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Results for “genetic test utilization”

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At least 217 records · Page 12Linked to original sources

PubMed1992

Genetic analysis of cleft lip with or without cleft palate in Madras, India.

We performed a genetic analysis of 331 non-syndromic cleft lip with or without cleft palate (CL +/- P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness-of-fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL +/- P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL +/- P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL +/- P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia.

Cleft Lip↗

PubMed1997

The use of two different APC resistance assay systems provides optimal sensitivity and specificity for diagnosing genetic APC resistance.

We compared the performance characteristics of a commercial dilute Russell's viper venom (DRVV)-based APC resistance assay (Gradipore PC Impedance Test) to a routinely utilized commercial APTT based assay (Coatest APC Resistance Assay). The DRVV based assay offers improved sensitivity and specificity for the factor V Leiden mutation. However, the routine use of both assays provides optimum reliability for diagnosis of genetic APC resistance. Our results suggest that when both tests are either positive or negative, DNA analysis is unnecessary. Interference by lupus anticoagulants is dramatically minimized by the phospholipid rich DRVV reagent used in the assay and it is insensitive to high factor VIII activity. Additionally, discrepant functional assay results allow identification of patients who may have an acquired APC resistant phenotype.

Animals↗

PubMed2004

Genetic testing for breast and ovarian cancer susceptibility: evaluating direct-to-consumer marketing--Atlanta, Denver, Raleigh-Durham, and Seattle, 2003.

Breast and ovarian cancer are the second and fifth leading causes of cancer death, respectively, among women in the United States. One in eight women will have breast cancer during their lifetimes, and one in 70 will have ovarian cancer. Mutations in two genes, BRCA1 and BRCA2 (BRCA1/2), are associated with predisposition for inherited breast and ovarian cancer and are identified in 5%-10% of women with breast or ovarian cancer (BOC). Since 1996, genetic testing for these mutations has been available clinically; however, population-based screening is not recommended because of the complexity of test interpretation and limited data on clinical validity and utility. Despite the test's limited applicability in the general population, the U.S. provider of clinical BRCA1/2 testing (Myriad Genetic Laboratories, Inc., Salt Lake City, Utah) conducted a pilot direct-to-consumer (DTC) marketing campaign in two cities (Atlanta, Georgia, and Denver, Colorado) during September 2002-February 2003. Although DTC advertisements have been used to raise consumer awareness about pharmaceuticals, this was the first time an established genetic test was marketed to the public. To assess the impact of the campaign on consumer behaviors and health-care provider practices, CDC and the respective state health departments for the pilot cities and two comparison cities (Raleigh-Durham, North Carolina, and Seattle, Washington) surveyed consumers and providers. This report summarizes results of those surveys, which indicated that consumer and provider awareness of BRCA1/2 testing increased in the pilot cities and that providers in these cities perceived an impact on their practice (e.g., more questions asked about testing, more BRCA1/2 tests requested, and more tests ordered). However, in all four cities, providers often lacked knowledge to advise patients about inherited BOC and testing. These findings underscore the need for evidence-based recommendations on appropriate use of genetic tests and education of providers and the public to achieve maximum individual and public health benefit from genetic testing.

Adult↗

PubMed2026

Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.

Genome sequencing is the first-line diagnostic method for primary mitochondrial diseases (PMDs), yet its effectiveness is limited by variants of uncertain significance or unresolved genetic findings. We systematically evaluated the clinical performance of fibroblast-based functional testing, comprised of respiratory chain enzyme assays, blue native polyacrylamide gel electrophoresis with in-gel activity staining (BN-PAGE), complex I assembly assay, and targeted protein abundance assessments, in a cohort of 204 genetically confirmed PMD patients, 51 healthy controls, and 53 patients with differential diagnoses. Individually, enzyme assays, BN-PAGE, and complex I assembly assay showed sensitivities of 46%, 40%, and 49%, with specificities of 93%, 98%, and 99%, respectively. Combined, the assays achieved an overall sensitivity of 76%, a specificity 93%, a positive predictive value 96%, and a negative predictive value of 67%. Sensitivity was highest for isolated respiratory chain deficiencies, nuclear DNA-encoded mitochondrial translation defects, cofactor deficiencies, and mitochondrial aminoacyl-tRNA synthetase disorders, whereas mitochondrial DNA variants and maintenance defects remained challenging. Secondary mitochondrial dysfunction was rare. The strong clinical utility of comprehensive fibroblast functional testing improves PMD diagnosis when used complementary to genomic sequencing.

