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Sample records for genetic screening patient

  1. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

  2. Genetic Screening

    PubMed Central

    Burke, Wylie; Tarini, Beth; Press, Nancy A.; Evans, James P.

    2011-01-01

    Current approaches to genetic screening include newborn screening to identify infants who would benefit from early treatment, reproductive genetic screening to assist reproductive decision making, and family history assessment to identify individuals who would benefit from additional prevention measures. Although the traditional goal of screening is to identify early disease or risk in order to implement preventive therapy, genetic screening has always included an atypical element—information relevant to reproductive decisions. New technologies offer increasingly comprehensive identification of genetic conditions and susceptibilities. Tests based on these technologies are generating a different approach to screening that seeks to inform individuals about all of their genetic traits and susceptibilities for purposes that incorporate rapid diagnosis, family planning, and expediting of research, as well as the traditional screening goal of improving prevention. Use of these tests in population screening will increase the challenges already encountered in genetic screening programs, including false-positive and ambiguous test results, overdiagnosis, and incidental findings. Whether this approach is desirable requires further empiric research, but it also requires careful deliberation on the part of all concerned, including genomic researchers, clinicians, public health officials, health care payers, and especially those who will be the recipients of this novel screening approach. PMID:21709145

  3. Genetic screening in patients with Retinoblastoma in Israel.

    PubMed

    Sagi, Michal; Frenkel, Avishag; Eilat, Avital; Weinberg, Naomi; Frenkel, Shahar; Pe'er, Jacob; Abeliovich, Dvorah; Lerer, Israela

    2015-09-01

    Retinoblastoma (Rb) is a childhood tumor (~1 in 20,000 live births) developing in the retina due to mutations in the RB1 gene. Identification of the oncogenic mutations in the RB1 gene is important for the clinical management and for genetic counseling to families with a child or a parent affected with the tumor. Here we present our experience in detecting the pathogenic mutations in blood samples, from 150 unrelated Rb patients and highlight the relevant counseling issues. Mutation screening in the RB1 gene was based on Sanger sequencing, mosaicism of recurrent CpG transition mutations was detected by allele specific PCR and multiplex ligation dependent probe amplification for detecting of large deletions/duplications. The overall detection rate of mutations in our cohort was 55% (82/150). In the familial cases it was 100% (17/17), in bilateral and unilateral-multifocal sporadic cases 91% (50/55), and in the unilateral sporadic cases 19% (15/78). Nonsense mutations and small deletions or insertions that results in transcripts with premature termination codons that are subject to nonsense mediated decay were the most frequent, detected in 50/82 (61%) of the patients. The rest were large deletions detected in 14/82 (17%), splice site mutations detected in 11/82 (13%), missense mutations in four patients and mutations in the promoter sequence in three patients. Mutation mosaicism ranging from 10 to 30% was detected by allele specific PCR in ten patients, 9% (5/55) of patients with bilateral tumor and 33% (5/15) of the patients with unilateral tumor. In three patients rare variants were detected as the only finding which was also detected in other healthy family members. Allele specific amplification of recurrent mutations raises in our cohort the identification rate from 82 to 91% in the sporadic bilateral cases and from 13 to 19% in the unilateral sporadic cases. Most mosaic cases could not be identified by Sanger sequencing and therefore screening for recurrent Cp

  4. Pathways to genetic screening: Patient knowledges, patient practices. Annual report

    SciTech Connect

    1994-12-31

    This study is design to assess the impacts of the integration of genetic knowledge in to the life of high-risk family members. The social and cultural barriers and bridges that incorporation of genetic information will have on these families as well as how they use this genetic information to increase reproductive options and improve the quality of family life are a major focus of this work.

  5. [HORMONAL-GENETIC SCREENING IN PATIENTS, SUFFERING GASTRODUODENAL ULCER HEMORRHAGE].

    PubMed

    Duzhiy, I D; Romanyuk, A M; Lyndin, M C; Bratushka, V V; Dubnytskiy, V Yu; Shevchenko, Yu Yu; Kharchenko, S V

    2015-11-01

    Genetic-hormonal regulation plays a key pathophysiologic role in a blood loss on background of complicated gastroduodenal ulcer disease, but a clinical significance of some genes of compensatory steroidogenesis remains unrevealed. Examination of 63 patients, using a chain reaction with polymerase (CRP); analysis of length of restriction fragments (CRP-RFLP) and immunohistochemical investigation of gastroduodenal mucosa were performed on the base of a Sumsky Rural Clinical Hospital. Trustworthy difference of distribution of polymorphic genes ESR1 and VKORC1 in patients of both gender in presence of the ulcer hemorrhage was not revealed, excluding genotype A/A VKORC1, what trustworthy more frequently was revealed in women (p < 0.05). There was established, that intact zone of gastric fundus owes immunoreactivity towards alpha-receptors of estrogen in nuclei of epitheliocytes and stromocytes. Diagnosis of polymorphic gene VKORC1 and expression of the estrogen receptors may serve the base for pathogenetic therapy in patients with hemorrhage occurrence. PMID:26939421

  6. Assessment of an Interactive Computer-Based Patient Prenatal Genetic Screening and Testing Education Tool

    ERIC Educational Resources Information Center

    Griffith, Jennifer M.; Sorenson, James R.; Bowling, J. Michael; Jennings-Grant, Tracey

    2005-01-01

    The Enhancing Patient Prenatal Education study tested the feasibility and educational impact of an interactive program for patient prenatal genetic screening and testing education. Patients at two private practices and one public health clinic participated (N = 207). The program collected knowledge and measures of anxiety before and after use of…

  7. Patient Physical Characteristics and Primary Care Physician Decision Making in Preconception Genetic Screening

    PubMed Central

    Bonham, V.L.; Knerr, S.; Feero, W.G.; Stevens, N.; Jenkins, J.F.; McBride, C.M.

    2010-01-01

    Background There has been growing emphasis on preconception care as a strategy to improve maternal and child health since the 1980s. Increasingly, development of genetic tests will require primary care providers to make decisions about preconception genetic screening. Limited research has been conducted on how primary care providers interpret patients’ characteristics and use constructs, such as ethnicity and race, to decide whom to offer preconception genetic screening. Objective This report assessed the influence of patient characteristics on decisions to offer preconception genetic screening. Methods A web-based survey of family physicians was conducted. Physicians reviewed a clinical vignette that was accompanied by a picture of either a black or a white patient. Physicians indicated whether they would offer genetic screening, and if yes, what tests they would offer and what factors influenced their decisions. Results The majority (69.2%) of physicians reported that they would not offer genetic screening. Respondents who reviewed the vignette accompanied by a picture of the black patient were more likely to offer screening (35% vs. 26%, p = 0.0034) and rated race as more important to their decision to offer testing than those who viewed the picture of the white patient (76% vs. 49%, p < 0.0001). Conclusions Our findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making is influenced by patients’ physical characteristics. The reticence of physicians in this sample to offer preconception screening is an important finding for public health and clinical practice. PMID:19940457

  8. Genetic screening of the LPL gene in hypertriglyceridaemic patients.

    PubMed

    Wright, William T; Young, Ian S; Nicholls, D Paul; Graham, Colin A

    2008-07-01

    Serum triglyceride (TG) level is an important independent risk factor for coronary heart disease, with the lipoprotein lipase (LPL) enzyme playing the major role in regulating the catabolism of TG rich lipoproteins. The complete sequence analysis of the LPL gene was carried out on 19 individuals with extreme hypertriglyceridaemia (HTG; TG>14 mmol/l) with a total of 42 sequence variants being identified, a number of which are novel to this study. A total of eight patients were shown to have functional variants (p.D36N, p.R197H, p.N318S, p.V340I) that alter amino acids at 11 of the 16 LPL alleles. Multiplex ligation-dependent probe amplification (MLPA) analysis showed no exonic deletion or duplications in this population. Further analysis of the p.N318S (also called N291S) variant identified in the sequencing screen, in larger case and control populations, identified this mutation to be strongly associated with HTG. This study has produced a more comprehensive SNP map of LPL and its surrounding area and identified p.N318S as a major predisposing factor to HTG in the Northern Irish population. PMID:18068174

  9. Genetic screening of Fabry patients with EcoTILLING and HRM technology

    PubMed Central

    2011-01-01

    Background Anderson-Fabry disease (FD) is caused by a deficit of the α-galactosidase A enzyme which leads to the accumulation of complex sphingolipids, especially globotriaosylceramide (Gb3), in all the cells of the body, causing the onset of a multi-systemic disease with poor prognosis in adulthood. In this article, we describe two alternative methods for screening the GLA gene which codes for the α-galactosidase A enzyme in subjects with probable FD in order to test analysis strategies which include or rely on initial pre-screening. Findings We analyzed 740 samples using EcoTILLING, comparing two mismatch-specificendonucleases, CEL I and ENDO-1, while conducting a parallel screening of the same samples using HRM (High Resolution Melting). Afterwards, all samples were subjected to direct sequencing. Overall, we identified 12 different genetic variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G, IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with the high genetic heterogeneity found in FD patients and carriers. All of the mutations were detected by HRM, whereas 17% of the mutations were not found by EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1 endonucleases were perfectly overlapping. Conclusion On the basis of its simplicity, flexibility, repeatability, and sensitivity, we believe thatHRM analysis of the GLA gene is a reliable presequencing screening tool. This method can be applied to any genomic feature to identify known and unknown genetic alterations, and it is ideal for conducting screening and population studies. PMID:21896204

  10. Genetic analysis and SOD1 mutation screening in Iranian amyotrophic lateral sclerosis patients.

    PubMed

    Alavi, Afagh; Nafissi, Shahriar; Rohani, Mohammad; Zamani, Babak; Sedighi, Behnaz; Shamshiri, Hosein; Fan, Jian-Bing; Ronaghi, Mostafa; Elahi, Elahe

    2013-05-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and the most common in European populations. Results of genetic analysis and mutation screening of SOD1 in a cohort of 60 Iranian ALS patients are here reported. Initially, linkage analysis in 4 families identified a disease-linked locus that included the known ALS gene, SOD1. Screening of SOD1 identified homozygous p.Asp90Ala causing mutations in all the linked families. Haplotype analysis suggests that the p.Asp90Ala alleles in the Iranian patients might share a common founder with the renowned Scandinavian recessive p.Asp90Ala allele. Subsequent screening in all the patients resulted in identification of 3 other mutations in SOD1, including p.Leu84Phe in the homozygous state. Phenotypic features of the mutation-bearing patients are presented. SOD1 mutations were found in 11.7% of the cohort, 38.5% of the familial ALS probands, and 4.25% of the sporadic ALS cases. SOD1 mutations contribute significantly to ALS among Iranians. PMID:23062701

  11. “Am I carrier?” The patient's lived experience of thrombophilia genetic screening and its outcome

    PubMed Central

    Graffigna, Guendalina; Leone, Daniela; Vegni, Elena

    2014-01-01

    How do patients with thrombophilia experience a physician's request to undergo a genetic test? How do they experience the test outcome? To answer these questions, we conducted an interpretative phenomenological analysis study, based on 10 in-depth interviews with patients who underwent genetic testing for thrombophilia in Italy, half with positive and half with negative results. The experience of undergoing genetic screening for thrombophilia plays an important role in reconfiguring patients' signification of their illness experience. A positive outcome becomes a cue to reorganize in a more adaptive way the illness meaning at the cognitive and emotive levels, whereas a negative outcome appears more distressing and confusing. As a clinical implication of the study, clinicians should consider communicating carefully with the patients regardless from the positive/negative test results and they should explore the patient's specific reaction and understanding of test result. PMID:25750812

  12. Pathways to genetic screening: Patient knowledges, Patient practices. Technical report of research progress

    SciTech Connect

    Not Available

    1994-08-29

    This study is designed to clarify the integration of genetic knowledge into the lived experience of high-risk family members. A major focus is elucidation of the social and cultural barriers and bridges to the use of genetic information to increase reproductive options and improve the quality of family life. They study focuses on families at risk for cystic fibrosis and sickle cell disease. These two disease groups were selected because they are among the most common potentially lethal genetic diseases and because while each has a similar pattern of inheritance and raises similarly serious bio-medical challenges and issues of information management, they primarily affect different racial and ethno-cultural groups permitting a naturally occurring experiment. In the variable penetration and meaning of genetic medicine in two populations. We have conducted intensive interviews with more than 300 individuals in approximately 88 families. We have attempted to balance the effort equally between the two groups, but have found we are able to penetrate the family systems of the cystic fibrosis families more easily than the sickle cell families.

  13. Genetic Counseling for Patients Considering Screening and Diagnosis for Chromosomal Abnormalities.

    PubMed

    Chard, Renée L; Norton, Mary E

    2016-06-01

    With the introduction of cell-free DNA screening for fetal aneuploidy and chromosomal microarray for prenatal diagnostic testing, options for pregnant women have become increasingly complex. Discussions regarding options for prenatal testing for aneuploidy should occur prior to any testing and should include pertinent risks and benefits of each alternative test. There is no single screening or diagnostic test option that is the right choice for all patients; patient decisions should be based on each individual woman's values and preferences after a discussion of all options. PMID:27235908

  14. Optimal screening for genetic diseases.

    PubMed

    Nævdal, Eric

    2014-12-01

    Screening for genetic diseases is performed in many regions and/or ethnic groups where there is a high prevalence of possibly malign genes. The propagation of such genes can be considered a dynamic externality. Given that many of these diseases are untreatable and give rise to truly tragic outcomes, they are a source of societal concern, and the screening process should perhaps be regulated. This paper incorporates a standard model of genetic propagation into an economic model of dynamic management to derive cost benefit rules for optimal screening. The highly non-linear nature of genetic dynamics gives rise to perhaps surprising results that include discontinuous controls and threshold effects. One insight is that any screening program that is in place for any amount of time should screen all individuals in a target population. The incorporation of genetic models may prove to be useful to several emerging fields in economics such as genoeconomics, neuroeconomics and paleoeconomics. PMID:25203815

  15. Phenylketonuria Genetic Screening Simulation

    ERIC Educational Resources Information Center

    Erickson, Patti

    2012-01-01

    After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

  16. Judaism, genetic screening and genetic therapy.

    PubMed

    Rosner, F

    1998-01-01

    Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

  17. National Newborn Screening and Genetics Resource Center

    MedlinePlus

    ... GENERAL INFORMATION Conditions Screened by US Programs General Resources Genetics Birth Defects Hearing Screening FOR PROFESSIONALS ACT Sheets(ACMG) General Resources Newborn Screening Genetics Birth Defects FOR FAMILIES FAQs ...

  18. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil

    PubMed Central

    2014-01-01

    Background Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil. Methods Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern. Results No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents. Conclusion This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study. PMID:25180051

  19. A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

    PubMed Central

    Wannhoff, Andreas; Folseraas, Trine; Brune, Maik; Rupp, Christian; Friedrich, Kilian; Knierim, Johannes; Weiss, Karl Heinz; Sauer, Peter; Flechtenmacher, Christa; Schirmacher, Peter; Stremmel, Wolfgang; Hov, Johannes R

    2015-01-01

    Background Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden’s index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P = 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies. PMID:26966527

  20. Population genetic screening programmes: principles, techniques, practices, and policies.

    PubMed

    Godard, Béatrice; ten Kate, Leo; Evers-Kiebooms, Gerry; Aymé, Ségolène

    2003-12-01

    This paper examines the professional and scientific views on the principles, techniques, practices, and policies that impact on the population genetic screening programmes in Europe. This paper focuses on the issues surrounding potential screening programmes, which require further discussion before their introduction. It aims to increase, among the health-care professions and health policy-makers, awareness of the potential screening programmes as an issue of increasing concern to public health. The methods comprised primarily the review of the existing professional guidelines, regulatory frameworks and other documents related to population genetic screening programmes in Europe. Then, the questions that need debate, in regard to different types of genetic screening before and after birth, were examined. Screening for conditions such as cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolemia, fragile X syndrome, hemochromatosis, and cancer susceptibility was discussed. Special issues related to genetic screening were also examined, such as informed consent, family aspects, commercialization, the players on the scene and monitoring genetic screening programmes. Afterwards, these questions were debated by 51 experts from 15 European countries during an international workshop organized by the European Society of Human Genetics Public and Professional Policy Committee in Amsterdam, The Netherlands, 19-20, November, 1999. Arguments for and against starting screening programmes have been put forward. It has been questioned whether genetic screening differs from other types of screening and testing in terms of ethical issues. The general impression on the future of genetic screening is that one wants to 'proceed with caution', with more active impetus from the side of patients' organizations and more reluctance from the policy-makers. The latter try to obviate the potential problems about the abortion and eugenics issues that might be perceived as a

  1. Emergency preparedness for newborn screening and genetic services.

    PubMed

    Pass, Kenneth A; Thoene, Jess; Watson, Michael S

    2009-06-01

    Patients identified in newborn screening programs can be among the most vulnerable during a disaster due to their need to have prompt diagnosis and medical management. Recent disasters have challenged the ability of newborn screening programs to maintain the needed continuity during emergency situations. This has significant implications for the newborn screening laboratories, the diagnostic confirmation providers, and the patients who either require diagnosis or maintenance of their therapeutic interventions. In 2007, the National Coordinating Center (NCC) for the Regional Genetics and Newborn Screening Collaboratives (RCs) sponsored a meeting involving representatives of the Regional Genetics and Newborn Screening Collaborative Groups, state newborn screening programs, providers of diagnosis and confirmation services, manufacturers of equipment, medical foods, and other treatments used in patients identified in newborn screening programs, and individuals from agencies involved in disaster response including the National Disaster Medical Service, the Centers for Disease Control and Prevention, the Emergency Management Assistance Compact, the Federal Emergency Management Agency, and others. In addition to developing contingency plans for newborn screening, we have considered other uses of genetics as it is used in DNA-based kinship identification of mass casualties. The meeting resulted in the description of a wide range of issues facing newborn screening programs, provider groups, and patients for which emergency preparedness development is needed in order that appropriate response is enabled. PMID:19444127

  2. Lactose intolerance genetic testing: is it useful as routine screening? Results on 1426 south-central Italy patients.

    PubMed

    Santonocito, Concetta; Scapaticci, Margherita; Guarino, Donatella; Annicchiarico, Eleonora Brigida; Lisci, Rosalia; Penitente, Romina; Gasbarrini, Antonio; Zuppi, Cecilia; Capoluongo, Ettore

    2015-01-15

    Adult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. Several studies suggested that the identification of C/T-13910 and G/A-22018 mutations, located upstream the gene encoding the lactase-phlorizin hydrolase (LPH), is a useful tool for the differential diagnosis of hypolactasia. We evaluated the frequencies of C/T-13910 and G/A-22018 variants in a central-south Italian population and the usefulness of lactase deficiency genetic testing in the clinic practice. The genomic DNA of 1426 patients and 1000 healthy controls from central-south Italy was isolated from peripheral whole blood and genotyped for the C/T-13910 and G/A-22018 polymorphisms by high-resolution melting analysis (HRMA) and sequencing. The frequencies of genotypes in the 1426 patients analysed were as follows: 1077 CC/GG (75.5%), 287 CT/GA (20.1%), 24 TT/AA (1.7%), 38 CC/GA (2.7%). Only 64 out of 1426 (4.5%) performed also L-BHT test, 29 of which were negative for L-BHT also in presence of different genotypes. Among the 35 individuals with L-BHT positive, 34 were CC/GG and only one CT/GA. Although lactose genetic test is a good predictor of persistence/non-persistence lactase in specific population, its use in the central-south Italy population should be limited given the high prevalence of the CCGG diplotype in normal individuals. PMID:25281930

  3. [The mutation spectrum of the GJB2 gene in Belarussian patients with hearing loss. Results of pilot genetic screening of hearing impairment in newborns].

    PubMed

    Bliznets, E A; Marcul', D N; Khorov, O G; Markova, T G; Poliakov, A V

    2014-02-01

    A total of 111 unrelated probands and their 8 sibs from Grodno oblast (Belarus) with bilateral isolated sensorineural hearing impairment were studied for the presence of mutations in the connexin 26--GJB2gene. Mutations were detected in 51 probands (46% of the sample). A significantly higher frequency of the GJB2gene mutations was observed in familial cases of the disease with the autosomal recessive type of inheritance (in 78% of families). Detected peculiarities of the GJB2 gene mutation spectrum demonstrated that use of the algorithm, which was developed for Russian patients, is optimal for the molecular study of patients from Be- larus. In the sample of patients with hearing loss, the highest (among other similar samples studied in the world) allele frequency of c.313_326de114 mutation (7% out of all pathological GJB2 alleles) was registered; Polish origin of this deletion was suggested. It was demonstrated that detection of the GJB2 gene mutation on only one patient's chromosome is insufficient to confirm a molecular genetic diagnosis of hearing loss of the DFNB1 genetic type (autosomal recessive hearing loss caused by the GJB2 gene mutations). Pilot screening in the presence of GJB2 gene mutations in newborns from Grodno oblast was conducted. The material from 235 children was studied during the screening; nine heterozygous carriers of the mutation were found. The c.35delG mutation was detected in a homozygous state in a single newborn (hearing loss of moderate severity was subsequently audiologically confirmed in this child). PMID:25711030

  4. RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling.

    PubMed

    Widowati, Titis; Melhem, Shamiram; Patria, Suryono Y; de Graaf, Bianca M; Sinke, Richard J; Viel, Martijn; Dijkhuis, Jos; Sadewa, Ahmad H; Purwohardjono, Rochadi; Soenarto, Yati; Hofstra, Robert Mw; Sribudiani, Yunia

    2016-06-01

    Hirschsprung disease (HSCR) is a major cause of chronic constipation in children. HSCR can be caused by germline mutations in RET and EDNRB. Defining causality of the mutations identified is difficult and almost exclusively based on in silico predictions. Therefore, the reported frequency of pathogenic mutations might be overestimated. We combined mutation analysis with functional assays to determine the frequencies of proven pathogenic RET and EDNRB mutations in HSCR. We sequenced RET and EDNRB in 57 HSCR patients. The identified RET-coding variants were introduced into RET constructs and these were transfected into HEK293 cells to determine RET phosphorylation and activation via ERK. An exon trap experiment was performed to check a possible splice-site mutation. We identified eight rare RET-coding variants, one possible splice-site variant, but no rare EDNRB variants. Western blotting showed that three coding variants p.(Pr270Leu), p.(Ala756Val) and p.(Tyr1062Cys) resulted in lower activation of RET. Moreover, only two RET variants (p.(Ala756Val) and p.(Tyr1062Cys)) resulted in reduced ERK activation. Splice-site assays on c.1880-11A>G could not confirm its pathogenicity. Our data suggest that indeed almost half of the identified rare variants are proven pathogenic and that, hence, functional studies are essential for proper genetic counseling. PMID:26395553

  5. Population screening for genetic susceptibility to disease.

    PubMed Central

    Clarke, A.

    1995-01-01

    Genetic screening for susceptibility to common diseases, such as the common cancers, cardiovascular disease, and diabetes, may soon be technically feasible. Commercial interests should not be allowed to introduce such screening before proper evaluation or without adequate counselling and support. The evaluation of such testing should include psychosocial and medical outcomes and outcomes for those given low risks as well as high risks. These tests may distract attention away from environmental factors contributing to disease, for which social and political measures may be more appropriate than individualised susceptibility screening and lifestyle modification. PMID:7613325

  6. Screening for fetal and genetic abnormalities.

    PubMed

    Simpson, J L

    1991-09-01

    Screening for genetic abnormalities is an integral part of obstetrics. Prior to initiating screening, however, several prerequisites must be met: (i) capacity to alter clinical management, (ii) cost effectiveness, (iii) reliable means (usually assays) of assessment, and (iv) capacity to handle problems. In all pregnancies one should determine in systematic fashion whether family history places a pregnant woman at increased risk over the background risk of 2-3% congenital anomalies. All women over age 35 years at delivery should be offered prenatal cytogenetic testing, and women of all ages should be offered maternal serum alpha-fetoprotein screening for neural tube defects. Screening ostensibly normal populations is appropriate in certain ethnic groups to determine heterozygosity for selected disorders: Blacks for sickle-cell anaemia, Mediterranean people for beta-thalassaemia, Southeast Asians and Filipinos for alpha-thalassaemia, Ashkenazi Jews and perhaps French-Canadians for Tay-Sachs disease. Cystic fibrosis screening (delta F508 mutations) is not currently recommended for the general populations, but should be offered to relatives of an individual having delta F508 cystic fibrosis. Irrespective of the extent of screening programmes for Mendelian traits, the mutant allele will remain in the general population because by far the greatest genetic load lies in clinically normal heterozygotes, affected contributing far less to the load despite the obvious clinical effect. PMID:1720071

  7. Sources of Error in Mammalian Genetic Screens.

    PubMed

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  8. Sources of Error in Mammalian Genetic Screens

    PubMed Central

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z.; Elledge, Stephen J.

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  9. Cancer Screening and Genetics: A Tale of Two Paradigms

    PubMed Central

    Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.

    2014-01-01

    The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to disease. Genetic risk information can have varying implications for the health and well-being of patients and their relatives, and has raised important questions about the evaluation and value of risk information. This paper explores the paradigms that are being applied to the evaluation of conventional cancer screening tests and emerging genetic and genomic tests of cancer susceptibility, and how these perspectives are shifting and evolving in response to advances in our ability to detect cancer risks. We consider several challenges germane to the evaluation of both categories of tests including defining benefits and harms in terms of personal and clinical utility, addressing healthcare consumers’ information preferences, and managing scientific uncertainty. We encourage research and dialogue aimed at developing a better understanding of the value of all risk information, non-genetic and genetic, to people’s lives. PMID:24706727

  10. Selection of competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for patients undergoing preimplantation genetic screening: a prospective study with sibling oocytes

    PubMed Central

    2014-01-01

    Background Recent advances in time-lapse monitoring in IVF treatment have provided new morphokinetic markers for embryonic competence. However, there is still very limited information about the relationship between morphokinetic parameters, chromosomal compositions and implantation potential. Accordingly, this study aimed at investigating the effects of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing on pregnancy and implantation outcomes for patients undergoing preimplantation genetic screening (PGS). Methods A total of 1163 metaphase II (MII) oocytes were retrieved from 138 PGS patients at a mean age of 36.6 ± 2.4 years. These sibling MII oocytes were then randomized into two groups after ICSI: 1) Group A, oocytes (n = 582) were cultured in the time-lapse system and 2) Group B, oocytes (n = 581) were cultured in the conventional incubator. For both groups, whole genomic amplification and array CGH testing were performed after trophectoderm biopsy on day 5. One to two euploid blastocysts within the most predictive morphokinetic parameters (Group A) or with the best morphological grade available (Group B) were selected for transfer to individual patients on day 6. Ongoing pregnancy and implantation rates were compared between the two groups. Results There were significant differences in clinical pregnancy rates between Group A and Group B (71.1% vs. 45.9%, respectively, p = 0.037). The observed implantation rate per embryo transfer significantly increased in Group A compared to Group B (66.2% vs. 42.4%, respectively, p = 0.011). Moreover, a significant increase in ongoing pregnancy rates was also observed in Group A compared to Group B (68.9% vs. 40.5%. respectively, p = 0.019). However, there was no significant difference in miscarriage rate between the time-lapse system and the conventional incubator (3.1% vs. 11.8%, respectively, p = 0.273). Conclusions This is the first prospective investigation using

  11. Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

    PubMed

    Lipska, Beata S; Iatropoulos, Paraskevas; Maranta, Ramona; Caridi, Gianluca; Ozaltin, Fatih; Anarat, Ali; Balat, Ayse; Gellermann, Jutta; Trautmann, Agnes; Erdogan, Ozlem; Saeed, Bassam; Emre, Sevinc; Bogdanovic, Radovan; Azocar, Marta; Balasz-Chmielewska, Irena; Benetti, Elisa; Caliskan, Salim; Mir, Sevgi; Melk, Anette; Ertan, Pelin; Baskin, Esra; Jardim, Helena; Davitaia, Tinatin; Wasilewska, Anna; Drozdz, Dorota; Szczepanska, Maria; Jankauskiene, Augustina; Higuita, Lina Maria Serna; Ardissino, Gianluigi; Ozkaya, Ozan; Kuzma-Mroczkowska, Elzbieta; Soylemezoglu, Oguz; Ranchin, Bruno; Medynska, Anna; Tkaczyk, Marcin; Peco-Antic, Amira; Akil, Ipek; Jarmolinski, Tomasz; Firszt-Adamczyk, Agnieszka; Dusek, Jiri; Simonetti, Giacomo D; Gok, Faysal; Gheissari, Alaleh; Emma, Francesco; Krmar, Rafael T; Fischbach, Michel; Printza, Nikoleta; Simkova, Eva; Mele, Caterina; Ghiggeri, Gian Marco; Schaefer, Franz

    2013-07-01

    Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome. PMID:23515051

  12. Two pediatric patients with Von Hippel-Lindau disease type 2b: from patient to screening, from screening to patient.

    PubMed

    Gonc, Nazli; Engiz, Ozlem; Neumann, Hartmut P H; Demirbilek, Huseyin; Ozon, Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

    2011-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL. PMID:21528828

  13. The art and design of genetic screens: maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

  14. A Chemical Genetic Screening Procedure for Arabidopsis thaliana Seedlings

    PubMed Central

    Bjornson, Marta; Song, Xingshun; Dandekar, Abhaya; Franz, Annaliese; Drakakaki, Georgia; Dehesh, Katayoon

    2016-01-01

    Unbiased screening approaches are powerful tools enabling identification of novel players in biological processes. Chemical genetic screening refers to the technique of using a reporter response, such as expression of luciferase driven by a promoter of interest, to discover small molecules that affect a given process when applied to plants. These chemicals then act as tools for identification of regulatory components that could not otherwise be detected by forward genetic screens due to gene family redundancy or mutant lethality. This protocol describes a chemical genetic screen using Arabidopsis thaliana seedlings, which has led to recognition of novel players in the plant general stress response.

