An analysis of the spectra of genetic activity produced by known or suspected human carcinogens

For 24 agents classified by the International Agency for Research on Cancer as known or suspected human carcinogens, we previously catalogued the qualitative genetic bioassay data available in the literature. In the present analysis, dose information, where available, was added to this data base: either the lowest effective dose (LED) or the highest ineffective dose (HID) was recorded for each agent and bioassay system. Bioassay systems were organized according to classes of genetic activity and subdivided by the phylogenetic level of the test organism. For each compound, the quantitative results in the test systems were represented by computer-generated bar graphs ('genetic activity spectra'). The x-axis unit values corresponded to the 100 different test systems, and the y-axis values were the logarithmically transformed LED or HID values. Statistical methods and pattern-recognition techniques were used to evaluate the genetic activity spectra. Spectra were compared among agents grouped according to target-organ specificity. In addition, the spectra of all possible pairs of compounds were compared to identify compounds displaying qualitatively or quantitatively similar genetic activity. Chemically similar compounds frequently produced similar spectra of genetic activity, and it was possible to identify the most appropriate test systems for some classes of compounds. As the data base for human carcinogens is enlarged, analysis of genetic activity spectra may contribute to our understanding of the structure-activity relationships and mechanisms of action of these agents.     

Study of the genetic code adaptability by means of a genetic algorithm

We used simulated evolution to study the adaptability level of the canonical genetic code. An adapted genetic algorithm (GA) searches for optimal hypothetical codes. Adaptability is measured as the average variation of the hydrophobicity that the encoded amino acids undergo when errors or mutations are present in the codons of the hypothetical codes. Different types of mutations and point mutation rates that depend on codon base number are considered in this study. Previous works have used statistical approaches based on randomly generated alternative codes or have used local search techniques to determine an optimum value. In this work, we emphasize what can be concluded from the use of simulated evolution considering the results of previous works. The GA provides more information about the difficulty of the evolution of codes, without contradicting previous studies using statistical or engineering approaches. The GA also shows that, within the coevolution theory, the third base clearly improves the adaptability of the current genetic code.     

系统生物科学与工程的高科技产业化

系统生物科学最早开创于贝塔郎菲的理论生物学和一般系统论。系统生物科学或生物系统科学研究分子、细胞、器官和群体各层次的生物系统,尤其是心智和遗传的信息系统。系统生物工程(曾邦哲1994年)采用实验分析和系统逻辑的双重方法论,探索改造和仿造生物系统的工程技术,包括:1)生化工程、生态工程,2)生物反应器、遗传工程,3)高分子传感器、仿生工程,4)生物遗传计算、智能工程等领域,将促进系统医学、转基因生物反应器、生物计算机、智能机器人和中医药现代化的发展。现代城市生态、工业网络的系统藕合、循环、再生的无污染、无烟化工业生态工程将带来自然、工业、人文之间的和谐。     

GENEVIEW and the DNACE data bus: computational tools for analysis, display and exchange of genetic information.

We describe an interactive computational tool, GENEVIEW, that allows the scientist to retrieve, analyze, display and exchange genetic information. The scientist may request a display of information from a GenBank locus, request that a restriction map be computed, stored and superimposed on GenBank information, and interactively view this information. GENEVIEW provides an interface between the GenBank data base and the programs of the Lilly DNA Computing Environment (DNACE). This interface stores genetic information in a simple, free format that has become the universal convention of DNACE; this format will serve as the convention for all future software development at Eli Lilly and Company, and could serve as a convention for genetic information exchange.     

IMGT, the international ImMunoGeneTics database

IMGT, the international ImMunoGeneTics database, freely available at http://imgt.cines.fr:8104, was created in 1989 at the Université Montpellier II, CNRS, Montpellier, France, and is a high quality integrated information system specialising in immunoglobulins, T cell receptors and major histocompatibility complex molecules of human and other vertebrates. IMGT provides researchers and clinicians with a common access to all nucleotide, protein, genetic and structural immunogenetics data. This information is of high value for medical and veterinary research, biotechnology related to antibody and T cell receptor engineering, genome diversity and evolution studies of the immune response.     

Information analysis of Fis binding sites.

Originally discovered in the bacteriophage Mu DNA inversion system gin, Fis (Factor for Inversion Stimulation) regulates many genetic systems. To determine the base frequency conservation required for Fis to locate its binding sites, we collected a set of 60 experimentally defined wild-type Fis DNA binding sequences. The sequence logo for Fis binding sites showed the significance and likely kinds of base contacts, and these are consistent with available experimental data. Scanning with an information theory based weight matrix within fis, nrd, tgt/sec and gin revealed Fis sites not previously identified, but for which there are published footprinting and biochemical data. DNA mobility shift experiments showed that a site predicted to be 11 bases from the proximal Salmonella typhimurium hin site and a site predicted to be 7 bases from the proximal P1 cin site are bound by Fis in vitro. Two predicted sites separated by 11 bp found within the nrd promoter region, and one in the tgt/sec promoter, were also confirmed by gel shift analysis. A sequence in aldB previously reported to be a Fis site, for which information theory predicts no site, did not shift. These results demonstrate that information analysis is useful for predicting Fis DNA binding.     

