拟南芥——一把打开植物生命奥秘大门的钥匙

在过去的20年中,拟南芥作为模式植物广泛用于植物生命科学研究。历时10年的模式植物拟南芥的全基因组测序工作于2000年完成,通过测序获得的拟南芥基因组核苷酸序列全部公布在互联网上,有力地推动了植物生命科学研究向前发展。科学家提出的“2010计划”旨在通过全世界植物科学家的努力,到2010年能够尽可能多地了解拟南芥基因的功能。通过拟南芥研究所获得的信息将有助于人类对控制不同植物复杂生命活动机制的认识。     

The human genome project--some implications of extensive "reverse genetic" medicine

Impressive progress has been made during the past several decades in understanding the pathogenesis of human genetic disease. The tools of molecular biology have allowed the isolation of many disease-related genes by forward and a few by reverse genetics, and the imminent completion of a complete human genetic linkage map will accelerate the genetic characterization of many more genetic diseases. The major impacts of the molecular characterization of human genetic diseases will be 1. To increase markedly the number of human diseases that we recognize to have major genetic components. We already understand that genetic diseases are not rare medical curiosities with negligible societal impact, but rather constitute a wide spectrum of both rare and extremely common diseases responsible for an immense amount of suffering in all human societies. The characterization of the human genome will lead to the identification of genetic factors in many more human diseases, even those that now seem too multifactorial or polygenic for ready understanding. 2. To allow the development of powerful new approaches to diagnosis, detection, screening and even therapy of these disorders aimed directly at the mutant genes rather than at the gene products. This should eventually allow much more accurate and specific management of human genetic disease and the genetic factors in many human maladies. The preparation of a fine-structure physical map of the entire human genome together with an overlapping contiguous set of clones spanning entire chromosomes or large portions of chromosomes is rapidly becoming feasible, and the information that will flow from this effort promises eventually to affect the management of many important genetic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetics of common disease: implications for therapy,screening and redefinition of disease.

Susceptibility to most common human diseases is, at least in part, determined by genetic factors. Rapid progress is being made in defining these genetic determinants for a range of diseases including breast cancer, colon cancer, diabetes, arthritis and dementia. The ability to define susceptibility in genetic terms has already led to a reclassification of some of these diseases on genetic and mechanistic grounds. This information is likely to have a profound effect on our approach to human diseases as it will allow a better definition of these disorders, permitting more effective therapeutic intervention, and will lead to both a more precise understanding of the natural history of these diseases and the possibility of identifying populations at risk. An understanding of the mechanisms underlying disease susceptibilty will also improve our ability to develop rational therapeutic interventions for many of these diseases. The role of genetic screening in these common diseases will be discussed, particularly in regard to the application of health care in populations.     

Loss of genetic diversity means loss of geological information: the endangered Japanese crayfish exhibits remarkable historical footprints

Intra-specific genetic diversity is important not only because it influences population persistence and evolutionary potential, but also because it contains past geological, climatic and environmental information. In this paper, we show unusually clear genetic structure of the endangered Japanese crayfish that, as a sedentary species, provides many insights into lesser-known past environments in northern Japan. Over the native range, most populations consisted of unique 16S mtDNA haplotypes, resulting in significant genetic divergence (overall F _ST = 0.96). Owing to the simple and clear structure, a new graphic approach unraveled a detailed evolutionary history; regional crayfish populations were comprised of two distinct lineages that had experienced contrasting demographic processes (i.e. rapid expansion vs. slow stepwise range expansion) following differential drainage topologies and past climate events. Nuclear DNA sequences also showed deep separation between the lineages. Current ocean barriers to dispersal did not significantly affect the genetic structure of the freshwater crayfish, indicating the formation of relatively recent land bridges. This study provides one of the best examples of how phylogeographic analysis can unravel a detailed evolutionary history of a species and how this history contributes to the understanding of the past environment in the region. Ongoing local extinctions of the crayfish lead not only to loss of biodiversity but also to the loss of a significant information regarding past geological and climatic events.     

