Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic tools”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

Evolution and ecology of spider coloration.

Genetic color variation provides a tangible link between the external phenotype of an organism and its underlying genetic determination and thus furnishes a tractable system with which to explore fundamental evolutionary phenomena. Here we examine the basis of color variation in spiders and its evolutionary and ecological implications. Reversible color changes, resulting from several mechanisms, are surprisingly widespread in the group and must be distinguished from true genetic variation for color to be used as an evolutionary tool. Genetic polymorphism occurs in a large number of families and is frequently sex limited: Sex linkage has not yet been demonstrated, nor have the forces promoting sex limitation been elucidated. It is argued that the production of color is metabolically costly and is principally maintained by the action of sight-hunting predators. Key avenues for future research are suggested.

Journal Article↗

Dishevelled is a component of the frizzled signaling pathway in Drosophila.

The tissue polarity genes in Drosophila are required to coordinate cell polarity within the plane of the epidermis. Evidence to date suggests that these genes may encode components of a novel signal transduction pathway. Three of the genes, frizzled (fz), dishevelled (dsh), and prickle (pk) share a similar tissue polarity phenotype, suggesting that they function together in a single process. dsh is also known to function as a mediator of wingless (wg) signaling in a variety of developmental patterning processes in the fly. In this study, we make use of a fz transgene and a hypomorphic fz allele as genetic tools in an attempt to order these genes in a genetic hierarchy. Our results argue that dsh encodes a dosage sensitive component required for fz function and that it likely acts downstream of fz in the generation of tissue polarity. Our findings suggest that dsh may have a general role in signal transduction, perhaps as a component of a receptor complex.

Adaptor Proteins, Signal Transducing↗

Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins.

The fruit fly Drosophila melanogaster is a powerful genetic model organism, which has been instrumental in the determination of essential developmental and neurological pathways conserved from invertebrates to humans. With the completion of both the human and Drosophila genomes, the revelation that we are more similar to this simple organism than previously suspected was realised. 75% of human genetic disease genes have clear homologues in the fly. By utilising an array of genetic tools available to disrupt or misexpress these proteins, it is now feasible to perform large-scale genetic screens in Drosophila to identify other members of a particular human genetic pathway. This review outlines some of the reasons Drosophila is a useful tool for the discovery of therapeutic targets, covers some of the tools available to manipulate this organism and discusses specific examples of how to use Drosophila as a genetic test tube for revealing proteins which act in a common pathway.

Animals↗

Targeted mutagenesis: analysis of phenotype without germ line transmission.

The available techniques for directed gene manipulation in the mouse are unprecedented in any multicellular organism and make the mouse an invaluable tool for unraveling all aspects of mammalian biology. To realize fully the potential of these genetic tools requires that phenotypic analysis be efficient, rapid, and complete. Genetic chimeras and mosaics, in which mutant cells are mixed with wild-type cells, can be used to augment standard analysis of intact mutant animals and alleviate the time required and the expense involved in generating and maintaining multiple strains of mutant mice.

Animals↗

The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen.

The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, has an unusual genome comprised of a linear chromosome and the largest plasmid complement of any characterized bacterium. Certain plasmid-encoded elements are required for virulence and viability, both in vitro and in vivo. The genetic tools to manipulate B. burgdorferi are sufficiently developed for precise molecular genetic investigations. B. burgdorferi now represents a prime system with which to address basic questions of plasmid biology and plasmid contributions to bacterial virulence and disease pathogenesis.

Animals↗

Improved tagging strategy for protein identification in mammalian cells.

BACKGROUND: The tagging strategy enables full-length endogenous proteins in mammalian cells to be expressed as green fluorescent fusion proteins from their authentic promoters. RESULTS: We describe improved genetic tools to facilitate protein tagging in mammalian cells based on a mobile genetic element that harbors an artificial exon encoding a protein tag. Insertion of the artificial exon within introns of cellular genes results in expression of hybrid proteins consisting of the tag sequence fused in-frame to sequences of a cellular protein. We have used lentiviral vectors to stably introduce enhanced green fluorescent protein (EGFP) tags into expressed genes in target cells. The data obtained indicate that this strategy leads to bona fide tripartite fusion proteins and that the EGFP tag did not affect the subcellular localization of such proteins. CONCLUSION: The tools presented here have the potential for protein discovery, and subsequent investigation of their subcellular distribution and role(s) under defined physiological conditions, as well as for protein purification and protein-protein interaction studies.

Animals↗

Periplasmic SacB as a robust counter-selection tool for genome engineering in the polyploid bacterium Zymomonas mobilis.

