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Results for “Genetic screen”

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PubMed2003

Genetic screen for monitoring hepatitis C virus NS3 serine protease activity.

We have developed a genetic system to monitor the activity of the hepatitis C virus (HCV) NS3 serine protease. This genetic system is based on the bacteriophage lambda regulatory circuit where the viral repressor cI is specifically cleaved to initiate the switch from lysogeny to lytic infection. An HCV protease-specific target, NS5A-5B, was inserted into the lambda phage cI repressor. The target specificity of the HCV NS5A-5B repressor was evaluated by coexpression of this repressor with a beta-galactosidase (betagal)-HCV NS3(2-181)/4(21-34) protease construct. Upon infection of Escherichia coli cells containing the two plasmids encoding the cI.HCV5AB-cro and the betagal-HCV NS3(2-181)/4(21-34) protease constructs, lambda phage replicated up to 8,000-fold more efficiently than in cells that did not express the HCV NS3(2-181)/4(21-34) protease. This simple, rapid, and highly specific assay can be used to monitor the activity of the HCV NS3 serine protease, and it has the potential to be used for screening specific inhibitors.

Amino Acid Sequence↗
PubMed2004

Psychosocial aspects of genetic screening of pregnant women and newborns: a systematic review.

OBJECTIVES: To address five broad questions concerned with knowledge, anxiety, factors associated with participation/non-participation in screening programmes and the long-term sequelae of false-positive, true-positive in newborns and true-negative results. DATA SOURCES: Five electronic databases, two journals and attempts were made to locate unpublished work. REVIEW METHODS: This review started from a substantial literature base that provided the basis for (a) scoping the literature, (b) informing search strategy terms and (c) identifying preliminary article inclusion and exclusion criteria. The main eligibility criteria were: any screening programme aimed at pregnant women or newborn babies that included a 'genetic' target condition, this included chromosomal anomalies; any study that reported psychosocial data collected directly from parents. The data extraction form developed for this study elicited data from the selected studies. The data were entered into a database, which provided a summary of the included papers. RESULTS: A total of 288 candidate publications were identified, 106 of which were eligible: 78 were concerned with antenatal screening and 28 with newborn screening. It was found that levels of knowledge adequate for decision-making were not being achieved despite information leaflets and videos having some effect. Studies that have succeeded in increasing knowledge have not observed a corresponding increase in anxiety, although some anxiety might be an appropriate response and may aid coping and decision-making. Anxiety is clearly raised in women receiving positive screening results, especially young women. However, evidence is lacking of a beneficial (i.e. reassuring) effect of receiving a screen-negative result. Anxiety in screen-positive women falls on receipt of subsequent reassuring results, but some residual anxiety may remain. A minority (perhaps up to 30%) of women receiving a screen-positive result in pregnancy expressed regret about their screening decision. Uptake of neonatal screening has been treated as a 'given' and not as a research topic. CONCLUSIONS: The results of this review have many implications for the work of the National Screening Committee. The most pressing of these, in order of priority, relate to: the inadequacy of current procedures for achieving informed consent; the cost of providing a satisfactory service; the unmet needs of 'false-positives', and the unmet needs of women's partners, particularly in carrier screening. It is suggested that research is conducted on the above four topics in order to fill gaps in the evidence base that relate to screening technologies which have been available for many years. In addition, future screening programmes will create a new list of research questions, based on the same main agenda but applied to new areas, for example, new conditions such as haemoglobinopathies and fragile X syndrome; new client groups such as young women and minority ethnic groups; and new testing modalities such as ultrasound.

Adult↗
PubMed2006

Methods for reverse genetic screening in zebrafish by resequencing and TILLING.

