[Genetic engineering in mammalian cells and its potential application to genetic diseases].
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “GENETICS”
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.
Minimum guidelines for the delivery of clinical genetics services. The Evaluation of Clinical Services Subcommittee, Great Lakes Regional Genetics Group.
Explore the source record for details and available documents.
Genetic Counseling↗
Genetics and the dead: implications for genetics research with samples from deceased persons.
Explore the source record for details and available documents.
Adult↗
ASHG statement. Professional disclosure of familial genetic information. The American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure.
Explore the source record for details and available documents.
Confidentiality↗
Superficial siderosis: a potentially important cause of genetic as well as non-genetic deafness.
Superficial siderosis is an important disease that is increasingly being recognized as a cause of sensorineural hearing loss. Hemosiderin, resulting from repeated episodes of subarachnoid bleeding, is deposited preferentially on the surface of the eighth nerve, cerebellum, and brain stem as a consequence of glial catabolism of ferritin within those structures. This deposition eventually results in destruction and demyelination within the central nervous system, leading to the cardinal clinical findings of superficial siderosis: hearing loss, ataxia, and myelopathy. This mechanism may contribute to the pathogenesis of several forms of genetic deafness, and should be considered as a diagnostic possibility in cases of late onset deafness even in the absence of an overt history of subarachnoid bleeding.
Adult↗
Nature of macrophage-T cell interaction in secondary helper cell generation in vitro. Genetic restriction of macrophage-T cell interaction, which determines T-B genetic restriction.
To investigate the histocompatibility requirements for the macrophage-T cell interaction in the secondary antibody response, splenic T cells from antigen (carrier)-primed F1 hybrid mice were restimulated in vitro with carrier-pulsed F1, parental or allogeneic macrophages. Surviving T cell were cocultured with hapten-primed F1 or parental "B cells" and restimulated with the appropriate hapten-carrier conjugate. The IgG antibody-forming cell response was then measured using a plaque assay. Mapping of the genetic restriction was performed by use of different strain combinations. T helper cells could be restimulated in the presence of macrophages only provided they shared the I-A subregion of the major histocompatibility complex with the F1 T cells frm F1 hybrids restimulated with parental or I-A-identical macrophages were shown to only cooperate with parental B cells of the same I-A haplotype as the macrophages used for restimulation. The defect was at the level of the macrophage, as addition of macrophages of the I-A haplotype used for the restimulation culture reconstituted ability of F1 helper cells to cooperate with the I-A-nonidentical B cells.
Animals↗
Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics.
Avian influenza A H5N1 viruses similar to those that infected humans in Hong Kong in 1997 continue to circulate in waterfowl and have reemerged in poultry in the region, raising concerns that these viruses could reappear in humans. The currently licensed trivalent inactivated influenza vaccines contain hemagglutinin (HA) and neuraminidase genes from epidemic strains in a background of internal genes derived from the vaccine donor strain, A/Puerto Rico/8/34 (PR8). Such reassortant candidate vaccine viruses are currently not licensed for the prevention of human infections by H5N1 influenza viruses. A transfectant H5N1/PR8 virus was generated by plasmid-based reverse genetics. The removal of the multibasic amino acid motif in the HA gene associated with high pathogenicity in chickens, and the new genotype of the H5N1/PR8 transfectant virus, attenuated the virus for chickens and mice without altering the antigenicity of the HA. A Formalin-inactivated vaccine prepared from this virus was immunogenic and protected mice from subsequent wild-type H5N1 virus challenge. This is the first successful attempt to develop an H5N1 vaccine seed virus resembling those used in currently licensed influenza A vaccines with properties that make it a promising candidate for further evaluation in humans.
Animals↗
Genetics, ontogeny, and testosterone inducibility of aldehyde oxidase isozymes in the mouse: evidence for two genetic loci (Aox-I and Aox-2) closely linked on chromosome 1.