  15. Antenatal screening and the gendering of genetic responsibility

    PubMed Central

    Reed, Kate

    2007-01-01

    Background The objective of this study is to explore men's and women's perceptions of antenatal blood screening. The study will assess the impact of these perceptions on decision-making regarding diagnostic testing and selective abortion, and on parental feelings of genetic responsibility. By exploring gender and antenatal screening in this way, the research aims to contribute to our understanding of lay perceptions of genetic screening and increase our knowledge of the decision-making process in screening. Research design This qualitative study will be based on semi-structured interviews with twenty pregnant women and twenty male partners in the post-industrial city of Sheffield, UK. All interviews will be taped, transcribed and analysed thematically using NVIVO, a qualitative software package. Discussion The findings of this study have relevance to existing debates on the social and ethical implications of reproductive genetics. A better understanding of male and female perceptions of the screening process could improve guidance and practice in antenatal screening and genetic counselling. It will also inform and contribute to the development of theory on gender and genetic screening. PMID:17903256

  16. Preparticipation athletic screening for genetic heart disease.

    PubMed

    Myerson, Merle; Sanchez-Ross, Monica; Sherrid, Mark V

    2012-01-01

    Sudden cardiac death (SCD) in young athletes is relatively uncommon but tragic when it occurs. Many of these deaths can be prevented by pre-exercise screening to identify cardiac abnormalities and those at high risk. Although recent research has provided much needed information on SCD in athletes, there remain significant gaps in the knowledge needed to determine an optimal screening protocol. This review examines the incidence and demographics of SCD in athletes and the difficulties in determining whether changes in an athlete's heart are due to training or represent a potentially malignant congenital abnormality. Current guidelines for screening and the intense debate over the use of the 12-lead electrocardiogram are discussed. Lastly, the importance of a response plan to an apparent SCD event that includes on-site/on-field automated external defibrillators will be discussed. A case study that illustrates the challenges in screening is presented. PMID:22687598

  17. Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

    PubMed

    Levin, M

    1999-01-01

    Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed. PMID:10464669

  18. Potential of plant genetic systems for monitoring and screening mutagens

    PubMed Central

    Nilan, R. A.

    1978-01-01

    Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations. Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be

  19. A Combined Analysis of 48 Type 2 Diabetes Genetic Risk Variants Shows No Discriminative Value to Predict Time to First Prescription of a Glucose Lowering Drug in Danish Patients with Screen Detected Type 2 Diabetes

    PubMed Central

    Hornbak, Malene; Allin, Kristine Højgaard; Jensen, Majken Linnemann; Lau, Cathrine Juel; Witte, Daniel; Jørgensen, Marit Eika; Sandbæk, Annelli; Lauritzen, Torsten; Andersson, Åsa; Pedersen, Oluf; Hansen, Torben

    2014-01-01

    Objective To investigate the genetic influence of 48 type 2 diabetes susceptibility variants on disease progression measured as risk of early prescription redemption of glucose lowering drugs in screen-detected patients with type 2 diabetes. Methods We studied type 2 diabetes progression in 1,480 patients with screen-detected type 2 diabetes from the ADDITION-Denmark study using information of redeemed prescriptions from the Register of Medicinal Products Statistics from 2001–2009 in Denmark. Patients were cluster randomized by general practitioners, who were randomized to treat type 2 diabetes according to either a conventional or a multifactorial intensive treatment algorithm. We investigated the genetic influence on diabetes progression by constructing a genetic risk score (GRS) of all 48 validated type 2 diabetes susceptibility variants, a GRS of 11 variants linked to β-cell function and a GRS of 3 variants linked to insulin sensitivity and assessed the association between number of risk alleles and time from diagnosis until first redeemed prescription of either any glucose lowering drug or an insulin drug. Results The GRS linked to insulin sensitivity only nominally increased the risk of an early prescription redemption with an insulin drug by 39% (HR [95% C.I.] = 1.39 [1.09–1.77], p = 0.009] in patients randomized to the intensive treatment group. Furthermore, the strongest univariate predictors of diabetes progression for the intensive treatment group (measured as time to first insulin) were younger age (HR [95% C.I.] = 0.96 [0.93–0.99]), increased BMI (1.05 [1.01–1.09]), increased HbA1c (1.50 [1.36–.66]), increased TG (1.24 [1.11–1.39]) and reduced fasting serum HDL (0.37 [0.17–0.80]) at baseline. Similar results were obtained for the conventional treatment group. Conclusion Higher levels of HbA1c, fasting circulating levels of triglyceride, lower HDL, larger BMI and younger age are significant determinants of early

  20. Motherhood and Genetic Screening: A Personal Perspective

    ERIC Educational Resources Information Center

    Place, Fiona

    2008-01-01

    According to the medical profession the direction and scope of reproductive services such as IVF and pre-natal screening are based on solid evidence; the evidence indicates these are effective and safe services. Moreover, women want them. As a consequence these services are usually presented to the wider community in a positive light with images…

  1. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know

    PubMed Central

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-01-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers. PMID:25564039

  2. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know.

    PubMed

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-09-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers. PMID:25564039

  3. Genetic Screening: A Unique Game of Survival

    ERIC Educational Resources Information Center

    Kurvink, Karen; Bowser, Jessica

    2004-01-01

    A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

  4. Recent advances in prenatal screening and diagnosis of genetic disorders.

    PubMed

    Bozzette, Maryann

    2002-11-01

    In any pregnancy, there is an approximate 3% to 5% chance that a fetal complication will occur. The most familiar prenatal diagnostics cannot be performed until the fetus is well into gestation, and most involve invasive procedures along with their inherent risks. In light of these facts, many noninvasive prenatal screening and diagnostic tests have been developed, the newest using recombinant deoxyribonucleic acid (DNA) technology in the examination of fetal cells. Through these procedures, genetic coding errors and chromosomal disruptions may be detected. This article discusses the currently available prenatal and screening diagnostic tests for genetic disorders with a focus on the latest technology. PMID:12473913

  5. Genetic Carrier Screening in the Twenty-first Century.

    PubMed

    Yao, Ruofan; Goetzinger, Katherine R

    2016-06-01

    Historically, carrier screening for a small number of autosomal recessive disorders has been offered to targeted populations based on ethnicity and family history. These chosen disorders are associated with severe morbidity or mortality, have a well-established carrier frequency in the targeted population, and have an acceptably high detection rate to make screening efficient. With advancing genetic technology, expanded panels rapidly are being designed and offered to the panethnic general population. This article reviews current recommendations for ethnicity-specific carrier screening for common disorders as well as the limitations and counseling complexities associated with expanded panels. PMID:27235912

  6. Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder.

    PubMed

    Friedel, S; Horro, F Fontenla; Wermter, A K; Geller, F; Dempfle, A; Reichwald, K; Smidt, J; Brönner, G; Konrad, K; Herpertz-Dahlmann, B; Warnke, A; Hemminger, U; Linder, M; Kiefl, H; Goldschmidt, H P; Siegfried, W; Remschmidt, H; Hinney, A; Hebebrand, J

    2005-01-01

    Several lines of evidence indicate an involvement of brain derived neurotrophic factor (BDNF) in body weight regulation and activity: heterozygous Bdnf knockout mice (Bdnf(+/-)) are hyperphagic, obese, and hyperactive; furthermore, central infusion of BDNF leads to severe, dose-dependent appetite suppression and weight loss in rats. We searched for the role of BDNF variants in obesity, eating disorders, and attention-deficit/hyperactivity disorder (ADHD). A mutation screen (SSCP and DHPLC) of the translated region of BDNF in 183 extremely obese children and adolescents and 187 underweight students was performed. Additionally, we genotyped two common polymorphisms (rs6265: p.V66M; c.-46C > T) in 118 patients with anorexia nervosa, 80 patients with bulimia nervosa, 88 patients with ADHD, and 96 normal weight controls. Three rare variants (c.5C > T: p.T2I; c.273G > A; c.*137A > G) and the known polymorphism (p.V66M) were identified. A role of the I2 allele in the etiology of obesity cannot be excluded. We found no association between p.V66M or the additionally genotyped variant c.-46C > T and obesity, ADHD or eating disorders. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html. PMID:15457498

  7. Coupled mutagenesis screens and genetic mapping in zebrafish.

    PubMed Central

    Rawls, John F; Frieda, Matthew R; McAdow, Anthony R; Gross, Jason P; Clayton, Chad M; Heyen, Candy K; Johnson, Stephen L

    2003-01-01

    Forward genetic analysis is one of the principal advantages of the zebrafish model system. However, managing zebrafish mutant lines derived from mutagenesis screens and mapping the corresponding mutations and integrating them into the larger collection of mutations remain arduous tasks. To simplify and focus these endeavors, we developed an approach that facilitates the rapid mapping of new zebrafish mutations as they are generated through mutagenesis screens. We selected a minimal panel of 149 simple sequence length polymorphism markers for a first-pass genome scan in crosses involving C32 and SJD inbred lines. We also conducted a small chemical mutagenesis screen that identified several new mutations affecting zebrafish embryonic melanocyte development. Using our first-pass marker panel in bulked-segregant analysis, we were able to identify the genetic map positions of these mutations as they were isolated in our screen. Rapid mapping of the mutations facilitated stock management, helped direct allelism tests, and should accelerate identification of the affected genes. These results demonstrate the efficacy of coupling mutagenesis screens with genetic mapping. PMID:12663538

  8. Genetic Signature of Histiocytic Sarcoma Revealed by a Sleeping Beauty Transposon Genetic Screen in Mice

    PubMed Central

    Been, Raha A.; Linden, Michael A.; Hager, Courtney J.; DeCoursin, Krista J.; Abrahante, Juan E.; Landman, Sean R.; Steinbach, Michael; Sarver, Aaron L.; Largaespada, David A.; Starr, Timothy K.

    2014-01-01

    Histiocytic sarcoma is a rare, aggressive neoplasm that responds poorly to therapy. Histiocytic sarcoma is thought to arise from macrophage precursor cells via genetic changes that are largely undefined. To improve our understanding of the etiology of histiocytic sarcoma we conducted a forward genetic screen in mice using the Sleeping Beauty transposon as a mutagen to identify genetic drivers of histiocytic sarcoma. Sleeping Beauty mutagenesis was targeted to myeloid lineage cells using the Lysozyme2 promoter. Mice with activated Sleeping Beauty mutagenesis had significantly shortened lifespan and the majority of these mice developed tumors resembling human histiocytic sarcoma. Analysis of transposon insertions identified 27 common insertion sites containing 28 candidate cancer genes. Several of these genes are known drivers of hematological neoplasms, like Raf1, Fli1, and Mitf, while others are well-known cancer genes, including Nf1, Myc, Jak2, and Pten. Importantly, several new potential drivers of histiocytic sarcoma were identified and could serve as targets for therapy for histiocytic sarcoma patients. PMID:24827933

  9. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

    PubMed Central

    Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.; Christensen, Lea C.; Williamson, James C.; Antrobus, Robin; Dougan, Gordon; Ellgaard, Lars; Lehner, Paul J.

    2016-01-01

    The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard' method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum-associated degradation (ERAD) of MHC class I molecules. The two approaches show high concordance (>70%), successfully identifying the majority of the known components of the canonical glycoprotein ERAD pathway. Both screens also identify a role for the uncharacterized gene TXNDC11, which we show encodes an EDEM2/3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox. PMID:27283361

  10. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens.

    PubMed

    Timms, Richard T; Menzies, Sam A; Tchasovnikarova, Iva A; Christensen, Lea C; Williamson, James C; Antrobus, Robin; Dougan, Gordon; Ellgaard, Lars; Lehner, Paul J

    2016-01-01

    The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing 'gold standard' method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum-associated degradation (ERAD) of MHC class I molecules. The two approaches show high concordance (>70%), successfully identifying the majority of the known components of the canonical glycoprotein ERAD pathway. Both screens also identify a role for the uncharacterized gene TXNDC11, which we show encodes an EDEM2/3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox. PMID:27283361

  11. Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System.

    PubMed

    Kim, Haseong; Kwon, Kil Koang; Seong, Wonjae; Lee, Seung-Goo

    2016-01-01

    The recent development of a high-throughput single-cell assay technique enables the screening of novel enzymes based on functional activities from a large-scale metagenomic library(1). We previously proposed a genetic enzyme screening system (GESS) that uses dimethylphenol regulator activated by phenol or p-nitrophenol. Since a vast amount of natural enzymatic reactions produce these phenolic compounds from phenol deriving substrates, this single genetic screening system can be theoretically applied to screen over 200 different enzymes in the BRENDA database. Despite the general applicability of GESS, applying the screening process requires a specific procedure to reach the maximum flow cytometry signals. Here, we detail the developed screening process, which includes metagenome preprocessing with GESS and the operation of a flow cytometry sorter. Three different phenolic substrates (p-nitrophenyl acetate, p-nitrophenyl-β-D-cellobioside, and phenyl phosphate) with GESS were used to screen and to identify three different enzymes (lipase, cellulase, and alkaline phosphatase), respectively. The selected metagenomic enzyme activities were confirmed only with the flow cytometry but DNA sequencing and diverse in vitro analysis can be used for further gene identification. PMID:27584951

  12. [Genetic variants associated to male infertility in Mexican patients].

    PubMed

    Piña-Aguilar, Raúl Eduardo; Chima-Galán, María del Carmen; Yerena-de-vega, María de la Concepción A; Regalado-Hernández, Miguel Angel; Sánchez-Guerrero, Cecilia; García-Ortiz, Liliana; Santillán-Hernández, Yuritzi; Moreno-García, Jesús Daniel

    2013-05-01

    Recently Mexican Federation of Obstetrics and Gynecology Colleges (Federación Mexicana de Colegios de Obstetricia y Ginecologia, FEMECOG) published the Mexican guideline forthe management of male infertility, which suggests performing genetic laboratory tests as part of diagnosis and management of infertile patients and states that these should receive genetic counseling. This paper reviews the genetic approach proposed by Mexican guideline. A systematic review of medical literature was performed in Pubmed and Web of Knowledge from 1980 to 2012 in order to find reports of genetic variants associated to male infertility in Mexican patients. Also it is discussed the current knowledge of these variants, their clinical implications and finally the guidelines and recommendations for their molecular diagnosis. Most genetic variants in Mexican infertile patients are chromosome abnormalities. In relation to other variants there is only a report of Y chromosome microdeletions, repeated CAG in androgen receptor and more common mutations in CFTR, and other article reporting mutations in CFTR in patients with congenital absence of vas deferens. Little is known about the genetics of Mexican infertile patients apart from chromosome abnormalities. However, the contribution of genetics as etiology of male infertility is taking more relevance and currently the consensual management of infertile male should include the screening of genetic background. This review pretends to be a quick guide for clinicians who want to know about reports of genetic variants related to male infertility in Mexican population and how to approach their diagnosis. PMID:23819425

  13. Combination of hearing screening and genetic screening for deafness-susceptibility genes in newborns

    PubMed Central

    YAO, GEN-DONG; LI, SHOU-XIA; CHEN, DING-LI; FENG, HAI-QIN; ZHAO, SU-BIN; LIU, YONG-JIE; GUO, LI-LI; YANG, ZHI-MING; ZHANG, XIAO-FANG; SUN, CAI-XIA; WANG, ZE-HUI; ZHANG, WEI-YONG

    2014-01-01

    The aim of this study was to determine the clinical significance of the results of screening of newborn hearing and the incidence of deafness-susceptibility genes. One thousand newborn babies in the Handan Center Hospital (Handan, China) underwent screening of hearing and deafness-susceptibility genes. The first screening test was carried out using otoacoustic emissions (OAEs). Babies with hearing loss who failed to pass the initial screening were scheduled for rescreening at 42 days after birth. Cord blood was used for the screening of deafness-susceptibility genes, namely the GJB2, SLC26A4 and mitochondrial 12S rRNA (MTRNR1) genes. Among the 1,000 neonates that underwent the first hearing screening, 25 exhibited left-sided hearing loss, 21 exhibited right-sided hearing loss and 15 cases had binaural hearing loss. After rescreening 42 days later, only one of the initial 61 cases exhibited hearing loss under OAE testing. The neonatal deafness gene tests showed two cases with 1555A>G mutation and two cases with 1494C>T mutation of the MTRNR1 gene. In the SLC26A4 gene screening, four cases exhibited the heterozygous IVS7-2A>G mutation and one case exhibited heterozygous 1226G>A mutation. In the GJB2 gene screening, two cases exhibited the homozygous 427C>T mutation and 10 exhibited the heterozygous 235delC mutation. The genetic screening revealed 21 newborns with mutations in the three deafness-susceptibility genes. The overall carrier rate was 2.1% (21/1,000). The association of hearing and gene screening may be the promising screening strategy for the diagnosis of hearing loss. PMID:24348793

  14. Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

    PubMed Central

    Majumdar, Gaurav; Majumdar, Abha; Lall, Meena; Verma, Ishwar C.; Upadhyaya, Kailash C.

    2016-01-01

    CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis. PMID:27382234

  15. Virus-Host Interactions: From Unbiased Genetic Screens to Function.

    PubMed

    Ramage, Holly; Cherry, Sara

    2015-11-01

    Deciphering the many interactions that occur between a virus and host cell over the course of infection is paramount to understanding mechanisms of pathogenesis and to the future development of antiviral therapies. Over the past decade, researchers have started to understand these complicated relationships through the development of methodologies, including advances in RNA interference, proteomics, and the development of genetic tools such as haploid cell lines, allowing high-throughput screening to identify critical contact points between virus and host. These advances have produced a wealth of data regarding host factors hijacked by viruses to promote infection, as well as antiviral factors responsible for subverting viral infection. This review highlights findings from virus-host screens and discusses our thoughts on the direction of screening strategies moving forward. PMID:26958926

  16. Forward genetic screen for auxin-deficient mutants by cytokinin

    PubMed Central

    Wu, Lei; Luo, Pan; Di, Dong-Wei; Wang, Li; Wang, Ming; Lu, Cheng-Kai; Wei, Shao-Dong; Zhang, Li; Zhang, Tian-Zi; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, Guang-Qin

    2015-01-01

    Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis. PMID:26143750

  17. Screening of the CFTR gene in Indian patients

    PubMed Central

    Deepak, Rani R.; Ashavaid, Tester F.

    2012-01-01

    Cystic fibrosis (CF) has been observed to be far more common in India, than was previously thought. Variability in CF clinical symptoms among individuals, results in diagnostic errors. Also, CF diagnostic facilities are not available at all diagnostic centers across India. Sweat test (gold standard for CF diagnosis) has some limitations. Mutation analysis, therefore, would be useful in detecting the mutant CF alleles in Indian patients. This study, aimed at identifying common CF transmembrane conductance regulator (CFTR) mutations, to develop a molecular diagnostic test in Indian patients, and establish genotype-phenotype correlation. Mutation identification was performed by single stranded conformation polymorphism (SSCP) screening, followed by DNA sequencing of regions with an abnormal SSCP pattern. ∆F508 accounts for about 53% of CF alleles. A substantial proportion of these patients have rare and/or novel mutations. Eight novel and 12 known polymorphisms were also identified. Considering the high percentage of rare/novel mutations, along with ethnic history of Indian population, we can speculate that the remaining uncharacterized mutations might also not be prevalent mutations. The total number of CF disease-causing mutations in Indian patients is very large. Thus, DNA-based population screening will be complicated, and an indirect genetic diagnosis (screening entire gene) would be necessary to characterize all mutations.

  18. Preimplantation genetic screening 2.0: the theory.

    PubMed

    Geraedts, Joep; Sermon, Karen

    2016-08-01

    During the last few years a new generation of preimplantation genetic screening (PGS) has been introduced. In this paper, an overview of the different aspects of this so-called PGS 2.0 with respect to the why (what are the indications), the when (which developmental stage, i.e. which material should be studied) and the how (which molecular technique should be used) is given. With respect to the aims it is clear that PGS 2.0 can be used for a variety of indications. However, the beneficial effect of PGS 2.0 has not been proved yet in RCTs. It is clear that cleavage stage is not the optimal stage for biopsy. Almost all advocates of PGS 2.0 prefer trophectoderm biopsy. There are many new methods that allow the study of complete aneuploidy with respect to one or more of the 24 chromosomes. Because of the improved vitrification methods, selection of fresh embryos for transfer is more and more often replaced by frozen embryo transfer. The main goal of PGS has always been the improvement of IVF success. However, success is defined by different authors in many different ways. This makes it very difficult to compare the outcomes of different studies. In conclusion, the introduction of PGS 2.0 will depend on the success of the new biopsy strategies in combination with the analysis of all 24 chromosomes. It remains to be seen which approach will be the most successful and for which specific groups of patients. PMID:27256482

  19. Screening for Depression Patients in Family Medicine

    PubMed Central

    Alic, Alma; Pranjic, Nurka; Selmanovic, Senada; Alibasic, Esad; Alic, Fahrudin; Ramic, Enisa; Spahic-Sarajlic, Selvedina

    2014-01-01

    ABSTRACT Goal: The aims are to establish the prevalence of newfound, unidentified cases of depressive disorder by screening with the Becks Depression scale; To establish a comparative relationship with self-identified cases of depression in the patients in the family medicine; To assess the significance of the BDI in screening practice of family medicine. Patients and methods: A prospective study was conducted anonymously by Beck's Depression scale (Beck Depression Questionnaire org.-BDI) and specially created short questionnaire. The study included 250 randomly selected patients (20-60 years), users of services in family medicine in “Dom Zdravlja” Zenica, and the final number of respondents with included in the study was 126 (51 male, 75 female; response or response rate 50.4%). Exclusion factor was previously diagnosed and treated mental disorder. Participation was voluntary and respondents acknowledge the validity of completing the questionnaire. BDI consists of 21 items. Answers to questions about symptoms were ranked according to the Likert type scale responses from 0-4 (from irrelevant to very much). Respondents expressed themselves on personal perception of depression, whether are or not depressed. Results: Depression was observed in 48% of patients compared to 31% in self estimate depression analyzed the questionnaires. The negative trend in the misrecognition of depression is -17% (48:31). Depression was significantly more frequent in unemployed compared to employed respondents (p=0.001). The leading symptom in both sexes is the perception of lost hope (59% of cases). Conclusion: All respondents in family medicine care in Zenica showed a high percentage of newly detected (17%) patients with previously unrecognized depression. BDI is a really simple and effective screening tool for the detection and identification of persons with symptoms of depression. PMID:24783910

  20. Nondirectiveness in prenatal genetics: patients read between the lines.

    PubMed

    Anderson, G

    1999-03-01

    For decades questionnaires have been used to measure the cognitive and psychological effects of prenatal genetic testing, but little is known about why some women undergo testing and others decline. Research indicates that many factors influence decision making, including values and beliefs. What is often denied rather than recognized is that the professional and personal values and beliefs held by the health care provider influence the patient's decision. It is assumed that, if genetic services are delivered in a nondirective manner, patients will not be affected by the provider's personal and professional standpoint. The qualitative research data reported here challenge this assumption. Getting to know patients' moral understanding and patterns of ethical reasoning by listening to their personal stories is recommended as a better way for nurses to help patients to make informed and autonomous decisions about prenatal genetic screening or diagnostic tests. PMID:10358528

  1. Using the patient's questionnaire data to screen laryngeal disorders.

    PubMed

    Verikas, A; Gelzinis, A; Bacauskiene, M; Uloza, V; Kaseta, M

    2009-02-01

    This paper is concerned with soft computing techniques for screening laryngeal disorders based on patient's questionnaire data. By applying the genetic search, the most important questionnaire statements are determined and a support vector machine (SVM) classifier is designed for categorizing the questionnaire data into the healthy, nodular and diffuse classes. To explore the obtained automated decisions, the curvilinear component analysis (CCA) in the space of decisions as well as questionnaire statements is applied. When testing the developed tools on the set of data collected from 180 patients, the classification accuracy of 85.0% was obtained. Bearing in mind the subjective nature of the data, the obtained classification accuracy is rather encouraging. The CCA allows obtaining ordered two-dimensional maps of the data in various spaces and facilitates the exploration of automated decisions provided by the system and determination of relevant groups of patients for various comparisons. PMID:19144329

  2. A practical approach to genetic screening for influenza virus variants.

    PubMed Central

    Zou, S

    1997-01-01

    This report describes a quick genetic approach to the screening of influenza virus variants. Multiplex reverse transcription (MRT) and multiplex PCR (MPCR) were used to amplify and differentiate the hemagglutinin (HA) genes of different types and subtypes of influenza viruses. Heteroduplex mobility assay (HMA) was then used to differentiate strains within the same type and subtype. Three primers complementary to the consensus 3' termini of viral genomic RNA segments of human influenza virus types A, B, and C were used in a single MRT reaction to prime the synthesis of cDNA of all the viral genome segments. The cDNA was then amplified in an MPCR containing primers for the HA genes of the H1 and H3 subtypes of type A, the HA gene of type B, and the counterpart of type C virus. Amplicons of the different types and subtypes differ in size, thus allowing typing and subtyping. The regions amplified cover most of the HA1 portion of the HA genes and therefore amplicons of variants identified by the described HMA can be sequenced directly. In the HMA, the amplicon of an individual strain was mixed with that of a reference strain and heteroduplexes derived from mismatches migrated more slowly than homoduplexes of the same size in electrophoresis, with the mobility shift pattern indicating the divergence of amplicons. The whole process from viral RNA extraction to HMA can be completed within 2 days and thus provides a quick screening before further analysis by hemagglutination inhibition testing and sequencing. In addition, all segments of the viral genome can be amplified from a single MRT reaction, which can yield valuable sources of products for future genetic analyses. This method should facilitate genetic screening and characterization of influenza virus variants. PMID:9316919

  3. Recent advances in preimplantation genetic diagnosis and screening.

    PubMed

    Lu, Lina; Lv, Bo; Huang, Kevin; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

    2016-09-01

    Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics. PMID:27272212

  4. Molecular screening of genetic defects with RNA-SSCP analysis: the PKU and cystinuria model.

    PubMed

    Giannattasio, S; Bisceglia, L; Lattanzio, P; Grifa, A; Dianzani, I; Gasparini, P; Marra, E

    1995-06-01

    RNA single-strand conformation polymorphism (rSSCP) is a recently developed method for detecting genetic defects. This technique requires DNA amplification with a polymerase chain reaction making use of one T7 promoter-containing primer. Amplification products are subsequently transcribed in vitro and the labelled transcripts are analysed for single-strand conformation changes. rSSCP has been applied to mutation screening of the phenylalanine hydroxylase gene and rBAT cDNA, from PKU and cystinuric patients, respectively. Experimental evidence shows that 83% and 86% of screened PKU and cystinuric mutations, respectively, give rise to detectable rSSCP signals. Thus, results obtained show that RNA single-strand conformation polymorphism analysis is generally applicable and is a suitable technique for detecting genetic disease causing mutations, both in basic research and in clinical practice. PMID:7477014

  5. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    PubMed

    2012-04-01

    screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines. PMID:22475884

  6. Pooled-matrix protein interaction screens using Barcode Fusion Genetics.

    PubMed

    Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P

    2016-01-01

    High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. PMID:27107012

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

    PubMed Central

    Bhavnani, M; Lloyd, D; Marples, J; Pendry, K; Worwood, M

    2006-01-01

    Objective To evaluate the clinical utility of a targeted screening approach for the detection of genetic haemochromatosis. Methods Screening by measuring fasting serum transferrin saturation (TS) and gene testing was carried out in patients in whom a raised serum alanine amino transferase (ALT) activity and raised random serum TS had been found on routine blood testing. Results During the 29 month study period, 32 patients homozygous for the C282Y genotype were detected from a catchment population of 330 000 by screening blood samples referred initially for routine laboratory liver function tests. By comparison, during the same period of time and within the same population, only seven patients were found by clinical suspicion alone. The patients in the study, after treatment by venesection, have shown both clinical and biochemical improvement. Conclusions The study shows that from a population of patients in whom a routine liver function profile had been requested, it is possible to detect subjects homozygous for the C282Y HFE genotype who have clinical or biochemical markers of iron overload. PMID:16644885

  8. Canadian guideline on genetic screening for hereditary renal cell cancers

    PubMed Central

    Reaume, M. Neil; Graham, Gail E.; Tomiak, Eva; Kamel-Reid, Suzanne; Jewett, Michael A.S.; Bjarnason, Georg A.; Blais, Normand; Care, Melanie; Drachenberg, Darryl; Gedye, Craig; Grant, Ronald; Heng, Daniel Y.C.; Kapoor, Anil; Kollmannsberger, Christian; Lattouf, Jean-Baptiste; Maher, Eamonn R.; Pause, Arnim; Ruether, Dean; Soulieres, Denis; Tanguay, Simon; Turcotte, Sandra; Violette, Philippe D.; Wood, Lori; Basiuk, Joan; Pautler, Stephen E.

    2013-01-01

    Background: Hereditary renal cell cancer (RCC) is an ideal model for germline genetic testing. We propose a guideline of hereditary RCC specific criteria to suggest referral for genetic assessment. Methods: A review of the literature and stakeholder resources for existing guidelines or consensus statements was performed. Referral criteria were developed by expert consensus. Results: The criteria included characteristics for patients with RCC (age ≤45 years, bilateral or multifocal tumours, associated medical conditions and non-clear cell histologies with unusual features) and for patients with or without RCC, but a family history of specific clinical or genetic diagnoses. Conclusions: This guideline represents a practical RCC-specific reference to allow healthcare providers to identify patients who may have a hereditary RCC syndrome, without extensive knowledge of each syndrome. RCC survivors and their families can also use the document to guide their discussions with healthcare providers about their need for referral. The criteria refer to the most common hereditary renal tumour syndromes and do not represent a comprehensive or exclusive list. Prospective validation of the criteria is warranted. PMID:24319509

  9. Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase

    PubMed Central

    Bhavnani, M; Lloyd, D; Bhattacharyya, A; Marples, J; Elton, P; Worwood, M

    2000-01-01

    BACKGROUND—In the UK approximately 1 in 140 people are homozygous for the C282Y mutation of the HFE gene and are at risk from iron overload caused by genetic haemochromatosis (GH). Early detection can prevent organ damage secondary to iron deposition and increase life expectancy.
AIM—To screen for GH in all blood samples sent to the laboratory for routine liver function tests in which raised serum alanine aminotransferase (ALT) activity was detected.
METHODS—ALT was measured in sera sent to the laboratory for routine liver function tests. In those samples found to have raised activity, transferrin saturation and ferritin were measured followed by genetic testing when transferrin saturation was increased.
RESULTS—Of the 35 069 serum samples assayed for routine liver function tests, 1490 (4.2%) had raised ALT levels (>50 u/l). Transferrin saturation and serum ferritin concentrations were measured in these patient samples, and in 56 transferrin saturation was >60%. Further blood samples were requested from these patients for genetic testing: 33 samples were obtained. There were nine patients homozygous for the C282Y mutation of the HFE gene and three compound heterozygotes (heterozygous for both C282Y and H63D mutations).
CONCLUSIONS—The association of raised ALT activity and transferrin saturation of >60% could provide a simple, cost effective method for detecting individuals with clinical haemochromatosis. Although many patients with GH may have been missed, this study suggests that the clinical penetrance of the disorder may be much lower than is generally supposed and that genetic screening will identify many people who may never develop clinical haemochromatosis.


