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 127 records · Page 7Linked to original sources

PubMed1988

Bayesian interval estimation of genetic relationships: application to paternity testing.

Using genetic marker data, we have developed a general methodology for estimating genetic relationships between a set of individuals. The purpose of this paper is to illustrate the practical utility of these methods as applied to the problem of paternity testing. Bayesian methods are used to compute the posterior probability distribution of the genetic relationship parameters. Use of an interval-estimation approach rather than a hypothesis-testing one avoids the problem of the specification of an appropriate null hypothesis in calculating the probability of paternity. Monte Carlo methods are used to evaluate the utility of two sets of genetic markers in obtaining suitably precise estimates of genetic relationship as well as the effect of the prior distribution chosen. Results indicate that with currently available markers a "true" father may be reliably distinguished from any other genetic relationship to the child and that with a reasonable number of markers one can often discriminate between an unrelated individual and one with a second-degree relationship to the child.

Bayes Theorem↗

PubMed2004

Score tests of genetic association in the presence of linkage based on the additive genetic gamma frailty model.

Nuclear families with multiple affected sibs are often collected for genetic linkage analysis of complex diseases. Once linkage evidence is established, dense markers are often typed in the linked region for genetic association analysis based on linkage disequilibrium (LD). Detection of association in the presence of linkage localizes disease genes more accurately than the methods that rely on linkage alone. However, test of association due to LD in the linked region needs to account for dependency of the allele transmissions to different sibs within a family. In this paper, we define a joint model for genetic linkage and association and derive the corresponding joint survival function of age of onset for the sibs within a sibship. The joint survival function is a function of both the inheritance vector and the genotypes at the candidate marker locus. Based on this joint survival function, we derive score tests for genetic association. The proposed methods utilize the phenotype data of all the sibs and have the advantages of family-based designs which can avoid the potential spurious association caused by population admixture. In addition, the methods can account for variable age of onset or age at censoring and possible covariate effects, and therefore provide important tools for modelling disease heterogeneity. Simulation studies and application to the data sets from the 12th Genetic Analysis Workshop indicate that the proposed methods have correct type 1 error rates and increased power over other existing methods for testing allelic association.

Adult↗

PubMed2000

Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research.

Our objective was to explore the barriers and motivations to: 1) appropriate diffusion of genetic services into primary care practice; and 2) primary care physicians' (PCPs) willingness to participate in clinical studies to assess the safety and effectiveness of emerging genetic technologies. A random sample (n = 994) of PCPs was invited to be interviewed. Of the 80 who agreed, 60 were interviewed, 52 by telephone. A semi-structured guide was used. A questionnaire mailed to 752 of the PCPs was used to elicit information from physicians who did not want to be interviewed. Among interviewees, uncertainty as to the clinical utility and clinical validity of predictive genetic testing were the leading barriers to incorporation of this technology into practice, being mentioned by 60 and 43% of subjects, respectively. Of the 100 (13. 3%) physicians returning the questionnaire who declined to be interviewed, 30% said they would be willing to participate in research on the safety and effectiveness of predictive genetic tests. Of those who were interviewed, 92% were willing to participate in such research. Most physicians do not see genetics as important in their practice today; many anticipate greater importance in the future. The proportion of physicians interested in participating in research to assess the safety and effectiveness of genetic tests is sufficient to make large scale, collaborative, practice-based evaluation feasible. Additionally, participation in research may serve as an effective medium for physician education in genetics.

Adult↗

PubMed2026

Real-world clinical utility of exome sequencing in pediatric drug-resistant epilepsy: Experience from a tertiary center in Thailand.

