PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “genetic test utilization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 415 records · Page 23Linked to original sources
PubMed1978

Introduction: utilization of higher plant systems as monitors of environmental mutagens.

Research over the past 10 years has clearly demonstrated the presence of mutagens among the numerous man-made and naturally occurring chemicals in our environment. These mutagens occur in all classes of chemicals, including foods, drugs, cosmetics, pesticides, household and industrial chemicals as well as in pollutants of both air and water. More recently, a high correlation has been found between carcinogenic and mutagenic activity; at least 90-95% of chemical carcinogens are mutagens. There is a widespread expectation that the discovery of mutagenic activity in chemical screening programs may alert us not only to mutagenic potential in man, but carcinogenic potential as well. The types of genetic damage which can be produced are numerous and the specificity of chemical mutagens makes it possible for one type of effect to be produced predominantly or exclusively. Thus, any screening program must consist of a battery of tests capable of detecting nondisjunction, chromosome aberrations, gene mutations (point mutations as well as interstitial deletion), in addition to more subtle effects of DNA repair. In addition, since innocuous chemicals can be converted by mammalian metabolism to potent mutagens and carcinogens, these metabolites must be evaluated as well as the parent compounds. Chemicals such as air pollutants present particular problems for mutagenicity testing using conventional microbial assays. Some of these problems can be overcome by using various higher plant systems. The general utility of these systems needs to be evaluated in terms of the types of genetic damage which can be detected, relative sensitivity, and general utility for use in mutagen screening and monitoring.

Biological Assay↗
PubMed1990

The genetics of insulin-dependent diabetes in the BB rat.

Very little is known about the genes involved in the pathogenesis of IDDM. One component is known to be linked to the major histocompatibility complex, but the other components are unknown. We know from the major animals models of IDDM, both the NOD mouse and the BB rat, that the disease is under multigenic control. However, due to the size and complexity of the mammalian genome as well as to the lack of useful clues, the location and identity of the other genes remains a mystery. This is compounded by the fact that well-characterized genetic markers are not available for all regions of the mammalian genome, and it is likely that at least some of the genes of interest are located in these regions. The testing of pedigrees for the linkage of RFLP with the genetic factors involved in IDDM promises to be the most effective means of mapping, and ultimately identifying, these genes. However, the number of genes which are theoretically necessary to test for linkage makes even this approach impractical. Here, we have described here how the amount of work and time can be significantly reduced by utilizing repetitive DNA sequences as probes for the linkage of random RFLPs to diabetes. With each screening, one can simultaneously test multiple unlinked loci in the genome. Preliminary results which show promising linkage to two of the genetic components have been presented, thereby supporting the usefulness of this approach.

Animals↗
PubMed2002

Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer.

PURPOSE: Identification of germline mutations in mismatch repair genes is increasingly being used to guide clinical practice in hereditary non-polyposis colon cancer. The aim of this study was to retrospectively assess the clinical utility of immunostaining and microsatellite instability testing in a group of individuals in whom germline testing of hMSH2 and hMLH1 had already been performed. METHODS: Individuals were identified from the records of family cancer clinics. A total of thirty-eight tumour blocks were retrieved from 28 kindreds. DNA was extracted and PCR amplification of six microsatellite markers was performed. Immunostaining was used to examine the expression of hMSH2 and hMLH1 protein. RESULTS: Of the 32 assessable tumours, 24 (75%) showed microsatellite instability. Most of the MSI-H cancers (92%) failed to express either hMLH1 or hMSH2. Deleterious germline mutations were identified in the proband in 12 of 28 families. Missense mutations were identified in 11 cases and no mutations in six probands. CONCLUSIONS: The use of germline genetic testing is indicated for a highly selected group of individuals. MSI testing and immunostaining are extremely useful tools which significantly improve the clinical interpretation of germline results. Ambiguity regarding the significance of missense mutations in hereditary bowel cancer suggests that these findings should be interpreted with caution.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder.

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.

Alleles↗
PubMed2002

Utilization of breast cancer screening in a clinically based sample of women after BRCA1/2 testing.

