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 253 records · Page 14Linked to original sources

PubMed2000

Comparative genomic hybridization studies in hydatidiform moles and choriocarcinoma: amplification of 7q21-q31 and loss of 8p12-p21 in choriocarcinoma.

Comparative genomic hybridization (CGH) was utilized to investigate genetic changes from archived cases of choriocarcinoma (n = 12) and hydatidiform moles (n = 7). Test DNA was extracted from paraffin-embedded tissues, amplified using total universal PCR, and co-hybridized with control DNA to normal metaphases. Comparative genomic hybridization findings showed chromosomal imbalances in 9 of 12 cases of choriocarcinoma. By contrast, all hydatidiform moles showed normal CGH profiles. Consistent findings in choriocarcinoma included deletion at 8p (5 cases) and amplification at 7q (4 cases). A tumor suppressor gene (e.g., N33) at 8p and/or a growth regulator at 7q could play a role in the initiation of choriocarcinoma and its progression. This is the first study showing specific alterations in choriocarcinomas by CGH, and illustrates the utility of this technique in elucidating genetic changes in gynecological tumors.

Adult↗

PubMed1987

Strategies to control cancer through genetics.

Although genetic factors may be essential in only a fraction of common cancers, it is important to identify individuals who merit genetic evaluation. The occurrence of cancer in an individual under one of the following circumstances may indicate an increased susceptibility to malignancy as a result of predisposing factors: cancer in both of paired organs, thought not to be the result of metastasis; more than one focus of cancer in a single organ (multifocal tumors); histologically similar malignant neoplasms in different parts of the same organ system; two histologically distinct cancers (multiple primary malignancies); cancer at an atypical age; at an atypical site; in the usually less often affected sex; associated with birth defects; associated with precursor lesions; in a person with immunodeficiency; or in a patient with one of the 200 Mendelian disorders where cancer is part of the clinical picture or a frequent complication. At risk are first-degree relatives of people who meet any of the above criteria. Also, a person should be considered at risk if two first-degree relatives had any form of cancer. A strategy to control cancers utilizing genetic knowledge should include such measures as: genetic counseling of individuals at risk for specific cancers because of a congenital or genetic disease in themselves or their relatives, or because of the pattern of cancer occurrence in the family; prenatal diagnosis for families with genetic conditions that predispose to cancer and are amenable to prenatal testing; surveillance of high-risk individuals to detect early manifestations of new or recurrent disease; prophylactic removal of the target organ or tissue in appropriate cases; limiting exposure of high-risk individuals to known carcinogens or supplementing diets of high-risk individuals with anticarcinogens; and educational and administrative measures to promote practical application of genetic knowledge and to increase awareness of genetic factors in the etiology of cancer. Far from all individuals who are exposed to carcinogenic factors contract cancer, and in another common disease, atherosclerosis, it is well known that there is genetically determined variation in response to environmental or lifestyle factors that can cause disease. The emerging fields of human ecogenetics and predictive testing together with research progress in medical and molecular genetics are likely to improve greatly the possibilities for utilizing genetic knowledge to control cancer.

Environment↗

PubMed1994

Diffusion of information about neurofibromatosis type 1 DNA testing.

There is little information available as to how individuals with genetic disorders receive information about the availability of DNA tests and what effect this has on their utilization. The purpose of this study was to survey centers where some individuals with neurofibromatosis type 1 (NF 1) are cared for, to establish how this type of information was disseminated. In 1990 announcement of the availability of testing for familial NF 1 was published in a newsletter of the National Neurofibromatosis Foundation (NNFF) and sent to individuals with NF 1 or NF 2 and their families, professionals, and NF centers in North America. Two years later these centers were surveyed to determine whether they had notified their patients of test availability. Of the 46 responding centers, 65% indicated they had attempted to notify their patients. The majority (80%) notified patients on an individual basis in clinic. The rest did so either on an individual basis in the clinic or by telephone or by letter or by a combination of these. Based on a survey response rate of 56% and approximately 1,000 enquiries received by the NNFF from families and physicians, it is concluded that 1) factors other than knowledge of test availability determined whether DNA testing for NF 1 was utilized; 2) some centers used testing more frequently than others; 100% of the referrals came from 40% of the centers, with 15% of referrals coming from a single center; 3) a significant percentage (35%) of NF centers did not inform their patients that DNA testing was available.

DNA↗

PubMed1990

Carcinogenicity results for 114 laboratory animal studies used to assess the predictivity of four in vitro genetic toxicity assays for rodent carcinogenicity.