Journal Article↗

PubMed1984

Genetic and physical maps of Klebsiella aerogenes genes for histidine utilization (hut).

Deletion derivatives of the hut-containing plasmid pCB101 were tested against point mutants defective in individual genes of the histidine utilization (hut) operons using a complementation/recombination assay. Location of the genes of the right operon, hutU and hutH, was confirmed by direct assay of the gene products, urocanase and histidase; location of the repressor gene was identified by measuring the ability of the plasmid-carried genes to repress the formation of histidase from a chromosomal location. The analysis of eight deletion plasmids unambiguously confirms the map order of the hut genes as hutI-G-C-U-H, and demonstrates that, in Klebsiella aerogenes, the hutU and hutH genes are transcribed from their own promoter. In addition, the genetic map of hut can be aligned with the restriction map of the hut DNA in plasmid pCB101. One of the deletion plasmids studied apparently encodes a defective histidase subunit that is trans-dominant to active histidase. Another deletion, which completely removes the left operon, hutIG, allows high level expression of the hutUH operon and thus overproduction of a toxic intermediate.

Escherichia coli↗

PubMed1976

Mutations affecting catabolite repression of the L-arabinose regulon in Escherichia coli B/r.

Expression of the L-arabinose regulon in Escherichia coli B/r requires, among other things, cyclic adenosine-3', 5'-monophosphate (cAMP) and the cAMP receptor protein (CRP). Mutants deficient in adenyl cyclase (cya-), the enzyme which synthesizes cAMP, or CRP (crp-) are unable to utilize a variety of carbohydrates, including L-arabinose. Ara+ revertants of a cya-crp- strain were isolated on 0.2% minimal L-arabinose plates, conditions which require the entire ara regulon to be activated in the absence of cAMP and CRP. Evidence from genetic and physiological studies is consistent with placing these mutations in the araC regulatory gene. Deletion mapping with one mutant localized the site within either araO or araC, and complementation tests indicated the mutants acted trans to confer the ability to utilize L-arabinose in a cya-crp- genetic background. Since genetic analysis supports the conclusion, that the mutant sites are in the araC regulatory gene, the mutants were designated araCi, indicating a mutation in the regulatory gene affecting the cAMP-CRP requirement. Physiological analysis of one mutant, araCi1, illustrates the trans-acting nature of the mutation. In a cya-crp- genetic background, araCi1 promoted synthesis of both isomerase, a product of the araBAD operon, and permease, a product of the araE operon. Isomerase and permease levels in araCi1 cya+ crp+ were hyperinducible, and the sensitivity of each to cAMP was altered. Two models are presented that show the possible mutational lesion in the araCi strains.

Adenylyl Cyclases↗

PubMed1985

[Foreign substances as indicators of liver function].

The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine. Recently, caffeine clearance in saliva has been studied extensively in this laboratory, and, on the basis of a constant relationship between caffeine concentrations in serum and saliva, overnight clearance measurements (requiring a saliva sample at bedtime and upon arising following a single oral dose of caffeine) have been shown to be closely related to ABT or GEC. This approach, which has been successfully used in children, may represent the first simple and innocuous test for quantifying of hepatic function in the pediatric age group. The clinical utility of these clearance tests is to assess severity of disease (or genetically determined impairment of function), thus yielding important clues to prognosis.

Aminopyrine↗

PubMed2002

Testing for genetic associations with the PAX gene family in a spina bifida population.

Neural tube defects (NTDs) are among the most common severely disabling birth defects in the United States, affecting approximately 1-2 of every 1,000 live births. The etiology of NTDs is multifactorial, involving the combined action of both genetic and environmental factors. A nonparametric linkage method, the transmission disequilibrium test (TDT), was utilized to determine if the genes in the PAX family play a role in the formation of NTDs. DNA from 459 spina bifida (SB) patients and their parents (430 mothers and 239 fathers, for a total population of 1,128 subjects) was tested for linkage and association utilizing polymorphic markers from within or very close to the PAX genes of interest. Significant findings were obtained for the following markers: marker locus D20S101 flanking the PAX1 gene (P = 0.019), marker locus D1S228 within the PAX7 gene (P = 0.011), and marker locus D2S110 within the PAX8 gene (P = 0.013). Even though our findings are only mildly significant, given the known expression patterns of the PAX genes in development and the availability of their sequences, we elected to follow up these results by testing these genes directly for mutations utilizing single-strand conformational analysis (SSCA) and direct sequencing. Multiple variations were detected in each of the PAX genes with significant TDT results; however, these variations were not passed from parent to child in phase with the positively transmitted allele. Therefore, it is unlikely that these variations contribute to susceptibility for SB, but rather are previously unreported polymorphisms.

