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At least 613 records · Page 34Linked to original sources
PubMed1989

Molecular dosimetry studies of forward mutation induced at the yg2 locus in maize by ethyl methanesulfonate.

The yg2 assay in Zea mays detects forward mutation in somatic cells within leaf primordia of embryos and it was used in an analysis of the molecular dosimetry of ethyl methanesulfonate (EMS). Parallel genetic and molecular dosimetry experiments were conducted in which the frequency of forward mutation and the level of covalently bound ethyl DNA adducts were determined. Prepared kernels were treated for 8 h at 20 degrees C with 1-10 mM EMS. EMS induced a direct concentration-dependent increase in mutation induction proportional to the exposure concentration (slope = 0.93). The kinetics of mutation induction demonstrated in the intact maize system were consistent with the kinetics observed earlier in in vitro model systems using cultured mammalian cells, and contrasted with the exponential increase in mutation induction characteristic of microbial species. Parallel molecular dosimetry experiments were conducted using [3H]EMS. DNA was extracted and purified from embryonic tissues containing the leaf primordia, the target tissue of the yg2 assay. A linear increase in the molecular dose was observed as a function of EMS concentration. Using concentration as a common parameter between the parallel genetic and dosimetry studies, mutation induction appeared to increase nearly in a direct proportion to the molecular dose. However, studies in other genetic systems indicate that the levels of specific DNA adducts, such as O6-ethylguanine (O6-EtGua) show a better correlation with mutation induction kinetics than molecular dose. Neither molecular dose, nor O6-EtGua levels account for differences in the absolute frequencies of mutation induction observed in different genetic systems. Therefore, reliable assessment of health risks posed to humans by chemical mutagens appears to require consideration of other factors in addition to DNA dose or adduct formation, including differences in repair capabilities and in the size of the genetic targets in humans relative to the model genetic systems under study.

Animals↗
PubMed1985

[The role of surface structures of recipient cells in bacterial conjugation].

Previously, while studying conjugation process in bacteria, the main attention was given to donors of plasmids. The aim of this review is to show that recipient cells indeed play an important role in this process too. The main attention is given to the structure of recipient cell walls, which is necessary for the recognition of donor cell pili and the establishment of the contact between the cells, i. e. to the first steps of conjugation between gram-negative microorganisms. The evidence concerning the influence of recipient cell walls defects on transmission of some plasmids is presented. The significant role of defects in lipopolysaccharide structure and of the intrinsic features of protein components of the outer membrane is considered. To the author's mind, the diversity in the cell wall structure creates the "outer barriers" for the plasmid exchange between different bacteria. Like the "inner barriers" (restriction, transcription, mistakes, plasmid incompatibility, etc) these "outer barriers" seem to be crucial for genetic isolation of bacterial species. Postulating this process, the author puts forward the idea of applicability of the conception of the biological species to prokaryotes.

Bacteria↗
PubMed2003

Mendel and modern genetics: the legacy for today.

The legacy of Mendel's pioneering studies of hybridization in the pea continues to influence the way we understand modern genetics. But what sort of picture did Mendel himself have of his work and its ultimate uses, and how does that picture compare with the collection of ideas and methodologies that was put forward in his name and later became known as 'Mendelism'? With genetics standing at the center of our present biomedical and biotechnological research, an examination of the history of our concepts in the field can help us better understand what we should and should not expect from current genetic claims. For that enterprise there is no better starting place than Mendel himself.

Agriculture↗
PubMed1999

Genetics and the British insurance industry.

Genetics and genetic testing raise key issues for insurance and employment. Governmental and public concern galvanised the British insurance industry into developing a code of practice. The history of the development of the code, issues of genetic discrimination, access to medical information, consent and the dangers of withholding information and the impact on the equity of pooled risk are explored. Proactive steps by the Association of British Insurers suggest that moral reflection not legislation is the way forward.

Disclosure↗
PubMed1993

Possible genetical pathways for the biosynthesis of blood group mucopolysaccharides. Vox Sang 1959:4:97-119.

