Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M
Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.
Vlahovich, Nicole; Fricker, Peter A; Brown, Matthew A; Hughes, David
As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identifica...
Hesse-Biber, Sharlene; An, Chen
Through an analysis of an online survey of women who tested positive for the BRCA genetic mutation for breast cancer, this research uses a social constructionist and feminist standpoint lens to understand the decision-making process that leads BRCA-positive women to choose genetic testing. Additionally, this research examines how they socially construct and understand their risk for developing breast cancer, as well as which treatment options they undergo post-testing. BRCA-positive women re-frame their statistical medical risk for developing cancer and their post-testing treatment choices through a broad psychosocial context of engagement that also includes their social networks. Important psychosocial factors drive women's medical decisions, such as individual feelings of guilt and vulnerability, and the degree of perceived social support. Women who felt guilty and fearful that they might pass the BRCA gene to their children were more likely to undergo risk reducing surgery. Women with at least one daughter and women without children were more inclined toward the risk reducing surgery compared to those with only sons. These psychosocial factors and social network engagements serve as a "nexus of decision making" that does not, for the most part, mirror the medical assessments of statistical odds for hereditary cancer development, nor the specific treatment protocols outlined by the medical establishment.
Lebowitz, Matthew S; Ahn, Woo-Kyoung
Depression, like other mental disorders and health conditions generally, is increasingly construed as genetically based. This research sought to determine whether merely telling people that they have a genetic predisposition to depression can cause them to retroactively remember having experienced it. U.S. adults (men and women) were recruited online to participate (Experiment 1: N = 288; Experiment 2: N = 599). After conducting a test disguised as genetic screening, we randomly assigned some participants to be told that they carried elevated genetic susceptibility to depression, whereas others were told that they did not carry this genetic liability or were told that they carried elevated susceptibility to a different disorder. Participants then rated their experience of depressive symptoms over the prior 2 weeks on a modified version of the Beck Depression Inventory-II. Participants who were told that their genes predisposed them to depression generally reported higher levels of depressive symptomatology over the previous 2 weeks, compared to those who did not receive this feedback. Given the central role of self-report in psychiatric diagnosis, these findings highlight potentially harmful consequences of personalized genetic testing in mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Vlahovich, Nicole; Fricker, Peter A; Brown, Matthew A; Hughes, David
As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science. PMID:27899345
Vlahovich, Nicole; Fricker, Peter A; Brown, Matthew A; Hughes, David
As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
... is often the only way to determine if symptoms could possibly be related to celiac disease. For a person who faces this situation, a negative gene test would indicate that symptoms are not the result of celiac disease. A positive gene test, however, does not diagnose ...
... genetic counselor can help you work through the pros and cons of genetic testing based on your ... showing symptoms or what their progression will be. Technology is changing rapidly and costs of testing are ...
... What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, is ... with other groups. For more information about genetic ancestry testing: The University of Utah provides video tutorials ...
... consumer genetic testing? What kinds of direct-to-consumer genetic tests are available? What is genetic ancestry testing? What are the benefits and risks of direct-to-consumer genetic testing? ...
... RefSeqGene UniGene All Genes & Expression Resources... Genetics & Medicine Bookshelf Database of Genotypes and Phenotypes (dbGaP) Genetic Testing ... ProtMap HomoloGene Protein Clusters All Homology Resources... Literature Bookshelf E-Utilities Journals in NCBI Databases MeSH Database ...
Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah
BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying...
Lyons, Leslie A
DNA testing for domestic cat diseases and appearance traits is a rapidly growing asset for veterinary medicine. Approximately 33 genes contain 50 mutations that cause feline health problems or alterations in the cat's appearance. A variety of commercial laboratories can now perform cat genetic diagnostics, allowing both the veterinary clinician and the private owner to obtain DNA test results. DNA is easily obtained from a cat via a buccal swab with a standard cotton bud or cytological brush, allowing DNA samples to be easily sent to any laboratory in the world. The DNA test results identify carriers of the traits, predict the incidence of traits from breeding programs, and influence medical prognoses and treatments. An overall goal of identifying these genetic mutations is the correction of the defect via gene therapies and designer drug therapies. Thus, genetic testing is an effective preventative medicine and a potential ultimate cure. However, genetic diagnostic tests may still be novel for many veterinary practitioners and their application in the clinical setting needs to have the same scrutiny as any other diagnostic procedure. This article will review the genetic tests for the domestic cat, potential sources of error for genetic testing, and the pros and cons of DNA results in veterinary medicine. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's internal genome. Copyright © 2010 Elsevier Inc. All rights reserved.
Verweij, K.J.H.; Burri, A.V.; Zietsch, B.P.
Sexual selection can cause evolution in traits that affect mating success, and it has thus been implicated in the evolution of human physical and behavioural traits that influence attractiveness. We use a large sample of identical and nonidentical female twins to test the prediction from mate choice
Moritani, Kohshiro; Matsuda, Yasuo; Ozaki, Masaharu; Ogawa, Hiroshi; Ichiyama, Masaji; Matsuda, Masako; Kusukawa, Reizo
Exercise tests with sublingual nitroglycerin were performed on 7 patients with true positive and 8 patients with false positive exercise test results. Four of 7 patients with true positive changes and 8 patients with false positive changes underwent exercise cardiac scintigraphy. Scintigrams showed perfusion defects in 4 patients with true positive outcomes, and no perfusion defect in 8 patients with false positive outcomes. Exercise tests with sublingual nitroglycerin were performed with the same load as that without nitroglycerin. In all 7 patients with true positive exercise test results, ST segment depression observed in the control exercise test was not observed in the nitroglycerin exercise test. In the false positive patients, ST segment depression observed in the control exercise test remained unchanged in 7 of 8 patients receiving nitroglycerin. Exercise tests with sublingual nitroglycerin as well as exercise cardiac scintigraphy are valuable tods in differentiating false positive from true positive patients. Furthermore, these data suggest that ST segment depression in the false positive patients may not be related to myocardial ischemia. (author)
Olwi, Duaa; Merdad, Leena; Ramadan, Eman
Genetic testing has been gradually permeating the practice of medicine. Health-care providers may be confronted with new genetic approaches that require genetically informed decisions which will be influenced by patients' knowledge of genetics and their attitudes toward genetic testing. This study assesses the knowledge of genetics and attitudes toward genetic testing among college students. A cross-sectional study was conducted using a multistage stratified sample of 920 senior college students enrolled at King Abdulaziz University, Saudi Arabia. Information regarding knowledge of genetics, attitudes toward genetic testing, and sociodemographic data were collected using a self-administered questionnaire. In general, students had a good knowledge of genetics but lacked some fundamentals of genetics. The majority of students showed positive attitudes toward genetic testing, but some students showed negative attitudes toward certain aspects of genetic testing such as resorting to abortion in the case of an untreatable major genetic defect in an unborn fetus. The main significant predictors of knowledge were faculty, gender, academic year, and some prior awareness of 'genetic testing'. The main significant predictors of attitudes were gender, academic year, grade point average, and some prior awareness of 'genetic testing'. The knowledge of genetics among college students was higher than has been reported in other studies, and the attitudes toward genetic testing were fairly positive. Genetics educational programs that target youths may improve knowledge of genetics and create a public perception that further supports genetic testing. © 2016 S. Karger AG, Basel.
... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...
Holtzman, N A
Pressures to lower health-care costs remain an important stimulus to eugenic approaches. Prenatal diagnosis followed by abortion of affected fetuses has replaced sterilization as the major eugenic technique. Voluntary acceptance has replaced coercion, but subtle pressures undermine personal autonomy. The failure of the old eugenics to accurately predict who will have affected offspring virtually disappears when prenatal diagnosis is used to predict Mendelian disorders. However, when prenatal diagnosis is used to detect inherited susceptibilities to adult-onset, common, complex disorders, considerable uncertainty is inherent in the prediction. Intolerance and the resurgence of genetic determinism are current pressures for a eugenic approach. The increasing use of carrier screening (to identify those at risk of having affected offspring) and of prenatal diagnosis could itself generate intolerance for those who refuse the procedures. Genetic determinism deflects society from social action that would reduce the burden of disease far more than even the maximum use of eugenics.