Cloning simulation in the cage environment.

The CAGE/GEM(TM) software toolkit for genetic engineering is briefly described. The system functionally uses color graphics and is menu driven. It integrates genetics and features information ("Overlays") with information based on sequence analysis ("Representations"). The system is structured around CAD (Computer Aided Design) principles. The CAGE (Computer Aided Genetic Engineering) aspects of the software are emphasized and illustrated by a simulated cloning of the hepatitis B core antigen gene into the BAMHI site of plasmid pBR322.     

辣椒抗病基因工程研究进展(综述)

辣椒易发生由细菌、真菌和病毒等引致的病害,基因工程技术为辣椒抗病育种开辟了新途径。本文就晚近以离体再生植株和转基因技术等为基础的辣椒抗病基因工程研究进展进行综述。     

Medical data base system with an ability of automated diagnosis.

We carried out an experiment on a medical information system in which a clinical data base is combined organically with computer programs for automated diagnosis. In this system, the parameters for automated diagnosis are devised to be renewed as the contents of the data base (patient's information) increase. This system can be regarded as a data base possessing a kind of diagnosing ability which grows up with time. We have named this system "Intelligent Data Base". The algorithm for computer diagnosis used in this study is based on maximum likelihood method, and each likelihood is weighted with a prior probability of each disease. The discrimination efficiency of this method is logically equal to that of the Bayes rule. First 27 cases were learnt by the system and correct diagnosis was obtained in 78% of the cases. When cases for learning increased to 82, the percentage of correct diagnosis was improved to 95%.     

Base excision repair of DNA: glycosylases

The review considers the role of base excision repair in maintaining the constancy of genetic information in the cell. The genetic control and biochemical mechanism are described for the first stage of base excision repair, which is catalyzed by specific enzymes, DNA glycosylases.     

Automating data manipulation for genetic analysis using a data base management system

Inefficient coding and manipulation of pedigree data have often hindered the progress of genetic studies. In this paper we present the methodology for interfacing a data base management system (DBMS) called MEGADATS with a linkage analysis program called LIPED. Two families that segregate a dominant trait and one test marker were used in a simulated exercise to demonstrate how a DBMS can be used to automate tedious clerical steps and improve the efficiency of a genetic analysis. The merits of this approach to data management are discussed. We conclude that a standardized format for genetic analysis programs would greatly facilitate data analysis.     

Taming plastids for a green future

Plant genetic engineering will probably contribute to the required continued increase in agricultural productivity during the coming decades, and moreover, plants can potentially provide inexpensive production platforms for pharmaceuticals and nutraceuticals. With the advent of technologies for altering the genetic information inside chloroplasts, a new attractive target for genetic engineering has become available to biotechnologists. Potential advantages over conventional nuclear transformation include high transgene expression levels and increased biosafety because of maternal organelle inheritance in most crops. This review summarizes the state of the art in chloroplast genetic engineering and describes how reverse genetics approaches enhance our understanding of photosynthesis and other important chloroplast functions. Furthermore, promising strategies by which chloroplast genetic engineering might contribute to the successful modification of plant metabolism are discussed.     

质体基因工程中选择标记基因研究进展

与细胞核基因工程相比,质体基因工程能更安全、精确和高效地对外源基因进行表达,作为下一代转基因技术已广泛用于基础研究和生物技术应用领域。与细胞核基因工程一样,质体基因工程中也需要合适的选择标记基因用于转化子的筛选和同质化,但基于质体基因组的多拷贝性和母系遗传特点,转化子的同质化需要一个长期的筛选过程,这就决定了质体基因工程中选择标记基因的选择标准将不同于细胞核基因工程中广泛使用的现行标准。目前,质体基因工程的遗传转化操作中使用较多的是抗生素选择标记基因,出于安全性考虑,需要找到可替换、安全的选择标记基因或有效的标记基因删除方法。本文在对质体基因工程研究的相关文献分析基础之上,对主要使用的选择标记基因及其删除体系进行了综述,并对比了其优缺点,同时探讨了质体基因工程中所使用的报告基因,以期为现有选择标记基因及其删除体系的改进和开发提供一定参考,进一步推动质体基因工程,尤其是单子叶植物质体基因工程的发展。     

Some theoretical aspects of reprogramming the standard genetic code

Reprogramming of the standard genetic code to include non-canonical amino acids (ncAAs) opens new prospects for medicine, industry, and biotechnology. There are several methods of code engineering, which allow us for storing new genetic information in DNA sequences and producing proteins with new properties. Here, we provided a theoretical background for the optimal genetic code expansion, which may find application in the experimental design of the genetic code. We assumed that the expanded genetic code includes both canonical and non-canonical information stored in 64 classical codons. What is more, the new coding system is robust to point mutations and minimizes the possibility of reversion from the new to old information. In order to find such codes, we applied graph theory to analyze the properties of optimal codon sets. We presented the formal procedure in finding the optimal codes with various number of vacant codons that could be assigned to new amino acids. Finally, we discussed the optimal number of the newly incorporated ncAAs and also the optimal size of codon groups that can be assigned to ncAAs.     