This paper put forward possible biosynthetic pathways for the formation of the blood group A, B, H and Lewis antigens based on the limited knowledge of their chemistry and genetics that was available in 1959. The schemes proposed that genes at four independent loci ABO, HH, Lele and Sese interacted to give the five specificities A, B, H, Lea and Leb found in secretions and that the primary products of the blood group genes were not the antigens but enzymes that catalysed the sequential addition of single sugars to complete the determinants.

ABO Blood-Group System↗
PubMed2005

Genetics of fibrosing lung diseases.

Genetic studies in familial lung fibrosis have demonstrated an association with surfactant protein C genes: two mutations have been found resulting in protein misfolding and causing type-II epithelial cell injury. Remarkably, different histological patterns were observed in the affected subjects, suggesting the influence of modifier genes and/or environmental factors. Surfactant protein C gene variations have not, however, been associated with sporadic cases, i.e. idiopathic pulmonary fibrosis (IPF). Susceptibility to IPF probably involves a combination of polymorphisms related to epithelial cell injury and abnormal wound healing. To date, the genetic associations with IPF that have been reported in different cohorts include the genes encoding tumour necrosis factor (TNF; -308 adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association with severity and progression (interleukin-6/TNF receptor II and transforming growth factor-beta1 (TGFB1; +869 cytosine)), but none of these associations have been replicated by others. Unlike in IPF, immunological inflammation seems to be more prominent in the pathogenesis of scleroderma lung fibrosis, being an autoimmune disease with specific autoantibodies, such as antitopoisomerase antibodies, in patients with diffuse lung disease, and anticentromere antibodies, in patients with pulmonary vascular disease. Antitopoisomerase antibody positivity is associated with the carriage of human leukocyte antigen DRB1*11 and DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif. Extended haplotype analysis also supports the conclusion that TNF may be the primary association with anticentromere positivity. Intriguingly, associations with TGFB1 and genes involved in extracellular matrix homeostasis have been reported in this disease. In conclusion, significant steps forward have been taken in the understanding of the genetic contribution to fibrosing lung diseases, but major challenges lay ahead. It is the present authors' opinion that only a combined approach studying large numbers of familial and sporadic cases, all clinically well phenotyped, using multiple distinct cohorts, and genotyped according to relevant gene ontologies will be successful. It will be necessary to be particularly vigilant with regard to phenotype; the absence of very strong reproducible associations may be because of the rigidity of phenotype definition, coupled with the possibility that idiopathic pulmonary fibrosis may still be a heterogeneous group of diseases, despite the more rigid definition set out by the European Respiratory Society/American Thoracic Society statement.

Hermanski-Pudlak Syndrome↗
PubMed2025

Time-lagged genomic erosion and future environmental risks in a bird on the brink of extinction.

Global biodiversity is rapidly declining due to habitat degradation and genomic erosion, highlighting the urgent need to monitor endangered species and their genetic health. Temporal genomics and ecological modelling offer finer resolution than single-time-point measurements, providing a comprehensive view of species' recent and future trajectories. We investigated genomic erosion and environmental suitability in the critically endangered regent honeyeater (Anthochaera phrygia) by sequencing whole genomes of historical and modern specimens and building multi-temporal species distribution models (SDMs) across the last century. The species has declined from hundreds of thousands of individuals to fewer than 300 over the past 100 years. SDMs correctly predicted known patterns of local extinction in southeast Australia. Our demographic reconstructions revealed a gradual population decline from 2000 to 2500 years ago, sharply accelerating in the last 500 years due to climate variability and habitat loss. Despite this substantial demographic collapse, the regent honeyeater has lost only 9% of its genetic diversity, with no evidence of inbreeding or connectivity loss. Also, it exhibits higher diversity than many other threatened bird species. Forward-in-time genomic simulations indicate that this time lag between population decline and genetic diversity loss conceals the risk of ongoing genomic erosion into a future of rapidly degrading environmental suitability. Our work underscores the need for targeted conservation efforts and continuous genetic monitoring to prevent species extinction.

Animals↗
PubMed2001

On new hypotheses about autosomal dominant polycystic kidney disease type 1.