Keywords: haemochromatosis; alanine aminotransferase PMID:10764716

  10. Screening for spinal stenosis in achondroplastic patients undergoing limb lengthening.

    PubMed

    Fernandes, James A; Devalia, Kailash L; Moras, Prem; Pagdin, Jonathan; Jones, Stanley; Mcmullan, John

    2014-03-01

    The need for a screening programme for spinal stenosis in children with achondroplasia undergoing limb lengthening was identified in a tertiary limb reconstruction service. The aim of this study was to evaluate whether screening would identify the 'at risk' group. A total of 26 achondroplastic patients underwent our screening programme. Canal diameters were measured by MRI. Neurosurgical interventions were recorded. Of the patients, 13 had severe foramen magnum narrowing. Six patients required single or multiple surgical decompressions. We identified female sex, delayed milestones and a tight cervicomedullary junction as high risks. We stress upon the importance of developing a nationalized screening programme with guidelines to identify a high-risk group. PMID:24345918

  11. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations. PMID:26141656

  12. Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles

    PubMed Central

    Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping

    2015-01-01

    Objective: To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. Methods: 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. Results: The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. Conclusion: In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes. PMID:26885112

  13. Screening for Depression in Hospitalized Pediatric Patients

    PubMed Central

    ESMAEELI, Mohammad-Reza; ERFANI SAYAR, Reza; SAGHEBI, Ali; ELMI, Saghi; RAHMANI, Shagheyegh; ELMI, Sam; RABBANI JAVADI, Akram

    2014-01-01

    Objective In chronically ill children who are hospitalized, many mood changes occur. For example, in children with cancer or renal failure, prolonged hospitalization and chemotherapy can lead to depression. With the improved survival of childhood malignancies, the effect of treatment on child’s psychosocial well-being becomes increasingly relevant. In this study, we examined the prevalence of depression in hospitalized children with chronic and acute conditions in Dr Sheikh Pediatrics Hospital in Mashhad. Materials & Methods After receiving the approval from the Ethics Committee of Mashhad University of Medical Sciences, we did this cross-sectional descriptive study, from April to June 2012 in Dr Sheikh Pediatric Hospital in Mashhad. Ninety children, between 8 to 16 years, were screened for depression. The sampling method was census. Children with a history of depressive or other mental disorders were excluded. Three groups of children (children with chronic renal disease, malignancy, and acute disease) were evaluated for depression using standard Children Depression Inventory Questionnaire (CDI). Two specifically trained nurses filled out the questionnaires at patients’ bedside under the supervision of a psychiatrist. Depression scores were then analyzed by SPSS software. Results Of 90 children, 43(47.7%) were male and 47(52.2%) were female. The Children’s mean age was 11±2.3 years, and the mean length of hospitalization was 8±5.3 days. Depression was detected in various degrees in 63% of patients (N=57), and 36.6% of children (N=32) had no symptoms of depression. Severe depression was not seen in any of the patients with acute illness. More than half of patients with cancer and chronic kidney disease had moderate to severe depression. There was a significant statistical relationship between the duration of illness and severity of depression. There was also a significant correlation between severity of depression and frequency of hospitalization. Children

  14. Predictive features of breast cancer on Mexican screening mammography patients

    NASA Astrophysics Data System (ADS)

    Rodriguez-Rojas, Juan; Garza-Montemayor, Margarita; Trevino-Alvarado, Victor; Tamez-Pena, José Gerardo

    2013-02-01

    Breast cancer is the most common type of cancer worldwide. In response, breast cancer screening programs are becoming common around the world and public programs now serve millions of women worldwide. These programs are expensive, requiring many specialized radiologists to examine all images. Nevertheless, there is a lack of trained radiologists in many countries as in Mexico, which is a barrier towards decreasing breast cancer mortality, pointing at the need of a triaging system that prioritizes high risk cases for prompt interpretation. Therefore we explored in an image database of Mexican patients whether high risk cases can be distinguished using image features. We collected a set of 200 digital screening mammography cases from a hospital in Mexico, and assigned low or high risk labels according to its BIRADS score. Breast tissue segmentation was performed using an automatic procedure. Image features were obtained considering only the segmented region on each view and comparing the bilateral di erences of the obtained features. Predictive combinations of features were chosen using a genetic algorithms based feature selection procedure. The best model found was able to classify low-risk and high-risk cases with an area under the ROC curve of 0.88 on a 150-fold cross-validation test. The features selected were associated to the differences of signal distribution and tissue shape on bilateral views. The model found can be used to automatically identify high risk cases and trigger the necessary measures to provide prompt treatment.

  15. Patient Test Preference for Colorectal Cancer Screening and Screening Uptake in an Insured Urban Minority Population.

    PubMed

    Wolf, Randi L; Basch, Charles E; Zybert, Patricia; Basch, Corey H; Ullman, Ralph; Shmukler, Celia; King, Fionnuala; Neugut, Alfred I

    2016-06-01

    The study examines the role of patient colorectal cancer (CRC) screening test preference and CRC screening uptake in an insured, urban minority population. Study subjects were enrolled in a randomized controlled trial to promote CRC screening. The interventions were educational, with an emphasis on colonoscopy screening. Subjects were 50+ years of age, fully insured for CRC screening, and out of compliance with current CRC screening recommendations. This paper includes those who answered a question about CRC screening test preference and indicated that they intended to receive such a test in the coming year (n = 453). CRC screening uptake was ascertained from medical claims data. Regardless of test preference, few received CRC screening (22.3 %). Those preferring the home stool test (HST) were less likely to get tested than those preferring a colonoscopy (16.6 vs 29.9 %, χ(2) = 9.9, p = .002). Preference for HST was more strongly associated with beliefs about colonoscopy than with knowledge about colonoscopy. In the context of an RCT emphasizing colonoscopy screening for CRC, patients expressing a preference for HST are at heightened risk of remaining unscreened. Colonoscopy should be recommended as the preferred CRC test, but HSTs should be accessible and encouraged for patients who are averse to colonoscopy.Clinical trials.gov: Identifier: NCT02392143. PMID:26585609

  16. Low Primary Lipid Screening among Medicare Patients with Rheumatoid Arthritis

    PubMed Central

    Bartels, Christie M; Kind, Amy JH; Everett, Christine; Mell, Matthew; McBride, Patrick; Smith, Maureen

    2011-01-01

    Objective Although reports demonstrate suboptimal preventive cancer screening in RA patients, primary lipid screening performance has not been systematically examined. We examined associations between primary lipid screening and visits to primary care providers (PCPs) and rheumatologists among a national sample of older RA patients. Methods This retrospective cohort study examines a 5% Medicare sample including 3,298 RA patients without baseline cardiovascular disease (CVD), diabetes, or hyperlipidemia, that were considered eligible for primary lipid screening (2004–2006). The outcome was probability of lipid screening by the relative frequency of primary care and rheumatology visits, or seeing a PCP at least once each year. Results Primary lipid screening was performed in only 45% of RA patients. Overall, 65% received both primary and rheumatology care, and half saw a rheumatologist as often as a PCP. Any primary care predicted more lipid screening than lone rheumatology (26%, 95% CI=21, 32). As long as a PCP was involved, lipid screening performance was similar regardless of the balance between primary and rheumatology visits, (44–48%, CI=41–51). Not seeing a PCP at least annually decreased screening 22% (adjusted risk ratio [ARR]=0.78, 0.71, 0.84). Conclusion Primary lipid screening was performed in fewer than half of eligible RA patients, highlighting a key target for CVD risk reduction efforts. Annual PCP visits improved lipid screening, though performance remained poor (51%). Half of RA patients saw their rheumatologist as often, or more often, than a PCP, illustrating the need to study optimal partnerships between primary care and rheumatologists for screening CVD risks. PMID:21305507

  17. The Regional Genetic and Newborn Screening Service Collaboratives: The First Two Years

    ERIC Educational Resources Information Center

    Puryear, Michele; Weissman, Gloria; Watson, Michael; Mann, Marie; Strickland, Bonnie; van Dyck, Peter C.

    2006-01-01

    Newborn screening and genetic technologies are expanding and changing rapidly, increasing the demand for genetic specialty services. Because of the scarcity and geographic maldistribution of genetic specialty services, access to these services is a critical issue. This article discusses some of the efforts initiated by the Maternal and Child…

  18. Accuracy of patients' recall of Pap and cholesterol screening.

    PubMed Central

    Newell, S; Girgis, A; Sanson-Fisher, R; Ireland, M

    2000-01-01

    OBJECTIVES: This study was undertaken in mid-1994 and assessed how accurately patients recall the recency and result of their most recent cholesterol and Papanicolaou (Pap) tests. METHODS: A cross-sectional, door-to-door community survey was used to gather self-report and, subsequently, pathology laboratory data for 195 individuals. RESULTS: In regard to cholesterol screening, 30% of individuals who reported being adequately screened were actually inadequately screened, 45% who reported normal cholesterol levels actually had elevated levels, and 21% of inadequately screened individuals and 56% of individuals with elevated levels were not identified by self-report. In terms of Pap screening, 28% of women who reported being adequately screened were actually inadequately screened, 11% of patients who reported a normal Pap test actually had abnormal or inadequate results, and 55% of inadequately screened individuals and 53% of individuals with abnormal or inadequate results were not identified by self-report. CONCLUSIONS: This study revealed self-report to be a less-than-adequate measure of individuals' recall of cholesterol and Pap screening. Relying exclusively on self-report surveys as indicators of screening coverage is likely to result in significant underestimations of the proportion of people who are inadequately screened or whose results indicate a need for intervention. PMID:10983202

  19. Ethical considerations of population screening for late-onset genetic disease.

    PubMed

    Golden-Grant, K; Merritt, J L; Scott, C R

    2015-12-01

    Population-based genetic screening has been a mainstay of public health in the United States for many years. The goal of genetic screening is to identify individuals at increased risk for treatable diseases. The evolution of genetic testing to include multi-disease panels allows for new screening applications which challenge the traditional model of clinical genetics care by the identification of late-onset disorders in an asymptomatic fetus, child, or adult. We present two unique examples of individuals referred to a biochemical genetics clinic due to the detection of late-onset Pompe disease by population-based screening modalities. We review early experiences in counseling and management of pre-symptomatic individuals and highlight some of the primary ethical factors warranting consideration as we enter the era of genomic medicine. PMID:25677830

  20. Screening for Intimate Partner Violence in Orthopedic Patients: A Comparison of Three Screening Tools

    ERIC Educational Resources Information Center

    Sprague, Sheila; Madden, Kim; Dosanjh, Sonia; Petrisor, Brad; Schemitsch, Emil H.; Bhandari, Mohit

    2012-01-01

    Accurately identifying victims of intimate partner violence (IPV) can be a challenge for clinicians and clinical researchers. Multiple instruments have been developed and validated to identify IPV in patients presenting to health care practitioners, including the Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS). The purpose…

  1. Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues.

    PubMed

    Janssens, Sandra; Chokoshvilli, Davit; Binst, Carmen; Mahieu, Inge; Henneman, Lidewij; De Paepe, Anne; Borry, Pascal

    2016-04-01

    Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting ~1 in 2500-4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program. PMID:26220700

  2. Genetic screening for cystic fibrosis: an overview of the science and the economics.

    PubMed

    Brice, Philippa; Jarrett, James; Mugford, Miranda

    2007-07-01

    The aim of this paper is to provide an overview of the current scientific and economic thinking on the use of genetic technologies for cystic fibrosis (CF) screening. The paper takes a public health genetics viewpoint and gives an overview of the genetics behind CF, then describes current practices in screening for the disease. We then discuss the current literature on the economic evaluations of screening for CF. As the "wet" science improves, there are direct implications for health service. Therefore, it is important to keep examining both clinical practice and economics behind the technologies. PMID:17369107

  3. Screening for coeliac disease in adult patients with type 1 diabetes mellitus: myths, facts and controversy.

    PubMed

    Bakker, Sjoerd F; Tushuizen, Maarten E; von Blomberg, Boudewina M E; Bontkes, Hetty J; Mulder, Chris J; Simsek, Suat

    2016-01-01

    This review aims at summarizing the present knowledge on the clinical consequences of concomitant coeliac disease (CD) in adult patients with type 1 diabetes mellitus (T1DM). The cause of the increased prevalence of CD in T1DM patients is a combination of genetic and environmental factors. Current screening guidelines for CD in adult T1DM patients are not uniform. Based on the current evidence of effects of CD on bone mineral density, diabetic complications, quality of life, morbidity and mortality in patients with T1DM, we advise periodic screening for CD in adult T1DM patients to prevent delay in CD diagnosis and subsequent CD and/or T1DM related complications. PMID:27478507

  4. 'Inside-out', back-to-front: a model for clinical population genetic screening.

    PubMed Central

    Shickle, D; Harvey, I

    1993-01-01

    Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician. PMID:8411031

  5. Impact of an immunohistochemistry-based universal screening protocol for Lynch syndrome in endometrial cancer on genetic counseling and testing

    PubMed Central

    Frolova, Antonina I.; Babb, Sheri A.; Zantow, Emily; Hagemann, Andrea R.; Powell, Matthew A.; Thaker, Premal H.; Gao, Feng; Mutch, David G.

    2015-01-01

    OBJECTIVE Evaluate effects of a Lynch syndrome universal screening protocol in newly diagnosed endometrial cancers on subsequent genetic counseling (GC) and germline testing (GT) referral and acceptance rates. METHODS We performed a retrospective cohort study of women who underwent a hysterectomy for endometrial cancer at Barnes Jewish Hospital in St. Louis, MO between 1/1/2011 and 12/31/2013 (n=637). An immunohistochemistry-based (IHC) universal screening protocol for Lynch syndrome was initiated on 12/17/2012. The cohorts consisted of women presenting prior to (Pre Em-USP; n=395) and those presenting following (Em-USP; n=242) initiation of the universal screening protocol. GC and GT referrals were based on risk factors and/or IHC results. Comparisons were made using the Fisher’s exact test and the Kruskal-Wallis test. RESULTS A greater proportion of individuals in the Em-USP cohort underwent GT than in Pre Em-USP (9.1% vs 4.8%, p<0.05). Of individuals with an IHC screening result suggestive of LS, those within the Em-USP cohort were significantly more likely to accept GC compared to those in the Pre-Em-USP cohort (95% vs 64%, p=0.02). Specifically within the Em-USP cohort, patients referred to GC due to a concerning IHC screening result, versus those who were referred based on other risk factors, had a higher counseling acceptance rate (95% vs 61%, p=0.03) and underwent genetic testing more readily (76% vs 30%, p<0.001). CONCLUSIONS Implementation of an IHC-based universal screening protocol for LS in endometrial cancer leads to higher acceptance of genetic counseling and higher rates of genetic testing compared to referral based on risk factors alone. PMID:25617771

  6. Screening Optimization of Latent Tuberculosis Infection in Rheumatoid Arthritis Patients

    PubMed Central

    Mehta, Bella; Zapantis, Ekaterini; Petryna, Olga; Efthimiou, Petros

    2015-01-01

    Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent tuberculosis infection (LTBI) but there are no clear guidelines for LTBI screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G). Methods. A retrospective study was conducted in a high risk, largely foreign-born, inner city, RA population. After screening 280 RA patients, 134 patients who had both TST and QFT-G testing performed during their initial evaluation were included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%) patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23 (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests. The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147–0.463, p = 0.081).  Conclusions. There was low-moderate agreement (κ = 0.305) between TST and QFT-G. In the absence of clearly defined gold standard and limitations associated with both tests, we propose early screening with both tests for patients who need prompt treatment with BRMs. Patients who are not immediate candidates for BRM treatment may be safely and cost effectively screened with a two-step process: initial screening with TST and if negative, IGRA testing. Patients positive for either test should be promptly treated. PMID:26294972

  7. Genetic screening for reproductive purposes at school: is it a good strategy?

    PubMed

    Frumkin, Ayala; Zlotogora, Joël

    2008-01-15

    Thalassemia and Tay-Sachs disease were the first diseases in which the criteria for heterozygote genetic screening were met and successful programs for reproductive purposes were initiated in populations at risk. However, many of the couples first discover the possibility of genetic screening during pregnancy and efforts are made to bring couples to consider screening tests before the first pregnancy. In this context, high school offers a convenient setting and several pilot programs have been very successful. All evaluations of these programs found that education plays a critical role in allowing informed decisions and minimizing the possible harms. While it has been suggested that high school may be the best setting for reproductive screening programs, guidelines of several societies of human genetics recommend the use of carrier screening only in individuals older than 18 years. There are several other problems related to genetic screening programs at school and some are discussed in the review. Our opinion is that school should be a place to provide the tools for decisions by education only; while the option to have the genetic tests later in life or in another setting should be offered to the students as part of the education session. This may allow the students to decide when and where to have a genetic test. PMID:18080324

  8. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  9. Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis

    PubMed Central

    Westerfield, Lauren; Darilek, Sandra; van den Veyver, Ignatia B.

    2014-01-01

    Prenatal genetic screening and testing provides prospective parents information about the health of their fetus. It is offered to find or address an increased risk for chromosomal abnormalities or other genetic conditions in the fetus or to identify the cause of fetal structural abnormalities detected by prenatal imaging. Genome-wide tests, such as the already widely-used chromosomal microarray analysis and emerging diagnostic whole exome and whole genome sequencing, have improved the ability to detect clinically significant findings, but have also increased the chance of detecting incidental findings and variants of uncertain significance. There is an extensive ongoing discussion about optimal strategies for diagnostic laboratories to report such findings and for providers to communicate them with patients. While consensus opinions and guidelines are beginning to appear, they often exclude the prenatal setting, due to its unique set of challenging considerations. These include more limited knowledge of the impact of genetic variants when prospectively detected in an ongoing pregnancy, the absence or limitations of detecting clinically recognizable phenotypes at the time of testing and the different decision-making processes that will ensue from testing. In this review, we examine these challenges within the medical ethical framework unique to prenatal care. PMID:26237491

  10. The Glycinergic System in Human Startle Disease: A Genetic Screening Approach

    PubMed Central

    Davies, Jeff S.; Chung, Seo-Kyung; Thomas, Rhys H.; Robinson, Angela; Hammond, Carrie L.; Mullins, Jonathan G. L.; Carta, Eloisa; Pearce, Brian R.; Harvey, Kirsten; Harvey, Robert J.; Rees, Mark I.

    2009-01-01

    Human startle disease, also known as hyperekplexia (OMIM 149400), is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission. Hyperekplexia is characterised by an exaggerated startle reflex in response to tactile or acoustic stimuli which first presents as neonatal hypertonia, followed in some with episodes of life-threatening infantile apnoea. Genetic screening studies have demonstrated that hyperekplexia is genetically heterogeneous with several missense and nonsense mutations in the postsynaptic glycine receptor (GlyR) α1 subunit gene (GLRA1) as the primary cause. More recently, missense, nonsense and frameshift mutations have also been identified in the glycine transporter GlyT2 gene, SLC6A5, demonstrating a presynaptic component to this disease. Further mutations, albeit rare, have been identified in the genes encoding the GlyR β subunit (GLRB), collybistin (ARHGEF9) and gephyrin (GPHN) – all of which are postsynaptic proteins involved in orchestrating glycinergic neurotransmission. In this review, we describe the clinical ascertainment aspects, phenotypic considerations and the downstream molecular genetic tools utilised to analyse both presynaptic and postsynaptic components of this heterogeneous human neurological disorder. Moreover, we will describe how the ancient startle response is the preserve of glycinergic neurotransmission and how animal models and human hyperekplexia patients have provided synergistic evidence that implicates this inhibitory system in the control of startle reflexes. PMID:20407582

  11. Moderating Effects of Autism on Parent Views of Genetic Screening for Aggression

    ERIC Educational Resources Information Center

    May, Michael E.; Brandt, Rachel C.; Bohannan, Joseph K.

    2012-01-01

    Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies…

  12. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues.

    PubMed

    Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V

    2014-07-01

    This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional. PMID:24859980

  13. [Preventive radical surgery of C-cell carcinoma in MEN-II syndrome based on genetic screening].

    PubMed

    Röher, H D; Simon, D; Goretzki, P E; Höppner, W; Lederbogen, S; Seppel, T

    1995-12-01

    Between April 1986 and July 1995 121 patients have been operated on for C-cell carcinoma with 70 (57.9%) patients presenting a sporadic type and 51 (42.1%) a hereditary type of disease (46/38% MEN IIa and 5/4.1% MEN IIb). Indication for operation in patients with familial disease (MEN II) was in 9 patients (18%) detection of a mutation in the ret protooncogen (group I), in 27 patients (53%) a pathologic biochemical screening (pentagastrin stimulation) (group II), and in 15 patients (29%) the first manifestation in a family (index) (group III). Distribution of stages showed a stage I (T1 N0 M0) in 8/9 (89%) in group I, in 17/27 (63%) in group II, and in 0/15 in group III. In 8 from 9 patients with genetic indication a multifocal microcarcinoma and in one patient a cell-cell hyperplasia could be demonstrated. Accordingly the rate of curative operations with postoperative normalization of basal and pentagastrin stimulated calcitonin levels was 100% (9/9) in group I, 59% (16/27) in group II, and 7% (1/15) in group III. The mean age was 14 (median 12) years in group I, 26 (median 24) years in group II, and 43 (median 40) years in group III). In patients with presymptomatic screening (genetic and biochemical) a thyroidectomy including lymph node dissection of the central compartment was performed as a standard procedure. Postoperative complication rate showed a recurrent nerve palsy of 0 in group I and 4% in group II and a hypoparathyroidism of 0 in group I and 4% in group II. The detection of a mutation correlated with positive histological findings of the disease in all patients. The prophylactic radical operation on the basis of a genetic screening proved to be a safe procedure with curative intention. The early age of manifestation underlines the importance of the genetic screening and the early indication for operation. PMID:8582162

  14. "This lifetime commitment": Public conceptions of disability and noninvasive prenatal genetic screening.

    PubMed

    Steinbach, Rosemary J; Allyse, Megan; Michie, Marsha; Liu, Emily Y; Cho, Mildred K

    2016-02-01

    Recently, new noninvasive prenatal genetic screening technologies for Down syndrome and other genetic conditions have become commercially available. Unique characteristics of these screening tests have reignited long-standing concerns about prenatal testing for intellectual and developmental disabilities. We conducted a web-based survey of a sample of the US public to examine how attitudes towards disability inform views of prenatal testing in the context of these rapidly advancing prenatal genetic screening technologies. Regardless of opinion toward disability, the majority of respondents supported both the availability of screening and the decision to continue a pregnancy positive for aneuploidy. Individuals rationalized their support with various conceptions of disability; complications of the expressivist argument and other concerns from the disability literature were manifested in many responses analyzed. PMID:26566970

  15. Lung cancer screening in patients with chronic obstructive pulmonary disease.

    PubMed

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo; Zulueta, Javier J

    2016-04-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  16. Lung cancer screening in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  17. DNA analysis of renal electrolyte transporter genes among patients suffering from Bartter and Gitelman syndromes: summary of mutation screening.

    PubMed

    Urbanová, M; Reiterová, J; Stěkrová, J; Lněnička, P; Ryšavá, R

    2011-01-01

    Patients with renal diseases associated with salt-losing tubulopathies categorized as Gitelman and classic form of Bartter syndrome have undergone genetic screening for possible mutation capture in two different genes: SLC12A3 and CLCNKB. Clinical symptoms of these two diseases may overlap. Patients with clinical symptoms of antenatal form of Bartter syndrome were screened for mutations in two different genes: KCNJ1 and SLC12A1. The aim was to establish genetic mutation screening of Bartter/Gitelman syndrome and to confirm the proposed diagnosis. We have identified seven different causative mutations in the SLC12A3 gene, four in the CLCNKB gene, two in the SLC12A1 gene, and none in the KCNJ1 gene. Nine of these mutations are novel. In one case, genetic analysis led to re-evaluation of diagnosis between the Gitelman and classic form of Bartter syndrome. PMID:21631963

  18. Efficacy of MCAD screening in SIDS patients in Tennessee

    SciTech Connect

    Phillips, J.A. III; Vnencak-Jones, C.L.; Ulm, J.E.

    1994-09-01

    Medium chain acyl-CoA deficiency (MCAD) is an autosomal recessive disorder of fatty acid oxidation. While several mutations have been identified in the MCAD gene, an A to G point mutation affecting codon 329 (K329E) represents >90% of those reported. Unfortunately, the reported carrier frequency of this mutation varies greatly between populations which reduces the efficiency of neonatal screening. Mounting evidence suggests a correlation between MCAD deficiency and sudden infant death syndrome (SIDS). To determine the utility of MCAD screening in SIDS patients, we screened for the K329E mutation in DNA extracted from paraffin blocks retrieved from 75 consecutive SIDS patients. Two of 75 (2.7%) had DNA findings consistent with MCAD. One patient (A) was homozygous for K329E while a second patient (B) was heterozygous for K329E. Although the second abnormal MCAD allele has not yet been identified in this patient, in a clinical setting of SIDS, this patient may well represent a compound heterozygote. Subsequent to the analysis, the family of A was contacted and a newborn sib was found to be homozygous for K329E. Carnitine supplementation and frequent feedings were started and the child is doing well. Evaluation of family B is planned. Our finding of 2/75 SIDS patients with DNA findings suggestive of MCAD demonstrates the efficacy of MCAD screening in this population in contrast to that of newborn screening in TN where the estimated K329E carrier frequency is 1/249 and the calculated incidence of MCAD disease is approximately 1/248,000. Our study (1) confirms the finding of MCAD in 2 to 3% of consecutive SIDS patients, (2) utility of DNA testing in presymtomatic sibs of SIDS patients attributable to MCAD and (3) provides accurate recurrent risks and enables prenatal testing for SIDS families where the diagnosis of MCAD has been established.

  19. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    SciTech Connect

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  20. [Why screen for lung cancer in patients with arterial disease?].

    PubMed

    Lederlin, M; Trédaniel, J; Priollet, P

    2015-12-01

    Lung cancer remains the leading cause of cancer death in France. Such a prognosis is explained by late diagnosis at a metastatic stage for half of the patients. Tobacco is the main risk factor for lung cancer, as it is for peripheral arterial disease. A review of literature shows that between 2.3% and 19% of patients with arterial disease also have lung cancer. When lung cancer is detected after treatment of arterial disease, it is at an advanced stage. But it can be diagnosed at an early stage when it is searched simultaneously with arterial disease treatment. There is no recommendation for lung cancer screening specifically for patients with arterial disease. However individual screening based on an annual low-dose chest scan is proposed for smokers meeting the criteria defined by the study of the National Lung Screening Trial (NLST). Such screening has two disadvantages : the high number of false positives and the irradiation induced by the accumulation of examinations. The ISET method would alternatively help to identify circulating tumor cells on a simple blood test for subjects not yet at solid tumor stage, provided this method be subject to multicentric validation. Thus one could consider that the management of a patient with arterial disease meeting NLST criteria should be accompanied with screening for lung cancer by searching for tumor cells associated with low-dose scanner. PMID:26276562

  1. Role of Genetic Testing in Patients with Ventricular Arrhythmias in Apparently Normal Hearts.

    PubMed

    Hofman, Nynke; Wilde, Arthur A M

    2016-09-01

    Ventricular arrhythmias without structural heart disease are responsible for ∼35% of patients who have sudden cardiac death before the age of 40 years. Molecular autopsy and/or cardiological investigation of nearby family members often reveals the diagnosis and genetic testing can be helpful in family screening and risk stratification in disease carriers. Extended gene panels can be screened in a short period of time at low cost. A multidisciplinary team of (genetically) specialized clinicians is necessary to judge all the available details and to decide on the significance of the variant and further strategies. PMID:27521086

  2. Onsite QTc interval screening for patients in methadone maintenance treatment.

    PubMed

    Fareed, Ayman; Vayalapalli, Sreedevi; Byrd-Sellers, Johnita; Casarella, Jennifer; Drexler, Karen; Amar, Richard; Smith-Cox, Jocelyn; Lutchman, Tamara Shaw

    2010-01-01

    To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated. Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment. Thus, 55 patient charts were selected for review. Most patients (95%) received baseline and annual electrocardiogram screening. The average baseline QTc was (417 +/- 30) and most recent QTc (442 +/- 25). This QTc prolongation from baseline showed statistical significance (P < .0001). Sixty-seven percent of patients had statistically significant QTc prolongation from baseline but was less than 450 ms (mean: 428 +/- 16, P = .008). Twenty-seven percent of patients had statistically significant QTc prolongation from baseline of more 450 ms but was less than 500 ms (mean: 460 +/- 8, P < .0001). Six percent of patients had statistically significant QTc prolongation from baseline of more 500 ms (mean: 503 +/- 1.15, P = .027). Recent cocaine use was the only individual variable that showed statistically significant correlation with QTc prolongation (F = 6.98, P = .01). The authors demonstrated in this study that providing an onsite electrocardiogram screening with a focus on patient education and limiting

  3. Genetic screening for gynecological cancer: where are we heading?

    PubMed

    Manchanda, Ranjit; Jacobs, Ian

    2016-01-01

    The landscape of cancer genetics in gynecological oncology is rapidly changing. The traditional family history-based approach has limitations and misses >50% mutation carriers. This is now being replaced by population-based approaches. The need for changing the clinical paradigm from family history-based to population-based BRCA1/BRCA2 testing in Ashkenazi Jews is supported by data that demonstrate population-based BRCA1/BRCA2 testing does not cause psychological harm and is cost effective. This article covers various genetic testing strategies for gynecological cancers, including population-based approaches, panel and direct-to-consumer testing as well as the need for innovative approaches to genetic counseling. Advances in genetic testing technology and computational analytics have facilitated an integrated systems medicine approach, providing increasing potential for population-based genetic testing, risk stratification, and cancer prevention. Genomic information along-with biological/computational tools will be used to deliver predictive, preventive, personalized and participatory (P4) and precision medicine in the future. PMID:26638726

  4. Genetic screening in couples experiencing recurrent assisted procreation failure.

    PubMed

    Dada, Rima; Kumar, R; Shamsi, M B; Tanwar, M; Pathak, D; Venkatesh, S; Kumar, M; Singh, H; Singh, K; Aron, M; Kumar, R; Singh, G; Sharma, R K; Gupta, N P

    2008-04-01

    Infertility is a major health problem affecting about 10-20% of couples in the reproductive age group. Male factor is assumed to be responsible in about 50% cases of infertility. The origin of reduced testicular sperm function is unknown in about 50-70% of cases and for such couples assisted reproduction techniques (ART) are a boon. Male infertility is often due to poor semen quality and may be associated with genetic defects. ART has revolutionized management of infertility and intracytoplasmic sperm injection (ICSI) is the ART procedure of choice in 60-80% cases. Despite major technological advancements and professional expertise in ART, the success rate and carry-home live birth rate of ICSI is low (18-25%). This study was aimed to understand the genetic etiopathology of recurrent ART failure. For this, 110 couples with 3 or more failed ART cycles were recruited. A detailed history was taken and only idiopathic ART failure cases were enrolled for this study. They were subjected to cytogenetic and Yq microdeletion analysis. Genetic abnormalities were detected in 19 couples. Since a large number (18.2%) cases harboured genetic abnormalities, it is important for all couples opting for ART to undergo a thorough genetic analysis to prevent recurrent emotional, physical and financial stress. PMID:21086725

  5. Dipstick urinalysis for diabetes screening in TB patients

    PubMed Central

    Restrepo, Blanca I.; Pino, Paula A.; Zarate, Izelda; Mora-Guzman, Francisco

    2013-01-01

    Introduction Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. Methods Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009–December 2010. Results Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). Conclusion We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes. PMID:24030116

  6. [Screening of peafowl microsatellite primers and analysis of genetic diversity].