Carcinogenicity results are presented for 114 long-term rodent studies carried out by the National Toxicology Program. Tumor rates are given for each positive or equivocal effect observed in 67 studies judged to show carcinogenic effects and in the 17 studies that show equivocal effects. The liver was found to be the most common site of carcinogenicity for both mice and rats; other frequent target sites included the lung, kidney, hematopoietic system, forestomach, thyroid gland, and mammary gland. The evaluative approach used in reaching decisions regarding the carcinogenicity of chemicals is discussed. No rigid statistical decision rules were employed, and biological as well as statistical factors were considered in the overall evaluation of the data. These long-term studies were utilized in a comprehensive evaluation of the ability of four in vitro genetic toxicity tests to predict rodent carcinogenicity. Details concerning these procedures and the results of this investigation are given elsewhere [Zeiger E, Haseman JK, Shelby MD, Margolin BH, Tennant RW 1990: Environ Mol Mutagen 16 (Supp. 18):1-14]. Interestingly, those chemicals evaluated at relatively low doses in the rodent experiments (because of the underlying toxicity of the chemicals) were far more likely to be positive in each of the four genetic toxicity assays than were "less toxic" chemicals evaluated in higher doses in the rodent studies.

Animals↗

PubMed2006

An algorithm for model construction and its applications to pharmacogenomic studies.

A model depicts the relationship between clinical phenotypes and genotypes on a set of genetic polymorphisms. After the model is constructed and validated, it may be used to predict clinical phenotypes such as traits of complex diseases. A pharmacogenomic model is used to predict the efficacies or adverse drug reactions of a medication. The construction of a model is a challenging task. This is because a single-locus polymorphism does not contain enough information to stratify patients in general, given the complex biological mechanisms involved. An exhaustive search for the correct combination of genotypes across multiple loci is, however, computationally infeasible. We are, thus, motivated to propose a novel algorithm for the construction of models using the multiple single-nucleotide polymorphism (SNP) information in diplotype forms. This algorithm utilizes the techniques of genetic algorithms and Boolean algebra (GABA). The proposed algorithm is tested on simulated data, as well as real genotype datasets of chronic hepatitis C patients treated with interferon-combined therapy. A model for predicting the treatment efficacy is constructed and validated. The results showed that the proposed algorithm is very effective in deriving models comprising multiple SNPs.

Algorithms↗

PubMed2004

Mouse models of human cancer as tools in drug development.

Histologically accurate mouse models of human cancers generated by somatic or germline genetic modification strategies recapitulate the genetic alterations found in human tumors. In this issue of Cancer Cell, test a novel signaling inhibitor in a genetically defined mouse medulloblastoma and show the utility of these models in drug development. They demonstrate that targeting signaling components downstream of tumor initiating mutations can be an effective therapeutic strategy for solid tumors.

Animals↗

PubMed2003

The use of genetically altered mice for breast cancer prevention studies.

Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive carcinoma formation, they may be particularly useful for determining cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/t-antigen transgenic mouse mammary cancer model has been utilized for chemopreventive research in which mammary tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary tumor development in this model, including retinoids, di-fluoromethylornithine (DFMO), dehydroepiandrosterone (DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human ductal carcinoma in situ (DCIS) to invasive carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action.

Animals↗

PubMed1998

Two new Rahnella genomospecies that cannot be phenotypically differentiated from Rahnella aquatilis.

Fifty-one Rahnella aquatilis and R. aquatilis-like strains from water, snails and human sources were characterized by routine biochemical tests, carbon source utilization tests, DNA relatedness (hydroxyapatite method) and 16S rRNA sequencing. The results of the genetic methods indicated that the strains comprised three closely related species within the genus Rahnella. It was not possible to differentiate R. aquatilis from the two newly recognized species. The new species were therefore given the vernacular names Rahnella genomospecies 2 and Rahnella genomospecies 3.

Animals↗

PubMed1999

Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration.

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.

Animals↗

PubMed1977

Short-term tests and mycotoxins.

Naturally-occurring fungal metabolites, such as aflatoxins and sterigmatocystin, are specific examples of toxic and hepatocarcinogenic environmental contaminants which are active in Fish, Birds, Mammals and, probably, Man. The biological potency of these substances has led to a search for other carcinogenic fungus-derived products. As screening techniques for selecting compounds to be tested for their genetic and carcinogenic potency in animals, various short-term tests can be currently utilized. The use of mutagenesis, DNA repair, chromosomal aberrations, cell transformation, cytological alterations and reaction with nucleic acids in vivo or in vitro as end-points in short-term tests to detect potential chemical carcinogens will be presented. Based on recent data in the literature and from our own research activities, 2 major aspects of various short-term tests will be critically reviewed: a. their predictive value, in order to assess the possible carcinogenic risk of mycotoxins, and b. their utility to investigate the mechanism of metabolic activation of these chemicals in Mammals and in Man.