The purpose of this paper is to suggest a partial explanation of the aetiology of autosomal dominant polycystic kidney disease type 1, one of the most common genetic diseases in humans. To this aim we put forward a number of interconnected ideas, based on a number of experimental evidences and plausibility arguments. We stress the major role played by the instability of some genomic tandem repeats, together with the DNA structures known as quadruplexes, the pseudogenes and the gene conversion. The model we propose can be considered a multi-hit generalization of the well-known two-hit model, a generalization that could well have a validity also outside the specific context. We finally provide an indication of the likely guilty DNA segment for the above disease, and we propose a possible simple experimental line of action aimed to confirm or disproof our suggestion.

Age of Onset↗
PubMed1983

Testing of chemicals for mutagenic activity with Schizosaccharomyces pombe.

Two genetic end-points are used for testing mutagens in Schizosaccharomyces pombe: forward mutations of the loci which encode steps early in the adenine synthetic pathway and reversion of certain selected mutants. 54 chemicals have been tested for at least one of the genetic end-points. The relevant literature has been reviewed through 1979.

Ascomycota↗
PubMed1993

Genetic linkage and schizophrenia: methods, recent findings and future directions.

Family, twin and adoption studies have shown that familial clustering in schizophrenia is predominantly due to genetic factors. On the basis of segregation analyses of the illness distribution in relatives of patients, various models of the mode of transmission have been put forward but as yet there is no consensus. Linkage analysis based on molecular genetic techniques provides a more direct approach to discovering precisely what is inherited (one gene, a small number of genes or many genes?) that generates vulnerability to schizophrenia. To date there has been no sufficiently replicated finding of one or more linked genes and many methodological complexities remain. However, the rate of progress in addressing these issues gives hope that genetic linkage analysis of schizophrenia will provide some answers.

Chromosome Mapping↗
PubMed1984

Biology of disease. Alcoholism and aldehydism: new biomedical concepts.

New results of biomedical research in alcoholism show great interindividual, as well as racial, variability with respect to metabolism of alcohol and its first oxidation product, acetaldehyde. Genetic factors play an important part. The enzymes of alcohol and aldehyde metabolism exhibit a genetically determined heterogeneity (isoenzymes and enzyme polymorphisms). This leads to a large variety of individually different enzyme phenotypes. Thus, the hypothesis is put forward that the individual and racial differences in alcohol metabolism are based on the genetically determined variability of the participating enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Alcohol metabolism and alcohol-induced disturbances of the intermediary metabolism are closely interrelated. Hence, genetic codetermination can also be expected in this regard. As a toxic intermediate of alcohol metabolism, acetaldehyde plays a central role. Three positive ranges of acetaldehyde levels can be defined: (a) the normal range, (b) the "acute aldehyde syndrome" with extremely high levels of acetaldehyde, (c) "chronic aldehydism" with slightly elevated acetaldehyde levels. In Orientals lacking the mitochondrial low Km aldehyde dehydrogenase, acetaldehyde accumulates and produces symptoms of intoxication. This acute aldehyde syndrome is highly aversive and, thus, prevents these individuals from drinking. The effect is similar to the consequences of the inhibition of aldehyde dehydrogenase with disulfiram, a commonly employed drug in the treatment of alcoholics. In alcoholics slightly elevated levels of blood acetaldehyde are observed. There are indications that this chronic aldehydism is not only the consequence of excessive drinking but may reflect a preexisting enzyme pattern that is genetically determined. Therefore, slightly elevated acetaldehyde concentrations could serve as a biologic marker for high risk drinking. Alcohol dehydrogenase is found in many organs and often in specialized cells within a particular tissue. A specific enzyme pattern in these cells could lead to elevated acetaldehyde concentrations, consequently inducing acetaldehyde-related damage. Such organs could represent direct targets even at low blood acetaldehyde levels.

Acetaldehyde↗
PubMed2003

Behavior genetics.

