNA and the loss of genetic information are two important mechanisms that contribute to strain-specific differences in genome content.
TL;DR: The main purpose of the PEDANT genome database is to quickly disseminate well-organized information on completely sequenced and unfinished genomes and in many cases serves as the only source of exhaustive information on a given genome.
Abstract: Motivation: Enormous demand for fast and accurate analysis of biological sequences is fuelled by the pace of genome analysis efforts. There is also an acute need in reliable up-to-date genomic databases integrating both functional and structural information. Here we describe the current status of the PEDANT software system for highthroughput analysis of large biological sequence sets and the genome analysis server associated with it. Results: The principal features of PEDANT are: (i) completely automatic processing of data using a wide range of bioinformatics methods, (ii) manual refinement of annotation, (iii) automatic and manual assignment of gene products to a number of functional and structural categories, (iv) extensive hyperlinked protein reports, and (v) advanced DNA and protein viewers. The system is easily extensible and allows to include custom methods, databases, and categories with minimal or no programming effort. PEDANT is actively used as a collaborative environment to support several on-going genome sequencing projects. The main purpose of the PEDANT genome database is to quickly disseminate well-organized information on completely sequenced and unfinished genomes. It currently includes 80 genomic sequences and in many cases serves as the only source of exhaustive information on a given genome. The database also acts as a vehicle for a number of research projects in bioinformatics. Using SQL queries, it is possible to correlate a large variety of pre-computed properties of gene products encoded in complete genomes with each other and compare them with data sets of special scientific interest. In particular, the availability of structural predictions for over 300 000 genomic proteins makes PEDANT the most extensive ∗ To whom correspondence should be addressed. structural genomics resource available on the web. Availability: The PEDANT genome analysis server is available at http://pedant.mips.biochem.mpg.de. Contact: Genome sequencing centres interested in inclusion of their sequences in the PEDANT database should contact Dmitrij Frishman
TL;DR: Systems biology was assessed by examining patterns of correlations that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.
Abstract: With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.