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At least 487 records · Page 27Linked to original sources
PubMed2003

A computer-aided diagnostic system to characterize CT focal liver lesions: design and optimization of a neural network classifier.

In this paper, a computer-aided diagnostic (CAD) system for the classification of hepatic lesions from computed tomography (CT) images is presented. Regions of interest (ROIs) taken from nonenhanced CT images of normal liver, hepatic cysts, hemangiomas, and hepatocellular carcinomas have been used as input to the system. The proposed system consists of two modules: the feature extraction and the classification modules. The feature extraction module calculates the average gray level and 48 texture characteristics, which are derived from the spatial gray-level co-occurrence matrices, obtained from the ROIs. The classifier module consists of three sequentially placed feed-forward neural networks (NNs). The first NN classifies into normal or pathological liver regions. The pathological liver regions are characterized by the second NN as cyst or "other disease." The third NN classifies "other disease" into hemangioma or hepatocellular carcinoma. Three feature selection techniques have been applied to each individual NN: the sequential forward selection, the sequential floating forward selection, and a genetic algorithm for feature selection. The comparative study of the above dimensionality reduction methods shows that genetic algorithms result in lower dimension feature vectors and improved classification performance.

Algorithms↗
PubMed2003

A nuclear receptor-mediated xenobiotic response and its implication in drug metabolism and host protection.

Regulation of the Phase I CYP enzymes and Phase II conjugating enzymes is implicated in both drug metabolism and drug-drug interactions. Moreover, the elimination of numerous xenobiotic and endobiotic toxic chemicals also requires a concerted function of Phase I and II enzymes, as well as the membrane spanning drug transporters. The genes that encode these enzymes and transporters are inducible by numerous xenobiotics, yet the inducibility shows clear species specificity. In the last 3-4 years, orphan nuclear receptors (NRs) such as PXR, CAR, and FXR have been established as species-specific xeno-sensors that regulate the expression of Phase I and II enzymes, as well as selected drug transporters. This transcriptional regulation is achieved by binding of these xenobiotic receptors to the NR response elements found within the promoter regions of target genes. The identification of NRs as xenosensors represents a major step forward in understanding the genetic mechanisms controlling the expression of drug metabolizing enzymes. The establishment of NR-mediated and mechanism-guided xenobiotic screening systems by using cultured cells or genetically engineered mouse models has not only advanced our understanding of the molecular complexity of this drug-induced xenobiotic response, but has also provided in vitro and in vivo platforms to facilitate the development of safer drugs.

Animals↗
PubMed1982

Evaluation of 2 different genetic markers for the detection of frameshift and missense mutagens in A. nidulans.

21 chemicals, known to induce missense and/or frameshift mutations directly, were assayed for their ability to forward mutate a haploid strain of A. nidulans. 2 genetic markers for forward mutations were used, namely 8-azaguanine resistance and induction of meth A1 suppressors. Missense mutagens were usually active when tested with the plate-incorporation technique, whereas frameshift agents were ineffective; some of these, on the other hand, turned out to be positive when tested with a liquid-test procedure. The 2 genetic markers used showed a similar sensitivity (with only 2 exceptions) in detecting the chemical mutagens assayed.

Aspergillus nidulans↗
PubMed1982

Mutagenic studies on the hair dye 2-(2',4'-diaminophenoxy)ethanol with different genetic systems.

A new hair-dye coupler, 2-(2',4'-diaminophenoxy)ethanol was analyzed for its potential mutagenic activity in different genotoxic assays, namely gene reverse mutations in Salmonella typhimurium, forward mutations in the yeast Schizosaccharomyces pombe, and in the V79 Chinese hamster cell line grown in vitro (HGPRT forward mutation system). Two other genetic test systems, measuring the mitotic gene conversion in Saccharomyces cerevisiae (strain D4) and the unscheduled DNA-repair synthesis in a HeLa cell line grown in vitro, were also used. 2,4-Diaminoanisole, a mutagenic/carcinogenic structurally related hair-dye coupler, and a group of well-known mutagens, namely methyl methanesulfonate, ethyl methanesulfonate, cychlophosphamide, hycanthone and N-nitrosodimethylamine, were used as positive controls. The new aromatic amine, 2-(2',4'-diaminophenoxy)ethanol, was negative in all the assays performed, under the same treatment conditions as in the case of all the positive controls.

Animals↗
PubMed1987

Genetic differentiation associated with gait within American standardbred horses.