Comparative genetic diversity in a sample of pony breeds from the U.K. and North America: a case study in the conservation of global genetic resources

Most species exist as subdivided ex situ daughter population(s) derived from a single original group of individuals. Such subdivision occurs for many reasons both natural and manmade. Traditional British and Irish pony breeds were introduced to North America (U.S.A. and Canada) within the last 150 years, and subsequently equivalent breed societies were established. We have analyzed selected U.K. and North American equivalent pony populations as a case study for understanding the relationship between putative source and derived subpopulations. Diversity was measured using mitochondrial DNA and a panel of microsatellite markers. Genetic signatures differed between the North American subpopulations according to historical management processes. Founder effect and stochastic drift was apparent, particularly pronounced in some breeds, with evidence of admixture of imported mares of different North American breeds. This demonstrates the importance of analysis of subpopulations to facilitate understanding the genetic effects of past management practices and to lead to informed future conservation strategies.     

The national DBS brain tissue network pilot study: need for more tissue and more standardization

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51?C92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.     

Genomics: Applications,Challenges, and Opportunities for the U.S. Environmental Protection Agency

Genomics information has great potential to enhance assessment of risks to human health and the environment. Although understanding genomic responses with respect to adverse ecological and human health outcomes is not, as yet, established, it is important to consider the likely future impacts of genomics technologies on risk assessment and decision-making. Four areas are identified as those likely to be influenced by the generation of genomics information within, and the submission of such information to, the U.S. Environmental Protection Agency (USEPA): risk assessment, prioritization of contaminants and contaminated sites, monitoring, and reporting provisions. For each of these risk assessment and regulatory applications, representative activities are presented to illustrate the application. Three major challenges for the USEPA associated with genomics are also identified in the areas of research, technical development, and capacity. The USEPA's initial activities to address these challenges are discussed. The Agency recognizes it must be prepared to use genomics information, and that many scientific, policy, ethical, and legal concerns will need to be addressed. The USEPA also recognizes it is essential to continue to collaborate with other federal agencies, academia, the regulated community, and other stakeholders in order to benefit from ongoing advances in genomics in the wider scientific and regulatory communities.     

Independent Isolates of the Emerging Subgroup J Avian Leukosis Virus Derive from a Common Ancestor

A new subgroup of avian leukosis virus (ALV) that includes a unique env gene, designated J, was identified recently in England. Sequence analysis of prototype English isolate HPRS-103 revealed several other unique genetic characteristics of this strain and provided information that it arose by recombination between exogenous and endogenous virus sequences. In the past several years, ALV J type viruses (ALV-J) have been isolated from broiler breeder flocks in the United States. We were interested in determining the relationship between the U.S. and English isolates of ALV-J. Based on sequence data from two independently derived U.S. field isolates, we conclude that the U.S. and English isolates of ALV-J derive from a common ancestor and are not the result of independent recombination events.     

DNA and recent human evolution

The study of recent human evolution, or the origin of modern humans, is currently dominated by two theories. The recent African origin hypothesis holds that there was a single origin of modern humans in Africa about 100,000 years ago, after which these humans dispersed throughout the rest of the world, mixing little or not at all with nonmodern populations. The multiregional evolution hypothesis holds that there was no single origin of modern humans but, instead, that the mutations and other traits that led to modern humans were spread in concert throughout the old world by gene flow, leading to genetic continuity among old world populations during the past million years. Although both of these theories are based on observations stemming from the fossil record, much discussion and controversy during the past six years has focused on the application and interpretation of studies of DNA variation, particularly mitochondrial DNA (mtDNA). The past year, especially, has brought new data, interpretations, and controversies. Indeed, I initially resisted writing this review, on the grounds that new information would be likely to render it obsolete by the time it was published. However, now that the dust is starting to settle, it seems timely to review various investigations and interpretations and where they are likely to lead. While the focus of this review is the mtDNA story, brief mention is made of studies of nuclear DNA variation (both autosomal and Y-chromosome DNA) and the implications of the genetic data with regard to the fossil record and our understanding of recent human evolution.     