    PubMed

    Bao, Wen-Bin; Chen, Guo-Hong; Shu, Jing-Ting; Xu, Qi; Li, Hui-Fang

    2006-10-01

    The applicability of chicken microsatellite primers to peafowl population was analyzed in the present paper, and the results showed 14 of 29 pairs of microsatellite primers from chicken could amplify peafowl DNA and produce specific allele patterns. A mean of 1.71 alleles was found for each locus. Seven pairs were highly polymorphic, and MCW0080 and MCW0098 were ideal markers for peafowl. Genetic diversity analysis within and between the green peafowl and the blue peafowl populations demonstrated that the expected heterozygosity of two peafowl populations were 0.2482 and 0.2744, respectively. The inbreeding index (FST), Reynolds' genetic distance and gene flow between the two populations were 0.078, 0.0603 and 3.896 respectively. These results indicate that the heterozygosity and the genetic diversity of these two peafowl populations were very low, and suggest a tendency towards intermixing. PMID:17035182

  7. Mouse Models of Cancer: Sleeping Beauty Transposons for Insertional Mutagenesis Screens and Reverse Genetic Studies

    PubMed Central

    Tschida, Barbara R.; Largaespada, David A.; Keng, Vincent W.

    2014-01-01

    The genetic complexity and heterogeneity of cancer has posed a problem in designing rationally targeted therapies effective in a large proportion of human cancer. Genomic characterization of many cancer types has provided a staggering amount of data that needs to be interpreted to further our understanding of this disease. Forward genetic screening in mice using Sleeping Beauty (SB) based insertional mutagenesis is an effective method for candidate cancer gene discovery that can aid in distinguishing driver from passenger mutations in human cancer. This system has been adapted for unbiased screens to identify drivers of multiple cancer types. These screens have already identified hundreds of candidate cancer-promoting mutations. These can be used to develop new mouse models for further study, which may prove useful for therapeutic testing. SB technology may also hold the key for rapid generation of reverse genetic mouse models of cancer, and has already been used to model glioblastoma and liver cancer. PMID:24468652

  8. The UCSF screening exam effectively screens cognitive and behavioral impairment in patients with ALS.

    PubMed

    Murphy, Jennifer; Ahmed, Fizaa; Lomen-Hoerth, Catherine

    2015-03-01

    The University of California San Francisco (UCSF) Screening Battery provides clinicians with a uniquely tailored tool to measure ALS patients' cognitive and behavioral changes, adjusting for dysarthria and hand weakness. The battery consists of the ALS-CBS ( 1 ), Written Fluency Test ( 2 ), and a new revision of the Frontal Behavior Inventory (FBI-ALS) ( 3 ). The validity of each component was tested by comparing results with a gold standard neuropsychological exam (GNE). Consensus criteria-based GNE diagnoses ( 4 ) were assigned (n = 24) and concurrent validity was tested for each screening exam component. Results showed that each of the four cognitive and behavioral screening test components were significantly associated with diagnoses confirmed by GNE. GNE diagnoses were significantly associated with FBI-ALS negative score, written S-words score, and ALS-CBS cognitive score. The total FBI-ALS score and C-words tests were less predictive of GNE-diagnosed impairment. In conclusion, the UCSF Cognitive Screening Battery demonstrates good external validity compared with GNE in this modest sample, encouraging its use in larger investigations. These data suggest that this battery may provide an effective screen to identify ALS patients who will then benefit from a full examination to confirm their diagnosis. PMID:25301548

  9. Role of Second-Trimester Genetic Sonography After Down Syndrome Screening

    PubMed Central

    Aagaard-Tillery, Kjersti M.; Malone, Fergal D.; Nyberg, David A.; Porter, T. Flint; Cuckle, Howard S.; Fuchs, Karin; Sullivan, Lisa; Comstock, Christine H.; Saade, George R.; Eddleman, Keith; Gross, Susan; Dugoff, Lorraine; Craigo, Sabrina D.; Timor-Tritsch, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; Bianchi, Diana W.; D’Alton, Mary E.

    2016-01-01

    OBJECTIVE To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each “soft” sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful. PMID:19935018

  10. Validation of a semiconductor next-generation sequencing assay for the clinical genetic screening of CFTR

    PubMed Central

    Trujillano, Daniel; Weiss, Maximilian E R; Köster, Julia; Papachristos, Efstathios B; Werber, Martin; Kandaswamy, Krishna Kumar; Marais, Anett; Eichler, Sabrina; Creed, Jenny; Baysal, Erol; Jaber, Iqbal Yousuf; Mehaney, Dina Ahmed; Farra, Chantal; Rolfs, Arndt

    2015-01-01

    Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the CFTR gene. We have explored a more efficient genetic screening strategy based on next-generation sequencing (NGS) of the CFTR gene. We validated this approach in a cohort of 177 patients with previously known CFTR mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq™ CFTR panel. The DNA libraries were pooled, barcoded, and sequenced using an Ion Torrent PGM sequencer. The combination of different robust bioinformatics tools allowed us to detect previously known pathogenic mutations and polymorphisms in the 177 samples, without detecting spurious pathogenic calls. In summary, the assay achieves a sensitivity of 94.45% (95% CI: 92% to 96.9%), with a specificity of detecting nonvariant sites from the CFTR reference sequence of 100% (95% CI: 100% to 100%), a positive predictive value of 100% (95% CI: 100% to 100%), and a negative predictive value of 99.99% (95% CI: 99.99% to 100%). In addition, we describe the observed allelic frequencies of 94 unique definitely and likely pathogenic, uncertain, and neutral CFTR variants, some of them not previously annotated in the public databases. Strikingly, a seven exon spanning deletion as well as several more technically challenging variants such as pathogenic poly-thymidine-guanine and poly-thymidine (poly-TG-T) tracts were also detected. Targeted NGS is ready to substitute classical molecular methods to perform genetic testing on the CFTR gene. PMID:26436105

  11. Screening Indochinese Refugee Patients: Result of 192 Cases

    PubMed Central

    Levinne, Nathan N.; Choong, Albert P.

    1980-01-01

    Between October and December 1979, 192 refugee patients received medical screening for hepatitis, intestinal parasites and tuberculosis at the Mount Sinai Hospital, Toronto. Of the 192 patients, 83 were found to harbor intestinal parasitic ova and cysts; 143 were tested for tuberculosis, of whom 50 were found to be positive; 192 were checked for hepatitis, of whom 21 had asymptomatic hepatitis B antigenemia. PMID:21293708

  12. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues

    SciTech Connect

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. . School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. . Coll. of Medicine)

    1993-01-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  13. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)

    PubMed Central

    2010-01-01

    Background Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. Methods In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. Results DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031). Discussion Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health. PMID:21067609

  14. Medical and lay attitudes towards genetic screening and testing in Finland.

    PubMed

    Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R; Hemminki, Elina

    2003-08-01

    The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively referred to as midwives in the following; n=800, response rate 79%), and lay people (n=2000, response rate 62%). Midwives were more worried about the consequences of genetic testing and stressed the autonomy of the customer more strongly than lay people did. Furthermore, professionals considered that lay peoples' expectations as regards to genetic testing are too high. Having more medical education was related to having less 'cannot say' and missing responses. Our results do not suggest that major conflicts about the direction of genetic testing and screening would arise in near future. However, different positions and interests should be considered. Reporting in public about new prospects and developments in medical genetics should pay more attention also to concerns for balancing promises and drawbacks. PMID:12891376

  15. A stepwise strategy for rapid and cost-effective RB1 screening in Indian retinoblastoma patients.

    PubMed

    Thirumalairaj, Kannan; Abraham, Aloysius; Devarajan, Bharanidharan; Gaikwad, Namrata; Kim, Usha; Muthukkaruppan, Veerappan; Vanniarajan, Ayyasamy

    2015-09-01

    India has the highest number of retinoblastoma (RB) patients among the developing countries owing to its increasing population. Of the patients with RB, about 40% have the heritable form of the disease, making genetic analysis of the RB1 gene an integral part of disease management. However, given the large size of the RB1 gene with its widely dispersed exons and no reported hotspots, genetic testing can be cumbersome. To overcome this problem, we have developed a rapid screening strategy by prioritizing the order of exons to be analyzed, based on the frequency of nonsense mutations, deletions and duplications reported in the RB1-Leiden Open Variation Database and published literature on Indian patients. Using this strategy for genetic analysis, mutations were identified in 76% of patients in half the actual time and one third of the cost. This reduction in time and cost will allow for better risk prediction for siblings and offspring, thereby facilitating genetic counseling for families, especially in developing countries. PMID:26084579

  16. Communication Between Breast Cancer Patients Who Received Inconclusive Genetic Test Results and Their Daughters and Sisters Years After Testing.

    PubMed

    Baars, Jessica E; Ausems, Margreet G E M; van Riel, Els; Kars, Marijke C; Bleiker, Eveline M A

    2016-06-01

    Inconclusive genetic test results including screening recommendations for the breast cancer patients and their first-degree relatives are the most common outcomes of BRCA 1/2 testing. Patients themselves should communicate these results to their relatives. Our aim was to explore communication of breast cancer genetic counseling results with daughters and sisters over a long period of time. Breast cancer patients, who had received an inconclusive DNA test result 7-14 years earlier, completed a self-report questionnaire. Additionally, in-depth interviews were conducted and analysed thematically. Of the 93 respondents, 85 (91 %) considered themselves responsible for communicating genetic test results to relatives. In-depth interviews (n = 14) showed, that counselees wanted 'to hand over' their responsibilities to communicate the test results and screening recommendations to their sisters. Although most patients had informed their daughters and sisters about the genetic test results, usually little is spoken about genetic test results and screening recommendations once the duty of informing is completed. We recommend that, similar to the procedure for BRCA1/2-mutation carriers, a separate letter for first-degree relatives of patients with an inconclusive test result should be provided. In this way information about risks and screening recommendations can be verified by family members years after genetic testing has been completed. PMID:26446011

  17. Genetic screens in human cells using the CRISPR/Cas9 system

    PubMed Central

    Wang, Tim; Wei, Jenny J.; Sabatini, David M.; Lander, Eric S.

    2014-01-01

    The bacterial CRISPR/Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, while another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Finally, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells. PMID:24336569

  18. Functional genomics platform for pooled screening and mammalian genetic interaction maps

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2014-01-01

    Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

  19. Attitude towards Pre-Marital Genetic Screening among Students of Osun State Polytechnics in Nigeria

    ERIC Educational Resources Information Center

    Odelola, J. O.; Adisa, O.; Akintaro, O. A.

    2013-01-01

    This study investigated the attitude towards pre-marital genetic screening among students of Osun State Polytechnics. Descriptive survey design was used for the study. The instrument for data collection was self developed and structured questionnaire in four-point likert scale format. Descriptive statistics of frequency count and percentages were…

  20. Genetic screening of prospective parents and of workers: some scientific and social issues.

    PubMed

    Hubbard, R; Henifin, M S

    1985-01-01

    Genetic screening programs are based on assumptions and values that reflect the history of racial and social eugenics in the United States and Europe. They stigmatize individuals by shifting the focus from social, economic, and political decisions that affect the health of prospective parents, newborns, and workers to "bad genes," that is, intrapersonal factors that are given the status of "causes" of disease. Prenatal screening, at best, can help the relatively few individuals who know that their future children are at risk for a particular inherited disease or disability; it has little positive value for the average person. Workplace genetic screening has not been shown to reduce occupational disease, but it has led to employment discrimination and has drawn attention away from controlling exposures to toxic chemicals in the workplace. PMID:3158618

  1. CRISPR-Cas9 for medical genetic screens: applications and future perspectives.

    PubMed

    Xue, Hui-Ying; Ji, Li-Juan; Gao, Ai-Mei; Liu, Ping; He, Jing-Dong; Lu, Xiao-Jie

    2016-02-01

    CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions. PMID:26673779

  2. Screening for Patients with Alcohol Problems: Severity of Patients Identified by the CAGE.

    ERIC Educational Resources Information Center

    Lairson, David R.; And Others

    1992-01-01

    Assessed CAGE (first letters of keywords in series of 4 questions about drinking: cut down, annoyed, guilty, eye-opener), instrument in routine screening for alcohol problems among 687 patients of 2 primary care physicians. Results showed that CAGE instrument was useful screening device for identifying those with mild to moderate substance abuse…

  3. Incidental findings, genetic screening and the challenge of personalisation.

    PubMed

    Petrini, Carlo; Alleva, Enrico

    2014-01-01

    Genetic tests frequently produce more information than is initially expected. Several documents have addressed this issue and offer suggestions regarding how this information should be managed and, in particular, concerning the expedience of revealing (or not revealing) it to the persons concerned. While the approaches to the management of these incidental findings (IFs) vary, it is usually recommended that the information be disclosed if there is confirmed clinical utility and the possibility of treatment or prevention. However, this leaves unsolved some fundamental issues such as the different ways of interpreting "clinical utility", countless sources of uncertainty and varying ways of defining the notion of "incidental". Guidelines and other reference documents can offer indications to those responsible for managing IFs but should not be allowed to relieve researchers and healthcare professionals of their responsibilities. PMID:25522069

  4. Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens.

    PubMed

    Marceau, Caleb D; Puschnik, Andreas S; Majzoub, Karim; Ooi, Yaw Shin; Brewer, Susan M; Fuchs, Gabriele; Swaminathan, Kavya; Mata, Miguel A; Elias, Joshua E; Sarnow, Peter; Carette, Jan E

    2016-07-01

    The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide. No approved antivirals are available to date and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates. Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available. Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies. A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER)-associated multi-protein complexes involved in signal sequence recognition, N-linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for infection by other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects. By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host-depenency factors between DENV and HCV, and illuminates new host targets for

  5. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion **

    PubMed Central

    Egan, Elizabeth S.; Jiang, Rays H.Y.; Moechtar, Mischka A.; Barteneva, Natasha S.; Weekes, Michael P.; Nobre, Luis V.; Gygi, Steven P.; Paulo, Joao A.; Frantzreb, Charles; Tani, Yoshihiko; Takahashi, Junko; Watanabe, Seishi; Goldberg, Jonathan; Paul, Aditya S.; Brugnara, Carlo; Root, David E.; Wiegand, Roger C.; Doench, John G.; Duraisingh, Manoj T.

    2015-01-01

    Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, precluding genetic manipulation in the cell where the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis. PMID:25954012

  6. MTDH genetic variants in colorectal cancer patients

    PubMed Central

    Gnosa, Sebastian; Ticha, Ivana; Haapaniemi, Staffan; Sun, Xiao-Feng

    2016-01-01

    The colorectal carcinogenesis is a complex process encompassing genetic alterations. The oncoprotein AEG-1, encoded by the MTDH gene, was shown previously to be involved in colorectal cancer (CRC). The aim of this study was to determine the frequency and the spectrum of MTDH variants in tumor tissue, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. The corresponding normal colorectal tissue was analyzed in the carriers of exonic variant to confirm germline or somatic origin. We detected 42 intronic variants, where 25 were novel. Furthermore, we found 8 exonic variants of which four, one missense (c.977C > G-germline) and three frameshift mutations (c.533delA-somatic, c.1340dupA-unknown origin, c.1731delA-unknown origin), were novel. In silico prediction analyses suggested four deleterious variants (c.232G > T, c.533delA, c.1340dupA, and c.1731delA). There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. We described several novel exonic and intronic variants of the MTDH gene. The detection of likely pathogenic truncating mutations and alterations in functional protein domains indicate their clinical significance, although none of the variants had prognostic potential. PMID:26983693

  7. A mosaic genetic screen for Drosophila neoplastic tumor suppressor genes based on defective pupation.

    PubMed

    Menut, Laurent; Vaccari, Thomas; Dionne, Heather; Hill, Joseph; Wu, Geena; Bilder, David

    2007-11-01

    The Drosophila neoplastic tumor suppressor genes (TSGs) coordinately control cell polarity and proliferation in epithelial and neuronal tissues. While a small group of neoplastic TSG mutations have been isolated and their corresponding genes cloned, the regulatory pathways that normally prevent inappropriate growth remain unclear. Identification of additional neoplastic TSGs may provide insight into this question. We report here the design of an efficient screen for isolating neoplastic TSG mutations utilizing genetically mosaic larvae. This screen is based on a defective pupation phenotype seen when a single pair of imaginal discs is homozygous for a neoplastic TSG mutation, which suggests that continuously proliferating cells can interfere with metamorphosis. Execution of this screen on two chromosome arms led to the identification of mutations in at least seven new neoplastic TSGs. The isolation of additional loci that affect hyperplastic as well as neoplastic growth indicates the utility of this screening strategy for studying epithelial growth control. PMID:17947427

  8. Large-Scale Single-Guide RNA Library Construction and Use for Genetic Screens

    PubMed Central

    Wang, Tim; Lander, Eric S.; Sabatini, David M.

    2016-01-01

    The ability to systematically disrupt genes serves as a powerful tool for understanding their function. The programmable Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system enables efficient targeting of large numbers of genes through the use of single-guide RNA (sgRNA) libraries. In cultured mammalian cells, collections of knockout mutants can be readily generated via transduction of Cas9/sgRNA lentiviral pools, screened for a phenotype of interest, and tracked using high-throughput DNA sequencing. This technique represents the first general method for undertaking systematic loss-of-function genetic screens in mammalian cells. In this chapter, we outline the steps for conducting CRISPR-based screens from the initial library design to final data analysis and provide guidelines for developing an appropriate screening strategy. PMID:26933254

  9. Successful birth of South India's first twins after preimplantation genetic screening of embryos

    PubMed Central

    Selvaraj, Priya; Selvaraj, Kamala; Srinivasan, Kalaichelvi; Sivakumar, Mahalakshmi

    2016-01-01

    We report the first documented successful birth of twins following preimplantation genetic screening (PGS) of cleavage stage embryos by array comparative genomic hybridization (CGH) technology, in South India. The case was a 28-year-old woman with the previous history of preclinical pregnancy and a miscarriage in two attempted in vitro fertilization cycles. Day 3 cleavage stage embryos were generated by conventional long protocol with the use of a gonadotropin-releasing hormone analog and a combination of recombinant folliculotropins and human menopausal gonadotropins. Intracytoplasmic sperm injection of oocytes thus obtained was performed, and 10 selected embryos underwent PGS using the array CGH technique. Two normal blastocysts were transferred to the patient, and she conceived twins. She delivered at 35 weeks of gestation by elective cesarean on November 19, 2014. She delivered a healthy male and female baby weighing 2.19 kg and 2.26 kg, respectively. Postnatal evaluation of babies was also normal, and the hospital course was uneventful. PGS has a definitive indication in assisted reproductive technology programs and can be utilized to improve pregnancy rates significantly. PMID:27382239

  10. [Screening for hereditary neuromuscular disorders with molecular genetic methods in the Roma population of Hungary].

    PubMed

    Herczegfalvi, Agnes; Pikó, Henriett; Karcagi, Veronika

    2008-11-30

    Recent medical genetic research has identified a number of novel, or previously known, but rare conditions, caused by private founder mutations. The Finnish and Ashkenazi Jew populations provide the best examples for identifying genes in unique genetic disorders. In these populations, research efforts and high-level medical services resulted in intense improvements of medical care and in organization of population-based screening programs. Hereditary disorders of the Roma populations are known for a long time. The genetic background of these diseases has been established by extensive molecular genetic studies. The Romas represent 6% of the Hungarian population and live under extremely bad health conditions. Therefore, our aim was to map the incidence of the hereditary neuromuscular disorders among the Hungarian Roma population. Moreover, we intended to provide proper information, genetic counseling and possible prevention strategies for the families at risk, which should represent a primer task in public health. Because of our experience in neuromuscular disorders, we choose six, frequent, autosomal recessive disorders for these clinical and genetic studies: hereditary motor and sensory neuropathy type Lom (HMSNL), hereditary motor and sensory neuropathy type Russe (HMSNR), congenital cataracts facial dysmorphism syndrome (CCFDN), limb-girdle muscular dystrophy 2C (LGMD2C), congenital myasthenic syndrome (CMS) and spinal muscular atrophy (SMA). Following identification of the founder mutations, the possibility of prenatal diagnosis and carrier screening for family members will contribute to the decrease of the recurrence risk for these severe, mostly untreatable disorders. PMID:19070320

  11. Misunderstandings Concerning Genetics Among Patients Confronting Genetic Disease

    PubMed Central

    Klitzman, Robert L.

    2010-01-01

    Critical questions arise about misunderstandings of genetics. We interviewed for 2 h each, 64 individuals who had or were at risk for Huntington’s disease (HD), breast cancer or Alpha-1 antitrypsin deficiency. These individuals revealed various misunderstandings that can affect coping, and testing, treatment and reproductive decisions. A therapeutic misconception about testing appeared: that testing would be helpful in and of itself. Many believed they could control genetic disorders (even HD), yet these beliefs were often incorrect, and could impede coping, testing, and treatment. Misunderstandings about statistics and genetics often fueled each other, and reflected denial, and desires for hope and control. Emotional needs can thus outweigh understandings of genetics and statistics, and providers’ input. Individuals often maintained non-scientific beliefs, though embarrassed by these. These data have implications for care, and public and professional education. Misunderstandings’ persistence, despite realization of their inaccuracy, suggests that providers need to address not just cognitive facts, but underlying emotional issues. PMID:20512408

  12. Dynamic visual acuity testing for screening patients with vestibular impairments.

    PubMed

    Peters, Brian T; Mulavara, Ajitkumar P; Cohen, Helen S; Sangi-Haghpeykar, Haleh; Bloomberg, Jacob J

    2012-01-01

    Dynamic visual acuity (DVA) may be a useful indicator of the function of the vestibulo-ocular reflex (VOR) but most DVA tests involve active head motion in the yaw plane. During gait the passive, vertical VOR may be more relevant and passive testing would be less likely to elicit compensatory strategies. The goal of this study was to determine if testing dynamic visual acuity during passive vertical motion of the subject would differentiate normal subjects from patients with known vestibular disorders. Subjects, normals and patients who had been diagnosed with either unilateral vestibular weaknesses or were post-acoustic neuroma resections, sat in a chair that could oscillate vertically with the head either free or constrained with a cervical orthosis. They viewed a computer screen 2 m away that showed Landholt C optotypes in one of 8 spatial configurations and which ranged in size from 0.4 to 1.0 logMAR. They were tested while the chair was stationary and while it was moving. Scores were worse for both groups during the dynamic condition compared to the static condition. In the dynamic condition patients' scores were significantly worse than normals' scores. Younger and older age groups differed slightly but significantly; the sample size was too small to examine age differences by decade. The data suggest that many well-compensated patients have dynamic visual acuity that is as good as age-matched normals. Results of ROC analyses were only moderate, indicating that the differences between patients and normals were not strong enough, under the conditions tested, for this test to be useful for screening people to determine if they have vestibular disorders. Modifications of the test paradigm may make it more useful for screening potential patients. PMID:23000614

  13. Risk of abnormal triple screen for Down syndrome is significantly higher in patients with female fetuses.

    PubMed

    Spong, C Y; Ghidini, A; Stanley-Christian, H; Meck, J M; Seydel, F D; Pezzullo, J C

    1999-04-01

    Previous studies have shown that mid-trimester maternal serum alpha-fetoprotein (AFP) levels are significantly higher and human chorionic gonadotrophin (hCG) levels significantly lower in women with male compared with female fetuses. We have evaluated whether triple-screen criteria are more likely to identify women with female fetuses as at risk for Down syndrome. From the Georgetown University genetics database we obtained the absolute values and corresponding multiples of the median (MoM) for AFP, hCG and unconjugated oestriol (uE3) in singleton gestations for the period database November 1992 July 1996. A Down syndrome risk of 1/270 or greater at mid-trimester was considered as high risk. A total of 977 patients with triple screen and outcome information were identified, including 502 female and 475 male fetuses. Patients with female fetuses were significantly more likely to have lower serum AFP (p=0.003) and a positive triple screen for Down syndrome (72 (14 per cent) versus 45 (9 per cent), p<0.02) than those with male fetuses. The gestational age at triple screen, maternal serum hCG and uE3, race and diabetes were not significantly different between the two groups. Since Down syndrome is less common in female than male fetuses, and the rates of female and male Down syndrome fetuses detected by triple screen and subsequent amniocentesis are not significantly different, the excess of positive mid-trimester maternal serum triple screen in women with female fetuses is likely due to false-positive results. PMID:10327139

  14. Genome-Wide Synthetic Genetic Screening by Transposon Mutagenesis in Candida albicans

    PubMed Central

    Horton, Brooke N.; Kumar, Anuj

    2016-01-01

    Transposon-based mutagenesis is an effective method for genetic screening on a genome-wide scale, with particular applicability in organisms possessing compact genomes where transforming DNA tends to integrate by homologous recombination. Methods for transposon mutagenesis have been applied with great success in the budding yeast Saccharomyces cerevisiae and in the related pathogenic yeast Candida albicans. In C. albicans, we have implemented transposon mutagenesis to generate heterozygous mutations for the analysis of complex haploinsufficiency, a type of synthetic genetic interaction wherein a pair of non-complementing heterozygous mutations results in a stronger phenotype then either individual mutation in isolation. Genes exhibiting complex haploinsufficiency typically function within a regulatory pathway, in parallel pathways, or in parallel branches within a single pathway. Here, we present protocols to implement transposon mutagenesis for complex haploinsufficiency screening in C. albicans, indicating methods for transposon construction, mutagenesis, phenotypic screening, and identification of insertion sites in strains of interest. In total, the approach is a useful means to implement large-scale synthetic genetic screening in the diploid C. albicans. PMID:25636616

  15. Genetic screening of targeted subpopulations: the role of communal discourse in evaluating sociocultural implications.

    PubMed

    Foster, M W; Eisenbraun, A J; Carter, T H

    Targeting socially identifiable subpopulations for genetic screening entails the risk of stigmatizing them. The potential for such harm should be considered before programs are initiated. There is an emerging consensus that targeted subpopulations should be actively involved in evaluating these risks. A process of communal discourse engages the community in discussions that reflect both public and private sociocultural contexts in which individual decisions about screening will be made. This allows the subpopulation to address the collective implications of testing in a culturally appropriate way. Communal discourse was used to evaluate the collective implications of genetic testing in two Native American communities. We found that private social units were more influential than public units in reaching communal consensus, that local sociocultural issues were of more concern than were general issues such as employment and insurance discrimination, and that heterogeneity within a subpopulation may be just as significant a consideration in designing a targeted screening program as diversity between subpopulations. Heterogeneity is constructed by using a dichotomy between community-specific and biomedical health representations and practices. How genetic screening is socially constructed using a community's existing dichotomy may be central to its success. PMID:10464656

  16. Promoting cancer screening within the patient centered medical home.

    PubMed

    Sarfaty, Mona; Wender, Richard; Smith, Robert

    2011-01-01

    While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening. PMID:22086728

  17. Patients' Attitudes Towards Disclosure of Genetic Test Results to Family Members: The Impact of Patients' Sociodemographic Background and Counseling Experience.