"Null"-activity and low-activity variants for the liver supernatant isozymes of aldehyde oxidase (designated AOX-1 and AOX-2) were observed in inbred strains and in Harwell linkage testing stocks of Mus musculus. The genetic loci determining the activity of these isozymes (designated Aox-1 and Aox-2, respecitively) are closely linked on chromosome 1 near Id-1 (encoding the soluble isozyme of isocitrate dehydrogenase). Linkage data of Aox-1 with Id-1 and Dip-1 (encoding a kidney peptidase) demonstrated that this gene coincides with or is closely linked to Aox (Watson et al., 1972). Ontogenetic analyses demonstrated that liver AOX-1 appeared just before birth and increased in activity during postnatal development, whereas liver AOX-2 was observed only during postnatal development. Adult male livers exhibited higher AOX-1 and AOX-2 activities than adult female livers. Both isozymes were significantly reduced in activity by castration of adult males and increased following testosterone administration to castrated males and normal female mice.
Alcohol Oxidoreductases↗
Genetic analysis of tumorigenesis: XII. Genetic control of the anchorage requirement in CHEF cells.
Chinese hamster somatic cell hybrids between diploid anchorage-independent CHEF/204Bu50 cells and diploid anchorage dependent CHEF/205-30 cells are anchorage dependent but can segregate subclones at low frequency which reexpress anchorage independence. Thus, anchorage independence, like other characteristics of the transformed phenotype, is suppressed in these hybrids. Anchorage-independent subclones were recovered from the anchorage-dependent hybrids under conditions which favored the retention of most chromosomes. Karyotype analysis of suppressed hybrids and their anchorage-independent subclones showed that segregation of anchorage dependence was correlated with the loss of one copy of chromosome 1 in CHEF Chinese hamster hybrids. Thus, suppression of anchorage independence has a chromosomal basis. Several genetic models are considered for the origin of anchorage-independent subclones from suppressed Chinese hamster hybrids.
Animals↗
Genetic analysis of complex gene clusters in Escherichia coli: the genetic analysis of F72 fimbrial genes.
Cloning techniques make it possible to accommodate bacterial genes on vector DNA molecules. On that basis the investigation of bacterial structures and functions got new impetus. The potentials of molecular genetics for detailed analysis of bacterial structures are illustrated in this paper for the gene cluster involved in the expression of F72 fimbriae associated with a uropathogenic Escherichia coli O6:K2:H1:F7 strain.
Bacterial Proteins↗
Genetic risk factors for erectile dysfunction and genetic determinants of drug response--on the way to improve drug safety?
Association studies give hint for the fact that the risk to develop cardiovascular disorders such as hypertension or coronary heart disease is influenced by the genotype in single nucleotide polymorphisms (SNPs). Considering the close relationship in the pathophysiology of these diseases and erectile dysfunction (ED), the analysis of the association of genotypes in SNPs and ED stands to reason. In an analysis of ED patients and their genotypes in the GNB3 C825T, the ACE I/D and the NOS3 G894T polymorphisms, there was no evidence for influence of the genotypes on the susceptibility to develop ED. At the same time, a significant variation in drug response to sildenafil dependent on the genotypes in the GNB3 C825T and ACE I/D polymorphisms was demonstrated. In the group of GNB3 825C allele carriers, only 50% of patients showed a positive response, while > 90% of the patients genotype TT responded adequately. In parallel, only 50% of ACE D allele carriers showed a positive response to sildenafil in contrast to men genotype II in the ACE I/D polymorphism, who had a response rate of 75%. Considering cardiovascular side effects under sildenafil treatment, it would be interesting to determine if genetic factors have an impact on the side effect profile of this drug.
Angiotensin I↗
Genetics of xenobiotic metabolism in Drosophila. I. Genetic and environmental factors affecting glutathione-S-transferase in larvae.