UNLABELLED: The alpha-proteobacterium Zymomonas mobilis exhibits exceptional ethanologenic physiology, which makes it a traditional alcoholic beverage producer and a promising chassis for biofuel production. Although genetic tools for this organism have expanded in recent years, a fundamental aspect of its chromosome organization remains to be understood. In particular, Z. mobilis has been suggested to exhibit polyploidy, but this feature is not fully confirmed because of discrepancies among studies reporting the copy number of chromosomes. Here, we tagged the chromosome-partitioning protein ParB with a fluorescent marker to visualize its cellular localization and estimate chromosome copy number in individual cells. Imaging showed that Z. mobilis exhibits several distinctive ParB foci throughout the cytoplasm and an accumulated focus at the pole, indicating that a single Z. mobilis cell contains >5 copies of the chromosome at the oriC regions. We then sought to establish an efficient counter-selection system, which is crucial for engineering multiple copies of the chromosome. We assessed the efficacy of levan-sucrase (SacB) toxicity in Z. mobilis. We found that, despite Z. mobilis secreting a native extracellular sucrase SacB, heterologous periplasmically localized Bacillus subtilis SacB rendered Z. mobilis cells sensitive to sucrose. We successfully used this effect for counter-selection when deleting and inserting targeted DNA sequences into the Z. mobilis genome. Together, this work provides important insights and tools for advancing Z. mobilis genetics and its biotechnological applications. IMPORTANCE: Zymomonas mobilis is a promising industrial bacterium with the capacity to convert sugars into ethanol at nearly maximum theoretical yield. With its expanding use in industrial applications, it is crucial to clarify if individual Z. mobilis cells carry multiple copies of the chromosome, as this has important implications for genome engineering. Two previous studies have used quantitative PCR to address this question, but their reported chromosome copy numbers varied widely from 20 to 100. Here, we used a cell biological approach to estimate the copy number and confirmed that a single Z. mobilis cell possesses multiple copies. In addition, we show that a SacB-based counter-selection works in Z. mobilis, enabling efficient and complete mutation of all chromosome copies.

Zymomonas↗

Genetic resources for the neonatologist.

Diagnosing genetic disorders and counselling the parents of babies with possible genetic conditions takes up a significant proportion of a neonatologist's clinical time. This article provides a guide to establishing genetic tools and a reference library on a neonatal unit. The availability of good resources may heighten staff awareness of genetic aetiologies in babies with subtle features, and enable possible diagnoses to be considered and a genetics consultation sought. In addition, when a diagnosis is made, information is then readily available to guide the neonatologist in his or her consultations with parents. It is not intended that the tools outlined here should be a replacement for the genetics consultation; their role is merely to facilitate the interaction of neonatologists with geneticists, to the benefit of the parents and the baby.

Databases, Genetic↗

[Genetic engineering in plants].

Until recent years, plant genetic was involved in heredity studies through the analysis of segregations in progenies after crossing. New potentiality arose as genetic tools with the use of dissociated plant elements, transforming and cultivating them in vitro. When plants are regenerated from manipulated tissues, new structures of varieties (clones) new genotypes (transgenic plants) and new regulations of genes expression (vitrovariants) open new ways for plant genetic engineering. Progressively these technological tools are integrated in the methods of plant breeding. Yet all possible consequences of these new types of heredity and of these new genetic structures must be evaluated. As first priority the analysis of possible incidences in the field of food, nutrition and health gives the basis for diagnostics and organisations aiming to avoid the release of genotypes which could have unwanted effects.

Biotechnology↗

Molecular tools for breeding basidiomycetes.

The industrial production of edible basidiomycetes is increasing every year as a response to the increasing public demand of them because of their nutritional properties. About a dozen of fungal species can be currently produced for food with sound industrial and economic bases. Notwithstanding, this production is threatened by biotic and abiotic factors that make it necessary to improve the fungal strains currently used in industry. Breeding of edible basidiomycetes, however, has been mainly empirical and slow since the genetic tools useful in the selection of the new genetic material to be introduced in the commercial strains have not been developed for these fungi as it was for other organisms. In this review we will discuss the main genetic factors that should be considered to develop breeding approaches and tools for higher basidiomycetes. These factors are (i) the genetic system controlling fungal mating; (ii) the genomic structure and organisation of these fungi; and (iii) the identification of genes involved in the control of quantitative traits. We will discuss the weight of these factors using the oyster mushroom Pleurotus ostreatus as a model organism for most of the edible fungi cultivated industrially.

Alleles↗

Development of the zebrafish lateral line.