Adolescent↗

PubMed1983

Effect of dietary aflatoxin concentration on the assessment of genetic variability of response in a randombred population of chickens.

The effect of graded levels of dietary aflatoxin on the assessment of genetic variability of body weight and gain and plasma protein response was tested utilizing the Athens-Canadian randombred population of chickens. Dietary aflatoxin was administered at levels of either 0, 1.25, 2.50 or 5.0 microg/g of diet ad libitum from 7 to 21 days of age to progeny from 58 sire families. Twenty-one-day body weights, gain and plasma protein concentration were used to assess the variation in response.-The administration of increasing levels of aflatoxin resulted in a dose-related decrease of gains and plasma protein concentrations. Plasma protein concentrations were significantly higher among males than females within the control group; however, this difference was reversed as the severity of the aflatoxin challenge increased. Heritability estimates for all responses increased as the level of aflatoxin administered increased. This change was most notable for total plasma protein concentration. Phenotypic correlations for plasma protein concentration and growth measurements tended to diminish with increasing levels of aflatoxin. A similar trend was noted for the genetic correlations; however, a moderate correlation between growth responses and plasma protein response was detected in the 5.0-microg/g aflatoxin treatment group. Genetic correlations were calculated for the same characters between the different levels of aflatoxin. Regardless of which aflatoxin challenges were compared, a very high genetic correlation for 21-day body weight and 7- to 21-day gain was estimated. This variation in growth potential in the toxic environment paralleled that observed in the control environment but at a lower plane. Genetic correlations for plasma protein response across aflatoxin levels diminished as the difference between the levels of aflatoxin administered increased. Plasma protein concentration in the control environment was positively correlated with plasma protein response in groups fed a low level of aflatoxin, but negatively correlated when an aflatoxin challenge of 2.5 microg/g or more was given, suggesting that selection for aflatoxin resistance using plasma protein response as a selection criterion should be made under an aflatoxin stress environment.

Aflatoxins↗

PubMed1981

The role of human genetic monitoring in the workplace.

The history and current state of some newer short-term tests for occupational genetic monitoring are reviewed. These are: cytogenetics, sister chromatid exchange, body fluid analysis, tests utilizing sperm, and detection of somatic cell variants. Occupational studies on benzene, vinyl chloride monomer, and epichlorohydrin are critically discussed from the standpoints of design and interpretation. It is concluded that these tests are not appropriate for risk assessment at the present time. Their clinical relevance, if any, is unknown. Proper validation and standardization have not been done, and design problems have often clouded the results of previous studies. There is a critical need for further research in the area of occupational genetic monitoring. Future applications should include integration with prospective morbidity and mortality studies, standardization of design and statistical methods, and development of new tests with genetically relevant endpoints.

Benzene↗

PubMed2004

Some implications of genetic biomarkers in occupational epidemiology and practice.

This paper addresses the use of genetic biomarkers in occupational epidemiology and some of the scientific, ethical, and social implications for epidemiologists and practitioners to consider, including issues involving individual risk estimation, the communication of epidemiologic results, and the translation of epidemiologic data into clinical or occupational health practice. Three scenarios from the occupational setting illustrate some of these issues and implications. The scenarios involve glutathione-S-transferase theta 1 (GSTT1) and hematopoietic cancer in hospital workers, human leukocyte antigen coding for glutamic acid in the 69th position (HLA DPB1(E69)) and chronic beryllium disease in beryllium workers, and peripheral myelin protein 22 (PMP22) deletion and carpal tunnel syndrome in railroad track workers. Epidemiologic research involving genetic biomarkers requires the application of genetic tests and can be considered on a continuum between basic sciences and clinical and occupational and public health practice for which questions of test relevance, validity, and utility become important.