    PubMed

    Gilbar, Roy; Shalev, Stavit; Spiegel, Ronen; Pras, Elon; Berkenstadt, Michal; Sagi, Michal; Ben-Yehuda, Adi; Mor, Pnina; Perry, Shlomit; Zaccai, Tzipora Falik; Borochowitz, Zvi; Barnoy, Sivia

    2016-04-01

    Many factors predict the intention to disclose genetic information to relatives. The article examines the impact of patients' socio-demographic factors on their intention to disclose genetic testing results to their relatives. Data were collected in eight genetic clinics in Israel. Patients were requested to fill in a questionnaire after counseling. A convenience sample of 564 participants who visited these clinics was collected for a response rate of 85 %. Of them, 282 participants came for susceptibility testing for hereditary cancers (cancer group), and 282 for genetic screening tests (prenatal group). In the cancer group, being secular and having more years of education correlated positively with the intention to disclose test results to relatives. In the prenatal group, being married and female correlated positively with the intention to disclose. In the cancer group, being religious and with less years of education correlated positively with the view that the clinician should deliver the results to the family. In the prenatal group, being male and unmarried correlated positively with this belief. In both groups, being of young age correlated with the perception that genetic information is private. Varied sociodemographic factors affect the intention to inform family members. Thus, knowing the social background of patients will shed light on people's attitudes to genetic information and will help clinicians provide effective counseling in discussions with patients about the implications of test results for relatives. PMID:26371363

  18. Is there a role for screening asymptomatic patients with diabetes?

    PubMed

    Veillet-Chowdhury, Mahdi; Blankstein, Ron

    2015-06-01

    Coronary artery disease (CAD) remains a leading cause of death among patients with diabetes mellitus. However, many patients with diabetes and CAD are asymptomatic and may sustain a myocardial infarction as their presenting symptom of CAD. Non-invasive cardiovascular imaging offers an opportunity to detect the presence and severity of CAD, or its hemodynamic consequences. The Detection of Ischemia in Asymptomatic Diabetics study and the FACTOR-64 study examined the utility of non-invasive imaging tests to evaluate asymptomatic individuals with diabetes mellitus. The results of these trials may have been negative with regard to promoting CAD screening of asymptomatic diabetic patients, but they do strengthen the position of optimal medical management in reducing cardiovascular events. However, performing a trial to include true high-risk patients who have CAD and are more likely to have silent ischemia could lead to prognostically beneficial coronary revascularizations. PMID:25979367

  19. Dynamic visual acuity testing for screening patients with vestibular impairments

    PubMed Central

    Peters, Brian T.; Mulavara, Ajitkumar P.; Cohen, Helen S.; Sangi-Haghpeykar, Haleh; Bloomberg, Jacob J.

    2013-01-01

    Dynamic visual acuity (DVA) may be a useful indicator of the function of the vestibulo-ocular reflex (VOR) but most DVA tests involve active head motion in the yaw plane. During gait the passive, vertical VOR may be more relevant and passive testing would be less likely to elicit compensatory strategies. The goal of this study was to determine if testing dynamic visual acuity during passive vertical motion of the subject would differentiate normal subjects from patients with known vestibular disorders. Subjects, normals and patients who had been diagnosed with either unilateral vestibular weaknesses or were post-acoustic neuroma resections, sat in a chair that could oscillate vertically with the head either free or constrained with a cervical orthosis. They viewed a computer screen 2 m away that showed Landholt C optotypes in one of 8 spatial configurations and which ranged in size from 0.4 to 1.0 logMAR. They were tested while the chair was stationary and while it was moving. Scores were worse for both groups during the dynamic condition compared to the static condition. In the dynamic condition patients’ scores were significantly worse than normals’ scores. Younger and older age groups differed slightly but significantly; the sample size was too small to examine age differences by decade. The data suggest that many well-compensated patients have dynamic visual acuity that is as good as age-matched normals. Results of ROC analyses were only moderate, indicating that the differences between patients and normals were not strong enough, under the conditions tested, for this test to be useful for screening people to determine if they have vestibular disorders. Modifications of the test paradigm may make it more useful for screening potential patients. PMID:23000614

  20. Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool.

    PubMed

    Jongmans, Marjolijn C J; Loeffen, Jan L C M; Waanders, Esmé; Hoogerbrugge, Peter M; Ligtenberg, Marjolijn J L; Kuiper, Roland P; Hoogerbrugge, Nicoline

    2016-03-01

    Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy. Cancer surveillance might also be warranted for affected relatives and detection of a genetic mutation can allow for reproductive counseling. Here we present an easy-to-use selection tool, based on a systematic review of pediatric cancer predisposing syndromes, to identify patients who may benefit from genetic counseling. The selection tool involves five questions concerning family history, the type of malignancy, multiple primary malignancies, specific features and excessive toxicity, which results in the selection of those patients that may benefit from referral to a clinical geneticist. PMID:26825391

  1. Does patient time spent viewing computer-tailored colorectal cancer screening materials predict patient-reported discussion of screening with providers?

    PubMed

    Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G; Jerant, Anthony

    2016-08-01

    The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program (IMCP) to activate patients to undergo CRC screening, deployed in primary care offices immediately before a visit. We employed usage time information stored in the IMCP to examine the association of patient time spent using the program with patient-reported discussion of screening during the visit, adjusting for previous CRC screening recommendation and reading speed.On average, patients spent 33 minutes on the program. In adjusted analyses, 30 minutes spent using the program was associated with a 41% increase in the odds of the patient having a discussion with their PCP (1.04, 1.59, 95% CI). In a separate analysis of the tailoring modules; the modules encouraging adherence to the tailored screening recommendation and discussion with the patient's PCP yielded significant results. Other predictors of screening discussion included better self-reported physical health and increased patient activation. Time spent on the program predicted greater patient-physician discussion of screening during a linked visit.Usage time information gathered automatically by IMCPs offers promise for objectively assessing patient engagement around a topic and predicting likelihood of discussion between patients and their clinician. PMID:27343254

  2. Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China.

    PubMed

    Mao, X

    1998-09-01

    To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace for alpha-antitrypsin deficiency (95%) and the predisposition of executives to heart disease, cancer, and diabetes (94%); that genetic testing should be included in preemployment physical examinations (86%); that governments should require premarital carrier tests (86%), newborn screening for sickle cell (77%), and Duchenne muscular dystrophy (71%); and that children should be tested for genes for late-onset disorders such as Huntington disease (85%), susceptibility to cancers (85%), familial hypercholesterolemia (84%), alcoholism (69%), and Alzheimer disease (61%). Most believed that partners should know each other's genetic status before marriage (92%), that carriers of the same defective gene should not mate with each other (91%), and that women should have a prenatal diagnosis if medically indicated (91%). The majority said that in China decisions about family planning were shared by the couple (82%). More than half had views that, in China, there were no laws to prohibit disability discrimination (64%), particularly to protect people with adult polycystic kidney disease (57%), cystic fibrosis (56%), or genetic predisposition to other diseases (50%). To some extent, these results might provide a basis for a discussion of eugenics in China, particularly about China's Maternal and Infant Health Care Law (1994). PMID:9718350

  3. Mutation Screening of Multiple Genes in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa by Targeted Resequencing

    PubMed Central

    González-del Pozo, María; Borrego, Salud; Barragán, Isabel; Pieras, Juan I.; Santoyo, Javier; Matamala, Nerea; Naranjo, Belén; Dopazo, Joaquín; Antiñolo, Guillermo

    2011-01-01

    Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing. PMID:22164218

  4. [Screening of celiac disease in patients with osteoporosis and osteopenia].

    PubMed

    Fojtík, P; Novosad, P; Kliment, M; Hrdý, P; Bóday, A; Richterová, R; Urban, O

    2011-12-01

    The celiac disease is traditionally viewed as the children's disease with a typical form accompanied mainly by intestinal symptoms and malabsorption. This opinion is still generally accepted by the medical community. Findings based on the area-wide screening show that the prevalence has risen from the original 1 : 1 000-1 500 to 1 : 70-550. The average prevalence in the western countries is nearly 1 : 100. The prevalence of the celiac disease in the Czech republic is estimated to be approximately 1 : 200-250. It means that the number of people in the Czech republic who are likely to be affected is about 40,000-50,000 people. Currently only 10-15% of the total number of the ill people are diagnosed and monitored. Adult patients represent the main diagnostic problem because their clinical pictures are individual and the main symptoms are atypical (nonenteral). These are anaemia (mainly sideropnic), early/premature osteoporosis, herpetiformic (Duhring) dermatitis, polyneurititis, ataxia, depression, behavioural disorders, menstrual cycle disorders and infertility. Therefore our attention is currently focused on the screening of these groups of subjects. The purpose of our study was to check the frequency of the celiac disease with patients with diagnosed osteoporosis and osteopenia. In our study we have confirmed the assumption that the prevalence ofthe celiac disease in the group of subjects was 1 : 50, which means that 2.2% of patients with osteoporosis and osteopenia are affected by celiac sprue and therefore screening examination of these patients with the subsequent causal treatment (gluten-free diet) is recommended. PMID:22277032

  5. A Simultaneous Genetic Screen for Zygotic and Sterile Mutants in a Hermaphroditic Vertebrate (Kryptolebias marmoratus)

    PubMed Central

    Sucar, Sofia; Moore, Ginger L.; Ard, Melissa E.; Ring, Brian C.

    2016-01-01

    The mangrove killifish, Kryptolebias marmoratus, is unique among vertebrates due to its self-fertilizing mode of reproduction involving an ovotestis. As a result, it constitutes a simplistic and desirable vertebrate model for developmental genetics as it is easily maintained, reaches sexual maturity in about 100 days, and provides a manageable number of relatively clear embryos. After the establishment and characterization of an initial mutagenesis pilot screen using N-ethyl-N-nitrosourea, a three-generation genetic screen was performed to confirm zygotic mutant allele heritability and simultaneously score for homozygous recessive mutant sterile F2 fish. From a total of 307 F2 fish screened, 10 were found to be 1° males, 16 were sterile, 92 wild-type, and the remaining 189, carriers of zygotic recessive alleles. These carriers produced 25% progeny exhibiting several zygotic phenotypes similar to those previously described in zebrafish and in the aforementioned pilot screen, as expected. Interestingly, new phenotypes such as golden yolk, no trunk, and short tail were observed. The siblings of sterile F2 mutants were used to produce an F3 generation in order to confirm familial sterility. Out of the 284 F3 fish belonging to 10 previously identified sterile families, 12 were found to be 1° males, 69 were wild-type, 83 sterile, and 120 were classified as */+ (either wild-type or carriers) with undefined genotypes. This screen provides proof of principle that K. marmoratus is a powerful vertebrate model for developmental genetics and can be used to identify mutations affecting fertility. PMID:26801648

  6. A Simultaneous Genetic Screen for Zygotic and Sterile Mutants in a Hermaphroditic Vertebrate (Kryptolebias marmoratus).

    PubMed

    Sucar, Sofia; Moore, Ginger L; Ard, Melissa E; Ring, Brian C

    2016-01-01

    The mangrove killifish, Kryptolebias marmoratus, is unique among vertebrates due to its self-fertilizing mode of reproduction involving an ovotestis. As a result, it constitutes a simplistic and desirable vertebrate model for developmental genetics as it is easily maintained, reaches sexual maturity in about 100 days, and provides a manageable number of relatively clear embryos. After the establishment and characterization of an initial mutagenesis pilot screen using N-ethyl-N-nitrosourea, a three-generation genetic screen was performed to confirm zygotic mutant allele heritability and simultaneously score for homozygous recessive mutant sterile F2 fish. From a total of 307 F2 fish screened, 10 were found to be 1° males, 16 were sterile, 92 wild-type, and the remaining 189, carriers of zygotic recessive alleles. These carriers produced 25% progeny exhibiting several zygotic phenotypes similar to those previously described in zebrafish and in the aforementioned pilot screen, as expected. Interestingly, new phenotypes such as golden yolk, no trunk, and short tail were observed. The siblings of sterile F2 mutants were used to produce an F3 generation in order to confirm familial sterility. Out of the 284 F3 fish belonging to 10 previously identified sterile families, 12 were found to be 1° males, 69 were wild-type, 83 sterile, and 120 were classified as */+ (either wild-type or carriers) with undefined genotypes. This screen provides proof of principle that K. marmoratus is a powerful vertebrate model for developmental genetics and can be used to identify mutations affecting fertility. PMID:26801648

  7. "It gives them more options": preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare.

    PubMed

    Archibald, Alison D; Hickerton, Chriselle L; Wake, Samantha A; Jaques, Alice M; Cohen, Jonathan; Metcalfe, Sylvia A

    2016-04-01

    This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an in-depth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community. PMID:26842720

  8. A Genetic Mosaic Screen of Essential Zygotic Genes in Caenorhabditis Elegans

    PubMed Central

    Bucher, E. A.; Greenwald, I.

    1991-01-01

    We have devised a simple genetic mosaic screen, which circumvents the difficulties posed by phenotypic analysis of early lethal mutants, to analyze essential zygotic genes in Caenorhabditis elegans. The screen attempts to distinguish genes involved in cell type and/or lineage specific processes such as determination, differentiation or morphogenesis from genes involved in general processes such as intermediary metabolism by using the pattern of gene function to classify genes: genes required in one or a subset of early blastomeres may have specific functions, whereas genes required in all early blastomeres may have general functions. We found that 12 of 17 genes examined function in specific early blastomeres, suggesting that many zygotic genes contribute to specific early processes. We discuss the advantages and limitations of this screen, which is applicable to other regions of the C. elegans genome. PMID:2071016

  9. Statement of The American Society of Human Genetics on cystic fibrosis carrier screening

    SciTech Connect

    Not Available

    1992-12-01

    The identification in 1989 of the cystic fibrosis (CF) gene and its most common mutation immediately raised the possibility of CF carrier detection by DNA analysis. The American Society of Human Genetics (ASHG) issued a statement recommending that CF carrier testing should be made available to individuals with a family history of CF. It was also stated that screening of individuals or couples in the general population should not be offered until the rate of CF carrier detection improves. An additional prerequisite emphasized the need for the establishment of effective educational and counseling programs consistent with previous widely accepted principles. An NIH workshop reached similar conclusions. ASHG recommendations are that screening be limited to individuals with a family history of CF, testing should be accompanied by education and counseling, screening should be voluntary and confidential with appropriate laboratory quality controls, and efforts should be expanded to educate health care providers and the public.

  10. A Real-Time Screening Alert Improves Patient Recruitment Efficiency

    PubMed Central

    Weng, Chunhua; Batres, Candido; Borda, Tomas; Weiskopf, Nicole G.; Wilcox, Adam B.; Bigger, J Thomas; Davidson, Karina W.

    2011-01-01

    The scarcity of cost-effective patient identification methods represents a significant barrier to clinical research. Research recruitment alerts have been designed to facilitate physician referrals but limited support is available to clinical researchers. We conducted a retrospective data analysis to evaluate the efficacy of a real-time patient identification alert delivered to clinical research coordinators recruiting for a clinical prospective cohort study. Data from log analysis and informal interviews with coordinators were triangulated. Over a 12-month period, 11,295 were screened electronically, 1,449 were interviewed, and 282 were enrolled. The enrollment rates for the alert and two other conventional methods were 4.65%, 2.01%, and 1.34% respectively. A taxonomy of eligibility status was proposed to precisely categorize research patients. Practical ineligibility factors were identified and their correlation with age and gender were analyzed. We conclude that the automatic prescreening alert improves screening efficiency and is an effective aid to clinical research coordinators. PMID:22195213

  11. Large genetic screens for gynogenesis and androgenesis haploid inducers in Arabidopsis thaliana failed to identify mutants

    PubMed Central

    Portemer, Virginie; Renne, Charlotte; Guillebaux, Alexia; Mercier, Raphael

    2015-01-01

    Gynogenesis is a process in which the embryo genome originates exclusively from female origin, following embryogenesis stimulation by a male gamete. In contrast, androgenesis is the development of embryos that contain only the male nuclear genetic background. Both phenomena are of great interest in plant breeding as haploidization is an efficient tool to reduce the length of breeding schemes to create varieties. Although few inducer lines have been described, the genetic control of these phenomena is poorly understood. We developed genetic screens to identify mutations that would induce gynogenesis or androgenesis in Arabidopsis thaliana. The ability of mutant pollen to induce either gynogenesis or androgenesis was tested by crossing mutagenized plants as males. Seedlings from these crosses were screened with recessive phenotypic markers, one genetically controlled by the female genome and another by the male genome. Positive and negative controls confirmed the unambiguous detection of both gynogenesis and androgenesis events. This strategy was applied to 1,666 EMS-mutagenised lines and 47 distant Arabidopsis strains. While an internal control suggested that the mutagenesis reached saturation, no gynogenesis or androgenesis inducer was found. However, spontaneous gynogenesis was observed at a frequency of 1/10,800. Altogether, these results suggest that no simple EMS-induced mutation in the male genome is able to induce gynogenesis or androgenesis in Arabidopsis. PMID:25814999

  12. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies.

    PubMed

    Carreño, Oriel; Corominas, Roser; Serra, Selma Angèlica; Sintas, Cèlia; Fernández-Castillo, Noèlia; Vila-Pueyo, Marta; Toma, Claudio; Gené, Gemma G; Pons, Roser; Llaneza, Miguel; Sobrido, María-Jesús; Grinberg, Daniel; Valverde, Miguel Ángel; Fernández-Fernández, José Manuel; Macaya, Alfons; Cormand, Bru

    2013-11-01

    Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing. PMID:24498617

  13. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

    PubMed Central

    Carreño, Oriel; Corominas, Roser; Serra, Selma Angèlica; Sintas, Cèlia; Fernández-Castillo, Noèlia; Vila-Pueyo, Marta; Toma, Claudio; Gené, Gemma G; Pons, Roser; Llaneza, Miguel; Sobrido, María-Jesús; Grinberg, Daniel; Valverde, Miguel Ángel; Fernández-Fernández, José Manuel; Macaya, Alfons; Cormand, Bru

    2013-01-01

    Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing. PMID:24498617

  14. Assessment of the Readability of Genetic Counseling Patient Letters.

    PubMed

    Brown, Emily; Skinner, Megan; Ashley, Stephanie; Reed, Kate; Dixon, Shannan DeLany

    2016-06-01

    Patient letters are a powerful tool that genetic counselors use to communicate with their patients. Patient letters are often sent to provide information on a new diagnosis, reiterate test results, and to serve as a permanent record of the visit. Patient letters, however, are only helpful if the patients can understand them. More than 50 % of the US population reads below a 9th grade reading level and over one-third of the population has low health literacy skills. In this study we evaluate the readability of genetic counseling patient letters by assessing reading level, image use, and terminology use. One hundred forty-nine genetic counselors participated in the survey and of these, 79 submitted a sample patient letter. Analyses of the letters revealed a mean reading level of 10.93. On average, 6 genetic terms were included in each letter, and only 25 % of these terms were defined. Analyses of survey responses revealed over 75 % of the genetic counselors did not include images in their patient letters. These results indicate there is room for improvement in order to make genetic counseling patient letters more accessible to the general population. PMID:26416185

  15. Routine Screening for CYP2C19 Polymorphisms for Patients being Treated with Clopidogrel is not Recommended

    PubMed Central

    Hong, Robert A; Khan, Zia R; Valentin, Mona R; Badawi, Ramy A

    2015-01-01

    Recent efforts directed at potential litigation in Hawai‘i have resulted in a renewed interest for genetic screening for cytochrome P450 2C19 (CYP2C19) polymorphisms in patients treated with clopidogrel. Clopidogrel is an antiplatelet agent, frequently used in combination with aspirin, for the prevention of thrombotic complications with acute coronary syndrome and in patients undergoing percutaneous coronary interventions. Cytochrome P-450 (CYP) 2C19 is an enzyme involved in the bioactivation of clopidogrel from a pro-drug to an active inhibitor of platelet action. Patients of Asian and Pacific Island background have been reported to have an increase in CYP2C19 polymorphisms associated with loss-of-function of this enzyme when compared to other ethnicities. This has created an interest in genetic testing for CYP2C19 polymorphisms in Hawai‘i. Based upon our review of the current literature, we do not feel that there is support for the routine screening for CYP2C19 polymorphisms in patients being treated with clopidogrel; furthermore, the results of genetic testing may not be helpful in guiding therapeutic decisions. We recommend that decisions on the type of antiplatelet treatment be made based upon clinical evidence of potential differential outcomes associated with the use of these agents rather than on the basis of genetic testing. PMID:25628978

  16. Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young.

    PubMed

    Methner, D Nicole R; Scherer, Steven E; Welch, Katherine; Walkiewicz, Magdalena; Eng, Christine M; Belmont, John W; Powell, Mark C; Korchina, Viktoriya; Doddapaneni, Harsha Vardhan; Muzny, Donna M; Gibbs, Richard A; Wolf, Dwayne A; Sanchez, Luis A; Kahn, Roger

    2016-09-01

    Each year in the United States, thousands of cases of sudden and unexpected deaths of infants, children, and young adults are assigned an undetermined cause of death after postmortem investigation and autopsy. Heritable genetic variants have been suggested as the cause of up to a third of sudden death (SD) cases. Elucidation of the genetic variants involved in SD cases is important to not only help establish cause and manner of death of these individuals, but to also aid in determining whether familial genetic testing should be considered. Previously, these types of postmortem screenings have not been a feasible option for most county medical examiners' and coroners' offices. We sequenced full exons of 64 genes associated with SD in the largest known cohort (351) of infant and young SD decedents using massively parallel sequencing at <$600 per sample. Genetic variants were assessed through literature review and clinical evaluation by a multidisciplinary consortium of experts. Thirteen individuals (3.7%), eight infants (2.8% of those <1 yr of age) and five children/young adults (7.0% of those >1 yr of age), were found to have a reportable genetic variant contributing to SD. These percentages represent an estimate lower than those previously reported. Overall yields and results likely vary between studies due to differences in evaluation techniques and reporting. Additionally, we recommend ongoing assessment of data, including nonreported novel variants, as technology and literature continually advance. This study demonstrates a strategy to implement molecular autopsies in medicolegal investigations of young SD decedents. PMID:27435932

  17. Patient understanding of the revised USPSTF screening mammogram guidelines: need for development of patient decision aids

    PubMed Central

    2012-01-01

    Background The purpose of the study was to examine patients’ understanding of the revised screening mammogram guidelines released by the United States Preventive Services Task Force (USPSTF) in 2009 addressing age at initiation and frequency of screening mammography. Methods Patients from the Departments of Family Medicine, Internal Medicine, and Obstetrics and Gynecology (n = 150) at a tertiary care medical center in the United States completed a survey regarding their understanding of the revised USPSTF guidelines following their release, within four to six months of their scheduled mammogram (March 2010 to May 2010). Results Of the patients surveyed, 97/147 (67%) indicated increased confusion regarding the age and frequency of screening mammography, 61/148 (41%) reported increased anxiety about mammograms, and 58/146 (40%) reported anxiety about their own health status following the release of the revised screening guidelines. Most of the patients surveyed, 111/148 (75%), did not expect to change their timing or frequency of screening mammograms in the future. Conclusion Results from this survey suggested increased confusion and possibly an increase in patients’ anxiety related to screening mammography and their own health status following the release of the revised USPSTF screening mammogram guidelines to the public and subsequent media portrayal of the revised guidelines. Although the study did not specifically address causality for these findings, the results highlight the need for improvements in the communication of guidelines to patients and the public. Development of shared decision-making tools and outcomes should be considered to address the communication challenge. PMID:23051022

  18. A Mosaic Genetic Screen for Genes Involved in the Early Steps of Drosophila Oogenesis

    PubMed Central

    Jagut, Marlène; Mihaila-Bodart, Ludivine; Molla-Herman, Anahi; Alin, Marie-Françoise; Lepesant, Jean-Antoine; Huynh, Jean-René

    2013-01-01

    The first hours of Drosophila embryogenesis rely exclusively on maternal information stored within the egg during oogenesis. The formation of the egg chamber is thus a crucial step for the development of the future adult. It has emerged that many key developmental decisions are made during the very first stages of oogenesis. We performed a clonal genetic screen on the left arm of chromosome 2 for mutations affecting early oogenesis. During the first round of screening, we scored for defects in egg chambers morphology as an easy read-out of early abnormalities. In a second round of screening, we analyzed the localization of centrosomes and Orb protein within the oocyte, the position of the oocyte within the egg chamber, and the progression through meiosis. We have generated a collection of 71 EMS-induced mutants that affect oocyte determination, polarization, or localization. We also recovered mutants affecting the number of germline cyst divisions or the differentiation of follicle cells. Here, we describe the analysis of nine complementation groups and eight single alleles. We mapped several mutations and identified alleles of Bicaudal-D, lethal(2) giant larvae, kuzbanian, GDP-mannose 4,6-dehydratase, tho2, and eiF4A. We further report the molecular identification of two alleles of the Drosophila homolog of Che-1/AATF and demonstrate its antiapoptotic activity in vivo. This collection of mutants will be useful to investigate further the early steps of Drosophila oogenesis at a genetic level. PMID:23450845

  19. Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation

    PubMed Central

    Gao, Hua; Chakraborty, Goutam; Lee-Lim, Ai Ping; Mavrakis, Konstantinos J.; Wendel, Hans-Guido; Giancotti, Filippo G.

    2014-01-01

    We have developed a screening platform for the isolation of genetic entities involved in metastatic reactivation. Retroviral libraries of cDNAs from fully metastatic breast-cancer cells or pooled microRNAs were transduced into breast-cancer cells that become dormant upon infiltrating the lung. Upon inoculation in the tail vein of mice, the cells that had acquired the ability to undergo reactivation generated metastatic lesions. Integrated retroviral vectors were recovered from these lesions, sequenced, and subjected to a second round of validation. By using this strategy, we isolated canonical genes and microRNAs that mediate metastatic reactivation in the lung. To identify genes that oppose reactivation, we screened an expression library encoding shRNAs, and we identified target genes that encode potential enforcers of dormancy. Our screening strategy enables the identification and rapid biological validation of single genetic entities that are necessary to maintain dormancy or to induce reactivation. This technology should facilitate the elucidation of the molecular underpinnings of these processes. PMID:25378704

  20. Y-STR genetic screening by high-resolution melting analysis.

    PubMed

    Deng, J Q; Liu, B Q; Wang, Y; Liu, W; Cai, J F; Long, R; Li, W H

    2016-01-01

    Currently, the widely used automated capillary electrophoresis-based short tandem repeat (STR) genotyping method for genetic screening in forensic practice is laborious, time-consuming, expensive, and technically challenging in some cases. Thus, new molecular-based strategies for conclusively identifying forensically relevant biological evidence are required. Here, we used high-resolution melting analysis (HRM) for Y-chromosome STR genotyping for forensic genetic screening. The reproducibility of the melting profile over dilution, sensitivity, discrimination power, and other factors was preliminarily studied in 10 Y-STR loci. The results showed that HRM-based approaches revealed more genotypes (compared to capillary electrophoresis), showed higher uniformity in replicate tests and diluted samples, and enabled successful detection of DNA at concentrations as low as 0.25 ng. For mixed samples, the melting curve profiles discriminated between mixed samples based on reference samples with high efficiency. The triplex Y-chromosome STR HRM assay was performed and provided a foundation for further studies such as a multiplex HRM assay. The HRM approach is a one-step application and the entire procedure can be completed within 2 h at a low cost. In conclusion, our findings demonstrate that the HRM-based Y-STR assay is a useful screening tool that can be used in forensic practice. PMID:26909950

  1. [Rare diseases: specific ethical and legal aspects of genetic counseling and screening].

    PubMed

    Sánchez-Caro, Javier

    2011-01-01

    This article analyses the specific rights of patients with rare diseases from a dual perspective. On the one hand, they concern a new generation of patients' rights that arise once the consolidation of basic rights has occurred, fundamentally after the application of Law 41/2002 (on Regulating Patient Autonomy and Rights and Obligations in the Field of Health Documentation and Information) and its development by the autonomous communities. On the other hand, the fundamental question raises a serious issue related to these patients, which involves the principles of equality, equity, non-discrimination and solidarity. This is aimed at promoting legislative measures to protect patients' equality of access to health and social services, with the ultimate aim of improving their quality of life. The author has given special relevance in his study to the treatment of rare diseases that are genetic in origin, and to the importance of adequate genetic counseling. PMID:22984752

  2. AB041. Genetic diversity of organic and fatty acid disorders detectable in expanded newborn screening in Asian countries

    PubMed Central

    Yamaguchi, Seiji; Fukao, Toshiyuki; Chí, Dũng Vũ; Thu, Nhan Nguen

    2015-01-01

    Recently, the increasing number of children with organic acidemias (OAs) and fatty acid oxidation defects (FAODs) has been detected with development of diagnostic tools, like GC/MS or MS/MS, for inborn metabolic disease (IMD). We have performed collaboration study with some Asian countries, and have noticed the diversity of disease contribution and genetic aspects. Diversity of disease distribution: metabolic screening of children at high risk using GC/MS and NS/MS has been performed in collaboration with several Asian countries. In India, Vietnam, and China, as well as Japan, methylmalonic acidemia (MMA) was most common, followed by urea cycle disorder (UCD), propionic academia (PPA). In Vietnam and India, 3-ketothiolase deficiency (BKTD), maple syrup urine disease (MSUD), and oxoprolinuria are also common, although they are extremely rare in Japan. In China, frequency of MMA seemed to be high, in particular combined MMA and homocystinuria many of which are B12 responsible. Genetic diversity: (I) MMA: in China, 42% of MMA are combined type of MMA and HCY due to CblC defect. 609G>A in MMACHC gene is a common mutation, covering 55%; (II) BKTD: in Vietnamese patients, c.662C>G in T2 gene is common, covering 72%; (III) PPA: in Japanese, Y435C mutation in PCCB gene is a common mutation in the mild form of PPA, at prevalence of 1 in 86 alleles in Japanese population; (IV) MCAD deficiency: common mutation 985A>C which covers about 90% of alleles among Caucasian is famous. A mutation study of Japanese cases, revealed a common mutation, c.449delCTGA, covering about 45% of the alleles. It is still unknown whether the mutation is Japanese specific, or East-Asian specific. Newborn mass screening (NBS) is increasingly popular in Asian countries. The diversity of disease distribution and genetic mutations will be made clear with the spread of collaboration studies and expanded NBS using MS/MS.