We conducted a prospective, observational study to determine breast cancer screening practices among self-referred high-risk women who pursued genetic testing for BRCA1 and BRCA2 mutations. Of the 107 unaffected women included in this study, 41 were BRCA1/2 carriers and 66 women tested negative for a mutation previously identified in their family. All of the women underwent comprehensive pre- and posttest genetic counseling, and completed baseline and 12-month follow-up telephone interviews. The baseline (pretest) interview assessed potential predictors of mammography use, including demographics and psychosocial variables. During the year after the receipt of BRCA1/2 test results, 47% of the noncarriers and 59% of the carriers reported that they had had a mammogram [chi(2) (1, n = 107) = 1.35; P = 0.24]. Only 39% of carriers ages 25-39 reported having a mammogram, versus 74% of carriers age > or =40 [chi(2) (1, n = 41) = 5.10; P = 0.02]. Among noncarriers ages 50 and older, 83% had an annual mammogram. Factors independently associated with mammography use included age (<40, > or =40; odds ratio, 7.5; confidence interval, 2.6-21.5) and test result (odds ratio, 4.6; confidence interval, 1.1-18.7). The effects of perceived likelihood of having a BRCA1/2 gene alteration and the interaction between test result and perceived likelihood were not significant. As expected, most carriers (95%) and noncarriers (77%) obtained a clinical breast exam within the year after the receipt of test results. These data suggest that in carriers, overall, the use of breast cancer screening including mammography is good, although there was a relatively low uptake rate of mammography in younger carriers. Noncarriers had very good adherence to general population screening guidelines.

Adult↗
PubMed1996

Measurement of genetic structure within populations using Moran's spatial autocorrelation statistics.

Spatial structure of genetic variation within populations, an important interacting influence on evolutionary and ecological processes, can be analyzed in detail by using spatial autocorrelation statistics. This paper characterizes the statistical properties of spatial autocorrelation statistics in this context and develops estimators of gene dispersal based on data on standing patterns of genetic variation. Large numbers of Monte Carlo simulations and a wide variety of sampling strategies are utilized. The results show that spatial autocorrelation statistics are highly predictable and informative. Thus, strong hypothesis tests for neutral theory can be formulated. Most strikingly, robust estimators of gene dispersal can be obtained with practical sample sizes. Details about optimal sampling strategies are also described.

Biological Evolution↗
PubMed2005

Genetically engineered murine models of prostate cancer: insights into mechanisms of tumorigenesis and potential utility.

There has been substantial progress made recently in the effort to model human prostate cancer in mice. Several mutant mice have been generated which mimic various aspects of the human disease, including the development of preneoplastic lesions, invasive carcinoma, and metastases. These mouse reagents provide the research community with valuable new tools for dissecting the mechanisms of tumorigenesis, as well as for testing new targeted therapies. This review will summarize some of these models and their utility, as well as propose future challenges for developing improved models.

Animals↗
PubMed2026

Genetic Testing in Cystic Kidney Disease.

Genomic investigation is playing an increasing role in the management of cystic kidney diseases, reflecting a broader shift toward precision medicine in nephrology. Recent updates to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline emphasize diagnostic genomics as a core component of autosomal dominant polycystic kidney disease care in particular, recognizing its utility across a range of clinical scenarios. Traditionally, diagnosis of autosomal dominant polycystic kidney disease has been clinical, using age-dependent imaging criteria for at-risk individuals via ultrasound and magnetic resonance imaging. Although these imaging modalities have good sensitivity, there are pitfalls in clinical diagnosis, particularly in patients with atypical clinical features, those without family history, or those at a young age. A confirmed genetic diagnosis can guide screening of at-risk family members, inform reproductive decisions, support safe selection of living related kidney donors, and provide the opportunity to use genotype-specific prognostication tools. In addition, as genotype-specific therapies enter the landscape, accurate genotyping will become essential for identifying which patients will benefit from treatment. This narrative review aims to provide a practical approach for the general nephrologist of when to offer genetic testing to patients with cystic kidney disease and outline the technical and genetic counseling considerations in the provision of patient-centered genetic investigation.

Humans↗
PubMed1993

Genetic analysis using polymerase chain reaction-amplified DNA and immobilized oligonucleotide probes: reverse dot-blot typing.

The reverse dot-blot method is a simple and rapid diagnostic procedure that allows screening of sample for a variety of mutations/polymorphisms in a single hybridization reaction. Several methods of immobilizing the oligonucleotide probes are discussed. The reverse dot-blot method has several unique properties that are valuable in a diagnostic setting: (1) the typing results from a single sample can be located on a single strip. This facilitates scanning and interpretation of the probe reactivity patterns and minimizes the potential for user error. (2) The test can utilize premade typing strips. This minimizes user labor as well as error potential and allows the use of standardized reagents. (3) Unlike dot-blot/oligonucleotide typing, only the PCR product is labeled, eliminating the potential problem of probes labeled to different specific activities. This method has already been used in the areas of forensic genetic typing (the HLA-DQ alpha Amplitype test), tissue typing for transplantation (the HLA-DR beta) test, cystic fibrosis screening, as well as in a variety of research applications.