The influence of hereditary and environmental factors is indispensable as the foundation on which the temperament of an animal is formed. Genetic research on animal temperament has experienced a turning point in recent years as a result of the development of molecular biology. In the near future, it may be possible to explain the formation process of animal temperament as the two fields share their research. We look forward to applying these research results to the development of new genetic treatment methods for problem behavior and training programs suited to the individual.

Animals↗
PubMed1999

Neuronal control of locomotion in C. elegans is modified by a dominant mutation in the GLR-1 ionotropic glutamate receptor.

How simple neuronal circuits control behavior is not well understood at the molecular or genetic level. In Caenorhabditis elegans, foraging behavior consists of long, forward movements interrupted by brief reversals. To determine how this pattern is generated and regulated, we have developed novel perturbation techniques that allow us to depolarize selected neurons in vivo using the dominant glutamate receptor mutation identified in the Lurcher mouse. Transgenic worms that expressed a mutated C. elegans glutamate receptor in interneurons that control locomotion displayed a remarkable and unexpected change in their behavior-they rapidly alternated between forward and backward coordinated movement. Our findings suggest that the gating of movement reversals is controlled in a partially distributed fashion by a small subset of interneurons and that this gating is modified by sensory input.

Amino Acid Sequence↗
PubMed1989

Separation of pigmented and albino melanocytes and the concomitant evaluation of endogenous peroxide content using flow cytometry.

Flow cytometry (FCM) has been used extensively to analyze various biological properties of the cell. In this report, we describe a method by which FCM was used to determine the light scattering profile of a mixed population of pigmented and non-pigmented melanocytes, plus its subsequent use for the sorting and separation of the two cell types. In addition, the relative peroxide content in pigmented and non-pigmented melanocytes was compared by flow cytometry. Cultured avian melanocytes from a pigmented control and from three genetically distinct albino sources were studied. FCM analysis of forward versus side light scatter within a mixed suspension of pigmented and amelanotic melanocytes distinguished two overlapping populations of cells. Sorting of these two populations demonstrated that the population exhibiting much side and minimal forward light scatter was primarily pigmented melanocytes, while conversely the population exhibiting less side and more forward scatter was principally non-pigmented cells. These two melanocyte types also demonstrated differences in levels of endogenous peroxides. The intracellular content of peroxide in the two subpopulations of cells was measured utilizing the nonfluorescent compound, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which within the cell is oxidized by intracellular peroxides to a fluorescent dichlorofluorescein (DCF). Non-pigmented albino melanocytes had the highest quantity of endogenous peroxides, while heavily pigmented cells had considerably less peroxide-related fluorescence. The amount of this DCF fluorescence could be enhanced by increasing concentrations of DCF used in the assay. These flow cytometric methods are useful for isolating and culturing subpopulations of melanocytes expressing various pigment levels and to investigate the relationship between melanin and its precursors with hydrogen and lipid peroxides in melanocytes.

Animals↗
PubMed2006

PINK-1 and DJ-1--new genes for autosomal recessive Parkinson's disease.

Our genetic knowledge of Parkinson's disease (PD) is moving forward at an impressive speed. In less then 10 years family-based linkage analysis and positional cloning have led to the identification of several genes for familial forms of PD, which has been of critical importance to the scientific advance of PD research as the causal genes have offered new tools to model and understand pathways leading to neurodegeneration in PD.

Genes, Recessive↗
PubMed1977

A conditional antimutator in E. coli.

A pleiotropic mutation in the purB gene of E. coli is described which lowers the spontaneous mutation frequency of other genes. The antimutator effect is very large for some genetic loci, but is absent at other sites. Both forward and reverse mutations are affected. This mutation in purB is temperature sensitive for both adenine auxotrophy and the antimutator action. Adenine, or adenosine, or low temperature growth abolish the antimutator effect. The mutagenicity of base analogs and nitrosoguanidine at several loci was found to be reduced by this purB mutation. The antimutator effect is recessive in strains merodiploid for the purB region. The frequency of reversion of mutation on F' episomes is affected by the chromosomal antimutator, which therefore acts in trans. Xray and UV sensitivity are normal in this mutant, which is the first antimutator characterized in E. coli.

Adenine↗