  3. Molecular newborn screening of four genetic diseases in Guizhou Province of South China.

    PubMed

    Huang, Shengwen; Xu, Yin; Liu, Xingmei; Zhou, Man; Wu, Xian; Jia, Yankai

    2016-10-10

    Genetic disorders have been a major concern for public health in China, especially in the rural regions. However, there is little information available about prevalence of many common single-gene disorders in Guizhou Province in the south western part of China. In the present study, we performed a molecular newborn screening for four genetic disorders, including beta-thalassemia (β-thal), glucose-6-phosphate dehydrogenase (G6PD) deficiency, phenylketonuria (PKU), and non-syndromic hearing loss and deafness (NSHL) in this region. A total of 515 newborns were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) developed for screening the mutations causing these four disorders, and then confirmed by Sanger sequencing. The results showed that 48 out of 515 newborns were carriers of mutations related to these four diseases, with a frequency of 1 in 11 (9.32%). The carrier frequencies for each disease are: β-thal 2.72%; G6PD deficiency 1.94%; PKU 0.78% and NSHL 4.47%. The genotyping results by MALDI-TOF MS were concordant with Sanger sequencing results within 30 randomly selected samples. This is the first study that reveals carrier frequencies of these four diseases in Guizhou Province. These data provide valuable information for the genetic counseling and disease prevention in Guizhou and southwest China. PMID:27395428

  4. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    PubMed Central

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10−9). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10−9), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA–approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  5. Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 signaling pathway.

    PubMed

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L; Siminovitch, Katherine A; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K; Worthington, Jane; Gupta, Namrata; Clemons, Paul A; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M

    2013-05-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10(-9)). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10(-9)), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA-approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  6. Genetic screens and functional genomics using CRISPR/Cas9 technology.

    PubMed

    Hartenian, Ella; Doench, John G

    2015-04-01

    Functional genomics attempts to understand the genome by perturbing the flow of information from DNA to RNA to protein, in order to learn how gene dysfunction leads to disease. CRISPR/Cas9 technology is the newest tool in the geneticist's toolbox, allowing researchers to edit DNA with unprecedented ease, speed and accuracy, and representing a novel means to perform genome-wide genetic screens to discover gene function. In this review, we first summarize the discovery and characterization of CRISPR/Cas9, and then compare it to other genome engineering technologies. We discuss its initial use in screening applications, with a focus on optimizing on-target activity and minimizing off-target effects. Finally, we comment on future challenges and opportunities afforded by this technology. PMID:25728500

  7. Visualism and technification—the patient behind the screen

    PubMed Central

    Almerud-Österberg, Sofia

    2010-01-01

    At stake in this study is the patient's credibility. The Cartesian philosophical standpoint, which holds sway in western thinking, questions with scepticism whether the reported symptoms are “real.” Do they reside in the body, or are they mentally concocted. However, from the caring perspective any symptom must be both listened and attended to in its own right, not just scrutinized as evidence for an accurate diagnosis. In cognitively and emotionally complex high-tech units caregivers are juggling a precarious handful of cards. Technical tasks take precedence or have more urgency than caring behaviour. Assuming an irremediable tension between object–subject and care–cure in nursing is futile dualism. By addressing the essence of technology—the non-neutral and highly visual technology—this paper aims to find, from a philosophical point of view, a more comprehensive understanding for the dominance visualism and technification within intensive care. Screens give us access to vital signs. Screens record numbers and lines that relate to a graph and afford superfine spiked “readings.” However, the most relevant vital signs may be missing. PMID:20640015

  8. New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

    PubMed Central

    2014-01-01

    The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200

  9. Effects of Screening for Psychological Distress on Patient Outcomes in Cancer: a Systematic Review

    PubMed Central

    Meijer, Anna; Roseman, Michelle; Delisle, Vanessa C.; Milette, Katherine; Levis, Brooke; Syamchandra, Achyuth; Stefanek, Michael E.; Stewart, Donna E.; de Jonge, Peter; Coyne, James C.; Thombs, Brett D.

    2013-01-01

    Objective Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identified as distressed; and (2) effects of screening for distress on distress outcomes. Methods CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO, and SCOPUS databases were searched through April 6, 2011 with manual searches of 45 relevant journals, reference list review, citation tracking of included articles, and trial registry reviews through June 30, 2012. Articles in any language on cancer patients were included if they (1) compared treatment for patients with psychological distress to placebo or usual care in a randomized controlled trial (RCT); or (2) assessed the effect of screening on psychological distress in a RCT. Results There were 14 eligible RCTs for treatment of distress, and 1 RCT on the effects of screening on patient distress. Pharmacological, psychotherapy and collaborative care interventions generally reduced distress with small to moderate effects. One study investigated effects of screening for distress on psychological outcomes, and it found no improvement. Conclusion Treatment studies reported modest improvement in distress symptoms, but only a single eligible study was found on the effects of screening cancer patients for distress, and distress did not improve in screened patients versus those receiving usual care. Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening. PMID:23751231

  10. A Nutrition Screening Form for Female Infertility Patients.

    PubMed

    Langley, Susie

    2014-12-01

    A Nutrition Screening Form (NSF) was designed to identify lifestyle risk factors that negatively impact fertility and to provide a descriptive profile of 300 female infertility patients in a private urban infertility clinic. The NSF was mailed to all new patients prior to the initial physician's visit and self-reported data were assessed using specific criteria to determine if a nutrition referral was warranted. This observational study revealed that 43% of the women had a body mass index (BMI) <20 or ≥25 kg/m(2), known risks for infertility. Almost half reported a history of "dieting" and unrealistic weight goals potentially limiting energy and essential nutrients. A high number reported eating disorders, vegetarianism, low fat or low cholesterol diets, and dietary supplement use. Fourteen percent appeared not to supplement with folic acid, 13% rated exercise as "extremely" or "very active", and 28% reported a "high" perceived level of stress. This preliminary research demonstrated that a NSF can be a useful tool to identify nutrition-related lifestyle factors that may negatively impact fertility and identified weight, BMI, diet, exercise, and stress as modifiable risk factors deserving future research. NSF information can help increase awareness among health professionals and patients about the important link between nutrition, fertility, and successful reproductive outcomes. PMID:26067073

  11. Molecular analysis of Gaucher disease: screening of patients in the Montreal/Quebec region.

    PubMed

    Choy, F Y; Woo, M; Der Kaloustian, V M

    1991-12-15

    Gaucher disease, the most prevalent lysosomal storage disease, is an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. Genomic DNA of the structural gene of glucocerebrosidase from normal individuals and fifteen unrelated patients with the three clinical forms of Gaucher disease from the Montreal/Quebec region were amplified by the polymerase chain reaction technique. Allele-specific oligonucleotide dot blot hybridization and restriction fragment length polymorphism were used to screen for five of the mutations [mutations 120, 370, 415, 444 (Nci), and 463] in exons 5, 9, and 10 of glucocerebrosidase gene. It was noted that all of the patients had at least one of the known mutant alleles. However, 9 patients (9/15 = 60%) had an unknown allele. Mutation 370 in exon 9 was present in the heteroallelic form in eight out of the nine patients with type 1 Gaucher disease, but was present in none of the six patients with type 2 or type 3 Gaucher disease. The Nci mutation in exon 10 was present in the heteroallelic form in three patients with type 1 Gaucher disease and in either the heteroallelic or homoallelic form in all of the six patients with type 2 or type 3 Gaucher disease. The 415/Nci mutations were found in a mildly affected 29-year-old patient with type 1 Gaucher disease, as well as in an infant with the type 2 form. These findings demonstrate the clinical and molecular genetic heterogeneities of Gaucher disease, the presence of unknown Gaucher allele(s) in most (60%) of the patients surveyed, and the occasional inexplicable lack of phenotype-genotype correlation among some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1776640

  12. Multimodality breast cancer screening in women with a familial or genetic predisposition

    PubMed Central

    Trop, I.; Lalonde, L.; Mayrand, M.H.; David, J.; Larouche, N.; Provencher, D.

    2010-01-01

    Background Women with a predisposition for breast cancer require a tailored screening program for early cancer detection. We evaluated the performance of mammography (mg), ultrasonography (us), and magnetic resonance imaging (mri) screening in these women. Patients and Methods In asymptomatic women either confirmed as BRCA1/2 carriers, or having a greater than 30% probability of being so as estimated by brcapro [Berry D, Parmigiani G. Duke spore (Specialized Program of Research Excellence) in Breast Cancer. 1999], we conducted a prospective comparative trial consisting of annual mri and mg, and biannual us and clinical breast examination. All evaluations were done within 30 days of one another. For each screening round, imaging tests were independently interpreted by three radiologists. Results The study enrolled 184 women, and 387 screening rounds were performed, detecting 12 cancers (9 infiltrating, 3 in situ), for an overall cancer yield of 6.5%. At diagnosis, 7 infiltrating cancers were smaller than 2 cm (T1); only 1 woman presented with axillary nodal metastases. All tumours were negative for the human epidermal growth factor receptor 2. Of the 12 cancers, mri detected 10, and mg, 7; us did not identify any additional cancers. The overall recall rate after mri was 21.8%, as compared with 11.4% for us and 16.1% for mg. Recall rates declined with successive screening rounds. In total, 45 biopsies were performed: 21 as a result of an us abnormality; 17, because of an mri lesion; and 7, because of a mg anomaly. Interpretation In high-risk women, mri offers the best sensitivity for breast cancer screening. The combination of yearly mri and mg reached a negative predictive value of 100%. The recall rate is greatest with mri, but declines for all modalities with successive screening rounds. PMID:20567624

  13. Aluminium tolerance in barley (Hordeum vulgare L.): physiological mechanisms, genetics and screening methods*

    PubMed Central

    Wang, Jun-ping; Raman, Harsh; Zhang, Guo-ping; Mendham, Neville; Zhou, Mei-xue

    2006-01-01

    Aluminium (Al) toxicity is one of the major limiting factors for barley production on acid soils. It inhibits root cell division and elongation, thus reducing water and nutrient uptake, consequently resulting in poor plant growth and yield. Plants tolerate Al either through external resistance mechanisms, by which Al is excluded from plant tissues or internal tolerance mechanisms, conferring the ability of plants to tolerate Al ion in the plant symplasm where Al that has permeated the plasmalemma is sequestered or converted into an innocuous form. Barley is considered to be most sensitive to Al toxicity among cereal species. Al tolerance in barley has been assessed by several methods, such as nutrient solution culture, soil bioassay and field screening. Genetic and molecular mapping research has shown that Al tolerance in barley is controlled by a single locus which is located on chromosome 4H. Molecular markers linked with Al tolerance loci have been identified and validated in a range of diverse populations. This paper reviews the (1) screening methods for evaluating Al tolerance, (2) genetics and (3) mechanisms underlying Al tolerance in barley. PMID:16972319

  14. A forward genetic screen reveals that calcium-dependent protein kinase 3 regulates egress in Toxoplasma.

    PubMed

    Garrison, Erin; Treeck, Moritz; Ehret, Emma; Butz, Heidi; Garbuz, Tamila; Oswald, Benji P; Settles, Matt; Boothroyd, John; Arrizabalaga, Gustavo

    2012-01-01

    Egress from the host cell is a crucial and highly regulated step in the biology of the obligate intracellular parasite, Toxoplasma gondii. Active egress depends on calcium fluxes and appears to be a crucial step in escaping the attack from the immune system and, potentially, in enabling the parasites to shuttle into appropriate cells for entry into the brain of the host. Previous genetic screens have yielded mutants defective in both ionophore-induced egress and ionophore-induced death. Using whole genome sequencing of one mutant and subsequent analysis of all mutants from these screens, we find that, remarkably, four independent mutants harbor a mis-sense mutation in the same gene, TgCDPK3, encoding a calcium-dependent protein kinase. All four mutations are predicted to alter key regions of TgCDPK3 and this is confirmed by biochemical studies of recombinant forms of each. By complementation we confirm a crucial role for TgCDPK3 in the rapid induction of parasite egress and we establish that TgCDPK3 is critical for formation of latent stages in the brains of mice. Genetic knockout of TgCDPK3 confirms a crucial role for this kinase in parasite egress and a non-essential role for it in the lytic cycle. PMID:23209419

  15. The importance to update the guidelines for the use of genetic testing in noncancer patients in Brazil

    PubMed Central

    Lajus, Tirzah Braz Petta

    2015-01-01

    The Brazilian National Regulatory Agency for Private Health Insurance and Plans has recently published a technical note defining the criteria for the coverage of genetic testing to diagnose hereditary cancer. In this study we show the case of a patient with a breast lesion and an extensive history of cancer referred to a private service of genetic counseling. The patient met both criteria for hereditary breast and colorectal cancer syndrome screening. Her private insurance denied coverage for genetic testing because she lacks current or previous cancer diagnosis. After she appealed by lawsuit, the court was favorable and the test was performed using next-generation sequencing. A deletion of MLH1 exon 8 was found. We highlight the importance to offer genetic testing using multigene analysis for noncancer patients. PMID:26465663

  16. A systematic review of patient acceptance of screening for oral cancer outside of dental care settings.

    PubMed

    Paudyal, Priyamvada; Flohr, Francesca D; Llewellyn, Carrie D

    2014-10-01

    This systematic review summarised the literature on patient acceptability of screening for oral cancer outside dental care settings. A comprehensive search of relevant literature was performed in EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, CINAHAL, psycINFO, CANCERLIT and BNI to identify relevant articles published between 1975 and Dec 2013. Studies reporting acceptability of oral cancer screening to undiagnosed individuals attending non-dental settings were eligible for inclusion. A total of 2935 references were initially identified from the computerised search but 2217 were excluded after screening the titles. From the abstracts of the remaining 178 articles, 47 full text articles were retrieved for further scrutiny, and 12 studies were found to be eligible for inclusion. In these studies, knowledge about oral cancer, anxiety related to the screening process, preference for care provision, and financial cost were influencing factors for the acceptance of screening. Written information provided to patients in primary care was reported to boost immediate knowledge levels of oral cancer, lessen anxiety, and increase intentions for screening. The majority of screening methods were entirely acceptable to patients; lack of acceptability from the patients' viewpoint was not a significant barrier to carrying out opportunistic screening of high-risk populations. In conclusion, the available evidence suggests that acceptance of, and satisfaction with oral cancer screening is high, particularly where patients have previously been educated about oral cancer. Further research focusing on patient's preferences would enable streamlining of the approach to oral cancer screening taken by any national programme. PMID:25127201

  17. New multiplex PCR methods for rapid screening of genetically modified organisms in foods

    PubMed Central

    Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products. PMID:26257724

  18. Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

    PubMed

    Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

    2016-07-01

    Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. PMID:26908592

  19. New multiplex PCR methods for rapid screening of genetically modified organisms in foods.

    PubMed

    Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products. PMID:26257724

  20. A microfluidic-based genetic screen to identify microbial virulence factors that inhibit dendritic cell migration

    PubMed Central

    McLaughlin, Laura M.; Xu, Hui; Carden, Sarah E.; Fisher, Samantha; Reyes, Monique; Heilshorn, Sarah C.; Monack, Denise M.

    2014-01-01

    Microbial pathogens are able to modulate host cells and evade the immune system by multiple mechanisms. For example, Salmonella injects effector proteins into host cells and evades the host immune system in part by inhibiting dendritic cell (DC) migration. The identification of microbial factors that modulate normal host functions should lead to the development of new classes of therapeutics that target these pathways. Current screening methods to identify either host or pathogen genes involved in modulating migration towards a chemical signal are limited because they do not employ stable, precisely controlled chemical gradients. Here, we develop a positive selection microfluidic-based genetic screen that allows us to identify Salmonella virulence factors that manipulate DC migration within stable, linear chemokine gradients. Our screen identified 7 Salmonella effectors (SseF, SifA, SspH2, SlrP, PipB2, SpiC and SseI) that inhibit DC chemotaxis toward CCL19. This method is widely applicable for identifying novel microbial factors that influence normal host cell chemotaxis as well as revealing new mammalian genes involved in directed cell migration. PMID:24599496

  1. A microfluidic-based genetic screen to identify microbial virulence factors that inhibit dendritic cell migration.

    PubMed

    McLaughlin, Laura M; Xu, Hui; Carden, Sarah E; Fisher, Samantha; Reyes, Monique; Heilshorn, Sarah C; Monack, Denise M

    2014-04-01

    Microbial pathogens are able to modulate host cells and evade the immune system by multiple mechanisms. For example, Salmonella injects effector proteins into host cells and evades the host immune system in part by inhibiting dendritic cell (DC) migration. The identification of microbial factors that modulate normal host functions should lead to the development of new classes of therapeutics that target these pathways. Current screening methods to identify either host or pathogen genes involved in modulating migration towards a chemical signal are limited because they do not employ stable, precisely controlled chemical gradients. Here, we develop a positive selection microfluidic-based genetic screen that allows us to identify Salmonella virulence factors that manipulate DC migration within stable, linear chemokine gradients. Our screen identified 7 Salmonella effectors (SseF, SifA, SspH2, SlrP, PipB2, SpiC and SseI) that inhibit DC chemotaxis toward CCL19. This method is widely applicable for identifying novel microbial factors that influence normal host cell chemotaxis as well as revealing new mammalian genes involved in directed cell migration. PMID:24599496

  2. Survival Analysis of Patients with Interval Cancer Undergoing Gastric Cancer Screening by Endoscopy

    PubMed Central

    Hamashima, Chisato; Shabana, Michiko; Okamoto, Mikizo; Osaki, Yoneatsu; Kishimoto, Takuji

    2015-01-01

    Aims Interval cancer is a key factor that influences the effectiveness of a cancer screening program. To evaluate the impact of interval cancer on the effectiveness of endoscopic screening, the survival rates of patients with interval cancer were analyzed. Methods We performed gastric cancer-specific and all-causes survival analyses of patients with screen-detected cancer and patients with interval cancer in the endoscopic screening group and radiographic screening group using the Kaplan-Meier method. Since the screening interval was 1 year, interval cancer was defined as gastric cancer detected within 1 year after a negative result. A Cox proportional hazards model was used to investigate the risk factors associated with gastric cancer-specific and all-causes death. Results A total of 1,493 gastric cancer patients (endoscopic screening group: n = 347; radiographic screening group: n = 166; outpatient group: n = 980) were identified from the Tottori Cancer Registry from 2001 to 2008. The gastric cancer-specific survival rates were higher in the endoscopic screening group than in the radiographic screening group and the outpatients group. In the endoscopic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer and the patients with interval cancer were nearly equal (P = 0.869). In the radiographic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer was higher than that of the patients with interval cancer (P = 0.009). For gastric cancer-specific death, the hazard ratio of interval cancer in the endoscopic screening group was 0.216 for gastric cancer death (95%CI: 0.054-0.868) compared with the outpatient group. Conclusion The survival rate and the risk of gastric cancer death among the patients with screen-detected cancer and patients with interval cancer were not significantly different in the annual endoscopic screening. These results suggest the potential of

  3. Development of a forward genetic screen to isolate oil mutants in the green microalga Chlamydomonas reinhardtii

    PubMed Central

    2013-01-01

    Background Oils produced by microalgae are precursors to biodiesel. To achieve a profitable production of biodiesel from microalgae, identification of factors governing oil synthesis and turnover is desirable. The green microalga Chlamydomonas reinhardtii is amenable to genetic analyses and has recently emerged as a model to study oil metabolism. However, a detailed method to isolate various types of oil mutants that is adapted to Chlamydomonas has not been reported. Results We describe here a forward genetic approach to isolate mutants altered in oil synthesis and turnover from C. reinhardtii. It consists of a three-step screening procedure: a primary screen by flow cytometry of Nile red stained transformants grown in 96-deep-well plates under three sequential conditions (presence of nitrogen, then absence of nitrogen, followed by oil remobilization); a confirmation step using Nile red stained biological triplicates; and a validation step consisting of the quantification by thin layer chromatography of oil content of selected strains. Thirty-one mutants were isolated by screening 1,800 transformants generated by random insertional mutagenesis (1.7%). Five showed increased oil accumulation under the nitrogen-replete condition and 13 had altered oil content under nitrogen-depletion. All mutants were affected in oil remobilization. Conclusion This study demonstrates that various types of oil mutants can be isolated in Chlamydomonas based on the method set-up here, including mutants accumulating oil under optimal biomass growth. The strategy conceived and the protocol set-up should be applicable to other microalgal species such as Nannochloropsis and Chlorella, thus serving as a useful tool in Chlamydomonas oil research and algal biotechnology. PMID:24295516

  4. A screening on Specific Learning Disorders in an Italian speaking high genetic homogeneity area.

    PubMed

    Cappa, Claudia; Giulivi, Sara; Schilirò, Antonino; Bastiani, Luca; Muzio, Carlo; Meloni, Fabrizio

    2015-01-01

    The aim of the present research is to investigate the prevalence of Specific Learning Disorders (SLD) in Ogliastra, an area of the island of Sardinia, Italy. Having experienced centuries of isolation, Ogliastra has become a high genetic homogeneity area, and is considered particularly interesting for studies on different kinds of pathologies. Here we are going to describe the results of a screening carried out throughout 2 consecutive years in 49 second grade classes (24 considered in the first year and 25 in the second year of the study) of the Ogliastra region. A total of 610 pupils (average age 7.54 years; 293 female, 317 male) corresponding to 68.69% of all pupils who were attending second grade in the area, took part in the study. The tool used for the screening was "RSR-DSA. Questionnaire for the detection of learning difficulties and disorders", which allowed the identification of 83 subjects at risk (13.61% of the whole sample involved in the study). These subjects took part in an enhancement training program of about 6 months. After the program, pupils underwent assessment for reading, writing and calculation abilities, as well as cognitive assessment. According to the results of the assessment, the prevalence of SLDs is 6.06%. For what concerns dyslexia, 4.75% of the total sample manifested this disorder either in isolation or in comorbidity with other disorders. According to the first national epidemiological investigation carried out in Italy, the prevalence of dyslexia is 3.1-3.2%, which is lower than the prevalence obtained in the present study. Given the genetic basis of SLDs, this result, together with the presence of several cases of SLD in isolation (17.14%) and with a 3:1 ratio of males to females diagnosed with a SLD, was to be expected in a sample coming from a high genetic homogeneity area. PMID:26296080

  5. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs.

    PubMed

    Clark, Matt Q; McCumsey, Stephanie J; Lopez-Darwin, Sereno; Heckscher, Ellie S; Doe, Chris Q

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines-chosen for sparse neuronal expression-to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  6. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

    PubMed Central

    Clark, Matt Q.; McCumsey, Stephanie J.; Lopez-Darwin, Sereno; Heckscher, Ellie S.; Doe, Chris Q.

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  7. A large-scale genetic screen in Arabidopsis to identify genes involved in pollen exine production.

    PubMed

    Dobritsa, Anna A; Geanconteri, Aliza; Shrestha, Jay; Carlson, Ann; Kooyers, Nicholas; Coerper, Daniel; Urbanczyk-Wochniak, Ewa; Bench, Bennie J; Sumner, Lloyd W; Swanson, Robert; Preuss, Daphne

    2011-10-01

    Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production. PMID:21849515

  8. Genetics and Management of the Patient with Orofacial Cleft

    PubMed Central

    Brito, Luciano Abreu; Meira, Joanna Goes Castro; Kobayashi, Gerson Shigeru; Passos-Bueno, Maria Rita

    2012-01-01

    Cleft lip or palate (CL/P) is a common facial defect present in 1 : 700 live births and results in substantial burden to patients. There are more than 500 CL/P syndromes described, the causes of which may be single-gene mutations, chromosomopathies, and exposure to teratogens. Part of the most prevalent syndromic CL/P has known etiology. Nonsyndromic CL/P, on the other hand, is a complex disorder, whose etiology is still poorly understood. Recent genome-wide association studies have contributed to the elucidation of the genetic causes, by raising reproducible susceptibility genetic variants; their etiopathogenic roles, however, are difficult to predict, as in the case of the chromosomal region 8q24, the most corroborated locus predisposing to nonsyndromic CL/P. Knowing the genetic causes of CL/P will directly impact the genetic counseling, by estimating precise recurrence risks, and the patient management, since the patient, followup may be partially influenced by their genetic background. This paper focuses on the genetic causes of important syndromic CL/P forms (van der Woude syndrome, 22q11 deletion syndrome, and Robin sequence-associated syndromes) and depicts the recent findings in nonsyndromic CL/P research, addressing issues in the conduct of the geneticist. PMID:23213504

  9. The Association of Perceived Provider-Patient Communication and Relationship Quality with Colorectal Cancer Screening

    ERIC Educational Resources Information Center

    Underhill, Meghan L.; Kiviniemi, Marc T.

    2012-01-01

    Background: Two-thirds of adults aged 50 years and older are adherent to recommendations for colorectal cancer screening. Provider-patient communication and characteristics of the patient-provider relationship may relate to screening behavior. Methods: The association of provider communication quality, relationship, and colorectal cancer screening…

  10. Patient and provider characteristics associated with colorectal, breast, and cervical cancer screening among Asian Americans

    PubMed Central

    Thompson, Caroline A.; Gomez, Scarlett Lin; Chan, Albert; Chan, John K.; McClellan, Sean R.; Chung, Sukyung; Olson, Cliff; Nimbal, Vani; Palaniappan, Latha P.

    2014-01-01

    BACKGROUND Routinely recommended screening for breast, cervical, and colorectal cancers can significantly reduce mortality from these types of cancer, yet screening is underutilized among Asians. Surveys rely on self-report and often are underpowered for analysis by Asian ethnicities. Electronic health records include validated (as opposed to recall-based) rates of cancer screening. In this paper we seek to better understand cancer screening patterns in a population of insured Asian Americans. METHODS We calculated rates of compliance with cervical, breast, and colorectal cancer screening among Asians from an EHR population, and compared them to non-Hispanic whites. We performed multivariable modeling to evaluate potential predictors (at the provider- and patient- level) of screening completion among Asian patients. RESULTS Aggregation of Asian subgroups masked heterogeneity in screening rates. Asian Indians and Native Hawaiians and Pacific Islanders had the lowest rates of screening in our sample, well below that of non-Hispanic whites. In multivariable analyses, screening completion was negatively associated with patient-physician language discordance for mammography (OR:0.81 95% CI:0.71–0.92) and colorectal cancer screening (OR:0.79 CI:0.72–0.87) and positively associated with patient-provider gender concordance for mammography (OR:1.16 CI:1.00–1.34) and cervical cancer screening (OR:1.66 CI:1.51–1.82). Additionally, patient enrollment in online health services increased mammography (OR:1.32 CI:1.20–1.46) and cervical cancer screening (OR:1.31 CI:1.24–1.37). CONCLUSIONS Language- and gender- concordant primary care providers, and culturally tailored online health resources may help improve preventive cancer screening in Asian patient populations. IMPACT This study demonstrates how use of EHR data can inform investigations of primary prevention practices within the healthcare delivery setting. PMID:25368396

  11. Patient and Provider Factors Associated With American Indian and Alaska Native Adolescent Tobacco Use Screening

    PubMed Central

    Hiratsuka, Vanessa Y.; Suchy-Dicey, Astrid M.; Garroutte, Eva M.; Booth-LaForce, Cathryn

    2015-01-01

    Introduction Tobacco use is the leading behavioral cause of death among adults 25 years or older. American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and of its sequelae. Primary care–based screening of adolescents is an integral step in the reduction of tobacco use, yet remains virtually unstudied. We examined whether delivery of tobacco screening in primary care visits is associated with patient and provider characteristics among AI/AN adolescents. Methods We used a cross-sectional analysis to examine tobacco screening among 4757 adolescent AI/AN patients served by 56 primary care providers at a large tribally managed health system between October 1, 2011 and May 31, 2014. Screening prevalence was examined in association with categorical patient characteristics (gender, age, clinic visited, insurance coverage) and provider characteristics (gender, age, tenure) using multilevel logistic regressions with individual provider identity as the nesting variable. Results Thirty-seven percent of eligible patients were screened. Gender of both providers and patients was associated with screening. Male providers delivered screening more often than female providers (odds ratio [OR] 1.6, 95% confidence interval [CI] 0.7–3.9). Male patients had 20% lower odds of screening receipt (OR 0.8, 95% CI 0.7–0.9) than female patients, independent of patient age and provider characteristics. Individual provider identity significantly contributed to variability in the mixed-effects model (variance component 2.2; 95% CI 1.4–3.4), suggesting individual provider effect. Conclusions Low tobacco screening delivery by female providers and the low receipt of screening among younger, male patients may identify targets for screening interventions. PMID:26319931

  12. Impact of the increased adoption of prenatal cfDNA screening on non-profit patient advocacy organizations in the United States.

    PubMed

    Meredith, Stephanie; Kaposy, Christopher; Miller, Victoria J; Allyse, Megan; Chandrasekharan, Subhashini; Michie, Marsha

    2016-08-01

    The 'Stakeholder Perspectives on Noninvasive Prenatal Genetic Screening' Symposium was held in conjunction with the 2015 annual meeting of the International Society for Prenatal Diagnosis. During the day-long meeting, a panel of patient advocacy group (PAG) representatives discussed concerns and challenges raised by prenatal cell-free DNA (cfDNA) screening, which has resulted in larger demands upon PAGs from concerned patients receiving prenatal cfDNA screening results. Prominent concerns included confusion about the accuracy of cfDNA screening and a lack of patient education resources about genetic conditions included in cfDNA screens. Some of the challenges faced by PAGs included funding limitations, lack of consistently implemented standards of care and oversight, diverse perspectives among PAGs and questions about neutrality, and lack of access to training and genetic counselors. PAG representatives also put forward suggestions for addressing these challenges, including improving educational and PAG funding and increasing collaboration between PAGs and the medical community. © 2016 John Wiley & Sons, Ltd. PMID:27244688

  13. Genetic Polymorphisms Influence Cognition in Patients Undergoing Carotid Interventions.

    PubMed

    Hitchner, Elizabeth; Morrison, Doug; Liao, Phoebe; Rosen, Allyson; Zhou, Wei

    2016-09-01

    While carotid interventions help decrease the risk of stroke, nearly 40% of patients experience cognitive deterioration. Genetic polymorphism in apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been implicated in cognitive impairment; however, it is unclear whether they may influence cognitive changes in patients undergoing carotid intervention. In this study, we seek to assess the role of genetic polymorphisms in carotid intervention-related cognitive change. Polymorphisms related to cognitive function were chosen for this preliminary analysis. Over 2 years, patients undergoing carotid interventions were prospectively recruited. Patients underwent neuropsychological testing 2 weeks prior to and at 1 month following their procedure. Saliva samples were collected for genetic analysis. Logistic regressions were used to identify associations between polymorphisms and cognitive measures. A total of 91 patients were included; all were male with an average age of 70 years. The majority of patients exhibited hypertension (95%) and a history of smoking (81%). Presence of ApoE 4 allele was associated with depression (p= 0.047). After correcting for age and genetic polymorphisms in BDNF and serotonin transporter (5-HTT), ApoE 4 allele was associated with depression (p= 0.044) and showed a trend with baseline cognitive impairment (p= 0.10). Age ≥ 70 years was associated with baseline cognitive impairment after adjusting for the three genetic polymorphisms (p= 0.03). Patients with ApoE 4 and BDNF A polymorphisms performed less well on the visual and verbal memory measures, respectively. Polymorphisms in ApoE and BDNF may provide insight on cognition in patients undergoing carotid interventions; however, the mechanism of this relationship remains unclear. PMID:27574384

  14. Cancer Worry, Perceived Risk and Cancer Screening in First-Degree Relatives of Patients with Familial Gastric Cancer.