Shakeshaft, Nicholas G.; Trzaskowski, Maciej; McMillan, Andrew; Krapohl, Eva; Simpson, Michael A.; Reichenberg, Avi; Cederlöf, Martin; Larsson, Henrik; Lichtenstein, Paul; Plomin, Robert
High intelligence (general cognitive ability) is fundamental to the human capital that drives societies in the information age. Understanding the origins of this intellectual capital is important for government policy, for neuroscience, and for genetics. For genetics, a key question is whether the genetic causes of high intelligence are qualitatively or quantitatively different from the normal distribution of intelligence. We report results from a sibling and twin study of high intelligence and its links with the normal distribution. We identified 360,000 sibling pairs and 9000 twin pairs from 3 million 18-year-old males with cognitive assessments administered as part of conscription to military service in Sweden between 1968 and 2010. We found that high intelligence is familial, heritable, and caused by the same genetic and environmental factors responsible for the normal distribution of intelligence. High intelligence is a good candidate for “positive genetics” — going beyond the negative effects of DNA sequence variation on disease and disorders to consider the positive end of the distribution of genetic effects. PMID:25593376
A new inverse approach for restoring the absolute coordinates of a ground -based station from three or four observed GPS pseudo-ranges is proposed. This stochastic method is based on simulations of natural evolution named genetic algorithms (GA). These iterative procedures provide fairly good and robust estimates of the absolute positions in the Earth's geocentric reference system. For comparison/validation, GA results are compared to the ones obtained using the classical linearized least-square scheme for the determination of the XYZ location proposed by Bancroft (1985) which is strongly limited by the number of available observations (i.e. here, the number of input pseudo-ranges must be four). The r.m.s. accuracy of the non -linear cost function reached by this latter method is typically ~10-4 m2 corresponding to ~300-500-m accuracies for each geocentric coordinate. However, GA can provide more acceptable solutions (r.m.s. errors < 10-5 m2), even when only three instantaneous pseudo-ranges are used, such as a lost of lock during a GPS survey. Tuned GA parameters used in different simulations are N=1000 starting individuals, as well as Pc=60-70% and Pm=30-40% for the crossover probability and mutation rate, respectively. Statistical tests on the ability of GA to recover acceptable coordinates in presence of important levels of noise are made simulating nearly 3000 random samples of erroneous pseudo-ranges. Here, two main sources of measurement errors are considered in the inversion: (1) typical satellite-clock errors and/or 300-metre variance atmospheric delays, and (2) Geometrical Dilution of Precision (GDOP) due to the particular GPS satellite configuration at the time of acquisition. Extracting valuable information and even from low-quality starting range observations, GA offer an interesting alternative for high -precision GPS positioning.
... are available for many inherited disorders. The main disadvantage is that diagnostic testing carries a very small ... chromosomes, arranged in order of size. Microarray: A technology that examines all of a person’s genes to ...
Davis, J G
The role that genetic factors play in medicine has expanded, owing to such recent advances as those made by the Human Genome Project and the work that has spun off from it. The project is focusing particularly on localization and characterization of recognized human genetic disorders, which in turn increases awareness of the potential for improved treatment of these disorders. Technical advances in genetic testing in the absence of effective treatment has presented the health profession with major ethical challenges. The example of the identification of the BRCA1 and BRCA2 genes in families at high risk for breast and ovarian cancer is presented to illustrate the issues of the sensitivity of the method, the degree of susceptibility a positive result implies, the need for and availability of counseling and patient education, and confidentiality of the test results. A compelling need exists for adequate education about medical genetics to raise the "literacy" rate among health professionals.
Topsakal, V; Van Camp, G; Van de Heyning, P
For some patients, genetic testing can reveal the etiology of their hearing impairment, and can provide evidence for a medical diagnosis. However, a gap between fundamental genetic research on hereditary deafness and clinical otology emerges because of the steadily increasing number of discovered genes for hereditary hearing impairment (HHI) and the comparably low clinical differentiation of the HHIs. In an attempt to keep up with the scientific progress, this article enumerates the indications of genetic testing for HHI from a clinical point of view and describes the most frequently encountered HHIs in Belgium. Domains of recent scientific interest, molecular biological aspects, and some pitfalls with HHIs are highlighted. The overview comprises bilateral congenital hearing loss, late-onset progressive high frequency hearing loss, progressive bilateral cochleo-vestibular deficit, and progressive low frequency hearing loss. Also, several syndromal forms of HHI are summarized, and the availability of genetic tests mentioned. Finally, the requirements for successful linkage analysis, an important genetic research tool for localizing the potential genes of a trait on a chromosome, are briefly described.
... Your Family's Health (National Institutes of Health) - PDF Topic Image MedlinePlus Email Updates Get Genetic Testing updates ... testing and your cancer risk Karyotyping Related Health Topics Birth Defects Genetic Counseling Genetic Disorders Newborn Screening ...
Jallinoja, P; Hakonen, A; Aro, A R
A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice and o...... studies on attitudes towards genetic testing as well as in the health care context, e.g. in genetic counselling.......A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice...... and on the confidence in control of the process of genetic testing and its implications. Our analysis indicated that some of the respondents have contradictory attitudes towards genetic testing. It is proposed that contradictory attitudes towards genetic testing should be given greater significance both in scientific...
... or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity). For more information about the uses of genetic testing: A Brief Primer on Genetic Testing , which ...
Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley
This study described the perceptions of genetic counseling and testing of adults (N = 116) attending a genetic education program. Understanding perceptions of genetic counseling, including the importance of counseling topics, will contribute to patient-focused care as clinical genetic applications for common, complex disorders evolve. Participants completed a survey addressing: the importance of genetic counseling topics, benefits and negative effects of genetic testing, and sharing test results. Topics addressing practical information about genetic conditions were rated most important; topics involving conceptual genetic/genomic principles were rated least important. The most frequently identified benefit and negative effect of testing were prevention/early detection/treatment and psychological distress. Participants perceived that they were more likely to share test results with first-degree than other relatives. Findings suggest providing patients with practical information about genetic testing and genetic contributions to disease, while also determining whether their self-care abilities would be enhanced by teaching genetic/genomic principles. Copyright © 2014 Elsevier Inc. All rights reserved.
Combs, Ryan; McAllister, Marion; Payne, Katherine; Lowndes, Jo; Devery, Sophie; Webster, Andrew R; Downes, Susan M; Moore, Anthony T; Ramsden, Simon; Black, Graeme; Hall, Georgina
The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning. Here, we report qualitative data about retinal dystrophy families' experiences of genetic testing in United Kingdom. The data were part of a wider study examining genetic eye service provision. Twenty interviewees from families in which a causative mutation had been identified by a genetic eye clinic were recruited to the study. Fourteen interviewees had chosen to have a genetic test and five had not; one was uncertain. In-depth telephone interviews were conducted allowing a thorough exploration of interviewees' views and experiences of the benefits of genetic counselling and testing. Transcripts were analysed using thematic analysis. Both affected and unaffected interviewees expressed mainly positive views about genetic testing, highlighting benefits such as diagnostic confirmation, risk information, and better preparation for the future. Negative consequences included the burden of knowledge, moral dilemmas around reproduction, and potential impact on insurance. The offer of genetic testing was often taken up, but was felt unnecessary in some cases. Interviewees in the study reported many benefits, suggesting genetic testing should be available to this patient group. The benefits and risks identified will inform future evaluation of models of service delivery. This research was part of a wider study exploring experiences of families with retinal dystrophy.
Zallen, Doris T.
Considers the opportunities and ethical issues involved in genetic testing. Reviews the history of genetics from the first discoveries of Gregor Mendel, through the spurious pseudo-science of eugenics, and up to the discovery of DNA by James Watson and Francis Crick. Explains how genetic tests are done. (MJP)
undergraduates of universities in Ibadan to genetic counseling and testing (GCT) for ... questionnaire, information on their understanding of GCT, perception of implications, and ... by genetic counseling from suitably trained health-care providers and genetic testing of selected high-risk individuals ..... Multiple sexual partners.
Dinc, Leyla; Terzioglu, Fusun
The aim of this descriptive study was to explore the psychological impact of genetic testing on parents whose children have been referred for genetic testing. Genetic tests enable individuals to be informed about their health status and to have the opportunity of early diagnosis and treatment of their diseases. However undergoing genetic testing and receiving a positive test result may also cause stress and anxiety. This descriptive study was carried out at the genetic departments of two university hospitals in Ankara. The sample of this study consisted of 128 individuals whose children have been referred for chromosomal analysis. Data were collected through using a semi-structured interview method with a data collection form and the anxiety inventory and analysed using the percentages and independent samples t-test. The majority of our participants experienced distress before genetic testing. Their general trait anxiety score before receiving the test results was 47.38, and following the test results the state anxiety score was 50.65. Having a previous child with an abnormality, a positive test result, and being a mother elevated the anxiety of individuals. This paper supports the findings of previous studies, which indicated that genetic test results might lead to anxiety in individuals and reveals the importance of genetic counselling. As the results of this study indicated, genetic testing causes distress and anxiety in individuals. Nurses can play an important role in minimizing anxiety of parents whose children undergo genetic testing by providing information about genetic testing and by taking part in the counselling process.
Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.
Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633
Brezina, Paul R; Kutteh, William H
Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most. © BMJ Publishing Group Ltd 2015.
Advances in technical developments of genetic diagnostics for more than 50 years, as well as the fact that human genetic testing is usually performed only once in a lifetime, with additional impact for blood relatives, are determining the extraordinary importance of quality assurance in human genetic testing. Abidance of laws, directives, and guidelines plays a major role. This article aims to present the major laws, directives, and guidelines with respect to quality assurance of human genetic testing, paying careful attention to internal and external quality assurance. The information on quality assurance of human genetic testing was obtained through a web-based search of the web pages that are referred to in this article. Further information was retrieved from publications in the German Society of Human Genetics and through a PubMed-search using term quality + assurance + genetic + diagnostics. The most important laws, directives, and guidelines for quality assurance of human genetic testing are the gene diagnostics law (GenDG), the directive of the Federal Medical Council for quality control of clinical laboratory analysis (RiliBÄK), and the S2K guideline for human genetic diagnostics and counselling. In addition, voluntary accreditation under DIN EN ISO 15189:2013 offers a most recommended contribution towards quality assurance of human genetic testing. Legal restraints on quality assurance of human genetic testing as mentioned in § 5 GenDG are fulfilled once RiliBÄK requirements are followed.