The enzyme glutathione-S-transferase, which plays a crucial role in xenobiotic detoxification, was investigated in Drosophila melanogaster. Based upon examination of substrate specificities and pH optima, it was observed that the enzyme in Drosophila is considerably more restricted in its activities than in mammals. The effects of various xenobiotics on activities in third instar larvae were examined. While beta-naphthoflavone and phenobarbital had no effect, pentamethyl benzene (PMB) administration resulted in a 50% increase in enzyme activity. Comparison of lines of known genetic composition indicates that the degree of response to PMB is modulated by genes on chromosome II, and that differences exist with respect to the patterns of response of activities towards the substrates 1-chloro-2, 4-dinitrobenzene and ethacrynic acid. Results obtained suggest the existence of at least two loci on chromosome II that code for glutathione S-transferase isozymes.
Benzene Derivatives↗
The genetic toxicology of 2-amino-N6-hydroxyadenine in eukaryotic organisms: significance for genetic risk assessment.
A collaborative study was designed to assess the mutagenicity of 2-amino-N6-hydroxylaminopurine (AHA) in a wide variety of eukaryotic assays systems in terms of potency and specificity. Earlier studies in Salmonella and Neurospora had shown that AHA was an extremely potent mutagen which appeared to cause predominantly AT to GC base-pair transitions. This discovery was viewed as an unusual opportunity to explore the general utility of different eukaryotic assay systems for genetic risk assessment. The objective was to determine whether AHA would show comparable potency and specificity in those eukaryotic organisms used to evaluate mutagenic potential of environmental chemicals for the human population. The data presented in this report show that AHA was mutagenic in all the eukaryotic assays utilized; however, the level of effect was found to be assay system-dependent. In addition, in assays where other base analogs were used as positive controls, differences in relative potency were observed from those obtained in the earlier studies with Salmonella and Neurospora. When alkylating agents were used as positive controls in the higher eukaryotic assays, AHA was found to have a mutagenic potency comparable to ethylnitrosourea (ENU), ethyl methanesulfonate (EMS) or methyl methanesulfonate (MMS) for many of the assays. With regard to mutagenic specificity, AHA appears to induce gene/point mutations in eukaryotic organisms, resulting predominantly from base-pair substitutions, predominantly AT to GC base-pair transitions; however, there was some unexplained variation in the ratio of these base-pair transitions and other transitions and transversions as a function of assay system. In addition, studies on the induction of micronuclei have shown that AHA induces chromosomal damage at high concentrations and low levels of survival.
Adenine↗
Genetic diagnosis from formalin-fixed fetal tissue using FISH: a new tool for genetic counseling in subsequent pregnancies.
We evaluated the feasibility of retrospective genetic testing for numerical chromosomal aberrations by applying the FISH technique to formalin-fixed fetal tissue. Fetal tissue from 10 old cases with known aneuploidy and from 13 cases with known fetal malformations, were tested with specific DNA probes for pericentromeric repeat regions of chromosomes 13/21, 18, X and Y. FISH diagnosis concurred with karyotype in all nine cases with sufficient cells. Numerical aberration was diagnosed in six out of 13 cases with fetal malformations.
Aneuploidy↗
New insights on inflammation in chronic kidney disease-genetic and non-genetic factors.
Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in chronic kidney disease (CKD). As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (which is interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (CRP) has been shown to independently predict mortality in CKD patients. The causes of the highly prevalent state of inflammation in CKD are multiple and include factors such as volume overload, co-morbidity, intercurrent clinical events, the dialysis procedure per se as well as genetic factors. Indeed, multiple cytokine DNA polymorphisms may affect the inflammatory state, the clinical phenotype as well as outcome in this patient population.
C-Reactive Protein↗
Virulence and pathogenesis of the MSW and MSD strains of Californian myxoma virus in European rabbits with genetic resistance to myxomatosis compared to rabbits with no genetic resistance.