Minimal information about T cell assays: the process of reaching the community of T cell immunologists in cancer and beyond

Many assays to evaluate the nature, breadth, and quality of antigen-specific T cell responses are currently applied in human medicine. In most cases, assay-related protocols are developed on an individual laboratory basis, resulting in a large number of different protocols being applied worldwide. Together with the inherent complexity of cellular assays, this leads to unnecessary limitations in the ability to compare results generated across institutions. Over the past few years a number of critical assay parameters have been identified which influence test performance irrespective of protocol, material, and reagents used. Describing these critical factors as an integral part of any published report will both facilitate the comparison of data generated across institutions and lead to improvements in the assays themselves. To this end, the Minimal Information About T Cell Assays (MIATA) project was initiated. The objective of MIATA is to achieve a broad consensus on which T cell assay parameters should be reported in scientific publications and to propose a mechanism for reporting these in a systematic manner. To add maximum value for the scientific community, a step-wise, open, and field-spanning approach has been taken to achieve technical precision, user-friendliness, adequate incorporation of concerns, and high acceptance among peers. Here, we describe the past, present, and future perspectives of the MIATA project. We suggest that the approach taken can be generically applied to projects in which a broad consensus has to be reached among scientists working in fragmented fields, such as immunology. An additional objective of this undertaking is to engage the broader scientific community to comment on MIATA and to become an active participant in the project.     

Genetic discrimination in insurance and employment

The results of the Human Genome project will eventually have a great impact on medicine. However, the expansion of genetic testing due to these results exacerbates ethical, legal, and economic problems related to the project even today. Virtually free access to the data of testing would present an encroachment on personal freedom, since it may lead to discrimination based on genetic characteristics, i.e., genetic discrimination. Examples of this discrimination are already known; they include unsubstantiated refusals to employ carriers of certain alleles and denials of life or health insurance coverage and the ability to adopt a child. The use of genetic information in the insurance and employment fields is of primary concern due to its economic importance. Consumers consider genetic discrimination in these areas to be intolerable moral and social injustice. Genetic discrimination may eventually lead to the formation of a class of people who cannot buy an insurance policy, and, in the employment field, rejection of persons with "undesirable" genes infringes on citizens' rights to equal opportunity. However, selection for genetic characteristics in employment is justified if these characteristics determine sensitivity to occupational hazards.     

Interphase cytogenetics

Conclusion Interphase cytogenetics is still in its infancy but the information which it is capable of providing will lead to a greater understanding not only of the normal interphase nucleus but also of the genetic content of tumor cells and will facilitate antenatal diagnosis of some hereditary diseases. Application to tumors will provide the ability to correlate chromosome complement (and ultimately single gene content) with tissue morphology and clinical tumor behaviour, perhaps providing prognostic information. We anticipate that this approach will give clues to consistent genetic abnormalities within tumors which can unambiguously be assigned to malignant as opposed to the normal stromal cell content of the tumor.Special issue dedicated to Dr. Sidney Udenfriend     

Genetics of rheumatoid arthritis: confronting complexity

The genetic basis for rheumatoid arthritis (RA) is likely to be extremely complex. Even the role of MHC genes remains to be fully defined, and may involve interactive genetic effects. The difficulty of precisely defining the clinical phenotype, as well as underlying genetic heterogeneity, complicates the problem. In addition, stochastic genetic or physiologic events may contribute to the low penetrance of susceptibility genes. This situation parallels developing paradigms for other autoimmune disorders, in which many different genes each appear to contribute a small amount to overall risk for disease, and where severity and specific phenotypic subtypes are subject to genetic effects. The completion of the human genome project, along with advances in informatics, will be required to reach a deeper understanding of RA. It is likely that this will involve an iterative and interactive process between several different scientific disciplines.     

The impact of future research on our understanding of parasitism

Future developments in science cannot be foreseen with any accuracy as they depend on ideas which cannot be predicted. The immediate future, like the recent past, will be very much dictated by technological developments but exploitation of these developments may be limited to a select few. Parasitologists must advertise discoveries of potential fundamental biological significance in order to attract new recruits to the discipline and maintain its scientific vigour. Our understanding of the nature of parasitism will ultimately depend upon the characterization of the genetic dependence of parasites on their hosts.     