Amino Acid Sequence↗
PubMed2004

HIV pharmacogenomics: closer to personalized therapy?

Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to predict adverse drug reactions (ADRs). Because ADRs are defined as any noxious, unintended, and undesired drug effects, loss of efficacy due to the development of antiretroviral drug resistance and both acute and cumulative adverse effects of antiretroviral therapy can be considered ADRs. In order to address these types of antiretroviral-associated ADRs, pharmacogenomic testing methods have expanded to include molecular assays that characterize extranuclear genetic material (e.g. HIV and mitochondrial genomes), as well as the host nuclear genetic material. Recent molecular advances permit high resolution resistance testing that detects loss of therapeutic efficacy through the use of phenotypic, genotypic and/or virtual phenotypic resistance testing. These assays use complex technical and interpretative methods to improve the therapeutic efficacy of antiretroviral therapy. The resistance assays demonstrate the utility of pharmacogenomic testing for patients undergoing lifelong and complex antiretroviral therapies. Future applications of antiretroviral-directed pharmacogenomic tests range from quantitative detection of mitochondrial depletion as an early surrogate marker for drug toxicity, to qualitative analysis of host immune haplotypes, and metabolic/transporter genetic polymorphisms for predicting disease progression. In summary, pharmacogenomic testing for HIV-positive patients provides proof of principle that these tests can be used clinically to improve outcomes for patients undergoing complex and sustained drug regimens.

Anti-HIV Agents↗
PubMed2002

In vivo haploid induction in maize.

Two haploid-inducing lines, MHI and M741H, were used for the production of maternal haploids. Haploids were obtained from all maternal genotypes involved in the experiment, including dent, flint and flintxdent maize. The maternal genotype had a significant influence on the frequency of haploids obtained. The frequency ranged from 2.7% to 8.0%. For chromosome-doubling seedlings were treated with colchicine solution, and 49.4% of the haploid plants produced fertile pollen, 39.0% could be selfed and 27.3% produced seeds after selfing. Synthetic populations, improved by haploid sib recurrent selection, were tested in a field trial. The results show that the utilization of maternal haploid plants has great potential for maize breeding and maize genetics.

Journal Article↗
PubMedDate not supplied

Use of an internal standard in a closed one-tube RT-PCR for the detection of equine arteritis virus RNA with fluorescent probes.

Routine detection of equine arteritis virus (EAV) can be achieved by virus isolation (VI) in cell culture, or by the amplification of viral genome by molecular methods. To simplify molecular diagnosis, a number of different Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and RT-nested PCR (RT-nPCR) assays were compared, and a one-tube method was developed and optimised utilizing a fluorogenic probe (TaqMan). An artificial RNA template (Mimic) and associated probe were also constructed to provide in-tube validation of the RT-PCR system. To assess the utility of the RT-PCR TaqMan assay, 28 different isolates of EAV representing different genetic groups of American and European strains were tested. Furthermore, the ability of VI and RT-PCR TaqMan assay to detect EAV in different biological matrices such as semen, nasal and faecal swabs and blood was compared. All 28 EAV strains were detected by the RT-PCR TaqMan assay. The results of TaqMan and VI testing were in agreement for 30 of the 33 semen samples and all of the 50 other clinical specimens examined: the RT-PCR TaqMan assay detected 18 positive semen samples, three more than VI. In conclusion, the one-tube RT-PCR TaqMan assay is a rapid, reliable method for the detection of EAV.

Animals↗
PubMed2006

Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome.

OBJECTIVE: To determine whether variants in the Slit and Trk-like 1 gene (SLITRK1) are present in American Caucasian population of patients with Tourette syndrome (TS). METHODS: We sequenced the 3'-untranslated region for var321 and the whole coding region in the SLITRK1 gene in 82 Caucasian patients with TS from North America. RESULTS: None of the 82 samples from patients with TS showed the non-coding sequence variant (var321). Only one patient with familial TS was heterozygous for a novel 708C > T (Ile236Ile) nucleotide variant. CONCLUSIONS: The var321 and mutation(s) in the coding region of the SLITRK1 gene probably are a rare cause of TS in a Caucasian population; therefore, genetic heterogeneity of TS should be considered. Tests designed to detect variant(s) in the SLITRK1 gene probably will not have a diagnostic utility in clinical practice.