Borry, Pascal; Evers-Kiebooms, Gerry; Cornel, Martina C
Although various guidelines and position papers have discussed, in the past, the ethical aspects of genetic testing in asymptomatic minors, the European Society of Human Genetics had not earlier endorsed any set of guidelines exclusively focused on this issue. This paper has served as a backgroun...
Bowen, Deborah J; Battuello, Kathryn M; Raats, Monique
Genetic tests are currently being offered to the general public with little oversight and regulation as to which tests are allowed to be sold clinically and little control over the marketing and promotion of sales and use. This article provides discussion and data to indicate that the general public holds high opinions of genetic testing and that current media outlets for public education on genetic testing are not adequate to increase accurate knowledge of genetics. The authors argue that more regulation is needed to control and correct this problem in the United States.
Cortesi, L; Razzaboni, E; Toss, A; De Matteis, E; Marchi, I; Medici, V; Tazzioli, G; Andreotti, A; De Santis, G; Pignatti, M; Federico, M
Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant. This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT. In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention. Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization.
... consumer genetic testing? What kinds of direct-to-consumer genetic tests are available? What is genetic ancestry testing? What are the benefits and risks of direct-to-consumer genetic testing? ...
Zighelboim, Israel; Powell, Matthew A; Babb, Sheri A; Whelan, Alison J; Schmidt, Amy P; Clendenning, Mark; Senter, Leigha; Thibodeau, Stephen N; de la Chapelle, Albert; Goodfellow, Paul J
We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister's colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified.
Full Text Available Genetic testing is a medical tool employed to screen changes in genes linked to cancer and other genetic diseases. Genetic tests are available for breast, ovarian, colon, thyroid, and some other cancers and they represent the main tool for early identification of the “risk” subjects. The choice to undergo genetic testing by a healthy or affected cancer patient with family history of the cancer has to be the fruit of a careful and prudent assessment of the advantages and disadvantages discussed during oncogenetic counselling. The latter, in turn, in the case of a patient's positive and informed choice, must constantly affiliate the genetic testing, in order to preserve the prediction and information role of the test as much as possible.
Taylor, Ann; Sajan, Samin
The polymerase chain reaction (PCR) is a Nobel Prize-winning technique that amplifies a specific segment of DNA and is commonly used to test for the presence of genetic modifications. Students use PCR to test corn meal and corn-muffin mixes for the presence of a promoter commonly used in genetically modified foods, the cauliflower mosaic virus 35S…
Full Text Available BACKGROUND: The availability of direct-to-consumer personalized genetic testing has enabled the public to access and interpret their own genetic information. Various genetic traits can be determined including resistance to norovirus through a nonsense mutation (G428A in the FUT2 gene. Although this trait is believed to confer resistance to the most dominant norovirus genotype (GII.4, the spectrum of resistance to other norovirus strains is unknown. The present report describes a cluster of symptomatic norovirus GI.6 infection in a family identified to have norovirus resistance through personalized genetic testing.
Xavier, Rose Mary; Vorderstrasse, Allison
Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms. This review of literature examines the recent advances (from 2011) in genetic exploration of positive and negative symptoms in schizophrenia. We searched electronic databases PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature using key words schizophrenia, symptoms, positive symptoms, negative symptoms, cognition, genetics, genes, genetic predisposition, and genotype in various combinations. We identified 115 articles, which are included in the review. Evidence from these studies, most of which are genetic association studies, identifies shared and unique gene associations for the symptom domains. Genes associated with neurotransmitter systems and neuronal development/maintenance primarily constitute the shared associations. Needed are studies that examine the genetic basis of specific symptoms within the broader domains in addition to functional mechanisms. Such investigations are critical to developing precision treatment and care for individuals afflicted with schizophrenia.
... patientinstructions/000842.htm Genetic testing and your cancer risk To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...
DuBois, James M
Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.
Fulda, K G; Lykens, K
As a result of the increase in genetic testing and the fear of discrimination by insurance companies, employers, and society as a result of genetic testing, the disciplines of ethics, public health, and genetics have converged. Whether relatives of someone with a positive predictive genetic test should be notified of the results and risks is a matter urgently in need of debate. Such a debate must encompass the moral and ethical obligations of the diagnosing physician and the patient. The decision to inform or not will vary depending on what moral theory is used. Utilising the utilitarian and libertarian theories produces different outcomes. The principles of justice and non‐maleficence will also play an important role in the decision. PMID:16507657
Fulda, K G; Lykens, K
As a result of the increase in genetic testing and the fear of discrimination by insurance companies, employers, and society as a result of genetic testing, the disciplines of ethics, public health, and genetics have converged. Whether relatives of someone with a positive predictive genetic test should be notified of the results and risks is a matter urgently in need of debate. Such a debate must encompass the moral and ethical obligations of the diagnosing physician and the patient. The decision to inform or not will vary depending on what moral theory is used. Utilising the utilitarian and libertarian theories produces different outcomes. The principles of justice and non-maleficence will also play an important role in the decision.
Mary P. Metcalf
Full Text Available Background: It is increasingly important that physicians have a thorough understanding of the basic science of human genetics and the ethical, legal and social implications (ELSI associated with genetic testing and counseling. Methods: The authors developed a series of web-based courses for medical students on these topics. The course modules are interactive, emphasize clinical case studies, and can easily be incorporated into existing medical school curricula. Results: Results of a ‘real world’ effectiveness trial indicate that the courses have a statistically significant effect on knowledge, attitude, intended behavior and self-efficacy related to genetic testing (p<0.001; N varies between 163 and 596 for each course. Conclusions: The results indicate that this curriculum is an effective tool for educating medical students on the ELSI associated with genetic testing and for promoting positive changes in students' confidence, counseling attitudes and behaviors.
... the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern. (Refer to What is genetic discrimination? for additional information.) Genetic testing can provide only ...
Lynch, Anthony M; Sasaki, Jennifer C; Elespuru, Rosalie; Jacobson-Kram, David; Thybaud, Véronique; De Boeck, Marlies; Aardema, Marilyn J; Aubrecht, Jiri; Benz, R Daniel; Dertinger, Stephen D; Douglas, George R; White, Paul A; Escobar, Patricia A; Fornace, Albert; Honma, Masamitsu; Naven, Russell T; Rusling, James F; Schiestl, Robert H; Walmsley, Richard M; Yamamura, Eiji; van Benthem, Jan; Kim, James H
The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow-up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Copyright © 2010 Wiley-Liss, Inc.
Full Text Available This paper uses the developed parallel version of Michalewicz's Genocop III Genetic Algorithm (GA searching technique to optimize the coil geometry of an eddy current non-destructive testing probe (ECTP. The electromagnetic field is computed using FEMM 2D finite element code. The aim of this optimization was to determine coil dimensions and positions that improve ECTP sensitivity to physical properties of the tested devices.
Nyrhinen, Tarja; Hietala, Marja; Puukka, Pauli; Leino-Kilpi, Helena
This study aimed to determine the extent to which the principles of privacy and equality were observed during diagnostic genetic testing according to views held by patients or child patients' parents (n = 106) and by staff (n = 162) from three Finnish university hospitals. The data were collected through a structured questionnaire and analysed using the SAS 8.1 statistical software. In general, the two principles were observed relatively satisfactorily in clinical practice. According to patients/parents, equality in the post-analytic phase and, according to staff, privacy in the pre-analytic phase, involved the greatest ethical problems. The two groups differed in their views concerning pre-analytic privacy. Although there were no major problems regarding the two principles, the differences between the testing phases require further clarification. To enhance privacy protection and equality, professionals need to be given more genetics/ethics training, and patients individual counselling by genetics units staff, giving more consideration to patients' world-view, the purpose of the test and the test result.
O'Callaghan, P.B.; Grambihler, A.J.; Graham, D.K.; Bradley, R.G.
HEDL has a requirement to ensure the identification of remote computer terminal operators on a real-time nuclear inventory data base. The integrity of this data base depends on input from authorized individuals. Thus, a key to developing such a system is the ability to positively identify people attempting access to the system. Small scale tests of the Identimat 2000T hand geometry unit with an adjusting alogrithm have suggested a promising solution. To prove operational suitability, HEDL, in cooperation with Sandia Laboratories, has designed a large scale test of the Identimat 2000T. Data gathering on error rates, reliability, maintainability, and user acceptance will determine if the Identimat 2000T is suitable for the HEDL application. If proven acceptable, use of the Identimat 2000T can be broadened to many general applications where security information, locations and systems are required
Yoshida, Kunihiro; Ohata, Takako; Muto, Kaori; Tsuchiya, Atsushi; Sawada, Jinichi; Hazama, Takanori; Ikeda, Shu-Ichi; Toda, Tatsushi
To clarify the attitude toward genetic testing for neuromuscular diseases, a questionnaire was sent to 4,762 neurologists certified by the Japanese Society of Neurology. By December 21, 2011, 1,493 questionnaires (31.4%) were returned. Of these, 1,233 (82.6%) had experienced genetic testing, but only 396 (26.5%) had referred to the guideline for genetic testing of the Japanese Society of Neurology (2009). The numbers of respondents who were positive, or more positive than negative for genetic testing for myotonic dystrophy type 1 (DM1), Huntington's disease (HD), and familial amyloid polyneuropathy (FAP) were 753 (50.4%), 915 (61.3%), and 980 (65.6%), respectively. The predominant reason for a positive attitude toward genetic testing was to confirm or exclude the diagnosis. Conversely, the predominant reason for a negative attitude toward genetic testing differed between the diseases. For DM1, it was to confirm the diagnosis without genetic testing. For HD, it was that genetic testing would not result in effective prevention or therapy. In FAP, it was that post-testing psychosocial support for the patient and their family was difficult. Common to DM1, HD, and FAP, a significant number of respondents (approximately 60%) felt it difficult to explain the negative aspects that might occur after the disclosure of test results. Concerning predictive or prenatal genetic testing, most respondents referred at-risk individuals to specialized genetic counseling clinics. In general, neurologists are likely to conduct genetic testing properly in consideration not only of the characteristics of the diseases but also of the circumstances of each patient and his or her family. To support neurologists who are involved in genetic testing, the guidelines should be more easily accessible. Many respondents wanted information on the institutions that provide genetic counseling and testing; however, financial support to such institutions is indispensable for fulfilling this requirement.