BACKGROUND: Genomic testing has increasingly contributed to the diagnosis and management of pediatric drug-resistant epilepsy (DRE), particularly in patients with suspected genetic etiologies. This study evaluated the diagnostic yield and real- world clinical utility of whole-exome sequencing (WES) in children with DRE. METHODS: Children with DRE and seizure onset before 15 years of age were enrolled between January 2020 and December 2023. Clinical data, including demographics, seizure characteristics, developmental history, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and prior investigations, were reviewed. WES was performed in all probands and, when available, their parents. Variants were interpreted according to standard guidelines. Clinical utility and 1-year seizure and developmental outcomes were assessed from follow-up records. RESULTS: Fifty-six patients (23 males, 33 females) were included. The median age at seizure onset was 1 year (interquartile range [IQR] 0.3-4 years), and 96.4% had developmental comorbidities. Pathogenic or likely pathogenic variants were identified in 39% (22/56), with the highest diagnostic yield in children with seizure onset before 3 years of age. Channelopathies accounted for most genetically solved cases (68%), predominantly involving sodium channel genes. Genetic diagnoses provided clinical utility in 73% (16/22) of solved cases by guiding treatment and precision management. At 1-year follow-up, genetically solved patients showed more favorable seizure and developmental outcomes than those with genetically unsolved patients. CONCLUSION: WES achieved a 39% diagnostic yield and substantial clinical utility in pediatric DRE, particularly in early-onset and channelopathy-related disorders. These findings support early molecular diagnosis to facilitate genotype-informed management in appropriately selected children. However, the more favorable developmental and seizure outcomes observed in genetically solved patients should be interpreted with caution, as they may have been influenced by multiple factors beyond genetic diagnosis. In resource-limited settings, careful clinical phenotyping remains essential for treatment decisions and for prioritizing children for genomic testing.

Clinical utility↗

PubMedDate not supplied

Oncologists' opinions on genetic testing for breast and ovarian cancer.

PURPOSE: To determine oncologists' practices and beliefs about genetic testing for hereditary breast and ovarian cancer and the extent to which oncologists are utilizing clinical genetics services. METHODS: A survey was mailed to oncologists who treat adult patients in Washington, Oregon, Idaho, or Alaska. RESULTS: Most oncologists (79%) had discussed genetic tests with their patients, and 76% indicated they would like patients considering genetic testing to consult with a genetic counselor. Yet few (19%) indicated their medical practice had the necessary services and staff to offer genetic testing, and only 11% had made referrals to medical genetics or genetic counselors. CONCLUSION: Most respondents support the use of genetic services, but few have made referrals to genetic counselors. Increased communication between oncologists and genetic counselors may enhance collaboration between these two disciplines.

Adult↗

PubMed2002

Paenibacillus brasilensis sp. nov., a novel nitrogen-fixing species isolated from the maize rhizosphere in Brazil.

Sixteen nitrogen-fixing strains isolated from the rhizosphere of maize planted in Cerrado soil, Brazil, which showed morphological and biochemical characteristics similar to the gas-forming Paenibacillus spp., were phenotypically and genetically characterized. Their identification as members of the genus Paenibacillus was confirmed by using specific primers based on the 16S rRNA gene. SDS-PAGE of whole-cell proteins, API 50CH, morphological and biochemical tests, amplified rDNA-restriction analysis (ARDRA), DNA-relatedness analyses, denaturing-gradient gel electrophoresis (DGGE) and 16S rRNA gene sequence determinations were performed to characterize the novel isolates and to compare them to strains of other nitrogen-fixing Paenibacillus spp. Phenotypic analyses showed that the 16 strains were very homogeneous and shared a high level of relatedness with Paenibacillus polymyxa and Paenibacillus peoriae. However, none of the novel isolates was able to ferment glycerol (positive test for P. polymyxa), L-arabinose or D-xylose (positive tests for P. polymyxa and P. peoriae) or utilize succinate (positive test for P. peoriae). Genetic approaches also indicated a high level of similarity among the novel isolates and P. polymyxa and P. peoriae, but the novel strains clearly could not be assigned to either of these two recognized species. On the basis of the features presented in this study, the 16 novel isolates were considered to represent members of a novel species within the genus Paenibacillus, for which the name Paenibacillus brasilensis is proposed. The type strain is PB1 72(T) (= ATCC BAA-413(T) = DSM 14914(T)).

Bacillus↗

PubMed2005

Sibling effects on smoking in adolescence: evidence for social influence from a genetically informative design.