3' Untranslated Regions↗
PubMed2006

Targeted screening for genetic haemochromatosis: a combined phenotype/genotype approach.

OBJECTIVE: To evaluate the clinical utility of a targeted screening approach for the detection of genetic haemochromatosis. METHODS: Screening by measuring fasting serum transferrin saturation (TS) and gene testing was carried out in patients in whom a raised serum alanine amino transferase (ALT) activity and raised random serum TS had been found on routine blood testing. RESULTS: During the 29 month study period, 32 patients homozygous for the C282Y genotype were detected from a catchment population of 330,000 by screening blood samples referred initially for routine laboratory liver function tests. By comparison, during the same period of time and within the same population, only seven patients were found by clinical suspicion alone. The patients in the study, after treatment by venesection, have shown both clinical and biochemical improvement. CONCLUSIONS: The study shows that from a population of patients in whom a routine liver function profile had been requested, it is possible to detect subjects homozygous for the C282Y HFE genotype who have clinical or biochemical markers of iron overload.

D-Alanine Transaminase↗
PubMed2005

Genetic polymorphisms and the risk of stroke after cardiac surgery.

BACKGROUND AND PURPOSE: Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery. METHODS: Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies. RESULTS: A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3'UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (P=0.0020). CONCLUSIONS: We demonstrate that common genetic variants of CRP (3'UTR 1846C/T) and IL-6 (-174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post-cardiac surgery stroke.

Aged↗
PubMed1997

Utility of the lethargic (lh/lh) mouse model of absence seizures in predicting the effects of lamotrigine, vigabatrin, tiagabine, gabapentin, and topiramate against human absence seizures.

PURPOSE: Traditional methods of preclinical screening have predicted the effects of a putative antiepileptic drug (AED) against human absence seizures by testing its efficacy against clonic seizures in the high-dose pentylenetetrazole (PTZ) model. This high-dose PTZ model correctly predicted the efficacy of ethosuximide (ESM), benzodiazepines, and valproate (VPA) and the lack of efficacy of phenytoin (PHT) and carbamazepine (CBZ). However, the high-dose PTZ model erred in predictions for (a) phenobarbital (PB) (PTZ: efficacy; human: nonefficacy); (b) lamotrigine (LTG) (PTZ: nonefficacy; human: efficacy); (c) vigabatrin (VGB) (PTZ: nonefficacy; human: proabsence effect); and (d) tiagabine (TGB) (PTZ: efficacy; human: possible proabsence). It also appears to have erred in predictions for gabapentin (GBP) (PTZ: efficacy) and topiramate (TPM) (PTZ: efficacy). Because the lh/lh genetic model of absence seizures correctly predicted effects of ESM, clonazepam, VPA, PHT, CBZ, and PB against human absence seizures, we performed this study to test the predictive utility of the lh/lh model for LTG, VGB, TGB, GBP, and TPM. METHODS: Bipolar recording electrodes were implanted bilaterally into frontal neocortex of 8-week-old male lh/lh mice. With the exception of VGB, vehicle or drugs were administered intraperitoneally (i.p.) on alternating days, and an EEG was used to record effects on seizure frequency. With VGB, vehicle was administered i.p. on day 1, and gradually increasing doses of VGB were administered on successive days. Drug and vehicle effects were compared in corresponding 15-min epochs of the 150-min period after administration. RESULTS: LTG (4.8-144 micromol/kg) significantly (p < 0.04) reduced seizure frequency (by 65%) compared with vehicle. In contrast, VGB (0.35-11 mmol/kg) and TGB (0.27-27 micromol/kg) significantly increased seizure frequency (300-700%) and seizure duration (1,700-1,800%; p < 0.001). GBP (18 micromol/kg to 1.8 mmol/kg) and TPM (8.9-295 micromol/kg) had no significant effect on seizure frequency. CONCLUSIONS: In contrast to the high-dose PTZ model, the lh/lh model correctly predicted the antiabsence effect of LTG, the possible proabsence effects of VGB and TGB, and the lack of effect of GBP and TPM. The lh/lh model appears to be superior to the high-dose PTZ model in predicting efficacy of putative AEDs against human absence seizures.

Acetates↗