Animals↗

PubMed2003

Animal models of human disease in drug safety assessment.

Animal models of human disease have been widely used in drug discovery, but they are rarely utilized in toxicological research and screening (except for transgenic models in carcinogenicity testing). Although genetic and/or acquired pathophysiological alterations associated with a particular disease may greatly exacerbate toxic responses to drugs in certain patient subsets, these pre-existing pathological conditions are usually not considered in preclinical safety assessment. Examples of disease-related determinants of susceptibility include disruption of the cytokine network in pro-inflammatory conditions, mitochondrial alterations and oxidative stress in certain neurodegenerative diseases, altered antioxidant defense in certain viral infections, and altered gene expression and mitochondrial dysfunction in type 2 diabetes. Hence, if cellular stress caused by drugs or metabolites and the disease-related effects are superimposed, then an individual can become sensitized to potential drug toxicity. Animal models of modest inflammation indeed can potentiate the toxicity of certain drugs. Similarly, rodent models of type 2 diabetes predispose the animals to hepatotoxic effects of thiazolidinediones antidiabetics. In conclusion, it is suggested that tailor-made and simplified models be adopted and increasingly used, in spite of clear limitations, as optimal substrates for satellite toxicity studies to facilitate candidate selection, help predict rare and unexpected toxicity, and identify new biomarkers.

Animals↗

PubMedDate not supplied

Genetic marker analysis in cases of disputed paternity when the alleged father is deceased.

Data are presented to demonstrate the utility of genetic marker analysis in cases of disputed paternity in which the alleged father is deceased prior to testing. The first case involves the histocompatibility (HLA) typing of the alleged father's parents and presumed mother and child, in which the deceased alleged father (AF) was not excluded from paternity. The second case involves a similar situation. However, the deceased AF was not clearly excluded from paternity in the HLA system owing to the inability to rule out gene suppression or deletion, but the deceased AF was excluded following red blood cell antigen typing of the man's parents. These two cases demonstrate the utility of genetic marker analysis in cases of disputed paternity in which the AF is deceased. This same type of analysis can be applied to cases in which the presumed mother is either deceased or missing and custody of the child is being sought by the alleged father.

Erythrocytes↗

PubMed2004

Development and integration of molecular genetic tests into clinical practice: the US experience.

The issues that arise in the development of genetic tests for prediction and diagnosis are described in the context of the authors' experience as laboratory directors in the USA. The goal is to identify gaps and weaknesses in the test validation process and to define the pivotal issues. Variables that influence a laboratory director's decision to develop a particular molecular genetic assay, including motivation, economics, intellectual property and the regulatory environment, are described. Issues of clinical and analytic validation are discussed, providing examples of tests with both good (cystic fibrosis carrier screening) and poor (apolipoprotein E genotyping for Alzheimer's disease) clinical utility. The decision-making process that occurs during the considered transition of a research-based molecular genetic assay into routine use in the clinical laboratory is summarized. Different factors will be weighted differently depending on the nature of the disease being tested, the complexity of its gene and mutations, the available technical platforms, potential regulatory and intellectual property restrictions, and whether the proposed test is to be offered by an academic or a commercial laboratory.

Alzheimer Disease↗

PubMed2003

Ethical issues raised by genetic testing with oligonucleotide microarrays.

Because genes and alterations within them determine the identity, characteristics, and inheritance of every individual, the application of genetic science to humans has long been surrounded by apprehension, controversy, and real or perceived potential for abuse. Crude eugenics practices of the past now find a theoretical rebirth and transformation through the use of modern molecular genetic technologies for mutation detection, predictive and prenatal diagnosis, and, ultimately, gene replacement. The advent of oligonucleotide microarray analysis, in which hundreds or thousands of genes and mutations can be tested in parallel, offers tremendous promise for more accurate, sensitive, and efficient genetic testing. At the same time, however, this powerful technology dramatically increases the number and scope of ethical concerns accompanying each individual test request. This article considers the evolution and implications of these concerns, from the initial ordering of a microarray test by the physician to such issues as informed consent, privacy, confidentiality, clinical utility, discrimination, stigmatization, ethnic and population impact, and reimbursement.

Confidentiality↗

PubMed2006

Genetic diagnosis and testing in clinical practice.