Genetic and environmental factors in complex diseases: the older Finnish Twin Cohort.

In studies on the Finnish Twin Cohort, we investigate genetic and environmental determinants of common, complex diseases, and their behavioral risk factors in Finland, a genetically unique and culturally homogenous population. We have formed the following databases: 1) Like-sexed twin pairs (13,888 pairs of known zygosity) form the older Twin Cohort. They have participated since 1975 in mail surveys, in clinical examinations for subsamples, and have been followed-up for morbidity using national medical registers; 2) The older Twin Cohort was expanded in 1996 to include opposite-sex pairs born 1938-1957 (c. 8000 pairs); 3) Two, new longitudinal studies of adolescent twins and their families, form a complementary, ongoing study base described in more detail in an accompanying article. Genetic and environmental effects vary over the life-span, and only longitudinal studies in genetically informative data sets permits the evaluation of such effects. Finally, the inclusion of DNA-based genetic information in a phenotypically rich family data base will offer a unique resource for research in genetic epidemiology and behavioral medicine.     

Quantitative Genetic Variation in Body Size of Mice from New Mutations

To measure the amount of new genetic variation in 6-week weight of mice arising each generation from mutation, selection lines derived from an initially inbred strain were maintained for 25 generations. An analysis using an animal model with restricted maximum likelihood was applied to estimate a mutational genetic component of variance for the infinitesimal model of many genes of small effect. Assuming that the inbred base population was at a mutation-drift equilibrium, it is estimated that the heritability for body size has increased by 1.0% per generation, with lower and upper confidence limits of 0.6% and 1.6%, respectively. A model which includes a mutational genetic component of variance fits the data much better than one involving only base population genetic variance. A model with no genetic component fits the data very poorly. An environmental covariance of body size of mother and offspring was included in the model and accounts for 10% of the variance. By using information only from the observed response to selection, the estimated increase in heritability from mutation is 0.3% per generation. These values are higher than published estimates for the increase in variance from spontaneous mutations in bristle traits of Drosophila, for which there are extensive data, but similar to estimates for various skeletal traits in mice.     

高等植物叶绿体基因工程

叶绿体基因工程作为一项新技术具有一系列传统核基因工程所不具备的优点,在基础性及应用性研究中极具吸引力,已经成功应用于了解质体基因组,调控植物代谢系统,农作物抗旱、抗虫、抗病、抗除草剂及以植物为生物反应器生产抗体、疫苗等方面的研究。本文主要介绍叶绿体基因工程的原理、操作体系及其在高等植物中的应用。     

Chinese sorghum genetic resources

In its long period of evolution and cultivation, Chinese sorghums have formed a rich genetic base in which unique characteristics have evolved. These resources and their characteristics have been identified and partially utilized within China’s breeding programs. Records and data have been compiled and updated into theAnnuals of Chinese Sorghum Varieties, Catalogue of Chinese Sorghum Variety Resources. These evaluations and recorded information provide a solid base from which further studies and utilization of this important source of genetic diversity can take place in the future.     

Genetic steady-state under BLUP selection for an infinite and homogeneous population with discrete generations

A matrix derivation is proposed to analytically calculate the asymptotic genetic variance-covariance matrix under BLUP selection according to the initial genetic parameters in a large population with discrete generations. The asymptotic genetic evolution of a homogeneous population with discrete generations is calculated for a selection operating on an index including all information (pedigree and records) from a non-inbred and unselected base population (BLUP selection) or on an index restricted to records of a few ancestral generations. Under the first hypothesis, the prediction error variance of the selection index is independent of selection and is calculated from the genetic parameters of the base population. Under the second hypothesis, the prediction error variance depends on selection. Furthermore, records of several generations of ancestors of the candidates for selection must be used to maintain a constant prediction error variance over time. The number of ancestral generations needed depends on the population structure and on the occurrence of fixed effects. Without fixed effects to estimate, accounting for two generations of ancestors is sufficient to estimate the asymptotic prediction error variance. The amassing of information from an unselected base population proves to be important in order not to overestimate the asymptotic genetic gains and not to underestimate the asymptotic genetic variances.