American Standardbred horses are divided into two groups based upon gait: the trot and the pace. The tendency to trot (diagonally opposite legs moving forward together) or pace (the two legs on the same side of the body moving forward together) appears to be genetically determined, although no formal genetic analysis has been undertaken. There is nearly complete assortative mating for gait; however, about 20% of the offspring sired by trotters are registered as pacers, while fewer than 1% of those sired by pacers are registered as trotters. Electrophoretically detectable genic variation at 13 protein loci has been analysed for 371 trotters and 856 pacers, and 10 blood group loci have been examined for 600 trotters and 1227 pacers. Trotters and pacers shared common alleles at 20 of the 23 loci; however, there were significant differences in allele frequencies at 21 of the 23 loci. Highly significant fixation indices (FSTS) were observed for 17 of the loci. The extent of genetic difference between Standardbred trotters and pacers was as great as or greater than that seen between some distinct horse breeds.

Alleles↗
PubMed1992

Adult-onset motor neuron disease and infantile Werdnig-Hoffmann disease (spinal muscular atrophy type 1) in the same family.

We describe a family in which infantile Werdnig-Hoffmann disease and adult-onset progressive muscular atrophy both occurred. The possibility of these two diseases developing within the same family by chance is unlikely, and several genetic hypotheses may be put forward to explain the association. We suggest that the molecular pathogenesis of these two subtypes of lower motor neuron degeneration may be linked. The genetic defect in the childhood spinal muscular atrophies has been mapped to chromosome 5q in close proximity to the microtubule-associated protein 1B locus. The association of diseases within this family suggests that chromosome 5q should also be studied in relation to adult-onset familial motor neuron disease.

Aged↗
PubMed1998

Schizophrenia and genetics: a review and critique for the psychiatric nurse.

Nursing authors such as McCrone and Gournay persist in the orthodox view that the genetic heritability of schizophrenia is an established scientific fact. In this article I take issue with the view they propound by way of an examination of the literature pertaining to schizophrenia and genetics. My reading of the literature suggests that the certainty they seek is not to be found in any of the scientific evidence so far put forward in support of the genetic hypothesis. Much of the early work in this field is fatally flawed and can no longer be used to support the genetic argument. More recent work tends to give increasing support to a greater role for environmental factors than is compatible with a hereditarian argument. Fifty years of research in this field has consistently failed to provide reliable scientific evidence in support of any of the genetic hypotheses relating to schizophrenia. Nurses, it is argued, should not be dispensing advice to patients on the basis of a genetic model that is at best mere hypothesis.

Adoption↗
PubMed1997

Genetic discrimination and health insurance: a call for legislative action.

Fear of genetic discrimination in health insurance is a growing reality. Individuals who might otherwise choose genetic testing may decline it based on their fear that they or their family members will not be able to obtain or maintain health insurance coverage. This commentary notes the evolving legislative efforts to address genetic discrimination in health insurance and urges physicians to help move this legislative agenda forward.

Genetic Diseases, Inborn↗
PubMed2004

Yeast as a model organism for studying the evolution of non-standard genetic codes.

During the last 30 years, a number of alterations to the standard genetic code have been uncovered both in prokaryotes and eukaryotic nuclear and mitochondrial genomes. But, the study of the evolutionary pathways and molecular mechanisms of codon identity redefinition has been largely ignored due to the assumption that non-standard genetic codes can only evolve through neutral evolutionary mechanisms and that they have no functional significance. The recent discovery of a genetic code change in the genus Candida that evolved through an ambiguous messenger RNA decoding mechanism is bringing that naive assumption to an abrupt end by showing, in a rather dramatic way, that genetic code changes have profound physiological and evolutionary consequences for the species that redefine codon identity. In this paper, the recent data on the evolution of the Candida genetic code are reviewed and an experimental framework based on forced evolution, molecular genetics and comparative and functional genomics methodologies is put forward for the study of non-standard genetic codes and genetic code ambiguity in general. Additionally, the importance of using Saccharomyces cerevisiae as a model organism for elucidating the evolutionary pathway of the Candida and other genetic code changes is emphasised.

Candida↗
PubMed2006

Research partnerships in relation to topics in animal breeding and genetics.

A total of 1,628 papers presented at the sixth and seventh World Congresses on Genetics Applied to Livestock Production were categorized into 20 topics according to research subjects. The aim was to determine, in relation to various topics in animal breeding and genetics, the forms of partnerships and the degree of attention given in different continents. North-North partnerships (defined as cooperation between and within developed countries) had a 68.80% representation of research papers presented, whereas North-South partnerships (cooperation between developed and developing countries) had the least representation with only 8.23% of papers. Asia contributed the most research papers in biochemical genetics, whereas Australia lead in research papers on breeding for fiber and fur. Europe contributed the most to the remaining topics, and Africa usually, but not always, contributed the least to most research topics. This study provided a useful indication of the current state of literature in animal breeding and genetics and will be useful to animal breeding and genetics researchers worldwide as they chart the way forward for research and development in the field of genetics applied to livestock production in different continents.