The discovery of genetic factors behind increasing number of human diseases and the growth of education of genetic knowledge to the public make demands for genetic testing increase rapidly. However, traditional genetic testing methods cannot meet all kinds of the requirements. Next generation seq...
Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.
Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)
... consumer genetic testing. Additional information about direct-to-consumer marketing of genetic tests and related research questions are ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...
Full Text Available Autonomy takes many shapes. The concept of “graduated autonomy” is conceived as comprising several unique features: (1 it is incremental, (2 it is proportional, and (3 it is related to the telos of the life stage during which it occurs. This paper focuses on graduated autonomy in the context of genetic testing during adolescence. Questions can be raised about other life stages as well, and some of these questions will be addressed by discussing a possible fourth characteristic of graduated autonomy, that is, its elasticity. Further scholarship and analysis is needed to refine the concept of graduated autonomy and examine its applications.
Chan-Smutko, Gayun; Patel, Devanshi; Shannon, Kristen M; Ryan, Paula D
In the genetic counseling setting, the health care provider can be challenged by opposing duties to members of the same family: protecting the privacy of the patient identified with a gene mutation and the ethical obligation to warn at-risk relatives. In a situation of nondisclosure between members of a family with a known disease-predisposing mutation, this type of dilemma can present in acute form for the provider who cares for different members of the family. This can hinder effective medical decision making. To minimize this effect, we recommend detailed pretest genetic counseling steps to empower the patient to communicate with their at-risk relatives their intent to pursue testing and willingness to share information. In addition, post-test counseling should reiterate the implications of a positive result for at-risk relatives and conclude with a written summary that patients can share with their family.
Hawkins, Alice K; Ho, Anita
Over the last several years, direct to consumer(DTC) genetic testing has received increasing attention in the public, healthcare and academic realms. DTC genetic testing companies face considerable criticism and scepticism,particularly from the medical and genetic counseling community. This raises the question of what specific aspects of DTC genetic testing provoke concerns, and conversely,promises, for genetic counselors. This paper addresses this question by exploring DTC genetic testing through an ethic allens. By considering the fundamental ethical approaches influencing genetic counseling (the ethic of care and principle-based ethics) we highlight the specific ethical concerns raised by DTC genetic testing companies. Ultimately,when considering the ethics of DTC testing in a genetic counseling context, we should think of it as a balancing act. We need careful and detailed consideration of the risks and troubling aspects of such testing, as well as the potentially beneficial direct and indirect impacts of the increased availability of DTC genetic testing. As a result it is essential that genetic counselors stay informed and involved in the ongoing debate about DTC genetic testing and DTC companies. Doing so will ensure that the ethical theories and principles fundamental to the profession of genetic counseling are promoted not just in traditional counseling sessions,but also on a broader level. Ultimately this will help ensure that the public enjoys the benefits of an increasingly genetic based healthcare system.
I sketch a libertarian argument for the right to test in the context of 'direct to consumer' (DTC) genetic testing. A libertarian right to genetic tests, as defined here, relies on the idea of a moral right to self-ownership. I show how a libertarian right to test can be inferred from this general libertarian premise, at least as a prima facie right, shifting the burden of justification on regulators. I distinguish this distinctively libertarian position from some arguments based on considerations of utility or autonomy, which are sometimes labelled 'libertarian' because they oppose a tight regulation of the direct to consumer genetic testing sector. If one takes the libertarian right to test as a starting point, the whole discussion concerning autonomy and personal utility may be sidestepped. Finally, I briefly consider some considerations that justify the regulation of the DTC genetic testing market, compatible with the recognition of a prima facie right to test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M
The modern field of clinical genetics has advanced beyond the traditional teachings familiar to most practicing cardiologists. Increased understanding of the roles of genetic testing may improve uptake and appropriateness of use. Clinical genetics has become integral to the management of patients with hereditary arrhythmia and cardiomyopathy diagnoses. Depending on the condition, genetic testing may be useful for diagnosis, prognosis, treatment, family screening, and reproductive planning. However, genetic testing is a powerful tool with potential for underuse, overuse, and misuse. In the absence of a substantial body of literature on how these guidelines are applied in clinical practice, we use a case-based approach to highlight key lessons and pitfalls. Importantly, in many scenarios genetic testing has become the standard of care supported by numerous class I recommendations; genetic counselors can improve accessibility to and appropriate use and application of testing. Optimal management of hereditary arrhythmias and cardiomyopathies incorporates genetic testing, applied as per consensus guidelines, with involvement of a multidisciplinary team.
Zhai, Weiwei; Nielsen, Rasmus; Slatkin, Montgomery
In this report, we investigate the statistical power of several tests of selective neutrality based on patterns of genetic diversity within and between species. The goal is to compare tests based solely on population genetic data with tests using comparative data or a combination of comparative...... and population genetic data. We show that in the presence of repeated selective sweeps on relatively neutral background, tests based on the d(N)/d(S) ratios in comparative data almost always have more power to detect selection than tests based on population genetic data, even if the overall level of divergence...... selection. The Hudson-Kreitman-Aguadé test is the most powerful test for detecting positive selection among the population genetic tests investigated, whereas McDonald-Kreitman test typically has more power to detect negative selection. We discuss our findings in the light of the discordant results obtained...
Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.
In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in ...
Harris, A.; Kelly, S.; Wyatt, S.
Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing
Li, Jing; Xu, Tengda; Yashar, Beverly M
The aims of this study were to explore the relationship between physicians' knowledge and utilization of genetic testing and to explore genetics educational needs in China. An anonymous survey about experience, attitudes, and knowledge of genetic testing was conducted among physicians affiliated with Peking Union Medical College Hospital during their annual health evaluation. A personal genetics knowledge score was developed and predictors of personal genetics knowledge score were evaluated. Sixty-four physicians (33% male) completed the survey. Fifty-eight percent of them had used genetic testing in their clinical practice. Using a 4-point scale, mean knowledge scores of six common genetic testing techniques ranged from 1.7 ± 0.9 to 2.4 ± 1.0, and the average personal genetics knowledge score was 2.1 ± 0.8. In regression analysis, significant predictors of higher personal genetics knowledge score were ordering of genetic testing, utilization of pedigrees, higher medical degree, and recent genetics training (P education. This study demonstrated a sizable gap between Chinese physicians' knowledge and utilization of genetic testing. Participants had high self-perceived genetics educational needs. Development of genetics educational platforms is both warranted and desired in China.Genet Med 17 9, 757-760.
Full Text Available Genetic testing for monogenic diabetes is important for patient care. Given the extensive genetic and clinical heterogeneity of diabetes, exome sequencing might provide additional diagnostic potential when standard Sanger sequencing-based diagnostics is inconclusive.The aim of the study was to examine the performance of exome sequencing for a molecular diagnosis of MODY in patients who have undergone conventional diagnostic sequencing of candidate genes with negative results.We performed exome enrichment followed by high-throughput sequencing in nine patients with suspected MODY. They were Sanger sequencing-negative for mutations in the HNF1A, HNF4A, GCK, HNF1B and INS genes. We excluded common, non-coding and synonymous gene variants, and performed in-depth analysis on filtered sequence variants in a pre-defined set of 111 genes implicated in glucose metabolism.On average, we obtained 45 X median coverage of the entire targeted exome and found 199 rare coding variants per individual. We identified 0-4 rare non-synonymous and nonsense variants per individual in our a priori list of 111 candidate genes. Three of the variants were considered pathogenic (in ABCC8, HNF4A and PPARG, respectively, thus exome sequencing led to a genetic diagnosis in at least three of the nine patients. Approximately 91% of known heterozygous SNPs in the target exomes were detected, but we also found low coverage in some key diabetes genes using our current exome sequencing approach. Novel variants in the genes ARAP1, GLIS3, MADD, NOTCH2 and WFS1 need further investigation to reveal their possible role in diabetes.Our results demonstrate that exome sequencing can improve molecular diagnostics of MODY when used as a complement to Sanger sequencing. However, improvements will be needed, especially concerning coverage, before the full potential of exome sequencing can be realized.