AIMS: Behavioral genetic research has suggested that sibling effects on smoking may reflect social rather than genetic processes. We utilize a genetically informative sample of adolescents to test this proposition, focusing on sibling relationship processes (social connectedness) shown to be influential in studies of deviancy. DESIGN: A combined twin-sibling design was employed to disentangle genetic and non-genetic effects. PARTICIPANTS: We utilized a sample of 1421 adolescent sibling pairs participating in the US National Longitudinal Study of Adolescent Health (Add Health). These sibling pairs represent a spectrum of genetic relatedness and include monozygotic twins, dizygotic twins, biological siblings, half-siblings and unrelated siblings. MEASUREMENTS: Participants completed self-report questionnaires on smoking behavior, quality of relationship with their sibling (social connectedness) and peer and parental smoking. FINDINGS: Main effects of both shared environment and genetics were found on adolescent smoking frequency. Social connectedness between siblings moderated shared environmental influences on smoking frequency at each time period, as well as on change in smoking frequency. Shared environmental effects were more pronounced when siblings reported high levels of social connectedness. These environmental sibling effects on smoking were significant after controlling for parent and peer smoking. CONCLUSIONS: This report extends prior research on sibling effects on smoking by identifying specific relationship dynamics that underlie transmission of risk within sibships and providing evidence that such relationship dynamics represent social rather than genetic processes.

Adolescent↗

PubMed2001

Psychosocial factors associated with the public's willingness to pay for genetic testing for cancer risk: a structural equations model.

An adaptation of Andersen's behavioral model of health services utilization is used to examine the psychosocial and socio-demographic factors that directly and indirectly influence the likelihood of undergoing genetic susceptibility testing for cancer, and the amount of money that individuals would be willing to pay out-of-pocket for such a test. Apart from willingness and likelihood, the model also included perceived benefits and barriers, perceived susceptibility, dispositional optimism, information seeking, family history of cancer, socioeconomic status (SES), and age, and explained 30.3% of the variation in willingness. We found as hypothesized that likelihood of undergoing such tests was central to understanding willingness to pay. Being aware of genetic susceptibility testing for cancer, and talking and seeking information about it was directly associated with an increased chance of being willing to pay more, independent of other indirect associations (effects). Interventions targeting those with a family history of cancer and those with a higher SES should generate more awareness about the potential positive and negative consequences to one's family of testing, and the interface between family history of cancer and perceived susceptibility. Interventions should also motivate people to talk and seek more information about genetic testing for cancer risk to enable them take well-informed decisions.

Adult↗

PubMed2003

Bilateral prophylactic oophorectomy and ovarian cancer screening following BRCA1/BRCA2 mutation testing.

PURPOSE: Despite the widespread availability of genetic testing for BRCA1/BRCA2 mutations, little is known about the impact of testing on ovarian cancer prevention and screening. For mutation testing to effect cancer mortality, positive test results must be followed by appropriate behavior change. In this study, we prospectively examined the impact of BRCA1/2 testing on the utilization of prophylactic oophorectomy and ovarian cancer screening. PARTICIPANTS AND METHODS: Participants were 289 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported receipt of bilateral prophylactic oophorectomy (BPO) and utilization of CA-125 and transvaginal ultrasound (TVU) in the year following testing, and examined the impact of test results on these outcomes. In addition, we examined the role of sociodemographic, medical, family history, and psychological variables on the receipt of BPO, CA-125, and TVU. RESULTS: Twenty-seven percent of mutation carriers, 5% of uninformative patients, and 2% of noncarriers received a BPO in the year following testing. In addition to test results, perceived risk for ovarian cancer and family history of ovarian cancer independently predicted receipt of BPO. The receipt of a positive test result was associated with increased utilization of CA-125 and TVU. Additional predictors included perceived risk for ovarian cancer (both CA-125 and TVU) and state anxiety (CA-125). CONCLUSION: These results demonstrate the significant behavioral impact of receiving a positive BRCA1/2 test result. The increased rate of oophorectomy among mutation carriers suggests that testing for BRCA1/2 mutations may ultimately impact ovarian cancer mortality.

Adult↗

PubMed2003

Laboratory testing for prothrombotic states: clinical utility.