The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was examined in European rabbits (Oryctolagus cuniculus) that were either susceptible to myxomatosis (laboratory rabbits) or had undergone natural selection for genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly lethal for both types of rabbits with average survival times of 7.3 and 9.4 days, respectively, and 100% mortality. Classical clinical signs of myxomatosis were not present except in one rabbit that survived for 13 days following infection. Previously described clinical signs of trembling and shaking were observed in laboratory but not wild rabbits. Despite the high resistance of wild rabbits to myxomatosis caused by South American strains of myxoma virus, the MSW strain was of such high virulence that it was able to overcome resistance. The acute nature of the infection, relatively low viral titers in the tissues and destruction of lymphoid tissues, suggested that death was probably due to an acute and overwhelming immunopathological response to the virus. No virus was found in the brain. The MSD strain was attenuated compared to previously published descriptions and therefore was only characterized in laboratory rabbits. It is concluded that Californian MSW strain of myxoma virus is at the extreme end of a continuum of myxoma virus virulence but that the basic pathophysiology of the disease induced is not broadly different to other strains of myxoma virus.
Animals↗
[Genetically-driven or supposed genetic-related insulinomas in adults: validation of the surgical strategy proposed by the A.F.C.E./G.E.N.E.M].
Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the Department of General and Endocrine Surgery of the Lille University Hospitals. The present report deals with 13 patients with proven multiple endocrine neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity differs from spontaneous insulinoma by the presence of multiple foci in the pancreas. Enucleation is not advised in this setting due to the strong likelihood of persistence or recurrence. Various studies suggest different strategies for preoperative localization and surgical approach. We analyzed retrospectively the surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this study was to validate the strategy, integrate the contribution of genotypic diagnosis, simplify preoperative imaging studies, and re-evaluate the value of intraoperative baseline secretin-stimulated insulin measurements. We recommend preoperative endoscopic ultrasonography of the pancreatic head only and routine left pancreatectomy with enucleation of cephalic tumors under intraoperative hormone monitoring. Preoperative invasive localization studies are proposed only if the endoscopic ultrasonography is negative for the pancreatic head. Intraoperative secretin stimulation test can be useful in difficult cases, especially with concurrent nesidioblastosis or in case of secondary surgery. All but one of the 13 patients achieved long-term cure with this strategy.
Genotype↗
Genetic pattern, histological structure, and cellular phenotype in early and advanced gastric cancers: evidence for structure-related genetic subsets and for loss of glandular structure during progression of some tumors.
Gastric cancer shows remarkable heterogeneity in histological pattern, cellular phenotype, and genotype. Tumor subsets identified by varying procedures have shown limited reciprocal correlation and have failed to provide a sound rationale for the characterization and classification of all tumors. Based on a case series of 130 gastric cancers that covered both early (70 cases) and advanced (60 cases) stages and that represented most histological types and structural patterns, this study investigated (1) microsatellite instability and p53 gene mutation by means of PCR-based molecular techniques and (2) p53 protein accumulation or tumor cell immunophenotype by means of immunoperoxidase procedures. It was found that microsatellite instability and p53 gene mutation involve two distinct subsets of both early and advanced-stage glandular (intestinal) cancer, and that, contrastingly, they leave purely diffuse cancers unaffected. Mixed cancers, namely, those in which glandular admixed with diffuse growths, showed scarce microsatellite instability at all stages, whereas prominent p53 gene mutation and p53 protein accumulation was limited to the advanced stage alone. No significant correlation was found between tumor cell immunophenotype and either genotype or histotype, although some correlation with particular structural patterns was detected. Comparison of intramucosal with invasive growths within any given tumor suggested that invasive cancers with diffuse-type growth arise in part from mucosal cancers of glandular or mixed structure through progressive loss of intercellular junctional systems. It is concluded that at least two genetically distinct subsets of glandular cancer, one with microsatellite instability and the other with p53 lesions, should be separated both from purely diffuse cancer and, at least in the advanced stage, from mixed cancer. Available evidence suggests distinct clinicopathologic profiles for such tumor entities.
Aged↗