Chung, Wendy; Marder, Karen; Shanmugham, Anita; Chin, Lisa J.; Stark, Meredith; Leu, Cheng-Shiun; Appelbaum, Paul S.
Many questions remain concerning whether, when, and how physicians order genetic tests, and what factors are involved in their decisions. We surveyed 220 internists from two academic medical centers about their utilization of genetic testing. Rates of genetic utilizations varied widely by disease. Respondents were most likely to have ordered tests for Factor V Leiden (16.8%), followed by Breast/Ovarian Cancer (15.0%). In the past 6 months, 65% had counseled patients on genetic issues, 44% had ordered genetic tests, 38.5% had referred patients to a genetic counselor or geneticist, and 27.5% had received ads from commercial labs for genetic testing. Only 4.5% had tried to hide or disguise genetic information, and genetic discrimination. Only 53.4% knew of a geneticist/genetic counselor to whom to refer patients. Most rated their knowledge as very/somewhat poor concerning genetics (73.7%) and guidelines for genetic testing (87.1%). Most felt needs for more training on when to order tests (79%), and how to counsel patients (82%), interpret results (77.3%), and maintain privacy (80.6%). Physicians were more likely to have ordered a genetic test if patients inquired about genetic testing (pgenetic counselor to whom to refer patients (pgenetic counselor in the past 6 months, had more comfort counseling patients about testing (pgenetics, larger practices (pgenetic discrimination (pgenetic test was associated with patients inquiring about testing, having referred patients to a geneticist/genetic counselor and knowing how to order tests., These data suggest that physicians recognize their knowledge deficits, and are interested in training. These findings have important implications for future medical practice, research, and education. PMID:22585186
Since 1990's, a business condition that company sells genetic testing services directly to consumers without through medical facility, so called "direct-to-consumers (DTC) genetic testing", has risen. They provide genetic testing for obesity, disease susceptibility or paternity, etc. There are serious problems in this kind of business. Most of the providers do not make sales with face-to-face selling, and do through internet instead. They do not provide genetic counseling by certified genetic counselor or clinical geneticist. Most DTC genetic testing services for disease susceptibility or predispositions including obesity, lack scientific validity, clinical validity and clinical utility. And also including paternity genetic testing, they all have risks of ethical legal and social issues (ELSI) in genetic discrimination and/or eugenics. The specific problem in Japan is that the healthcare section of the government still has not paid attention and not taken seriously the requirement to deploy safety net.
Galvez-Ruiz, Alberto; Galindo-Ferreiro, Alicia; Schatz, Patrik
In this study, the authors present a sample of 71 patients with hereditary optic neuropathy and negative genetic test results for OPA1/OPA3/LHON. All of these patients later underwent genetic testing to rule out WFS. As a result, 53 patients (74.7%) were negative and 18 patients (25.3%) were positive for some type of mutation or variation in the WFS gene. The authors believe that this study is interesting because it shows that a sizeable percentage (25.3%) of patients with hereditary optic 25 neuropathy and negative genetic test results for OPA1/OPA3/LHON had WFS mutations or variants.
Spörndly-Nees, Søren; Dåsberg, Brian; Nielsen, Rasmus Oestergaard
.08 degrees, ICC = 0.91. Discussion: The present data support The Navicular Position Test as a reliable test of the navicular bone position during rest and loading measured in a simple test set-up. Conclusion: The Navicular Position Test was shown to have a high intraday-, intra- and inter-tester reliability...
Brøndum-Nielsen, Karen; Jensen, Hanne; Timshel, Susanne
Advances in genetics have made genetic testing in patients with inherited eye disease increasingly accessible, and the initiation of clinical intervention trials makes it increasingly clinically relevant. Based on a multidisciplinary collaboration between ophthalmologists and clinical geneticists...
Peery, M. Zachariah; Kirby, Rebecca; Reid, Brendan N.; Stoelting, Ricka; Doucet-Beer, Elena; Robinson, Stacie; Vasquez-Carrillo, Catalina; Pauli, Jonathan N.; Palsboll, Per J.
The identification of population bottlenecks is critical in conservation because populations that have experienced significant reductions in abundance are subject to a variety of genetic and demographic processes that can hasten extinction. Genetic bottleneck tests constitute an appealing and
May, Katharina; Brügemann, Kerstin; Yin, Tong; Scheper, Carsten; Strube, Christina; König, Sven
Keeping dairy cows in grassland systems relies on detailed analyses of genetic resistance against endoparasite infections, including between- and within-breed genetic evaluations. The objectives of this study were (1) to compare different Black and White dairy cattle selection lines for endoparasite infections and (2) the estimation of genetic (co)variance components for endoparasite and test-day milk production traits within the Black and White cattle population. A total of 2,006 fecal samples were taken during 2 farm visits in summer and autumn 2015 from 1,166 cows kept in 17 small- and medium-scale organic and conventional German grassland farms. Fecal egg counts were determined for gastrointestinal nematodes (FEC-GIN) and flukes (FEC-FLU), and fecal larvae counts for the bovine lungworm Dictyocaulus viviparus (FLC-DV). The lowest values for gastrointestinal nematode infections were identified for genetic lines adopted to pasture-based production systems, especially selection lines from New Zealand. Heritabilities were low for FEC-GIN (0.05-0.06 ± 0.04) and FLC-DV (0.05 ± 0.04), but moderate for FEC-FLU (0.33 ± 0.06). Almost identical heritabilities were estimated for different endoparasite trait transformations (log-transformation, square root). The genetic correlation between FEC-GIN and FLC-DV was 1.00 ± 0.60, slightly negative between FEC-GIN and FEC-FLU (-0.10 ± 0.27), and close to zero between FLC-DV and FEC-FLU (0.03 ± 0.30). Random regression test-day models on a continuous time scale [days in milk (DIM)] were applied to estimate genetic relationships between endoparasite and longitudinal test-day production traits. Genetic correlations were negative between FEC-GIN and milk yield (MY) until DIM 85, and between FEC-FLU and MY until DIM 215. Genetic correlations between FLC-DV and MY were negative throughout lactation, indicating improved disease resistance for high-productivity cows. Genetic relationships between FEC-GIN and FEC-FLU with milk
Han, Ming-yu; Huang, Sha-sha; Wang, Guo-jian; Yuan, Yong-yi; Kang, Dong-yang; Zhang, Xin; Dai, Pu
Analyzed the molecular pathogenesis of probands by means of genetic test and assisted the local Family Planning Institute by providing prenatal genetic counseling and instruction for deaf families who eager to have more baby. Total of forty-three deaf families were recruited by two institutes for family planning from Guangzhou and Weifang. Forty-two families had one deaf child with normal hearing parents. One family was that parents and their child were all deaf. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) 12SrRNA were firstly performed in probands and their parents, following medical history, physical examination, auditory test and CT scan of temporal bone were completed. And then the genetic information and instruction were provided to each deaf family. Fifteen of these 43 families had positive results of genetic test. In fifteen families, one family was confirmed that the parents and their child all carried homozygous GJB2 mutations and the recurrence risk was 100%. Twelve families were confirmed that the probands carried homozygous/compound GJB2 or SLC26A4 mutations while their parents were GJB2 or SLC26A4 carriers, and the recurrence risk was 25%. One family was confirmed that the proband, diagnosed with enlarged vestibular aqueduct syndrome (EVAS) by CT scan, carried heterozygous SLC26A4 mutation from the mother, and the recurrence risk was still 25% based on the hereditary pattern of EVAS although another SLC26A4 mutation from the father was not found. One family was confirmed that the proband carried a heterozygous GJB2 mutation from the mother and the possibility to be GJB2 carrier for offsprings was 50%. The rest 28 families were that all probands and their parents did not carry GJB2, SLC26A4 and mtDNA 12SrRNA pathological mutation. Genetic testing can provide more accurate and useful prenatal genetic counseling and instruction to deaf families. Meanwhile, it is an ideal way to develop a cooperative relationship with the institute for
Green, Michael J; Botkin, Jeffrey R
Predictive genetic tests are now available for assessing susceptibility to a variety of conditions, including breast and colon cancer, hemochromatosis, and Alzheimer and Huntington disease. Much controversy surrounds the application of these tests, stemming from their similarities to and differences from other tests commonly used in asymptomatic persons. Some have argued that genetic tests are unique and therefore justify special consideration with regard to informed consent and privacy. This paper examines the arguments for such "genetic exceptionalism" and concludes that no clear, significant distinctions between genetic and nongenetic tests justify a different approach to testing by clinicians. Nevertheless, with many genetic tests, the results may cause stigmatization, family discord, and psychological distress. Regardless of whether a test is genetic, when this combination of characteristics is present and when health care providers are not specifically trained to interpret results, testing should be performed with particular caution and the highest standards of informed consent and privacy protection should be applied.