Environmental Monitoring↗

PubMed1999

Clinical utility of direct mutation testing for congenital nephrogenic diabetes insipidus in families.

OBJECTIVE: To ascertain the clinical scenarios in which genetic testing for congenital nephrogenic diabetes insipidus (NDI) by direct detection of mutations might prove valuable, and to assess the use of automated sequencing for testing. METHODS: We reviewed NDI cases referred to our research laboratory for enrollment in our study of mutations in the AVPR2 gene that is disrupted in the X-linked form of the disease. We selected 5 cases that illustrate the value of genetic testing in different clinical situations. Clinical information was obtained from the patient's personal physicians and the patients' families. Direct automated fluorescent DNA sequencing of AVPR2 gene amplification product was used to identify disease-associated mutations in patients. The presence or absence of mutations in family members was then established by using automated sequencing, restriction enzyme analysis, or both. RESULTS: In 2 of the 5 selected cases, the diagnosis of a genetic form of NDI was confirmed by mutation analysis in a sporadic case of an affected boy. In 2 cases, a suspected diagnosis of X-linked NDI was confirmed in an affected girl. In 4 of the cases, 1 or more unaffected female relatives were determined to carry or not to carry the disease-associated gene. In 2 cases, testing of the newborn child of a known or suspected carrier confirmed the clinical suspicion of affected status and justified proactive therapy. In 4 of the 5 cases, the mode of inheritance was not clear from the family history and was established as X-linked by the testing. Assay for restriction sites changed by disease-associated mutations agreed with the automated sequencing results. CONCLUSIONS: We conclude that direct mutation analysis in patients suspected of NDI and in selected family members is indicated. The results of testing can confirm a clinical diagnosis of disease, which may otherwise be difficult to make in girls. It can further establish the mode of inheritance, unambiguously distinguish carriers from noncarriers, and justify special observation or treatment of newborns at risk, thereby averting dehydration and the attendant complications. We also conclude that, with proper controls, automated sequencing is the preferred method of testing, because it is sufficiently robust, sensitive, and adaptable for this short gene with a large variety of causative mutations.

Base Sequence↗

PubMed2004

Genetics and alcoholism among at-risk relatives II: interest and concerns about hypothetical genetic testing for alcoholism risk.

One purpose of this study was to examine hypothetical interest in genetic predisposition testing for alcoholism among at-risk relatives. Qualitative interviews and several quantitative tools were administered to 27 individuals who had at least one first-degree relative affected by alcoholism. Data analysis revealed that participants' interest in genetic testing for susceptibility to alcoholism was moderate. Lower educational level and a stronger belief in 'others' influencing health were related to participants' having a stronger interest in genetic testing. Participants' concerns about future use of genetic testing ranged from doubts about its usefulness in affecting behavior to apprehension regarding detrimental societal effects such as breaches in confidentiality and fear of being labeled an 'alcoholic.' Younger age and stronger interest in genetic testing were associated with deterministic or fatalistic beliefs, while drinking behaviors, gender, and other demographics were not. Participants questioned the utility of this type of testing. Their interest in testing and concerns about its hypothetical use may prove important for at-risk relatives who may face decisions about genetic testing in the future. Data from this study can provide direction for researchers and health care providers as genetic testing for this and other behavioral conditions emerges. Scientists and the public should address the social concerns expressed by participants, including the fear of labeling. Also, we can begin to anticipate characteristics common in those who may have fatalistic responses, and who may possibly make adverse behavior choices, to results from alcoholism susceptibility testing.

Adolescent↗

PubMed2006

Putting the "landscape" in landscape genetics.

Landscape genetics has emerged as a new research area that integrates population genetics, landscape ecology and spatial statistics. Researchers in this field can combine the high resolution of genetic markers with spatial data and a variety of statistical methods to evaluate the role that landscape variables play in shaping genetic diversity and population structure. While interest in this research area is growing rapidly, our ability to fully utilize landscape data, test explicit hypotheses and truly integrate these diverse disciplines has lagged behind. Part of the current challenge in the development of the field of landscape genetics is bridging the communication and knowledge gap between these highly specific and technical disciplines. The goal of this review is to help bridge this gap by exposing geneticists to terminology, sampling methods and analysis techniques widely used in landscape ecology and spatial statistics but rarely addressed in the genetics literature. We offer a definition for the term "landscape genetics", provide an overview of the landscape genetics literature, give guidelines for appropriate sampling design and useful analysis techniques, and discuss future directions in the field. We hope, this review will stimulate increased dialog and enhance interdisciplinary collaborations advancing this exciting new field.