The lateral line system is simple (comprising six cell types), its sense organs form according to a defined and reproducible pattern, and its neurons are easily visualized. In the zebrafish, these advantages can be combined with a wealth of genetic tools, making this system ideally suited to a combined molecular, cellular and genetic analysis. Recent progress has taken advantage of these various qualities to elucidate the mechanism that drives the migration from head to tail of the sense organ precursor cells, and to approach the questions surrounding axonal guidance and target recognition.

Animals↗

Fluorescent labelling of intracellular bacteria in living host cells.

The fluorescent reagent, CellTracker, labels metabolically-active cells and was used here to label Chlamydia in vivo during their exponential phase of growth in infected cells. HeLa cells infected with C. psittaci were labelled with the CellTracker reagents between 15 and 48 h post-infection. The fluorescent label accumulated in the host-cell membrane compartment (inclusion) within which Chlamydia reside and replicate, and was also incorporated by the bacteria. Labelling with the CellTracker affected neither the growth nor the differentiation of the chlamydiae, and labelled chlamydiae isolated from infected cells were infectious. Our results demonstrate that the CellTracker could become a valuable tool for in vivo labelling of obligate intracellular parasites for which no genetic tools exist.

Bacterial Adhesion↗

Genetic transformation of the fungal pathogen responsible for rice blast disease.

The analysis of complex genetic determinants that control the ability of a fungus to colonize its host has been impaired by the lack of sophisticated genetic tools for characterizing important pathogens. We have developed a system for the genetic transformation of Magnaporthe grisea, the causal agent of rice blast disease, to overcome this limitation. A M. grisea arginine auxotroph was shown to contain a mutation (arg3-12) that abolishes ornithine carbamoyltransferase activity. M. grisea strains that contain arg3-12 were used as recipients in transformation experiments with plasmid pMA2, which carries the ArgB(+) gene from Aspergillus nidulans. Stable prototrophic transformants arose at a frequency of about 35 per microgram of plasmid DNA. Integration of single or multiple plasmid copies occurred at a single site in the genome of each transformant; rearrangements were often created during integration. When M. grisea genomic segments were incorporated into pMA2, the presence of any one of five different M. grisea segments did not greatly affect the efficiency of transformation. Integration via homologous recombination occurred when the donor plasmid was linearized by cleaving at a unique restriction site within the M. grisea segment.

Journal Article↗

Modification of the mycobacteriophage Ms6 attP core allows the integration of multiple vectors into different tRNAala T-loops in slow- and fast-growing mycobacteria.

BACKGROUND: Mycobacteriophage Ms6 integrates into Mycobacterium smegmatis and M. bovis BCG chromosome at the 3' end of tRNAala genes. Homologous recombination occurs between the phage attP core and the attB site located in the T-loop. Integration-proficient vectors derived from Ms6 are useful genetic tools, but their insertion sites in the BCG chromosome remain poorly defined. The primary objective of this study was to identify Ms6 target genes in M. smegmatis and BCG. We then aimed to modify the attP site in Ms6-derived vectors, to switch integration to other tRNAala loci. This provided the basis for the development of recombinant M. bovis BCG strains expressing several reporter genes inserted into different tRNAala genes. RESULTS: The three tRNAala genes are highly conserved in M. smegmatis and BCG. However, in the T-loop of tRNAalaU and tRNAalaV containing the attB site, a single base difference was observed between the two species. We observed that the tRNAalaU gene was the only site into which Ms6-derived integration-proficient vectors integrated in M. smegmatis, whereas in BCG, the tRNAalaV gene was used as the target. No integration occurred in the BCG tRNAalaU T-loop, despite a difference of only one base from the 26-base Ms6 attP core. We mutated the attP core to give a perfect match with the other tRNAala T-loops from M. smegmatis and BCG. Modification of the seven-base T-loop decreased integration efficiency, identifying this site as a possible site of strand exchange. Finally, two Ms6 vectors were constructed to integrate two reporter genes into the tRNAalaU and tRNAalaV T-loops of the same BCG chromosome. CONCLUSION: Small changes in the 7 bp T-loop attP site of Ms6 made it possible to use another attB site, albeit with a lower integration efficiency. These molecular studies on BCG tRNAala genes made it possible to create valuable tools for the site-directed insertion of several genes in the same BCG strain. These tools will be useful for the development of novel multivalent vaccines and genetic studies.

Attachment Sites, Microbiological↗

A new marker, black, a useful recombination suppressor, In(2)2, and a balanced lethal for chromosome 2 of the mosquito Anopheles gambiae.