Kratzer, A; Bär, W
In Switzerland paternity investigations are carried out using DNA analysis only since 1991. DNA patterns are inherited and only with the exception of genetically identical twins they are different in everyone and therefore unique to an individual. Hence DNA-systems are an excellent tool to resolve paternity disputes. DNA polymorphisms used for paternity diagnosis are length polymorphisms of the highly polymorphic VNTR loci [variable number of tandem repeats]. The most frequently applied systems are the DNA single locus systems. In addition to the DNA single locus systems the application of PCR (PCR = polymerase chain reaction) based DNA systems has increased particularly in difficult deficiency cases or in cases where only small evidential samples or partially degraded DNA are available. Normally four independent DNA single probes are used to produce a DNA profile from the mother, the child and the alleged father. A child inherits half the DNA patterns from its mother and the other half from its true biological father. If an alleged father doesn't possess the paternal specific DNA pattern in his DNA profile he is excluded from the paternity. In case of non-exclusion the probability for paternity is calculated according to Essen-Möller. When applying four highly polymorphic DNA single locus systems the biostatistical evaluation leads always to W-values exceeding 99.8% [= required value for positive proof of paternity]. DNA analysis is currently the best available method to achieve such effective conclusions in paternity investigations.
Jonsdottir, Thordis; Valdimarsdottir, Heiddis; Tryggvadottir, Laufey; Lund, Sigrun Helga; Thordardottir, Marianna; Magnusson, Magnus Karl; Valdimarsdottir, Unnur
Introduction The aim of this study was to explore the attitudes of Icelandic women towards existing genetic information, genetic counseling and genetic testing for BRCA mutations which dramatically increase risk for aggressive cancers. Materials and methods Women attending the cancer prevention clinic in Reykjavik, capital of Iceland, from October 12th until November 20th 2015 received an invitation to participate. Participation involved answering a short online questionnaire about background, family history of cancer as well as attitudes towards genetic counseling, BRCA testing and preventive use of such information. Descriptive statistics and chi-square tests were used to describe differences in attitudes towards those questions between subgroups of women. Results 1129 women (69% response rate) answered the questionnaire. Mean age was 47 years (span 21-76 years). Around half (47%) had heard fairly much about the mutations. Independent of family history of cancer, the majority of women were positive towards receiving genetic counseling (79%) and to undergo genetic testing (83%) for BRCA mutation with younger women being more interested than older women. On the other hand, only 4% of the women had already received genetic counseling and 7% undergone genetic testing. Women with family history of cancer were more knowledgeable about BRCA mutations (pcounseling and testing for BRCA mutations although half of them worry that a positive result might affect their health insurance. Nevertheless, almost all women believe that existing genetic information should be used to inform carriers for preventive purposes.
Cunningham, G C
The dangers of do-it-yourself pregnancy testing have been recognized in California resulting in the passing of legislation. Pregnancy is a c ondition which requires skill, medical assistance, and occasionally inte rvention or objective counseling. There are 4 arguments against do-it-y ourself testing: 1) it may be inaccurate or inexpertly done, 2) reagents can be hazardous to the health of users or small children, 3) it fails to save money because confirmation by health professionals is usually required, and 4) the individual may not have access to appropriate healt h care resources. California counties have been providing an increasing volume of tests that have served to encourage earlier prenatal care, earlier and safer pregnancy termination, or attendance at family planning clinics. The success of this program warrants implementation by other state governments.
Lee, G H; Payne, S J; Melville, A; Clark, S K
There have been recent advances in genetic testing enabling accurate diagnosis of polyposis syndromes by identifying causative gene mutations, which is essential in the management of individuals with polyposis syndrome and predictive genetic testing of their extended families. There are some similarities in clinical presentation of various polyposis syndromes, which may pose a challenge to diagnosis. In this review, we discuss the clinical presentation of the main polyposis syndromes and the process of genetic testing, including the latest advancement and future of genetic testing. We aim to reiterate the importance of genetic testing in the management of polyposis syndromes, potential pitfalls associated with genetic testing and recommendations for healthcare professionals involved with the care of polyposis patients. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.
Koros, Jessica; Musson, John
Beam position monitors (BPMs) are used to measure lateral beam position. Two pairs of modified wire BPMs are being evaluated for installation into the injector at Jefferson Lab (JLab). The BPMs were coated with a Non-Evaporable Getter (NEG) to aid in pumping at the electron gun, as an ultra-high vacuum is required to protect the gun and to avoid scattering the beam. Beam in the injector has a large diameter, allowing extraction of second moments to give information about beam profile and emittance. The purpose of this project is to determine the effects of NEG coating on the BPMs and to calculate second moments from beam models on the Goubau Line (G-Line). Using the G-Line, scans of the BPMs were taken before and after NEG coating. Each scan produced an electrical field map, which characterizes properties of the BPM, including scale factors and coupling. Second moments were calculated using superposition of previous scan data, and verification of this method was attempted using several beam models. Results show the BPMs responded well to NEG and that measurement of second moments is possible. Once the BPMs are installed, they will enhance gun vacuum and enable monitoring of shape and trajectory of the beam as it exits the electron gun to ensure quality beam for experiments. This work is made possible through support from NSF award 1659177 to Old Dominion University.
Smith, Corrine O; Lipe, Hillary P; Bird, Thomas D
With the exception of Huntington disease, the psychological and psychosocial impact of DNA testing for neurogenetic disorders has not been well studied. To evaluate the psychosocial impact of genetic testing for autosomal dominant forms of hereditary ataxia and neuromuscular disorders. Patients Fifty subjects at risk for autosomal dominant forms of spinocerebellar ataxia (n = 11), muscular dystrophy (n = 28), and hereditary neuropathy (n = 12). A prospective, descriptive, observational study in a university setting of individuals who underwent genetic counseling and DNA testing. Participants completed 3 questionnaires before testing and at regular intervals after testing. The questionnaire set included the Revised Impact of Event Scale, the Hospital Anxiety and Depression Scale, demographic information, and an assessment of attitudes and feelings about genetic testing. Thirty-nine subjects (78%) completed 6 months to 5 years of posttest follow-up. Common reasons for pursuing genetic testing were to provide an explanation for symptoms, emotional relief, and information for future planning. Thirty-four (68%) had positive and 16 (32%) had negative genetic results. In those with a positive result, 26 (76%) had nonspecific signs or symptoms of the relevant disorder. Forty-two participants (84%) felt genetic testing was beneficial. Groups with positive and negative test results coped well with results. However, 13 subjects (10 with positive and 3 with negative results) reported elevated anxiety levels, and 3 (1 with positive and 2 with negative results) expressed feelings of depression during the follow-up period. The test result was not predictive of anxiety or depression. Most individuals find neurogenetic testing to be beneficial, regardless of the result. Anxiety or depression may persist in some persons with positive or negative test results. Testing can have a demonstrable impact on family planning and interpersonal relationships. Further studies are needed to
Sui, Suli; Sleeboom-Faulkner, Margaret
This paper provides an empirical account of commercial genetic testing in China. Commercial predictive genetic testing has emerged and is developing rapidly in China, but there is no strict and effective governance. This raises a number of serious social and ethical issues as a consequence of the enormous potential market for such tests. The paper…
significant resources that have been invested in basic biomedical .... knowledge, could be misled into thinking that genetic testing can be done for any .... strands of hair, bubble gum or cigarette butts. .... Lesage S, Ibanez P, Lohmann E, et al.
Riley, Jacquelyn D; Procop, Gary W; Kottke-Marchant, Kandice; Wyllie, Robert; Lacbawan, Felicitas L
The ordering of molecular genetic tests by health providers not well trained in genetics may have a variety of untoward effects. These include the selection of inappropriate tests, the ordering of panels when the assessment of individual or fewer genes would be more appropriate, inaccurate result interpretation and inappropriate patient guidance, and significant unwarranted cost expenditure. We sought to improve the utilization of molecular genetic tests by requiring providers without specialty training in genetics to use genetic counselors and molecular genetic pathologists to assist in test selection. We used a genetic and genomic test review process wherein the laboratory-based genetic counselor performed the preanalytic assessment of test orders and test triage. Test indication and clinical findings were evaluated against the test panel composition, methods, and test limitations under the supervision of the molecular genetic pathologist. These test utilization management efforts resulted in a decrease in genetic test ordering and a gross cost savings of $1,531,913 since the inception of these programs in September 2011 through December 2013. The combination of limiting the availability of complex genetic tests and providing guidance regarding appropriate test strategies is an effective way to improve genetic tests, contributing to judicious use of limited health care resources. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
Mahon, Suzanne M
Using direct-to-consumer genetic testing (DTCGT), individuals can order a genetic test, collect and submit a saliva sample, and obtain results about their genetic risk for a variety of traits and health conditions without involving a healthcare provider. Potential benefits of DTCGT include personal control over genetic information and health management decisions, whereas potential risks include misinterpretation of results, psychosocial distress, and lack of informed consent. Oncology nurses can provide education, support, and advocacy to enable patients to truly understand the positives and negatives associated with DTCGT. .
Bråred Christensson, Johanna; Andersen, Klaus E; Bruze, Magnus
to oxidized R-limonene. OBJECTIVE: To study the exposure to limonene among consecutive dermatitis patients reacting to oxidized R-limonene in an international setting, and to assess the relevance of the exposure for the patients' dermatitis. METHODS: Oxidized R-limonene 3.0% (containing limonene...... hydroperoxides at 0.33%) in petrolatum was tested in 2900 consecutive dermatitis patients in Australia, Denmark, the United Kingdom, Singapore, Spain, and Sweden. A questionnaire assessing exposure to limonene-containing products was completed. RESULTS: Overall, exposure to products containing limonene was found...