Agriculture↗
PubMed2003

The evolution of genomic imprinting via variance minimization: an evolutionary genetic model.

A small number of mammalian loci exhibit genomic imprinting, in which only one copy of a gene is expressed while the other is silenced. At some such loci, the maternally inherited allele is inactivated; others show paternal inactivation. Several hypotheses have been put forward to explain how this genetic system could have evolved in the face of the selective advantages of diploidy. In this study, we examine the variance-minimization hypothesis, which proposes that imprinting arose through selection for reduced variation in levels of gene expression. We present an evolutionary genetic model incorporating both this selection pressure and deleterious mutations to elucidate the conditions under which imprinting could evolve. Our analysis implies that additional mechanisms such as genetic drift are required for imprinting to evolve from an initial nonimprinting state. Other predictions of this hypothesis do not appear to fit the available data as well as predictions for two alternative hypotheses, genetic conflict and the ovarian time bomb. On the basis of this evidence, we conclude that the variance-minimization hypothesis appears less adequate to explain the evolution of genomic imprinting.

Algorithms↗
PubMed1984

[Semantics of genetic correlation analysis].

A theory of genetic-correlation analysis has been put forward on the basis of notions concerning general and special codispersions . The complete set of genetic-correlation indexes is received and their genetic-statistical meaning revealed. The models for genetical component analysis of general and special codispersions of correlative connections are constructed.

Genetic Variation↗
PubMed2004

Congenital hereditary cataracts.

Congenital cataracts are rare and occur in developed countries with a frequency of 30 cases among 100,000 births with a further 10 cases being diagnosed during childhood. They reflect mainly genetically caused developmental alterations in the lens and surrounding ocular tissues. Even if modern Human Genetics has made large steps forward in the characterization of human hereditary disorders, the underlying developmental processes can only be investigated in model organisms. The mouse is such a good model because of its similarity (as a mammal) and its genetic characterization. This review brings together our genetic and developmental knowledge of congenital, human cataracts with the corresponding mouse models. First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important. From a genetic point of view it becomes obvious that cataract-causing mutations are not distributed randomly. The discovery of a broad variety of genes important for eye and lens development made much progress in the recent years. Nevertheless, there still remains a long list of mutations to be characterized and functionally investigated both in mouse and man indicating a broad genetic heterogeneity in that which clinicians simply refer to as a "cataract".

Alleles↗
PubMed2003

The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. The Alternatives to Carcinogenicity Testing Committee ILSI HESI.

The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds. The data from this testing program have made an important contribution to the general understanding of how these models can be best applied in hazard identification; however, questions still exist regarding methodology and data interpretation. To address these issues, ILSI HESI hosted a February 2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The purpose of this workshop was to reach an understanding of how data from genetically modified mouse models are viewed by different regulatory bodies in the pharmaceutical sector and, based on this understanding, to identify areas in which more experimental work may be needed to increase the utility of data derived from these assays. In the course of discussions, various data gaps related to model selection and protocol issues were identified. Based on the outcome of the workshop, various studies are proposed to provide data to improve the utility of currently available assays for cancer hazard identification and risk assessment purposes.

Animals↗
PubMed1986

A yeast screening system for simultaneously monitoring multiple genetic endpoints.

Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. We describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. Strain XD83 can detect forward mutation, back nuclear frameshift and base-pair substitution mutation, nuclear intragenic and intergenic recombination, and mitochondrial forward point mutations and deletions. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant (P less than 0.01) increases in the frequencies of each genetic change, increases in the absolute numbers (yields) of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose and should be considered a part of the spectrum of change induced by ultraviolet light. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints.

Dose-Response Relationship, Radiation↗
PubMed1990

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)

Chromosome Mapping↗
PubMed2004

Inherited arrhythmogenic diseases: the complexity beyond monogenic disorders.

Twelve years after the identification of the molecular bases of the long-QT syndrome, it is now possible to express some considerations on the impact that genetic findings have had in the understanding of inherited arrhythmogenic diseases. Along with the excitement for the emerging data on genotype/phenotype correlation and for the development of the first recommendations for gene-specific management of patients, it is also important to acknowledge the unexpected complexity that has emerged. The focus of this article is to analyze the elusive aspects of the relationship between genetic defects and clinical manifestations and to propose some research directions that may provide the needed answers to move forward in the understanding of the genetics of heart rhythm abnormalities.

Ankyrins↗
PubMed2006

Statistical methods in genetics.

In recent years, a very large variety of statistical methodologies, at various levels of complexity, have been put forward to analyse genotype data and detect genetic variations that may be responsible for increasing the susceptibility to disease. This review provides a concise account of a number of selected statistical methods for population-based association mapping, from single-marker tests of association to multi-marker data mining techniques for gene-gene interaction detection.

Genetic Markers↗