    PubMed

    Li, Jenny; Hart, Tae L; Aronson, Melyssa; Crangle, Cassandra; Govindarajan, Anand

    2016-06-01

    Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants' high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping. PMID:26493173

  15. A group approach to genetic counselling of cardiomyopathy patients: satisfaction and psychological outcomes sufficient for further implementation.

    PubMed

    Otten, Ellen; Birnie, Erwin; Ranchor, Adelita V; van Tintelen, J Peter; van Langen, Irene M

    2015-11-01

    The introduction of next-generation sequencing in everyday clinical genetics practise is increasing the number of genetic disorders that can be confirmed at DNA-level, and consequently increases the possibilities for cascade screening. This leads to a greater need for genetic counselling, whereas the number of professionals available to provide this is limited. We therefore piloted group genetic counselling for symptomatic cardiomyopathy patients at regional hospitals, to assess whether this could be an acceptable alternative to individual counselling. We performed a cohort study with pre- and post-counselling patient measurements using questionnaires, supplemented with evaluations of the group counselling format by the professionals involved. Patients from eight regional hospitals in the northern part of the Netherlands were included. Questionnaires comprised patient characteristics, psychological measures (personal perceived control (PPC), state and trait anxiety inventory (STAI)), and satisfaction with counsellors, counselling content and design. In total, 82 patients (mean age 57.5 year) attended one of 13 group sessions. Median PPC and STAI scores showed significantly higher control and lower anxiety after the counselling. Patients reported they were satisfied with the counsellors, and almost 75% of patients were satisfied with the group counselling. Regional professionals were also, overall, satisfied with the group sessions. The genetics professionals were less satisfied, mainly because of their perceived large time investment and less-than-expected group interaction. Hence, a group approach to cardiogenetic counselling is feasible, accessible, and psychologically effective, and could be one possible approach to counselling the increasing patient numbers in cardiogenetics. PMID:25649380

  16. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  17. Multiplex screening for RB1 germline mutations in 106 patients with hereditary retinoblastoma

    SciTech Connect

    Lohmann, D.R.; Brandt, B.; Passarge, E.

    1994-09-01

    The identification of germline mutations in the retinoblastoma susceptibility gene (RB1) is important for genetic counseling in hereditary retinoblastoma. Due to the complex genomic organization of this gene and the heterogeneity of mutations, efficient screening procedures are important for rapid mutation detection. We have developed methods based on simultaneous analysis of multiple regions of this gene in an ABI automated DNA fragment analyzer to examine 106 patients with hereditary retinoblastoma in which no alteration was identified by Southern blot hybridization. Primers for the amplification of all 27 exons of the RB1 gene as well as the promoter and poly(A) signal sequences were labelled with distinct fluorescent dyes (FAM, HEX, TAMRA) to enable simultaneous electrophoretic analysis of PCR products with similar mobility. PCR fragments distinguishable by size or color were co-amplified by multiplex PCR and analyzed for length by GENESCAN analysis. Using this approach, small deletions ranging from 1 bp to 22 bp were identified in 24 patients (23%). Short sequence repeats or polypyrimidine runs were present in the vicinity of most of these deletions. In 4 patients (4%), insertions from 1 bp to 4 bp were found. The majority of length mutations resulted in a truncated gene product due to frameshift and premature termination. No mutation was identified in exons 25 to 27 possibly indicating that the encoded protein domains have minor functional importance. In order to screen for base substitutions that are not detectable by fragment length analysis, we adapted heteroduplex analysis for the use in the DNA fragment analyzer. During the optimization of this method we detected 10 single base substitutions most of which generated stop codons. Intriguingly, two identical missense mutations were identified in two unrelated families with a low-penetrance phenotype.

  18. Validation of screening tools to assess appetite among geriatric patients.

    PubMed

    Hanisah, R; Suzana, S; Lee, F S

    2012-07-01

    Poor appetite is one of the main contributing factors of poor nutritional status among elderly individuals. Recognizing the importance of assessment of appetite, a cross sectional study was conducted to determine the validity of appetite screening tools namely, the Council on Nutrition Appetite questionnaire (CNAQ) and the simplified nutritional appetite questionnaire (SNAQ) against the appetite, hunger and sensory perception questionnaire (AHSPQ), measures of nutritional status and food intake among geriatric patients at the main general hospital in Malaysia. Nutritional status was assessed using the subjective global assessment (SGA) while food intake was measured using the dietary history questionnaire (DHQ). Anthropometric parameters included weight, height, body mass index (BMI), calf circumference (CC) and mid upper arm circumference (MUAC). A total of 145 subjects aged 60 to 86 years (68.3 ± 5.8 years) with 31.7% men and 68.3% women were recruited from outpatients (35 subjects) and inpatients (110 subjects) of Kuala Lumpur Hospital of Malaysia. As assessed by SGA, most subjects were classified as mild to moderately malnourished (50.4%), followed by normal (38.6%) and severely malnourished (11.0%). A total of 79.3% and 57.2% subjects were classified as having poor appetite according to CNAQ and SNAQ, respectively. CNAQ (80.9%) had a higher sensitivity than SNAQ (69.7%) when validated against nutritional status as assessed using SGA. However, the specificity of SNAQ (62.5%) was higher than CNAQ (23.2%). Positive predictive value for CNAQ and SNAQ were 62.6% and 74.7%, respectively. Cronbach's alpha for CNAQ and SNAQ were 0.546 and 0.578, respectively. History of weight loss over the past one year (Adjusted odds ratio 2.49) (p < 0.01) and thiamine intake less than the recommended nutrient intake (RNI) (Adjusted odds ratio 3.04) (p < 0.05) were risk factors for poor appetite among subjects. In conclusion, malnutrition and poor appetite were prevalent among the

  19. A Bacteriophage Lambda-Based Genetic Screen for Characterization of the Activity and Phenotype of the Human Immunodeficiency Virus Type 1 Protease

    PubMed Central

    Martínez, Miguel-Angel; Cabana, Marta; Parera, Mariona; Gutierrez, Arantxa; Esté, José A.; Clotet, Bonaventura

    2000-01-01

    Human immunodeficiency virus type 1 (HIV-1) resistance to antiretroviral drugs is the main cause of patient treatment failure. Despite the problems associated with interpretation of HIV-1 resistance testing, resistance monitoring should help in the rational design of initial or rescue antiretroviral therapies. It has previously been shown that the activity of the HIV-1 protease can be monitored by using a bacteriophage lambda-based genetic assay. This genetic screening system is based on the bacteriophage lambda regulatory circuit in which the viral repressor cI is specifically cleaved to initiate the lysogenic to lytic switch. We have adapted this simple lambda-based genetic assay for the analysis of the activities and phenotypes of different HIV-1 proteases. Lambda phages that encode HIV-1 proteases either from laboratory strains (strain HXB2) or from clinical samples are inhibited in a dose-dependent manner by the HIV-1 protease inhibitors indinavir, ritonavir, saquinavir, and nelfinavir. Distinct susceptibilities to different drugs were also detected among phages that encode HIV-1 proteases carrying different resistance mutations, further demonstrating the specificity of this assay. Differences in proteolytic processing activity can also be directly monitored with this genetic screen system since two phage populations compete in culture with each other until one phage outgrows the other. In summary, we present here a simple, safe, and rapid genetic screening system that may be used to predict the activities and phenotypes of HIV-1 proteases in the course of viral infection and antiretroviral therapy. This assay responds appropriately to well-known HIV-1 protease inhibitors and can be used to search for new protease inhibitors. PMID:10770741

  20. Designer babies on tap? Medical students' attitudes to pre-implantation genetic screening.

    PubMed

    Meisenberg, Gerhard

    2009-03-01

    This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition. PMID:19579681

  1. A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States.

    PubMed

    Chiu, Cindy N; Rihel, Jason; Lee, Daniel A; Singh, Chanpreet; Mosser, Eric A; Chen, Shijia; Sapin, Viveca; Pham, Uyen; Engle, Jae; Niles, Brett J; Montz, Christin J; Chakravarthy, Sridhara; Zimmerman, Steven; Salehi-Ashtiani, Kourosh; Vidal, Marc; Schier, Alexander F; Prober, David A

    2016-02-17

    Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway. PMID:26889812

  2. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues. Progress report

    SciTech Connect

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S.; Crandall, L.A.; Moseley, R.E.; Armotrading, D.

    1993-03-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia`s system of Children`s Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  3. ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent.

    PubMed

    2009-10-01

    Certain autosomal recessive disease conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American College of Obstetricians and Gynecologists recommended that individuals of Eastern European Jewish ancestry be offered carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to justify offering carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists' Committee on Genetics recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease. PMID:19888064

  4. Genetic testing of leiomyoma tissue in women younger than 30 years old might provide an effective screening approach for the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC).

    PubMed

    Martínek, Petr; Grossmann, Petr; Hes, Ondřej; Bouda, Jiří; Eret, Viktor; Frizzell, Norma; Gill, Anthony J; Ondič, Ondrej

    2015-08-01

    We have studied the viability of targeted molecular screening for the identification of female patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Affected patients harbor a germ-line heterozygous mutation of the fumarate hydratase (FH) gene. Clinically, some patients present with aggressive renal cell carcinoma. Concerning women, in almost all cases, this is preceded by symptomatic uterine leiomyoma. We aimed to identify women operated on for symptomatic leiomyoma by the age of 30. Archived paraffin-embedded leiomyoma tissue was tested for the FH gene mutation in 14 cases. Two patients with multiple leiomyomas and with the confirmed germ-line mutations c.1433_1434dupAAA, p.(Lys477dup) and c.953A>T, p.(His318Leu) were identified and enrolled in a surveillance program. Statistically significant correlation between the presence of multiple uterine leiomyomas (more than seven in our experience) and the FH gene mutation was found. The immunohistochemical expression pattern, of simultaneous FH absence and S-(2-succino)cysteine (2SC) positivity, correlated with the results of the molecular genetic study in only one case. The histomorphologically simultaneous detection of enlarged nucleoli with a clear halo of leiomyocyte nuclei, their fibrillary cytoplasm, the presence of eosinophilic globules, and staghorn vessels proved to be only a partially sensitive indicator of HLRCC-associated leiomyoma and fully correlated with immunohistochemistry and molecular genetic study only in one case. Molecular genetic testing is presently the only reliable diagnostic tool able to identify HLRCC patients. The sensitivity and specificity of the presence of multiple leiomyomas in women with the FH gene mutation who are younger than 30 years old should be confirmed in larger scale studies. The applied targeted molecular screening protocol proved to be effective, resulting in identification of two positive patients out of fourteen tested individuals. PMID:25985877

  5. Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing.

    PubMed

    Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H

    2016-03-01

    Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. Birth Defects Research (Part C) 108:98-102, 2016. © 2015 Wiley Periodicals, Inc. PMID:26598285

  6. Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity

    PubMed Central

    Brough, Rachel; Hodny, Zdenek; Ashworth, Alan; Bartek, Jiri; Lord, Christopher J.

    2015-01-01

    Based on a series of basic, preclinical and clinical studies, the Poly (ADP-ribose) Polymerase 1 (PARP1) inhibitor, olaparib, has recently been approved for use in ovarian cancer patients with BRCA1 or BRCA2 mutations. By identifying novel predictive biomarkers of tumour cell sensitivity to olaparib, it is possible that the utility of PARP inhibitors could be extended beyond this patient subgroup. Many of the known genetic determinants of PARP inhibitor response have key roles in DNA damage response (DDR) pathways. Although protein ubiquitylation is known to play an important role in regulating the DDR, the exact mechanisms by which this occurs are not fully understood. Using two parallel RNA interference-based screening approaches, we identified the E3 ubiquitin ligase, CBLC, as a candidate biomarker of response to olaparib. We validated this observation by demonstrating that silencing of CBLC causes increased sensitivity to olaparib in breast cancer cell line models and that defective homologous recombination (HR) DNA repair is the likely cause. This data provides an example of how defects in the ubiquitin machinery have the potential to influence the response of tumour cells to PARP inhibitors. PMID:25883215

  7. Screening for mutations in rhodopsin and peripherin/RDS in patients with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Rodriguez, J.A.; Gannon, A.M.; Daiger, S.P.

    1994-09-01

    Mutations in rhodopsin account for approximately 30% of all cases of autosomal dominant retinits pigmentosa (adRP) and mutations in peripherin/RDS account for an additional 5% of cases. Also, mutations in rhodopsin can cause autosomal recessive retinitis pigmentosa and mutations in peripherin/RDS can cause dominant macular degeneration. Most disease-causing mutations in rhodopsin and peripherin/RDS are unique to one family or, at most, to a few families within a limited geographic region, though a few mutations are found in multiple, unrelated families. To further determine the spectrum of genetic variation in these genes, we screened DNA samples from 134 unrelated patients with retinitis pigmentosa for mutations in both rhodopsin and peripherin/RDS using SSCP followed by genomic sequencing. Of the 134 patients, 86 were from families with apparent adRP and 48 were either isolated cases or were from families with an equivocal mode of inheritance. Among these patients we found 14 distinct rhodopsin mutations which are likely to cause retinal disease. Eleven of these mutations were found in one individual or one family only, whereas the Pro23His mutation was found in 14 {open_quotes}unrelated{close_quotes}individuals. The splice-site mutation produces dominant disease though with highly variable expression. Among the remaining patients were found 6 distinct peripherin/RDS mutations which are likely to cause retinal disease. These mutations were also found in one patient or family only, except the Gly266Asp mutation which was found in two unrelated patients. These results confirm the expected frequency and broad spectrum of mutations causing adRP.

  8. Resected Lung Cancer Patients Who Would and Would Not Have Met Screening Criteria

    PubMed Central

    Farjah, Farhood; Wood, Douglas E.; Zadworny, Megan E.; Rusch, Valerie W.; Rizk, Nabil P.

    2016-01-01

    Background Current eligibility criteria for lung cancer screening may underestimate the risk of malignancy for some individuals. We compared the predicted risk of lung cancer among patients who would have met screening criteria to those who would not have despite being at moderate-risk. Methods A retrospective cohort study was performed of resected lung cancer patients. The screen eligible group was based on criteria provided by the United States Preventive Services Task Force—age 55–80 and a ≥30 pack-year smoking history. The screen ineligible group was based on criteria provided by the National Comprehensive Cancer Network for a moderate-risk individual not recommended screening—age >50 years, >20 pack-year smoking history, and no history of asbestos exposure or chronic obstructive pulmonary disease. A recently validated risk-prediction model was used to compare the risk of lung cancer across eligibility groups based on measured and imputed patient-level variables. Results Screen ineligible patients (n=88) had a lower estimated probability of lung cancer than screen eligible patients (n=419)—1.3% versus 3.1%, p<0.001. However, 20% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the prevalence of lung cancer (3.7%) among National Lung Screening Trial participants; 17% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the American Association for Thoracic Surgery threshold (5%) defining high-risk individuals. Conclusions Current eligibility criteria for lung cancer screening underestimate the risk of lung cancer for some individuals who might benefit from lung cancer screening. PMID:26298169

  9. A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

    PubMed Central

    Heijink, Anne Margriet; Blomen, Vincent A.; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Foijer, Floris; van Vugt, Marcel A. T. M.

    2015-01-01

    The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability. PMID:26598692

  10. Serological Screening for Celiac Disease in Adult Chinese Patients With Diarrhea Predominant Irritable Bowel Syndrome.

    PubMed

    Wang, Hongling; Zhou, Guoying; Luo, Linjie; Crusius, J Bart A; Yuan, Anlong; Kou, Jiguang; Yang, Guifang; Wang, Min; Wu, Jing; von Blomberg, B Mary E; Morré, Servaas A; Peña, A Salvador; Xia, Bing

    2015-10-01

    Celiac disease (CD) is common in Caucasians, but thought to be rare in Asians. Our aim was to determine the prevalence of CD in Chinese patients with chronic diarrhea predominant irritable bowel syndrome (IBS-D).From July 2010 to August 2012, 395 adult patients with IBS-D and 363 age and sex-matched healthy controls were recruited in Zhongnan Hospital of Wuhan University and Xiaogan Central Hospital in Hubei province, central China. Patients with IBS-D were diagnosed according to the Rome III criteria. Serum Immunoglobulin (IgA/IgG) anti-human tissue transglutaminase (anti-htTG)-deamidated gliadin peptide (DGP) antibodies were measured in a single ELISA (QUANTA Lite h-tTG/DGP Screen). Upper endoscopy with duodenal biopsies and HLA-DQA1 and HLA-DQB1 genotyping were performed in seropositive subjects and a gluten-free diet was prescribed.Seven IBS-D patients (7/395, 1.77%) and 2 healthy controls (2/363, 0.55%), were positive for anti-htTG/DGP antibodies. Of these 9 cases, 1 was lost to follow-up, 3 were suspected to have CD and 5 were eventually diagnosed as CD with intestinal histological lesions classified as Marsh Type II in 2 and Type III in 3. Of these 5 diagnosed CD patients, 4 (4/395, 1.01%) were from the IBS-D group and 1 (1/363, 0.28%) from the healthy control had asymptomatic CD. Two Type III CD patients with relatively high titers in the serologic assay were homozygous and heterozygous for haplotype HLA-DQA1*03-DQB1*03:03 (HLA-DQ9.3), respectively.In the present study, CD was present in 1.01% of patients with IBS-D and in 0.28% of the control group. We like to suggest that the haplotype HLA-DQA1*03-DQB1*03:03 (HLA-DQ9.3), which is common in Chinese, is a new susceptibility factor for CD in China. Larger screening and genetic studies are needed in the Chinese population of different regions. PMID:26496305

  11. Serological Screening for Celiac Disease in Adult Chinese Patients With Diarrhea Predominant Irritable Bowel Syndrome

    PubMed Central

    Wang, Hongling; Zhou, Guoying; Luo, Linjie; Crusius, J. Bart A.; Yuan, Anlong; Kou, Jiguang; Yang, Guifang; Wang, Min; Wu, Jing; von Blomberg, B. Mary E.; Morré, Servaas A.; Peña, A. Salvador; Xia, Bing

    2015-01-01

    Abstract Celiac disease (CD) is common in Caucasians, but thought to be rare in Asians. Our aim was to determine the prevalence of CD in Chinese patients with chronic diarrhea predominant irritable bowel syndrome (IBS-D). From July 2010 to August 2012, 395 adult patients with IBS-D and 363 age and sex-matched healthy controls were recruited in Zhongnan Hospital of Wuhan University and Xiaogan Central Hospital in Hubei province, central China. Patients with IBS-D were diagnosed according to the Rome III criteria. Serum Immunoglobulin (IgA/IgG) anti-human tissue transglutaminase (anti-htTG)-deamidated gliadin peptide (DGP) antibodies were measured in a single ELISA (QUANTA Lite h-tTG/DGP Screen). Upper endoscopy with duodenal biopsies and HLA-DQA1 and HLA-DQB1 genotyping were performed in seropositive subjects and a gluten-free diet was prescribed. Seven IBS-D patients (7/395, 1.77%) and 2 healthy controls (2/363, 0.55%), were positive for anti-htTG/DGP antibodies. Of these 9 cases, 1 was lost to follow-up, 3 were suspected to have CD and 5 were eventually diagnosed as CD with intestinal histological lesions classified as Marsh Type II in 2 and Type III in 3. Of these 5 diagnosed CD patients, 4 (4/395, 1.01%) were from the IBS-D group and 1 (1/363, 0.28%) from the healthy control had asymptomatic CD. Two Type III CD patients with relatively high titers in the serologic assay were homozygous and heterozygous for haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), respectively. In the present study, CD was present in 1.01% of patients with IBS-D and in 0.28% of the control group. We like to suggest that the haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), which is common in Chinese, is a new susceptibility factor for CD in China. Larger screening and genetic studies are needed in the Chinese population of different regions. PMID:26496305

  12. Preimplantation genetic screening- the required RCT that has not yet been carried out.

    PubMed

    Orvieto, Raoul

    2016-01-01

    The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. The ongoing discussion on the unrestricted clinical adoption of preimplantation genetic screening (PGS) has called for a proper randomized controlled trial (RCT), aiming to further evaluate the cumulative live birth rates (LBRs) following a single oocyte retrieval, utilizing all fresh and frozen embryos. Since this study seems not to appear for various reasons, we present herewith, the hypothetical required RCT based on the hitherto published literature.After implementing data from the hitherto published literature on blastulation and aneuploidy rates, the rate of mosaicism and technical errors and implantation rates/LBRs of non-PGS day-3 and blastocyst and PGS blastocyst, we could clearly demonstrate the superiority of non-PGS embryo (day-3 and blastocyst) transfer over PGS blastocyst transfer, in terms of cumulative LBR (18.2-50 % vs 7.6-12.6 %, respectively).We therefore believe that until the proper, non-hypothetical RCT on the efficacy of this procedure will appear, PGS should be offered only under study conditions, and with appropriate informed consents. PMID:27342051

  13. A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

    PubMed

    Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

    2015-09-01

    Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. PMID:26031293

  14. Cumulative genetic risk and prefrontal activity in patients with schizophrenia.

    PubMed

    Walton, Esther; Turner, Jessica; Gollub, Randy L; Manoach, Dara S; Yendiki, Anastasia; Ho, Beng-Choon; Sponheim, Scott R; Calhoun, Vince D; Ehrlich, Stefan

    2013-05-01

    The lack of consistency of genetic associations in highly heritable mental illnesses, such as schizophrenia, remains a challenge in molecular psychiatry. Because clinical phenotypes for psychiatric disorders are often ill defined, considerable effort has been made to relate genetic polymorphisms to underlying physiological aspects of schizophrenia (so called intermediate phenotypes), that may be more reliable. Given the polygenic etiology of schizophrenia, the aim of this work was to form a measure of cumulative genetic risk and study its effect on neural activity during working memory (WM) using functional magnetic resonance imaging. Neural activity during the Sternberg Item Recognition Paradigm was measured in 79 schizophrenia patients and 99 healthy controls. Participants were genotyped, and a genetic risk score (GRS), which combined the additive effects of 41 single-nucleotide polymorphisms (SNPs) from 34 risk genes for schizophrenia, was calculated. These risk SNPs were chosen according to the continuously updated meta-analysis of genetic studies on schizophrenia available at www.schizophreniaresearchforum.org. We found a positive relationship between GRS and left dorsolateral prefrontal cortex inefficiency during WM processing. GRS was not correlated with age, performance, intelligence, or medication effects and did not differ between acquisition sites, gender, or diagnostic groups. Our study suggests that cumulative genetic risk, combining the impact of many genes with small effects, is associated with a known brain-based intermediate phenotype for schizophrenia. The GRS approach could provide an advantage over studying single genes in studies focusing on the genetic basis of polygenic conditions such as neuropsychiatric disorders. PMID:22267534

  15. A bacteria colony-based screen for optimal linker combinations in genetically encoded biosensors

    PubMed Central

    2011-01-01

    Background Fluorescent protein (FP)-based biosensors based on the principle of intramolecular Förster resonance energy transfer (FRET) enable the visualization of a variety of biochemical events in living cells. The construction of these biosensors requires the genetic insertion of a judiciously chosen molecular recognition element between two distinct hues of FP. When the molecular recognition element interacts with the analyte of interest and undergoes a conformational change, the ratiometric emission of the construct is altered due to a change in the FRET efficiency. The sensitivity of such biosensors is proportional to the change in ratiometric emission, and so there is a pressing need for methods to maximize the ratiometric change of existing biosensor constructs in order to increase the breadth of their utility. Results To accelerate the development and optimization of improved FRET-based biosensors, we have developed a method for function-based high-throughput screening of biosensor variants in colonies of Escherichia coli. We have demonstrated this technology by undertaking the optimization of a biosensor for detection of methylation of lysine 27 of histone H3 (H3K27). This effort involved the construction and screening of 3 distinct libraries: a domain library that included several engineered binding domains isolated by phage-display; a lower-resolution linker library; and a higher-resolution linker library. Conclusion Application of this library screening methodology led to the identification of an optimized H3K27-trimethylation biosensor that exhibited an emission ratio change (66%) that was 2.3 × improved relative to that of the initially constructed biosensor (29%). PMID:22074568

  16. Genetic Screening of LCA in Belgium: Predominance of CEP290 and Identification of Potential Modifier Alleles in AHI1 of CEP290-related Phenotypes

    PubMed Central

    Coppieters, Frauke; Casteels, Ingele; Meire, Françoise; De Jaegere, Sarah; Hooghe, Sally; van Regemorter, Nicole; Van Esch, Hilde; Matulevičienė, Aušra; Nunes, Luis; Meersschaut, Valérie; Walraedt, Sophie; Standaert, Lieve; Coucke, Paul; Hoeben, Heidi; Kroes, Hester Y; Vande Walle, Johan; de Ravel, Thomy; Leroy, Bart P; De Baere, Elfride

    2010-01-01

    Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease. © 2010 Wiley-Liss, Inc. PMID:20683928

  17. Clinical Genetic Testing for Patients With Autism Spectrum Disorders

    PubMed Central

    Shen, Yiping; Dies, Kira A.; Holm, Ingrid A.; Bridgemohan, Carolyn; Sobeih, Magdi M.; Caronna, Elizabeth B.; Miller, Karen J.; Frazier, Jean A.; Silverstein, Iris; Picker, Jonathan; Weissman, Laura; Raffalli, Peter; Jeste, Shafali; Demmer, Laurie A.; Peters, Heather K.; Brewster, Stephanie J.; Kowalczyk, Sara J.; Rosen-Sheidley, Beth; McGowan, Caroline; Duda, Andrew W.; Lincoln, Sharyn A.; Lowe, Kathryn R.; Schonwald, Alison; Robbins, Michael; Hisama, Fuki; Wolff, Robert; Becker, Ronald; Nasir, Ramzi; Urion, David K.; Milunsky, Jeff M.; Rappaport, Leonard; Gusella, James F.; Walsh, Christopher A.; Wu, Bai-Lin; Miller, David T.

    2014-01-01

    BACKGROUND Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%–2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%–0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%–21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%–8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changesin7.3%(51 of 697) and 5.3%(8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance

  18. Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.

    PubMed

    Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Pariente, Jérémie; Brice, Alexis; Kabashi, Edor

    2013-08-01

    The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. PMID:23582661

  19. RAGE Genetic Polymorphisms Are Associated with Risk, Chemotherapy Response and Prognosis in Patients with Advanced NSCLC

    PubMed Central

    Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren

    2012-01-01

    Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, −429T/C, −374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC. PMID:23071492

  20. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans

    PubMed Central

    Li, Shiwei; Xu, Shibin; Ma, Yanli; Wu, Shuang; Feng, Yu; Cui, Qingpo; Chen, Lifeng; Zhou, Shuang; Kong, Yuanyuan; Zhang, Xiaoyu; Yu, Jialei; Wu, Mengdi; Zhang, Shaobing O.

    2016-01-01

    To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 105 mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion. PMID:27261001

  1. Strategy for the customized mass screening of genetic sensorineural hearing loss in koreans.

    PubMed

    Chang, Mun Young; Choi, Byung Yoon

    2014-09-01

    Hearing loss is one of the most common sensorineural disorder. More than half of congenital bilateral profound deafness cases have been estimated to be attributed to genetic cause. Identification of genetic cause can provide valuable information. We developed new diagnostic strategy combining phenotype-driven candidate gene approach and targeted exome sequencing to find out the causative mutation of hearing loss. The causative mutation detection rates of this strategy were 78.1% and 54.8% in Korean multiplex families and sporadic severe to profound hearing loss families, respectively. The most frequent causative genes of Korean multiplex families were SLC26A4 and POU3F4. The other causative genes were MRNR1, WFS1, COCH, TECTA, MYO6, COL11A2, EYA4, GJB3, OTOF, STRC, MYO3A, and GJB2. The most frequent causative gene of Korean sporadic severe to profound hearing loss families was SLC26A4 followed by GJB2, CHD7, and CDH23. Based upon the results, the value of this strategy as a diagnostic tool seems to be promising. Although whole genome and exome sequencing have advanced as the development of next-generation sequencing, this new strategy could be a good screening and diagnostic tool to find the causative mutations. PMID:25279224

  2. Strategy for the Customized Mass Screening of Genetic Sensorineural Hearing Loss in Koreans

    PubMed Central

    Chang, Mun Young

    2014-01-01

    Hearing loss is one of the most common sensorineural disorder. More than half of congenital bilateral profound deafness cases have been estimated to be attributed to genetic cause. Identification of genetic cause can provide valuable information. We developed new diagnostic strategy combining phenotype-driven candidate gene approach and targeted exome sequencing to find out the causative mutation of hearing loss. The causative mutation detection rates of this strategy were 78.1% and 54.8% in Korean multiplex families and sporadic severe to profound hearing loss families, respectively. The most frequent causative genes of Korean multiplex families were SLC26A4 and POU3F4. The other causative genes were MRNR1, WFS1, COCH, TECTA, MYO6, COL11A2, EYA4, GJB3, OTOF, STRC, MYO3A, and GJB2. The most frequent causative gene of Korean sporadic severe to profound hearing loss families was SLC26A4 followed by GJB2, CHD7, and CDH23. Based upon the results, the value of this strategy as a diagnostic tool seems to be promising. Although whole genome and exome sequencing have advanced as the development of next-generation sequencing, this new strategy could be a good screening and diagnostic tool to find the causative mutations. PMID:25279224

  3. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans.