Animal models provide an in vivo system to study gene function by transgenic and knockout approaches. Targeted knockout approaches have been very successful in mice, but are currently not feasible in zebrafish due to the inability to grow embryonic stem cells. As an alternative, a reverse genetic approach that utilizes screening by resequencing and/or TILLING (Targeting Induced Local Lesions INGenomes) of mutagenized genomes has recently gained popularity in the zebrafish field. Spermatogonia of healthy males are mutagenized using ENU (N-ethyl-N-nitrosourea) and F1 progeny is collected by breeding treated males with healthy wild type females. Sperm and DNA banks are generated from F1 males. DNA is screened for ENU-induced mutations by sequencing or TILLING. These mutations can then be studied by in vitro fertilization (IVF) from the cryopreserved sperm of the corresponding F1 male followed by breeding to homozygosity. A high-throughput method of screening for rare heterozygotes and efficient recovery of mutant lines are important in identification of a large number of mutations using this approach. This article provides optimized protocols for resequencing and TILLING based on our experiences. We performed a pilot screen on 1235 F1 males by resequencing 54 exons from 17 genes and analyzed the sequencing data using multiple programs to maximize the mutation detection with minimal false positive detection. As an alternative to sequencing, we developed the protocols for TILLING by capillary electrophoresis using an ABI Genetic analyzer 3100 platform followed by fragment analysis using GeneScan and Genotyper softwares. PCR products generated by fluorescently labeled universal primers and tailed exon-specific primers were pooled 4-fold prior to heteroduplex formation. Overall, our pilot screen shows that a combination of TILLING and sequencing is optimal for achieving cost-effective, high-throughput screening of a large number of samples. Amplicons with fewer common SNPs are ideal for TILLING whereas amplicons with multiple SNPs and in/del polymorphisms are best suited for sequencing followed by analysis with SNPdetector.

Animals↗
PubMed1996

Genetic screening for colorectal cancer and intervention.

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.

Clinical Trials as Topic↗
PubMed1981

The centralized prenatal genetics screening program of New York City: II. Establishment of prenatal diagnosis laboratory.

Prenatal diagnosis of genetic disorders is now being made available to an increasing number of New York City women through the establishment of a large centralized laboratory. This laboratory contracts to provide genetic diagnostic services to municipal and private hospitals throughout the New York City area. It is the first project of such magnitude in the United States. Prior to the receipt of samples for diagnostic purposes, the laboratory was required to meet the highest technical standards, as established by a Cytogenetics Advisory Committee. A set of guidelines was drawn up detailing the procedure and protocols for all the analyses and the reporting of results, including a timetable according to which results were to be obtained. The Cytogenetics Advisory Committee continues to review cases on a regular schedule. One of the unique aspects of the laboratory has been the development of back-up agreements with other area laboratories to assist in dealing with any problem that might disrupt the routine diagnostic service. The first year of operation of the laboratory has shown that financial, legal, and physical problems associated with designing and instituting a megacenter can be over-come. Similar programs should be encouraged.

Female↗
PubMed1998

Psychosocial predictors of interest in prenatal genetic screening.

The purpose of the study was to identify psychosocial predictors of interest in prenatal genetic testing. Analysis of data from 886 responses in the 1996 Louisville Metropolitan Survey indicate that factors such as demographic characteristics and scores on health locus of control that predict utilization of other preventive health care are less applicable to predicting attitudes toward genetic testing. Regression analyses indicated that political orientation, identification with religion, and attitudes against abortion predicted less favorable responses to a question about prenatal genetic testing. Abortion attitudes were particularly strong indicators of respondents' stated interests in testing. The findings have practical implications in terms of promoting preventive health care. Personal values may lead individuals to believe that prenatal testing leads to the intention of abortion.

Abortion, Induced↗
PubMed1993

[Genetic screening for markers of individual sensitivity to the action of biological factors].

HLA and ABO genetic markers were determined in 406 workers exposed to occupational and ecologic specific factors of industrial biotechnology. The study proved the importance of genotype in determination of individual sensitivity to those factors. The genetic markers of hypersensitivity and resistance were revealed. A medical and genetic concept was suggested for primary prophylaxis of occupational and ecologic diseases.

Biological Factors↗
PubMed1995

Hereditary breast and ovarian cancer: epidemiology, genetics, screening and predictive testing.

Inherited predisposition to cancer has become an increasingly important part of the practice of clinical genetics. Hereditary breast and ovarian cancer form a significant part of this new field. There are approximately 13,000 new cases of breast cancer diagnosed every year in Canada, and 5% of these can be expected to have a hereditary basis. Large studies implicated a dominant gene with a population frequency of 0.33% and high penetrance. Linkage analysis localised one such gene to chromosome 17q21 in 1990, and 1994 BRCA1 was cloned. The BRCA1 gene is large, and mutations are spread over the entire gene. There is evidence of common origins for some of the mutations. Early detection of hereditary breast and ovarian cancer is problematic. There is no evidence that early diagnosis by population-based mammography improves survival in sporadic premenopausal breast cancer. Multimodal screening for ovarian cancer has not been adequately assessed. Moreover, there is little evidence that such procedures are more likely to be effective in high-risk groups. Women who may gain initial benefit from the cloning of BRCA1 are from BRCA1-linked families who have living affected relatives. Over the next few years, it is likely that predictive testing for hereditary breast and ovarian cancer will become a routine clinical service in large centres.

Breast Neoplasms↗