It is possible to detect a genetic contribution to venous thrombosis in a significant proportion of patients. This has led to a huge expenditure in clinical time and health resource. However, the gains to be made from the uncritical investigation of the causes of venous thromboembolism are limited and the approach raises significant issues in relation to the appropriateness of this form of genetic testing. In contrast, there are some acquired prothrombotic states that should be identified because the risk of further thrombosis may be sufficient to influence therapy. These states include antiphospholipid syndrome, myeloproliferative disorders, and cancer.

Humans↗

PubMed2000

Evaluation of fine mapping strategies for a multifactorial disease locus: systematic linkage and association analysis of IDDM1 in the HLA region on chromosome 6p21.

The positional cloning of multifactorial disease genes is a major challenge in human genetics. We have therefore empirically tested the utility of the available polymorphic microsatellite map to locate the already identified type 1 diabetes locus IDDM1 (sibling risk/population prevalence ratio lambda(s)= 2.7) within a 14 Mb region of chromosome 6p21 linked to disease. In a two-stage approach to fine mapping, linkage was evaluated in 385 affected sib-pair families using 13 evenly spaced polymorphic microsatellite markers. The whole 14 Mb showed strong linkage. Then, each marker was analysed for evidence of allelic association, revealing evidence of disease association at one marker located within the 95% confidence interval of 1.7 cM obtained by linkage. Analysis of an additional 12 markers flanking this marker revealed a highly specific region of 570 kb associated with disease ( P = 7.5 x 10(-35)), which included the HLA class II genes, known to be the primary determinants of IDDM1. The peak of association was as close as 85 kb centromeric of the disease-predisposing class II gene HLA-DQB1. We investigated the importance of the underlying inter-marker linkage disequilibrium, marker informativity and recombination for fine mapping and demonstrate that the majority of disease association in the region can be explained by linkage disequilibrium with the class II susceptibility genes. Recombination within the major histocompatibility complex was rare and nearly absent in the class III region. We demonstrate that fine mapping of a multifactorial disease gene is possible with high accuracy even in a region with extraordinary linkage disequilibrium across distances of several Mb. The results will be applicable to association studies of disease loci with lambda(s)values <2.7 except that much larger data sets will be required.

Adolescent↗

PubMed2003

The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. The Alternatives to Carcinogenicity Testing Committee ILSI HESI.

The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds. The data from this testing program have made an important contribution to the general understanding of how these models can be best applied in hazard identification; however, questions still exist regarding methodology and data interpretation. To address these issues, ILSI HESI hosted a February 2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The purpose of this workshop was to reach an understanding of how data from genetically modified mouse models are viewed by different regulatory bodies in the pharmaceutical sector and, based on this understanding, to identify areas in which more experimental work may be needed to increase the utility of data derived from these assays. In the course of discussions, various data gaps related to model selection and protocol issues were identified. Based on the outcome of the workshop, various studies are proposed to provide data to improve the utility of currently available assays for cancer hazard identification and risk assessment purposes.

Animals↗

PubMed2003

The development and evaluation of consensus chloroplast primer pairs that possess highly variable sequence regions in a diverse array of plant taxa.