Genetic testing is defined as "the analysis of human DNA, RNA, chromosomes, proteins and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes or karyotypes for clinical purposes." This article focuses on diagnostic and predictive genetic testing. The latter includes presymptomatic testing, which identifies individuals who are expected to become ill in the future and predisposition testing, which identifies those who are at increased risk of becoming ill. Decisions regarding genetic testing must be based not only on the analytic accuracy, availability and cost of the test, but on the clinical utility as well, including the sensitivity, specificity and interpretability of results. Clinical information, including the medical and family history and the findings of the physical examination, is vital for the selection of appropriate diagnostic tests, as well as the interpretation of the results. Presymptomatic genetic testing is a very personal choice that should only be made after the patient has had sufficient counseling to develop an understanding of the risks and benefits of the test and is able to make an informed decision. The same principle applies to predisposition testing; however, additional factors, such as the probability of a positive result, the likelihood that the disease will actually develop in those with positive results, the effect on the management of the index patient, the effects on family members, the risk of false reassurance if the result is negative or the potential for loss of hope if it is positive, all contribute to the assessment of risk versus benefit. Clinical evaluation and counseling of the patient who is at risk for a genetic disorder are labor intensive but essential for the selection and interpretation of genetic tests.

Cost-Benefit Analysis↗

PubMed1996

Utility of a test for chromosomal malsegregation in Saccharomyces cerevisiae strain D61.M for the detection of antianeugens: test of the model combination of chlorophyllin and nocodazole.

Despite the fact that aneuploidy is a major genetic cause of human morbidity and mortality, antimutagenicity studies have used predominantly short-term tests that detect gene mutations, chromosomal aberrations, and micronuclei. Therefore, the major deficiency in the use of short-term tests for antimutagenicity studies is those that detect chromosomal malsegregation leading to aneuploidy. Thus, we initiated a study on the utility of short-term tests for the detection of antianeugenic activity. We selected strain D61.M of Saccharomyces cerevisiae, nocodazole, and chlorophyllin as a model short-term test, aneugen, and antimutagen, respectively, for our initial study. Chlorophyllin strongly inhibited the aneugenic activity of nocodazole, but had no effect on the endpoints when tested alone, in strain D61.M. To our knowledge, this is the first report of an antianeugen. Furthermore, we conclude that strain D61.M can be used as a relatively simple, inexpensive, and rapid short-term test for the study of antianeugenicity.

Aneuploidy↗

PubMedDate not supplied

Genetic evaluation for coronary artery disease.

There is substantial evidence that genetic factors contribute to coronary artery disease (CAD). Currently, family history collection and interpretation is the best method for identifying individuals with genetic susceptibility to CAD. Family history reflects not only genetic susceptibility, but also interactions between genetic, environmental, cultural, and behavioral factors. Stratification of familial risk into different risk categories (e.g., average, moderate, or high) is possible by considering the number of relatives affected with CAD and their degree of relationship, the ages of CAD onset, the occurrence of associated conditions, and the gender of affected relatives. Familial risk stratification should improve standard CAD risk assessment methods and treatment guidelines (e.g., Framingham CAD risk prediction score and Adult Treatment Panel III guidelines). Individuals with an increased familial risk for CAD should be targeted for aggressive risk factor modification. Individuals with a high familial risk might also benefit from early detection strategies and biochemical and DNA-based testing, which can further refine risk for CAD. In addition, individuals with the highest familial risk might have mendelian disorders associated with a large magnitude of risk for premature CAD. In these cases, referral for genetic evaluation should be considered, including pedigree analysis, risk assessment, genetic counseling and education, discussion of available genetic tests, and recommendations for risk-appropriate screening and preventive interventions. Research is needed to assess the feasibility, clinical validity, clinical utility, and ethical, legal, and social issues of an approach that uses familial risk stratification and genetic evaluation to enhance CAD prevention efforts.

Coronary Artery Disease↗

PubMed2025

Genomic sequencing in diverse and underserved pediatric populations: Parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

PURPOSE: Limited evidence evaluates parents' perceptions of their child's clinical genome-scale sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap. METHODS: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure. We assessed outcomes' associations with child- and parent-related factors: child age; type of GS finding; and parent health literacy, numeracy, and education. RESULTS: A total of 1763 parents completed surveys; 83% met "underserved" criteria based on race, ethnicity, and risk factors for barriers to access. We observed high perceived understanding and personal utility and low test-related distress. Outcomes were associated with the type of GS finding; parents of children with a pathogenic or likely pathogenic finding endorsed higher personal utility and more test-related distress than those whose children had a variant of uncertain significance or normal finding. Personal utility was higher in parents who met the criteria for "underserved." CONCLUSION: Our findings shed light on correlates of parents' cognitive and emotional responses to their child's GS findings and emphasize the need for tailored support in disclosure discussions.

Humans↗