A new marker for the second chromosome of Anopheles gambiae, black, was isolated from progeny of 60Co-irradiated mosquitoes. The black mutation increases melanization of larval setae and portions of the cuticle that are heavily sclerotized such as the saddle and head capsule. Adults have a sooty color that almost completely eliminates white banding on wings, tarsi, and palps. Fertility and general vigor of black individuals is reduced relative to wild-type; however, this does not prevent routine use for genetic crossing. The black marker was mapped to an interval on chromosome 2 between collarless and Dieldrin resistance 22 centiMorgans (cM) from collarless and 39 cM from Dieldrin resistance. We also isolated from 60Co-irradiated mosquitoes a pericentric inversion, In(2)2, that was marked with dominant alleles of the independently assorting genes collarless and Dieldrin resistance. This inversion is in coupling with the pericentric inversion 2Rd and covers approximately two-thirds of chromosome 2 from divisions 9 to 22. While inbreeding In(2)2 heterozygotes, we isolated a stock in which the inversion was in repulsion to a chromosome marked with c b DlS and an unidentified recessive lethal. This arrangement produced a useful and stable chromosome 2 balancer system that has remained intact for 26 generations without selection. These genetic tools will reduce the effort requires to isolate, among other things, the genetic factors affecting malaria parasite interactions with the mosquito host.

Animals↗

New genetic approaches to craniofacial growth and malformation in the mouse.

New genetic tools that have been developed in the mouse for the study of genetic variation and molecular biology can be applied to the study of craniofacial growth and malformation. D.W. Bailey (Journal of Heredity, 76:107-114, 1985, 77:17-25, 1986) has used congenic and recombinant inbred strains to identify a large number of genes that result in growth variation in local regions of the mandible. The function of "morphogenes" have not been characterized, but they may act as switches that regulate already recognized structural genes. We have studied the cartilage matrix deficiency (cmd/cmd) mutant mouse and found that their chondrocytes fail to synthesize the cartilage-specific proteoglycan at both protein and mRNA levels. In vitro experiments demonstrate biochemical feedback control in the formation of the cartilage extracellular matrix. Abnormalities of cartilage matrix result in facial clefts and in dental malocclusion in mice. A recombinant plasmid containing the type II collagen promoter and enhancer fused to a reporter gene, chloramphenicol acetyl transferase, has been used to produce transgenic mice. These mice reveal that the type II collagen enhancer controls the high level of tissue-specific expression of the gene. The transgenic mice provide a potential test system for study of development and teratogenesis at the gene level.

Animals↗

Functional genomic approaches using the nematode Caenorhabditis elegans as a model system.

Since the completion of the genome project of the nematode C. elegans in 1998, functional genomic approaches have been applied to elucidate the gene and protein networks in this model organism. The recent completion of the whole genome of C. briggsae, a close sister species of C. elegans, now makes it possible to employ the comparative genomic approaches for identifying regulatory mechanisms that are conserved in these species and to make more precise annotation of the predicted genes. RNA interference (RNAi) screenings in C. elegans have been performed to screen the whole genome for the genes whose mutations give rise to specific phenotypes of interest. RNAi screens can also be used to identify genes that act genetically together with a gene of interest. Microarray experiments have been very useful in identifying genes that exhibit co-regulated expression profiles in given genetic or environmental conditions. Proteomic approaches also can be applied to the nematode, just as in other species whose genomes are known. With all these functional genomic tools, genetics will still remain an important tool for gene function studies in the post genome era. New breakthroughs in C. elegans biology, such as establishing a feasible gene knockout method, immortalized cell lines, or identifying viruses that can be used as vectors for introducing exogenous gene constructs into the worms, will augment the usage of this small organism for genome-wide biology.

Animals↗

Molecular mapping of a gene 'ld(t)' controlling cleistogamy in rice.

Cleistogamy is the self-pollination within closed spikelets and is expected to be a useful genetic tool for prevention of possible gene transfer in transgenic crops, for maintenance of genetic purity in autogamous crops, and for increased tolerance to biotic and abiotic stresses. Mapping of the gene ld(t), which is responsible for lack of lodicules inside spikelets and causes cleistogamy, was carried out using F2 and F3 populations derived from a cleistogamous (CL) mutant CL-SNU x Milyang 23 cross. A number of STS markers along chromosomes were developed and bulked segregant analysis was adopted for preliminary mapping. The results showed that the ld(t) was located at the end region of chromosome 1L, flanked by S01178b (an STS marker developed for the locus at 178 cM based on the rice genetic map reported by Japanese Rice Genome Project) at 0.8 cM and co-segregated with S01181a and S01181b (an STS marker developed for the locus at 181 cM).

Chromosomes, Plant↗