Exploring Complex Ornamental Genomes: The Rose as a Model Plant

Despite its high economic importance, little is known about rose genetics, genome structure, and the function of rose genes. Reasons for this lack of information are polyploidy in most cultivars, simple breeding strategies, high turnover rates for cultivars, and little public funding. Molecular and biotechnological tools developed during the genomics era now provide the means to fill this gap. This will be facilitated by a number of model traits as e.g., a small genome, a large genetic diversity including diploid genotypes, a comparatively short generation time and protocols for genetic engineering. A deeper understanding of genetic processes and the structure of the rose genome will serve several purposes: Applications to the breeding process including marker-assisted selection and direct manipulation of relevant traits via genetic engineering will lead to improved cultivars with new combinations of characters. In basic research, unique characters, e.g., the biosynthesis and emission of particular secondary metabolites will provide new information not available in model species. Furthermore comparative genomics will link information about the rose genome to ongoing projects on other rosaceous crops and will add to our knowledge about genome evolution and speciation. This review is intended as a presentation and is the compilation of the current knowledge on rose genetics and genomics, including functional genomics and genetic engineering. Furthermore, it is intended to show ways how knowledge on rose genetics and genomics can be linked to other species in the Rosaceae in order to utilize this information across genera.     

Progress and promise in understanding the genetic basis of common diseases

Susceptibility to common human diseases is influenced by both genetic and environmental factors. The explosive growth of genetic data, and the knowledge that it is generating, are transforming our biological understanding of these diseases. In this review, we describe the technological and analytical advances that have enabled genome-wide association studies to be successful in identifying a large number of genetic variants robustly associated with common disease. We examine the biological insights that these genetic associations are beginning to produce, from functional mechanisms involving individual genes to biological pathways linking associated genes, and the identification of functional annotations, some of which are cell-type-specific, enriched in disease associations. Although most efforts have focused on identifying and interpreting genetic variants that are irrefutably associated with disease, it is increasingly clear that—even at large sample sizes—these represent only the tip of the iceberg of genetic signal, motivating polygenic analyses that consider the effects of genetic variants throughout the genome, including modest effects that are not individually statistically significant. As data from an increasingly large number of diseases and traits are analysed, pleiotropic effects (defined as genetic loci affecting multiple phenotypes) can help integrate our biological understanding. Looking forward, the next generation of population-scale data resources, linking genomic information with health outcomes, will lead to another step-change in our ability to understand, and treat, common diseases.     

The Tomato Sequencing Project, the first cornerstone of the International Solanaceae Project (SOL)

The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, The Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the ‘International Solanaceae Genome Project (SOL): Systems Approach to Diversity and Adaptation’. The goal of this grassroots initiative, launched in November 2003, is to establish a network of information, resources and scientists to ultimately tackle two of the most significant questions in plant biology and agriculture: (1) How can a common set of genes/proteins give rise to a wide range of morphologically and ecologically distinct organisms that occupy our planet? (2) How can a deeper understanding of the genetic basis of plant diversity be harnessed to better meet the needs of society in an environmentally friendly and sustainable manner? The Solanaceae and closely related species such as coffee, which are included in the scope of the SOL project, are ideally suited to address both of these questions. The first step of the SOL project is to use an ordered BAC approach to generate a high quality sequence for the euchromatic portions of the tomato as a reference for the Solanaceae. Due to the high level of macro and micro-synteny in the Solanaceae the BAC-by-BAC tomato sequence will form the framework for shotgun sequencing of other species. The starting point for sequencing the genome is BACs anchored to the genetic map by overgo hybridization and AFLP technology. The overgos are derived from approximately 1500 markers from the tomato high density F2-2000 genetic map (http://sgn.cornell.edu/). These seed BACs will be used as anchors from which to radiate the tiling path using BAC end sequence data. Annotation will be performed according to SOL project guidelines. All the information generated under the SOL umbrella will be made available in a comprehensive website. The information will be interlinked with the ultimate goal that the comparative biology of the Solanaceae—and beyond—achieves a context that will facilitate a systems biology approach.     

Framework for Human Health Risk Assessment

The U.S. Environmental Protection Agency has recognized the need to develop a framework for human health risk assessment that puts a perspective on the approaches in practice throughout the Agency. In response, the Agency's Risk Assessment Forum has begun the long-term process of developing a framework for human health risk assessment. The framework will be a communication piece that will lay out the scientific basis, principles, and policy choices underlying past and current risk assessment approaches and will provide recommendations for integrating/harmonizing risk assessment methodologies for all human health endpoints.