    PubMed

    Li, Shiwei; Xu, Shibin; Ma, Yanli; Wu, Shuang; Feng, Yu; Cui, Qingpo; Chen, Lifeng; Zhou, Shuang; Kong, Yuanyuan; Zhang, Xiaoyu; Yu, Jialei; Wu, Mengdi; Zhang, Shaobing O

    2016-01-01

    To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 10(5) mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion. PMID:27261001

  4. Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion

    PubMed Central

    Kleinfelter, Lara M.; Jangra, Rohit K.; Jae, Lucas T.; Herbert, Andrew S.; Mittler, Eva; Stiles, Katie M.; Wirchnianski, Ariel S.; Kielian, Margaret; Brummelkamp, Thijn R.

    2015-01-01

    ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the New World. No vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. We performed a haploid genetic screen in human cells to identify host factors required for entry by Andes virus, a highly virulent New World hantavirus. We found that multiple genes involved in cholesterol sensing, regulation, and biosynthesis, including key components of the sterol response element-binding protein (SREBP) pathway, are critical for Andes virus entry. Genetic or pharmacological disruption of the membrane-bound transcription factor peptidase/site-1 protease (MBTPS1/S1P), an SREBP control element, dramatically reduced infection by virulent hantaviruses of both the Old World and New World clades but not by rhabdoviruses or alphaviruses, indicating that this pathway is broadly, but selectively, required by hantaviruses. These results could be fully explained as arising from the modest depletion of cellular membrane cholesterol that accompanied S1P disruption. Mechanistic studies of cells and with protein-free liposomes suggested that high levels of cholesterol are specifically needed for hantavirus membrane fusion. Taken together, our results indicate that the profound dependence on target membrane cholesterol is a fundamental, and unusual, biophysical property of hantavirus glycoprotein-membrane interactions during entry. PMID:26126854

  5. A genetic screen identifies genes essential for development of myelinated axons in zebrafish.

    PubMed

    Pogoda, Hans-Martin; Sternheim, Nitzan; Lyons, David A; Diamond, Brianne; Hawkins, Thomas A; Woods, Ian G; Bhatt, Dimple H; Franzini-Armstrong, Clara; Dominguez, Claudia; Arana, Naomi; Jacobs, Jennifer; Nix, Rebecca; Fetcho, Joseph R; Talbot, William S

    2006-10-01

    The myelin sheath insulates axons in the vertebrate nervous system, allowing rapid propagation of action potentials via saltatory conduction. Specialized glial cells, termed Schwann cells in the PNS and oligodendrocytes in the CNS, wrap axons to form myelin, a compacted, multilayered sheath comprising specific proteins and lipids. Disruption of myelinated axons causes human diseases, including multiple sclerosis and Charcot-Marie-Tooth peripheral neuropathies. Despite the progress in identifying human disease genes and other mutations disrupting glial development and myelination, many important unanswered questions remain about the mechanisms that coordinate the development of myelinated axons. To address these questions, we began a genetic dissection of myelination in zebrafish. Here we report a genetic screen that identified 13 mutations, which define 10 genes, disrupting the development of myelinated axons. We present the initial characterization of seven of these mutations, defining six different genes, along with additional characterization of mutations that we have described previously. The different mutations affect the PNS, the CNS, or both, and phenotypic analyses indicate that the genes affect a wide range of steps in glial development, from fate specification through terminal differentiation. The analysis of these mutations will advance our understanding of myelination, and the mutants will serve as models of human diseases of myelin. PMID:16875686

  6. Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis

    PubMed Central

    MA, DINGYUAN; ZHANG, JINGJING; LUO, CHUNYU; LIN, YING; JI, XIUQING; HU, PING; XU, ZHENGFENG

    2016-01-01

    The aim of the present study was to investigate the genetic etiology of patients with nonsyndromic hearing impairment through gene analysis, and provide accurate genetic counseling and prenatal diagnosis for deaf patients and families with deaf children. Previous molecular etiological studies have demonstrated that the most common molecular changes in Chinese patients with nonsyndromic hearing loss (NSHL) involved gap junction protein β 2, solute carrier family 26, member 4 (SLC26A4), and mitochondrial DNA 12S rRNA. A total of 117 unrelated NSHL patients were included. Mutation screening was performed by Sanger sequencing in GJB2, 12S rRNA, and the hot-spot regions of SLC26A4. In addition, patients with a single mutation of SLC26A4 in the hot-spot regions underwent complete exon sequencing to identify a mutation in the other allele. A total of 36 of the 117 deaf patients were confirmed to have two pathogenic mutations, which included 4 deaf couples, husband or wife in 11 deaf couples and 17 deaf individuals. In addition, prenatal diagnoses was performed in 7 pregnant women at 18–21 weeks gestation who had previously given birth to a deaf child, and the results showed that two fetal genotypes were the same as the proband's genotypes, four fetuses carried one pathogenic gene from their parents, and one fetus was identified to have no mutations. Taken together, the genetic testing of deaf patients can provide reasonable guidance to deaf patients and families with deaf children. PMID:26783197

  7. Impact of gene patents and licensing practices on access to genetic testing and carrier screening for Tay-Sachs and Canavan disease.

    PubMed

    Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2010-04-01

    Genetic testing for Tay-Sachs and Canavan disease is particularly important for Ashkenazi Jews, because both conditions are more frequent in that population. This comparative case study was possible because of different patenting and licensing practices. The role of DNA testing differs between Tay-Sachs and Canavan diseases. The first-line screening test for Tay-Sachs remains an enzyme activity test rather than genotyping. Genotyping is used for preimplantation diagnosis and confirmatory testing. In contrast, DNA-based testing is the basis for Canavan screening and diagnosis. The HEXA gene for Tay-Sachs was cloned at the National Institutes of Health, and the gene was patented but has not been licensed. The ASPA gene for Canavan disease was cloned and patented by Miami Children's Hospital. Miami Children's Hospital did not inform family members and patient groups that had contributed to the gene discovery that it was applying for a patent, and pursued restrictive licensing practices when a patent issued in 1997. This led to intense controversy, litigation, and a sealed, nonpublic 2003 settlement that apparently allowed for nonexclusive licensing. A survey of laboratories revealed a possible price premium for ASPA testing, with per-unit costs higher than for other genetic tests in the Secretary's Advisory Committee on Genetics, Health, and Society case studies. The main conclusion from comparing genetic testing for Tay-Sachs and Canavan diseases, however, is that patenting and licensing conducted without communication with patients and advocates cause mistrust and can lead to controversy and litigation, a negative model to contrast with the positive model of patenting and licensing for genetic testing of cystic fibrosis. PMID:20393311

  8. Use of the Photoactic Ability of a Bacterium to Teach the Genetic Principles of Random Mutagenesis & Mutant Screening

    ERIC Educational Resources Information Center

    Din, Neena; Bird, Terry H.; Berleman, James E.

    2007-01-01

    In this article, the authors present a laboratory activity that relies on the use of a very versatile bacterial system to introduce the concept of how mutagenesis can be used for molecular and genetic analysis of living organisms. They have used the techniques of random mutagenesis and selection/screening to obtain strains of the organism "R.…

  9. Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes

    PubMed Central

    Machado-Neto, João Agostinho; Traina, Fabiola; Lazarini, Mariana; de Melo Campos, Paula; Pagnano, Katia Borgia Barbosa; Lorand-Metze, Irene; Costa, Fernando Ferreira; Olalla Saad, Sara T

    2011-01-01

    INTRODUCTION: Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia. OBJECTIVE: To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients. METHODS: Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression. RESULTS: In the genes studied, no mutations were detected in the patients at the time of diagnosis. One patient with chronic myelomonocytic leukemia was heterozygous for a Janus kinase 2 mutation after disease progression. CONCLUSIONS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression. PMID:21789382

  10. Serum Globotriaosylceramide Assay as a Screening Test for Fabry Disease in Patients with ESRD on Maintenance Dialysis in Korea

    PubMed Central

    Kim, Jeong-Yup; Hyun, Young-Youl; Lee, Ji-Eun; Yoon, Hye-Ran; Kim, Gu-Hwan; Yoo, Han-Wook; Cho, Seong-Tae; Chun, No-Won; Jeoung, Byoung-Chunn; Kim, Hwa-Jung; Kim, Keong-Wook; Kim, Seong-Nam; Kim, Yung-A; Lee, Hyun-Ah; Lee, Jong-Young; Lee, Yung-Chun; Lim, Hun-Kwan; Oh, Keong-Sik; Son, Seong-Hwan; Yu, Beong-Hee; Wee, Kyeong-So; Lee, Eun-Jong; Lee, Young-Ki; Noh, Jung-Woo; Kim, Seung-Jung; Choi, Kyu-Bok; Yu, Suk-Hee; Pyo, Heui-Jung

    2010-01-01

    Background/Aims Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. Methods A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. Results Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. Conclusions Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease. PMID:21179280

  11. Screening of Duchenne Muscular Dystrophy (DMD) Mutations and Investigating Its Mutational Mechanism in Chinese Patients

    PubMed Central

    Chen, Chen; Ma, Hongwei; Zhang, Feng; Chen, Lu; Xing, Xuesha; Wang, Shusen; Zhang, Xue; Luo, Yang

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a common X-linked recessive disease of muscle degeneration and death. In order to provide accurate and reliable genetic counseling and prenatal diagnosis, we screened DMD mutations in a cohort of 119 Chinese patients using multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) followed by Sanger sequencing. In these unrelated DMD patients, we identified 11 patients with DMD small mutations (9.2%) and 81 patients with DMD deletions/duplications (del/dup) (68.1%), of which 64 (79.0%) were deletions, 16 (19.8%) were duplications, and one (1.2%) was both deletion and duplication. Furthermore, we analyzed the frequency of DMD breakpoint in the 64 deletion cases by calculating exon-deletion events of certain exon interval that revealed a novel mutation hotspot boundary. To explore why DMD rearrangement breakpoints were predisposed to specific regions (hotspot), we precisely characterized junction sequences of breakpoints at the nucleotide level in 21 patients with exon deleted/duplicated in DMD with a high-resolution SNP microarray assay. There were no exactly recurrent breakpoints and there was also no significant difference between single-exon del/dup and multiple-exon del/dup cases. The data from the current study provided a comprehensive strategy to detect DMD mutations for clinical practice, and identified two deletion hotspots at exon 43–55 and exon 10–23 by calculating exon-deletion events of certain exon interval. Furthermore, this is the first study to characterize DMD breakpoint at the nucleotide level in a Chinese population. Our observations provide better understanding of the mechanism for DMD gene rearrangements. PMID:25244321

  12. Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells

    PubMed Central

    Monfort, Asun; Di Minin, Giulio; Postlmayr, Andreas; Freimann, Remo; Arieti, Fabiana; Thore, Stéphane; Wutz, Anton

    2015-01-01

    Summary In mammals, the noncoding Xist RNA triggers transcriptional silencing of one of the two X chromosomes in female cells. Here, we report a genetic screen for silencing factors in X chromosome inactivation using haploid mouse embryonic stem cells (ESCs) that carry an engineered selectable reporter system. This system was able to identify several candidate factors that are genetically required for chromosomal repression by Xist. Among the list of candidates, we identify the RNA-binding protein Spen, the homolog of split ends. Independent validation through gene deletion in ESCs confirms that Spen is required for gene repression by Xist. However, Spen is not required for Xist RNA localization and the recruitment of chromatin modifications, including Polycomb protein Ezh2. The identification of Spen opens avenues for further investigation into the gene-silencing pathway of Xist and shows the usefulness of haploid ESCs for genetic screening of epigenetic pathways. PMID:26190100

  13. Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.

    PubMed

    Monfort, Asun; Di Minin, Giulio; Postlmayr, Andreas; Freimann, Remo; Arieti, Fabiana; Thore, Stéphane; Wutz, Anton

    2015-07-28

    In mammals, the noncoding Xist RNA triggers transcriptional silencing of one of the two X chromosomes in female cells. Here, we report a genetic screen for silencing factors in X chromosome inactivation using haploid mouse embryonic stem cells (ESCs) that carry an engineered selectable reporter system. This system was able to identify several candidate factors that are genetically required for chromosomal repression by Xist. Among the list of candidates, we identify the RNA-binding protein Spen, the homolog of split ends. Independent validation through gene deletion in ESCs confirms that Spen is required for gene repression by Xist. However, Spen is not required for Xist RNA localization and the recruitment of chromatin modifications, including Polycomb protein Ezh2. The identification of Spen opens avenues for further investigation into the gene-silencing pathway of Xist and shows the usefulness of haploid ESCs for genetic screening of epigenetic pathways. PMID:26190100

  14. Diagnostic quality versus patient exposure with five panoramic screen-film combinations

    SciTech Connect

    D'Ambrosio, J.A.; Schiff, T.G.; McDavid, W.D.; Langland, O.E.

    1986-04-01

    Five film-screen combinations were used to make five density-matched panoramic radiographs of a tissue-equivalent phantom skull using the Midwest/Morita Panoral x-ray machine. The radiographs were evaluated as to their diagnostic quality by twenty dental radiologists. The results demonstrate that proper screen-film selection can significantly reduce patient exposure without compromising diagnostic quality.

  15. Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis.

    PubMed

    Colling, Richard; Church, David N; Carmichael, Juliet; Murphy, Lucinda; East, James; Risby, Peter; Kerr, Rachel; Chetty, Runjan; Wang, Lai Mun

    2015-12-01

    Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs. PMID:26201544

  16. [Monitoring pregnant patients from risk countries with sickle cell disease and thalassemia. Clinical aspects, screening and prenatal diagnosis].

    PubMed

    Dickerhoff, R; Kulozik, A E; Kohne, E

    1993-04-01

    At the present time, about 3.5 million people from Turkey, Greece, Italy, the Middle East, Africa and Asia are living in Germany. They are potential carriers of beta-thalassaemia and haemoglobinopathies such as sickle cell disease. These diseases are new for most of us and represent a challenge to physicians, taking care of these patients. Not only do we have to learn about the clinical problems of homozygous patients and how to handle them, we also have to become acquainted with the problems related to the heterozygous carrier stage. The large number of asymptomatic pregnant carriers of beta-globin anomalies is a particular challenge for obstetricians. They need to identify carriers through haemoglobin electrophoresis screening, inform the carrier about the meaning of being a carrier, screen the woman's partner, refer for genetic counselling and suggest and explain prenatal diagnosis in case the partner is also a carrier. There is as yet no cure for thalassaemia and sickle cell disease, except for bone marrow transplantation in a few selected cases. Therefore, prenatal diagnosis presents a valuable method of preventing severe chronic diseases. Screening does not only allow genetic counselling, the information gained has also clinical implications for carriers of beta-thalassaemia. In this paper a summary is given of the pathophysiological and clinical features of thalassaemia and sickle cell disease and molecular biology methods to diagnose thalassaemias and sickle cell disease are discussed. In addition, a screening programme for pregnant women from countries at risk is suggested to enable physicians to give optimal care and initiate prenatal diagnosis. PMID:8491363

  17. Incidental retinal vascular occlusions on hydroxychloroquine screening in patients with systemic lupus erythematosus

    PubMed Central

    Bajwa, Asima; Khurana, Gitanjali; Kimpel, Donald; Reddy, Ashvini K

    2015-01-01

    Objective The proportion of patients with systemic lupus erythematosus (SLE) who manifest retinal involvement increases many fold in patients with active systemic disease. The objective of this report is to stress upon the significance of comprehensive ophthalmic assessment of all SLE patients to prevent and manage blinding ocular manifestations of the disease. Methods Retrospective case review. Results Incidental retinal vascular complications seen in patients undergoing baseline hydroxychloroquine screening. Conclusion The purpose of comprehensive ophthalmic screening in SLE patients is twofold. It will aid in the diagnosis and treatment of blinding ocular complications of the disease and monitor hydroxychloroquine macular toxicity. PMID:26064074

  18. Parasitic disease screening among HIV patients from endemic countries in a Toronto clinic

    PubMed Central

    Costiniuk, Cecilia T; Cooper, Curtis L; Doucette, Steve; Kovacs, Colin M

    2012-01-01

    BACKGROUND: Many North American-based HIV patients originate from parasitic disease-endemic regions. Strongyloidiasis, schistosomiasis and filariasis are important due to their wide distribution and potential for severe morbidity. OBJECTIVES: To determine the prevalence, as determined by serological screening, of strongyloidiasis, schistosomiasis and filariasis among patients in an HIV-focused, primary care practice in Toronto, Ontario. A secondary objective was to determine factors associated with positive serological screens. METHODS: A retrospective review of electronic patient records was conducted. Results of serological screens for parasites and relevant laboratory data were collected. RESULTS: Ninety-seven patients were identified. The patients’ mean CD4+ count was 0.45×109/L, median viral load was undetectable and 68% were on highly active antiretroviral therapy (HAART). Most originated from Africa (37%) and South America (35%). Of the 97 patients, 10.4% and 8.3% had positive or equivocal screening results for strongyloidiasis, respectively, 7.4% and 4.2% had positive or equivocal screening results for schistosomiasis and 5.5% and 6.8% had positive or equivocal screens for filariasis. Persons with positive parasitic serologies were more often female (28% versus 9%, P=0.03), younger in age (36 versus 43 years of age, P<0.01), had been in Canada for a shorter duration (5 versus 12 years, P<0.0001) and had a higher viral load (10,990 copies/mL versus <50 copies/mL, P <0.001). All patients were asymptomatic. Eosinophilia was not associated with positive screening results. CONCLUSIONS: Using symptoms and eosinophilia to identify parasitic infection was not reliable. Screening for strongyloidiasis and schistosomiasis among patients with HIV from parasite-endemic countries is simple and benign, and may prevent future complications. The clinical benefits of screening for filariasis require further elucidation, but this practice appears to be the least warranted

  19. [Genetic, population and phenotypic characteristics of patients with Hirschsprung disease].

    PubMed

    Ruiz Aja, E; Vega Hernández, L; Martínez Ezquerra, N; De Diego García, E; Pérez Marrodan, A; Alvarez-Buhilla, P López

    2012-07-01

    Hirschsprung disease (HSCR) is caused by the absence of ganglion cells in the intestine due to defects in the migration of enteric nervous system cells during embryologic development. The incidence is one in every 5000 births, more common in men than women. There are two main phenotypes according to the aganglionic segment length: Short (S-HSCR, (80% of patients) and Long (L-HSCR, 20%). Variations have been detected in the coding sequence of the RET proto-oncogene in patients with HSCR, suggesting a genetic predisposition to the disease. Our aim is to find and analyze polymorphisms (SNPs) associated with the disease. We are interested also in stablish an association between sex and type of aganglionic segment. We analyzed the RET promoter as well a polymorphism in exon 13 strongly associated to the disease. The populations for the study were a group of 56 patients with sporadic HSCR and 178 healthy controls. The results obtained show that the disease is more common in men than in women (3:1). The RET genotype shows that alleles A and G of the promoter (c.-200A > G and c.-196C > A) and G of exon 13 (c.2307T > G) are associated with the affected population. Our data suggest neither association between the disease phenotype and the distribution of the polymorphisms analyzed nor with the sex of the patients. The presence of certain polymorphisms in the RET sequence indicates a genetic predisposition (combined with other genetic or environmental factors) to the disease. PMID:23480009

  20. A large-scale genetic screen for mutants with altered salicylic acid accumulation in Arabidopsis

    PubMed Central

    Ding, Yezhang; Shaholli, Danjela; Mou, Zhonglin

    2014-01-01

    Salicylic acid (SA) is a key defense signal molecule against biotrophic and hemibiotrophic pathogens in plants, but how SA is synthesized in plant cells still remains elusive. Identification of new components involved in pathogen-induced SA accumulation would help address this question. To this end, we performed a large-scale genetic screen for mutants with altered SA accumulation during pathogen infection in Arabidopsis using a bacterial biosensor Acinetobacter sp. ADPWH_lux-based SA quantification method. A total of 35,000 M2 plants in the npr1-3 mutant background have been individually analyzed for the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326-induced SA accumulation. Among the mutants isolated, 19 had SA levels lower than npr1 (sln) and two exhibited increased SA accumulation in npr1 (isn). Complementation tests revealed that seven of the sln mutants are new alleles of eds5/sid1, two are sid2/eds16 alleles, one is allelic to pad4, and the remaining seven sln and two isn mutants are new non-allelic SA accumulation mutants. Interestingly, a large group of mutants (in the npr1-3 background), in which Psm ES4326-induced SA levels were similar to those in the wild-type Columbia plants, were identified, suggesting that the signaling network fine-tuning pathogen-induced SA accumulation is complex. We further characterized the sln1 single mutant and found that Psm ES4326-induced defense responses were compromised in this mutant. These defense response defects could be rescued by exogenous SA, suggesting that SLN1 functions upstream of SA. The sln1 mutation was mapped to a region on the north arm of chromosome I, which contains no known genes regulating pathogen-induced SA accumulation, indicating that SLN1 likely encodes a new regulator of SA biosynthesis. Thus, the new sln and isn mutants identified in this genetic screen are valuable for dissecting the molecular mechanisms underlying pathogen-induced SA accumulation in plants. PMID:25610446

  1. A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection

    PubMed Central

    Riblett, Amber M.; Blomen, Vincent A.; Jae, Lucas T.; Altamura, Louis A.; Doms, Robert W.; Brummelkamp, Thijn R.

    2015-01-01

    ABSTRACT Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. IMPORTANCE Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral

  2. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients.

    PubMed

    George, Angela; Riddell, Daniel; Seal, Sheila; Talukdar, Sabrina; Mahamdallie, Shazia; Ruark, Elise; Cloke, Victoria; Slade, Ingrid; Kemp, Zoe; Gore, Martin; Strydom, Ann; Banerjee, Susana; Hanson, Helen; Rahman, Nazneen

    2016-01-01

    Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases. PMID:27406733

  3. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients

    PubMed Central

    George, Angela; Riddell, Daniel; Seal, Sheila; Talukdar, Sabrina; Mahamdallie, Shazia; Ruark, Elise; Cloke, Victoria; Slade, Ingrid; Kemp, Zoe; Gore, Martin; Strydom, Ann; Banerjee, Susana; Hanson, Helen; Rahman, Nazneen

    2016-01-01

    Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases. PMID:27406733

  4. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients.

    PubMed

    Mori, Kentaro; Moteki, Hideaki; Miyagawa, Maiko; Nishio, Shin-Ya; Usami, Shin-Ichi

    2016-01-01

    Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500-1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434) and the total numbers of cases associated with at least one mutation was 44.07% (316/717). Among these, we were able to diagnose 212 (30%) patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8%) had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall) were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes. PMID:27627659

  5. Genetic damage in patients moving from hemodialysis to online hemodiafiltration.

    PubMed

    Rodríguez-Ribera, Lara; Pastor, Susana; Corredor, Zuray; Silva, Irene; Diaz, Juan Manuel; Ballarin, José; Marcos, Ricardo; Coll, Elisabeth

    2016-03-01

    End-stage renal failure patients exhibit a high incidence of genetic damage and genomic instability. Part of this genetic damage is assumed to be caused by the hemodialysis (HD) procedure. To reduce these effects, different alternative HD procedures have been proposed, such as the use of high efficiency convective therapies to improve the reactive oxygen species/antioxidant ratio. To determine the efficiency of online hemodiafiltration (HDF) technique on the levels of DNA damage, we have measured the frequency of micronucleus in peripheral blood lymphocytes of 33 individuals moving from low-flux HD to post-dilution online HDF. In addition to basal levels of genetic damage, potential changes in radiosensitivity were measured as indicators of genomic instability. Plasma antioxidant capacity was also determined. Second samples were obtained after 6 months on the HDF protocol. Results indicate that moving to online HDF therapy produce a significant reduction of the basal levels of genetic damage, but does not affect the genomic instability status. In addition, a greater increase in plasma antioxidant capacity was observed. In spite of the lack of correlation between these parameters, our results confirm the usefulness of the online HDF technique as a way to reduce DNA damage in HD patients. PMID:26285921

  6. Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tay-Sachs and Canavan Disease

    PubMed Central

    Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2011-01-01

    Genetic testing for Tay-Sachs and Canavan disease is particularly important for Ashkenazi Jews, as both conditions are more frequent in that population. This comparative case study was possible because of different patenting and licensing practices. The role of DNA testing differs between Tay-Sachs and Canavan diseases. The first-line screening test for Tay-Sachs remains an enzyme activity test, rather than genotyping. Genotyping is used for preimplantation diagnosis and confirmatory testing. In contrast, DNA-based testing is the basis for Canavan screening and diagnosis. The HEXA gene was cloned at the National Institutes of Health, and the gene was patented but has not been licensed. The ASPA gene was cloned and patented by Miami Childrens Hospital (MCH). MCH did not inform family members and patient groups that had contributed to the gene discovery that it was applying for a patent, and pursued restrictive licensing practices when a patent issued in 1997. This led to intense controversy, litigation, and a sealed, nonpublic 2003 settlement that apparently allowed for nonexclusive licensing. A survey of laboratories revealed a possible price premium for ASPA testing, with per-unit costs higher than for other genetic tests in the SACGHS case studies. The main conclusion from comparing genetic testing for Tay-Sachs and Canavan diseases, however, is that patenting and licensing conducted without communication with patients and advocates causes mistrust and can lead to controversy and litigation, a negative model to contrast with the positive model of patenting and licensing for genetic testing of cystic fibrosis. PMID:20393311

  7. Genetic Variation of the Brca1 and Brca2 Genes in Macedonian Patients

    PubMed Central

    Maleva, I; Madjunkova, S; Bozhinovski, G; Smickova, E; Kondov, G; Spiroski, Z; Arsovski, A; Plaseska-Karanfilska, D

    2012-01-01

    The most significant and well characterized genetic risk factors for breast and/or ovarian cancer are germline mutations in the BRCA1 and BRCA2 genes. The BRCA1 and BRCA2 gene mutations strikingly increase breast cancer risk, suggesting that polymorphisms in these genes are logical candidates in seeking to identify low penetrance susceptibility alleles. The aim of this study was to initiate a screen for BRCA1/2 gene mutations in order to identify the genetic variants in the Republic of Macedonia, and to evaluate the association of several single nucleotide polymorphisms (SNPs) in these genes with breast cancer risk. In this study, we included 100 patients with invasive breast cancer from the Republic of Macedonia, classified according to their family history and 100 controls. The methodology included direct sequencing, single nucleotide primer extension method and multiplex ligation probe amplification (MLPA) analysis, all followed by capillary electrophoresis (CE) on an ABI PRISM™ 3130 Genetic Analyzer. We identified a total of seven carriers of mutations in the BRCA1/2 genes. None of the tested polymorphisms was associated with sporadic breast cancer risk, however, polymorphism rs8176267 in BRCA1 and N372H in BRCA2 showed an association with breast cancer risk in patients with at least one family member with breast cancer. PMID:24052750

  8. MRI safety: a report of current practice and advancements in patient preparation and screening.

    PubMed

    Weidman, Elizabeth K; Dean, Kathryn E; Rivera, William; Loftus, Michael L; Stokes, Thomas W; Min, Robert J

    2015-01-01

    MRI offers detailed diagnostic images without ionizing radiation; however, there are considerable safety concerns associated with high electromagnetic field strength. With increasing use of high and ultra high (7T) magnetic field strength, adequate patient preparation and screening for ferrous material is increasingly important. We review current safety standards for patient screening and preparation and how they are implemented at our institution. In addition, we describe a novel supplemental screening technique wherein the lights are dimmed in response to detected ferrous metal at the threshold of Zone IV. PMID:26422769

  9. Validation of a brief screen for Post-Traumatic Stress Disorder with substance use disorder patients.

    PubMed

    Kimerling, Rachel; Trafton, Jodie A; Nguyen, Brian

    2006-11-01

    To evaluate a 4-item screen for Post-Traumatic Stress Disorder (PTSD) for use with patients diagnosed with substance use disorders, 97 patients were recruited from substance use disorder treatment clinics at a large medical center. Participants completed the self-administered 4-item PTSD screen. Psychologists interviewed patients using the Clinician Administered PTSD Scale (CAPS). Sensitivity and specificity were calculated using the CAPS as the criterion for PTSD. Results were compared to chart diagnoses. The prevalence of PTSD was 33%. The screen identified 91% of PTSD cases, where only 25% of PTSD cases were diagnosed in the medical chart. The screen demonstrated good test-retest reliability (r=.80) and yielded a sensitivity of .91 and specificity of .80 using a cut score of 3. Likelihood ratios indicate that the screen has good ability to detect PTSD in this population, and that patients with positive screens that do not meet criteria for PTSD are likely to report significant subthreshold symptoms. Screening for PTSD in SUD treatment settings is time efficient and may increase the detection of previously unrecognized PTSD. PMID:16574331

  10. A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

    PubMed Central

    Moriarity, Branden S; Otto, George M; Rahrmann, Eric P; Rathe, Susan K; Wolf, Natalie K; Weg, Madison T; Manlove, Luke A; LaRue, Rebecca S; Temiz, Nuri A; Molyneux, Sam D; Choi, Kwangmin; Holly, Kevin J; Sarver, Aaron L; Scott, Milcah C; Forster, Colleen L; Modiano, Jaime F; Khanna, Chand; Hewitt, Stephen M; Khokha, Rama; Yang, Yi; Gorlick, Richard; Dyer, Michael A; Largaespada, David A

    2016-01-01

    Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma. PMID:25961939