Although universal or consensus chloroplast primers are available, they are limited by their number and genomic distribution. Therefore, a set of consensus chloroplast primer pairs for simple sequence repeats (ccSSRs) analysis was constructed from tobacco (Nicotiana tabacum L.) chloroplast sequences. These were then tested for their general utility in the genetic analysis of a diverse array of plant taxa. In order to increase the number of ccSSRs beyond that previously reported, the target sequences for SSR motifs was set at A or T ( n >/= 7) mononucleotide repeats. Each SSR sequence motif, along with +/-200-bp flanking sequences from the first of each mononucleotide base repeat, was screened for homologies with chloroplast DNA sequences of other plant species in GenBank databases using BLAST search procedures. Twenty three putative marker loci that possessed conserved flanking sequence spans were selected for consensus primer pair construction using commercially available computer algorithms. All primer pairs produced amplicons after PCR employing genomic DNA from members of the Cucurbitaceae (six species) and Solanaceae (four species). Sixteen, 22 and 19 of the initial 23 primer pairs were successively amplified by PCR using template DNA from species of the Apiaceae (two species), Brassicaceae (one species) and Fabaceae (two species), respectively. Twenty of 23 primer pairs were also functional in three monocot species of the Liliaceae [onion (Allium cepa L.) and garlic (Allium sativum L.)], and the Poaceae [oat (Avena sativa L.)]. Sequence analysis of selected ccSSR fragments suggests that ccSSR length and sequence variation could be useful as a tool for investigating the genetic relationships within a genus or closely related taxa (i.e., tribal level). In order to provide for a marker system having significant coverage of the cucumber chloroplast genome, ccSSR primers were strategically "recombined" and named recombined consensus chloroplast primers (RCCP) for PCR analysis. Successful amplification after extended-length PCR of 16 RCCP primer pairs from cucumber ( Cucumis sativus L.) DNA suggested that the amplicons detected are representative of the cucumber chloroplast genome. These RCCP pairs, therefore, could be useful as an initial molecular tool for investigation of traits related to a chloroplast gene(s) in cucumber, and other closely related species.

Base Sequence↗

PubMed1991

High-fidelity amplification using a thermostable DNA polymerase isolated from Pyrococcus furiosus.

A thermostable DNA polymerase which possesses an associated 3'-to-5' exonuclease (proofreading) activity has been isolated from the hyperthermophilic archaebacterium, Pyrococcus furiosus (Pfu). To test its fidelity, we have utilized a genetic assay that directly measures DNA polymerase fidelity in vitro during the polymerase chain reaction (PCR). Our results indicate that PCR performed with the DNA polymerase purified from P. furiosus yields amplification products containing less than 10% of the number of mutations obtained from similar amplifications performed with Taq DNA polymerase. The PCR fidelity assay is based on the amplification and cloning of lacI, lacO and lacZ alpha gene sequences (lacIOZ alpha) using either Pfu or Taq DNA polymerase. Certain mutations within the lacI gene inactivate the Lac repressor protein and permit the expression of beta Gal. When plated on a chromogenic substrate, these LacI- mutants exhibit a blue-plaque phenotype. These studies demonstrate that the error rate per nucleotide induced in the 182 known detectable sites of the lacI gene was 1.6 x 10(-6) for Pfu DNA polymerase, a greater than tenfold improvement over the 2.0 x 10(-5) error rate for Taq DNA polymerase, after approx. 10(5)-fold amplification.

Archaea↗

PubMed2001

Evaluation and refinement of tmRNA structure using gene sequences from natural microbial communities.

DNA harvested directly from complex natural microbial communities by PCR has been successfully used to predict RNase P RNA structure, and can potentially provide an abundant source of information for structural predictions of other RNAs. In this study, we utilized genetic variation in natural communities to test and refine the secondary and tertiary structural model for the bacterial tmRNA. The variability of proposed tmRNA secondary structures in different organisms and the lack of any predicted tertiary structure suggested that further refinement of the tmRNA could be useful. To increase the phylogenetic representation of tmRNA sequences, and thereby provide additional data for statistical comparative analysis, we amplified, sequenced, and compared tmRNA sequences from natural microbial communities. Using primers designed from gamma proteobacterial sequences, we determined 44 new tmRNA sequences from a variety of environmental DNA samples. Covariation analyses of these sequences, along with sequences from cultured organisms, confirmed most of the proposed tmRNA model but also provided evidence for a new tertiary interaction. This approach of gathering sequence information from natural microbial communities seems generally applicable in RNA structural analysis.

Base Sequence↗

PubMed1996

Competitive selection in vivo by a cell for one variant over another: implications for RNA virus quasispecies in vivo.