Animals↗

PubMed1997

Interspecific microsatellite markers for the study of pinniped populations.

Microsatellites have rapidly become the marker of choice for a wide variety of population genetic studies. Here we describe 20 pinniped microsatellite markers which have been tested across 18 pinniped species. The majority of these markers have broad utility in all pinnipeds and provide a strong base for detailed population genetic studies in the Pinnipedia.

Animals↗

PubMed2000

Adverse selection and categorical discrimination in the health insurance markets: the effects of genetic tests.

In this paper, the effects of new methods for risk classification, e.g., genetic tests, on health insurance markets are studied using an insurance model with state contingent utility functions. The analysis focuses on the case of treatment costs higher than the patient's willingness to pay where standard models of asymmetric information are not applicable. In this case, the benefit from signing a fair insurance contract will be positive only if illness probability is low. In contrast to the common perception, additional risk classification under symmetric information can be efficiency enhancing. Under asymmetric information about illness risks, however, there can be complete market failure.

Genetic Testing↗

PubMed1987

Plant genetic resources: prediction by isozyme markers and ecology.

Linkage or association of genetic markers to quantitative traits of agronomic importance can substantially simplify the genetic analysis of complex quantitative traits. Enzyme marker genes are ideal candidates for quantitative genetic analysis. We have recently applied this powerful methodology to the analysis of genetic resources of wild cereals in Israel, primarily wild emmer wheat, Triticum dicoccoides, and wild barley, Hordeum spontaneum, the progenitors of cultivated wheats and barley, respectively. We have found that allelic isozyme markers and ecological factors provide an important predictive method for identifying elite genotypes characterized by single or multiple disease resistances, high protein content, and a variety of quantitative traits of agronomic importance including germination, earliness, biomass, and yield variables. Our predictive methodology could be improved by additional crossing tests in an attempt to verify the results derived from the correlation analysis and thus establish the linkage relationships between the marker gene and the quantitative trait under discussion. This methodology, if further developed by additional isozyme and DNA markers, verified by crossing tests and gene mapping, could substantially contribute to the sampling and utilization of the genetic resources of wild gene pools for crop improvement.

Agriculture↗

PubMed1992

A conserved region in human and Chinese hamster X chromosomes can induce cellular senescence of nickel-transformed Chinese hamster cell lines.

Cellular senescence is the genetically programmed cessation of cellular proliferation. We have recently mapped a putative senescence gene(s) on the X chromosome of Chinese hamster embryo (CHE) cells. In the present study, we have utilized microcell-mediated chromosome transfer (microcell fusion) to test whether: (i) the human X chromosome exhibits similar genetic potential to induce senescence and (ii) the deletion or inactivation of the X-linked senescence gene(s) in CHE cells is associated with nickel-induced immortalization. A normal CHE or human X chromosome was first introduced into mouse-cell hybrids, then transferred by microcell fusion into a nickel-transformed, immortal male CHE cell line (Ni-2/TGR) with an X deletion (Xq1). Microcell fusion of the normal CHE X chromosome into tumorigenic Ni-2/TGR cells yielded senescence of all X recipient clones. The normal human X chromosome induced dominant senescence of tumorigenic Ni-2/TGR cells in only 17% of the resulting microcell hybrids (14/81). Karyotypic analyses of 13 non-senescing human X chromosome-derived microcell hybrid clones revealed that none of these clones retained the complete X. A normal CHE X chromosome induced senescence of 75% of hybrids obtained with another immortal and tumorigenic nickel-transformed male CHE cell line (Ni-6/TGR), which exhibited no visible deletion of the X chromosome, while the normal human X chromosome, only induced senescence in 19% of these hybrids. Transfer of the normal CHE or human X chromosome into spontaneously transformed and tumorigenic cell lines, CHO/TGR or V79/TGR, had little or no effect on their growth. These data suggest that both human and CHE cells possess similar X-linked genetic activities that regulate the process of cellular senescence, and that in Chinese hamster cells nickel-induced immortalization but not that of CHO or V79 cells is associated with inactivation of an X-linked senescence gene.

Animals↗