Infidelity of genome applications of RNA viruses leads to the generation of viral quasispecies both in vitro and in vivo. However, the biological significance of such generated variants in vivo is largely unknown and controversial. To study this issue, we continued our evaluation of the tropism of a lymphocytic choriomeningitis virus (LCMV) variant termed clone 13 with its parental virus clonal pool ARM 53b (wild-type parent) for neuronal cells in vivo. Earlier in vivo and in vitro studies noted that the wild-type virus contained a Phe at glycoprotein (GP) residue 260 which correlated with neuron tropism compared with LCMV variants containing a Leu at residue 260 which showed selected tropism for cells of the immune system (C.F. Evans, P. Borrow, J. C. de la Torre, and M. B. A. Oldstone J. Virol. 68:7367-7373, 1994; L. Villarete, T. Somasundaram, and R. Ahmed, J. Virol 68:7490-7496, 1994). Here we (i) evaluated the ability of the viral variants with either a Phe or Leu at GP residue 260 to replicate in vivo in the spleen, liver, or brain, (ii) analyzed the ability of these viruses to compete against each other for cell (neuron)-specific selection following a single viral inoculation of different ratios of both viruses, and (iii) utilized genetic reassortants of both viruses to test their ability to replicate in neurons in vivo. We found that viral variants containing either a Phe or Leu at GP residue 260 were equally capable of replicating in neurons, but when inoculated together, neurons selected for the viral population containing Phe at GP residue 260 over viruses containing a Leu at this position. This was in contrast to selection in the liver and spleen that favored viruses with Leu and not Phe at GP residue 260. Analysis of inoculations with viral reassortants indicated that genes encoded on the short RNA (the GP and nucleoprotein, not the L [polymerase] and Z proteins that are encoded by the large RNA) were associated with neurotropism. Since the nucleoprotein sequences of wild-type Armstrong and clone 13 are identical, it is likely that specific cytoplasmic factors of the neurons play a fundamental role in the selection of virus with Phe at GP residue 260.

Animals↗

PubMed2006

[Diagnostic and therapeutic activity moderation. Quaternary and genetic prevention].

Medical activities have more positive than negative outcomes. Because this balance, medicine has a great social recognition. But with new technology and more aggressive diagnostic and therapeutic interventions, there is a decreasing gap in between benefits and harms. Risk increases because more interventions, and because placing patients in more technology environments. As a consecuence, patient safety decreases. Quantity becomes as important as quality, and the place of care is crucial for patient safety. Medical activities should be of < >, performed in the low level of care possible. Then, quaternary prevention (to avoid unnecessary use and risk of medical interventions) should be a continuous parallel clinical activity. I consider four examples of needed quaternary prevention, with Spanish data: 1) cardiovascular prevention (where there is an inverse use of resources, as patients who need more receive less); 2) use of new antidepressants (which has provoke an artificial epidemic of <<depression"); 3) use of antibiotics (frequently, unnecessary use), and 4) genetic diagnosis (with the example of screening of haemochromatosis, and a commentary about genetics and medicalisation).

Anti-Bacterial Agents↗

PubMed1987

A comparison of methods for ranking boars from different central test stations.

Data were received from 24 test stations on 3,999 boars tested in fall 1984 and spring 1985. In an effort to increase the connectedness between stations, one reference sire was selected to produce sons (reference boars) through artificial insemination to be tested in the different stations. Fifty-two reference boars were placed across 17 of the test stations. The performance traits analyzed were average daily gain (ADG) and backfat adjusted to 105 kg (ABF). The methods used to rank boars were: 1) individual record (ADG, ABF), 2) individual record deviated from the contemporary group mean, and 3/4) individual record plus performance of relatives (including/excluding reference boars) using expected progeny differences (EPD) estimated from a reduced animal model (RAM) statistical procedure. Ranks of boars using these four methods of genetic evaluation were compared using Spearman rank correlation methodology. The ranks of the boars changed significantly as the complexity of analysis increased for both ADG and ABF. Rank correlations between individual record and contemporary group deviations for ADG and BF were .47 and .20, respectively. Rank correlations between contemporary group deviations and RAM estimates of EPD for ADG and ABF were .53 and .41, respectively. These were significantly different from 1.0. However, there was no significant difference between rankings based on EPD including vs excluding the reference boars. The importance of rank changes coupled with the increased accuracy of these more complex evaluation methods strongly suggest that best linear unbiased predictors of genetic value be utilized in comparing boars in central test stations.

Animals↗