A toss of the coin by the modern-day employer reveals two options regarding genetic testing in the workplace. The employer may choose to take advantage of increasingly precise, available, and affordable genetic testing in order to ascertain the genetic characteristics--and deficiencies--of its employees. This outcome exposes the employer to a vast array of potential litigation and liability relating to the Americans with Disabilities Act, the Fourth Amendment, Title VII of the Civil Rights Act, and state legislation designed to protect genetic privacy. Alternatively, the employer may neglect to indulge in this trend of genetic testing and may face liability for employer negligence, violations of federal legislation such as OSHA regulations, and increased costs associated with insuring the health of genetically endangered employees. In the rapidly developing universe of genetic intelligence, the employer is faced with a staggering dilemma.
This report summarises the controversy of genetic tests and insurance, with a focus on the UK situation during the past decade. UK experience provides insight for future strategies to help people with genetic disadvantages make insurance provision for themselves and their families. Non-disclosure of genetic test results (already carried out for clinical purposes) may not benefit people at risk of genetic disorders or with positive genetic tests. The pressure of geneticists over a decade to prevent disclosure to insurers may have masked opportunities to use insurance to provide help for people with genetic disadvantages. To seize the opportunities now, there must be collaboration, not conflict. Politicians, geneticists, social scientists and all elements of the insurance industry can contribute to wise solutions.
Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.
Objective: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,
Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.
OBJECTIVE: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,
... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...
Research Article. Genetic ... Melbourne, Australia and Department of Animal Science, School of Life .... The patients were assessed according to the International Cooperative Ataxia Rating ..... The Indian Journal of Medical Research 126(5):.
Kirkpatrick, Brianne E; Rashkin, Misha D
Ancestry testing is a home DNA test with many dimensions; in some cases, the implications and outcomes of testing cross over into the health sphere. Common reasons for seeking ancestry testing include determining an estimate of customer's ethnic background, identifying genetic relatives, and securing a raw DNA data file that can be used for other purposes. As the ancestry test marketplace continues to grow, and third-party vendors empower the general public to analyze their own genetic material, the role of the genetic counselor is likely to evolve dramatically. Roles of the genetic counselor may include assisting clients with the interpretation of and adaptation to these results, as well as advising the companies involved in this sector on the ethical, legal, and social issues associated with testing. This paper reviews the history, fundamentals, intended uses, and unintended consequences of ancestry genetic testing. It also discusses the types of information in an ancestry testing result, situations that might involve a clinical genetic counselor, and the benefits, limitations, and functions that ancestry genetic testing can play in a clinical genetics setting.
Foulkes, William D; Knoppers, Bartha Maria; Turnbull, Clare
The current standard model for identifying carriers of high-risk mutations in cancer-susceptibility genes (CSGs) generally involves a process that is not amenable to population-based testing: access to genetic tests is typically regulated by health-care providers on the basis of a labour-intensive assessment of an individual's personal and family history of cancer, with face-to-face genetic counselling performed before mutation testing. Several studies have shown that application of these selection criteria results in a substantial proportion of mutation carriers being missed. Population-based genetic testing has been proposed as an alternative approach to determining cancer susceptibility, and aims for a more-comprehensive detection of mutation carriers. Herein, we review the existing data on population-based genetic testing, and consider some of the barriers, pitfalls, and challenges related to the possible expansion of this approach. We consider mechanisms by which population-based genetic testing for cancer susceptibility could be delivered, and suggest how such genetic testing might be integrated into existing and emerging health-care structures. The existing models of genetic testing (including issues relating to informed consent) will very likely require considerable alteration if the potential benefits of population-based genetic testing are to be fully realized.
Roediger, Henry L; Marsh, Elizabeth J
Multiple-choice tests are commonly used in educational settings but with unknown effects on students' knowledge. The authors examined the consequences of taking a multiple-choice test on a later general knowledge test in which students were warned not to guess. A large positive testing effect was obtained: Prior testing of facts aided final cued-recall performance. However, prior testing also had negative consequences. Prior reading of a greater number of multiple-choice lures decreased the positive testing effect and increased production of multiple-choice lures as incorrect answers on the final test. Multiple-choice testing may inadvertently lead to the creation of false knowledge.
Aro, A R; Hakonen, A; Hietala, M
in favour of mandatory genetic testing than other respondents. Respondents with university education were more critical towards genetic testing and expressed their worry about eugenics more often than other education groups. In conclusion, there are age, education and gender related differences...
Full Text Available Noura S Abul-Husn,1,* Aniwaa Owusu Obeng,2,3,* Saskia C Sanderson,1 Omri Gottesman,2 Stuart A Scott11Department of Genetics and Genomic Sciences, 2The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, 3Department of Pharmacy, Mount Sinai Hospital, New York, NY, USA*These authors contributed equally to this manuscriptAbstract: Clinical genetic testing began over 30 years ago with the availability of mutation detection for sickle cell disease diagnosis. Since then, the field has dramatically transformed to include gene sequencing, high-throughput targeted genotyping, prenatal mutation detection, preimplantation genetic diagnosis, population-based carrier screening, and now genome-wide analyses using microarrays and next-generation sequencing. Despite these significant advances in molecular technologies and testing capabilities, clinical genetics laboratories historically have been centered on mutation detection for Mendelian disorders. However, the ongoing identification of deoxyribonucleic acid (DNA sequence variants associated with common diseases prompted the availability of testing for personal disease risk estimation, and created commercial opportunities for direct-to-consumer genetic testing companies that assay these variants. This germline genetic risk, in conjunction with other clinical, family, and demographic variables, are the key components of the personalized medicine paradigm, which aims to apply personal genomic and other relevant data into a patient's clinical assessment to more precisely guide medical management. However, genetic testing for disease risk estimation is an ongoing topic of debate, largely due to inconsistencies in the results, concerns over clinical validity and utility, and the variable mode of delivery when returning genetic results to patients in the absence of traditional counseling. A related class of genetic testing with analogous issues of clinical utility and
... a genetic test is valid and useful? How can consumers be sure a genetic test is valid ... particular gene or genetic change. In other words, can the test accurately detect whether a specific genetic ...
This paper considers the extent to which the geneticization of 'race' and ethnicity is the prevailing outcome of genetic testing for genealogical purposes. The decoding of the human genome precipitated a change of paradigms in genetics research, from an emphasis on genetic similarity to a focus on molecular-level differences among individuals and groups. This shift from lumping to splitting spurred ongoing disagreements among scholars about the significance of 'race' and ethnicity in the genetics era. I characterize these divergent perspectives as 'pragmatism' and 'naturalism'. Drawing upon ethnographic fieldwork and interviews, I argue that neither position fully accounts for how understandings of 'race' and ethnicity are being transformed with genetic genealogy testing. While there is some acquiescence to genetic thinking about ancestry, and by implication, 'race', among African-American and black British consumers of genetic genealogy testing, test-takers also adjudicate between sources of genealogical information and from these construct meaningful biographical narratives. Consumers engage in highly situated 'objective' and 'affiliative' self-fashioning, interpreting genetic test results in the context of their 'genealogical aspirations'. I conclude that issues of site, scale, and subjectification must be attended to if scholars are to understand whether and to what extent social identities are being transformed by recent developments in genetic science.
the decision is exclusively brought by the pregnant woman. Critics of prenatal genetic testing claim that the woman’s autonomous choice is seriously prejudiced, as the women are pressured first with genetic testing and then with abortion, if the test is positive. However, there are views that many parents are left to bring their decisions in a vacuum because the physicians do not discuss all possible available options with them out of fear that they will be perceived as orders. Genetic counseling has an aim to facilitate informed reproductive decisions. Rigid application of policies on non-directive genetic counseling make pregnant women and families unaware of the nature and consequences of the genetic state which could affect the future child. If the real goal is an informed choice then it is the obligation of the physician-specialist to inform the parents with the facts and familiarize them with the true state. Managing pregnancies today medicalizes and pathologizes all pregnancies, and not only the risky ones. Since these techniques are becoming a routine part of medicalized pregnancy managing, pregnant women find it difficult to resist undertaking such technologies or to refuse them. Thus the question on how much these technologies offer sensible choices is imposed. Generally speaking, it is stated that women are becoming observers rather than active participants in giving birth to a new life. Attempts of legal control over a pregnant woman for the protection of "the life of the fetus" violate the woman’s human rights in democratic societies.
Roth, Stephen M
Talent identification for future sport performance is of paramount interest for many groups given the challenges of finding and costs of training potential elite athletes. Because genetic factors have been implicated in many performance- related traits (strength, endurance, etc.), a natural inclination is to consider the addition of genetic testing to talent identification programs. While the importance of genetic factors to sport performance is generally not disputed, whether genetic testing can positively inform talent identification is less certain. The present paper addresses the science behind the genetic tests that are now commercially available (some under patent protection) and aimed at predicting future sport performance potential. Also discussed are the challenging ethical issues that emerge from the availability of these tests. The potential negative consequences associated with genetic testing of young athletes will very likely outweigh any positive benefit for sport performance prediction at least for the next several years. The paper ends by exploring the future possibilities for genetic testing as the science of genomics in sport matures over the coming decade(s).
Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.
SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225
person, such as a genetic nurse, should inform them of their options and then refer them to a ... cation and counselling could fall to primary care doctors and nurses. Few pri- mary health care ... no prevention, treatment or cure, is very different.
To better understand ethical issues involved in the field of human genetics and promote debate within the scientific community, the author surveyed scientists who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. This study contributes systematic data on attitudes of scientific experts. The survey finds respondents are highly supportive of voluntary testing and the right to know one's genetic heritage. The majority consider in utero testing and consequent pregnancy termination acceptable for cases involving likelihood of serious disease but disapprove for genetic reasons they consider arbitrary, leaving a gray area of distinguishing between treatment of disorders and enhancement still to be resolved. While safeguarding patient confidentiality versus protecting at-risk third parties (kin, reproductive partners) presents a dilemma, preserving privacy from misuse by institutional third parties (employers, insurers) garners strong consensus for legislation against discrimination. Finally, a call is made for greater genetic literacy.
Selle, Benny; Muttil, Nitin
SummaryGenetic Programming is able to systematically explore many alternative model structures of different complexity from available input and response data. We hypothesised that Genetic Programming can be used to test the structure of hydrological models and to identify dominant processes in hydrological systems. To test this, Genetic Programming was used to analyse a data set from a lysimeter experiment in southeastern Australia. The lysimeter experiment was conducted to quantify the deep percolation response under surface irrigated pasture to different soil types, watertable depths and water ponding times during surface irrigation. Using Genetic Programming, a simple model of deep percolation was recurrently evolved in multiple Genetic Programming runs. This simple and interpretable model supported the dominant process contributing to deep percolation represented in a conceptual model that was published earlier. Thus, this study shows that Genetic Programming can be used to evaluate the structure of hydrological models and to gain insight about the dominant processes in hydrological systems.
Progress in the genetics of dementing disorders and the availability of clinical tests for practicing physicians increase the need for a better understanding of multifaceted issues associated with genetic testing. The genetics of dementia is complex, and genetic testing is fraught with many ethical concerns. Genetic testing can be considered for patients with a family history suggestive of a single gene disorder as a cause of dementia. Testing of affected patients should be accompanied by competent genetic counseling that focuses on probabilistic implications for at-risk first-degree relatives. Predictive testing of at-risk asymptomatic patients should be modeled after presymptomatic testing for Huntington's disease. Testing using susceptibility genes has only a limited diagnostic value at present because potential improvement in diagnostic accuracy does not justify potentially negative consequences for first-degree relatives. Predictive testing of unaffected subjects using susceptibility genes is currently not recommended because individual risk cannot be quantified and there are no therapeutic interventions for dementia in presymptomatic patients.
Meisel, S F; Wardle, J
The availability of genetic tests for multifactorial conditions such as obesity raises concerns that higher-risk results could lead to fatalistic reactions or lower-risk results to complacency. No study has investigated the effects of genetic test feedback for the risk of obesity in non-clinical samples. The present study explored psychological and behavioral reactions to genetic test feedback for a weight related gene (FTO) in a volunteer sample (n = 18) using semi-structured interviews. Respondents perceived the gene test result as scientifically objective; removing some of the emotion attached to the issue of weight control. Those who were struggling with weight control reported relief of self-blame. There was no evidence for either complacency or fatalism; all respondents emphasized the importance of lifestyle choices in long-term weight management, although they recognized the role of both genes and environment. Regardless of the test result, respondents evaluated the testing positively and found it motivating and informative. Genetic test feedback for risk of weight gain may offer psychological benefits beyond its objectively limited clinical utility. As the role of genetic counselors is likely to expand, awareness of reasons for genetic testing for common, complex conditions and reactions to the test result is important.
Paul R. Brezina MD, MBA
Full Text Available The past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by developing embryos in the context of an in vitro fertilization (IVF cycle. This information is then used to determine which embryos are selected for uterine transfer. Many societies have enacted legislation to protect against possible abuses utilizing this technology. However, it is incumbent upon society to continue ensuring that preimplantation genetic diagnosis (PGD–-and genetic testing in general–-is applied in a way that utilizes its potential in a responsible manner to improve health care.
Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz
Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.
Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.
Jie, He; Hao, Zhang; Lili, Zhang
Based on the present situation and the development of experiment tests in universities, we introduced a reform in tests of genetics experiments. According to the teaching goals and course contents of genetics experiment, the tests of genetics experiments contain four aspects on the performance of students: the adherence to the experimental procedures, the depth of participation in experiment, the quality of experiment report, and the mastery of experiment principles and skills, which account for 10 %, 20 %, 40 % and 30 % in the total scores, respectively. All four aspects were graded quantitatively. This evaluation system has been tested in our experiment teaching. The results suggest that it has an effect on the promotion of teaching in genetics experiments.
Smart, Andrew; Bolnick, Deborah A; Tutton, Richard
It is becoming increasingly difficult to keep information about genetic ancestry separate from information about health, and consumers of genetic ancestry tests are becoming more aware of the potential health risks associated with particular ancestral lineages. Because some of the proposed associations have received little attention from oversight agencies and professional genetic associations, scientific developments are currently outpacing governance regimes for consumer genetic testing. We highlight the recent and unremarked upon emergence of biomedical studies linking markers of genetic ancestry to disease risks, and show that this body of scientific research is becoming part of public discourse connecting ancestry and health. For instance, data on genome-wide ancestry informative markers are being used to assess health risks, and we document over 100 biomedical research articles that propose associations between mitochondrial DNA and Y chromosome markers of genetic ancestry and a wide variety of disease risks. Taking as an example an association between coronary heart disease and British men belonging to Y chromosome haplogroup I, we show how this science was translated into mainstream and online media, and how it circulates among consumers of genetic tests for ancestry. We find wide variations in how the science is interpreted, which suggests the potential for confusion or misunderstanding. We recommend that stakeholders involved in creating and using estimates of genetic ancestry reconsider their policies for communicating with each other and with the public about the health implications of ancestry information.
Fitzgerald, Benjamin T; Scalia, William M; Scalia, Gregory M
Exercise stress testing is a well validated cardiovascular investigation. Accuracy for treadmill stress electrocardiograph (ECG) testing has been documented at 60%. False positive stress ECGs (exercise ECG changes with non-obstructive disease on anatomical testing) are common, especially in women, limiting the effectiveness of the test. This study investigates the incidence and predictors of false positive stress ECG findings, referenced against stress echocardiography (SE) as a standard. Stress echocardiography was performed using the Bruce treadmill protocol. False positive stress ECG tests were defined as greater than 1mm of ST depression on ECG during exertion, without pain, with a normal SE. Potential causes for false positive tests were recorded before the test. Three thousand consecutive negative stress echocardiograms (1036 females, 34.5%) were analysed (age 59+/-14 years. False positive (F+) stress ECGs were documented in 565/3000 tests (18.8%). F+ stress ECGs were equally prevalent in females (194/1036, 18.7%) and males (371/1964, 18.9%, p=0.85 for the difference). Potential causes (hypertension, left ventricular hypertrophy, known coronary disease, arrhythmia, diabetes mellitus, valvular heart disease) were recorded in 36/194 (18.6%) of the female F+ ECG tests and 249/371 (68.2%) of the male F+ ECG tests (preinforce the value of stress imaging, particularly in women. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.
Selle, B.; Muttil, N.
Genetic Programming is able to systematically explore many alternative model structures of different complexity from available input and response data. We hypothesised that genetic programming can be used to test the structure hydrological models and to identify dominant processes in hydrological systems. To test this, genetic programming was used to analyse a data set from a lysimeter experiment in southeastern Australia. The lysimeter experiment was conducted to quantify the deep percolation response under surface irrigated pasture to different soil types, water table depths and water ponding times during surface irrigation. Using genetic programming, a simple model of deep percolation was consistently evolved in multiple model runs. This simple and interpretable model confirmed the dominant process contributing to deep percolation represented in a conceptual model that was published earlier. Thus, this study shows that genetic programming can be used to evaluate the structure of hydrological models and to gain insight about the dominant processes in hydrological systems.
Murphy, Sinead M
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.
Lawrence, Ryan E; Appelbaum, Paul S.
The advent of genetic testing for psychiatric conditions raises difficult questions about when and how the tests should be used. Development of policies regarding these issues may be informed in a variety of ways by the views of key stakeholders: patients, family members, healthcare professionals, and the general public. Here we review empirical studies of attitudes towards genetic testing among these groups. Patients and family members show strong interest in diagnostic and predictive genetic testing, and to a considerable extent psychiatrists share their enthusiasm. Prenatal test utilization seems likely to depend both on parental views on abortion and the seriousness of the disorder. Parents show a surprising degree of interest in predictive testing of children, even when there are no preventive interventions available. Many persons report themselves ready to alter their lifestyles and plans for marriage and family in response to test results. Respondents also fear negative consequences, from discrimination to being unable to cope with knowledge of their “genetic fate.” Empirical studies of beliefs about genetic testing suggest tests are likely to be embraced widely, but the studies have methodologic limitations, reducing the certainty of their conclusions, and indicating a need for further research with more representative samples. PMID:22168293
Benatar, Michael; Stanislaw, Christine; Reyes, Eliana; Hussain, Sumaira; Cooley, Anne; Fernandez, Maria Catalina; Dauphin, Danielle D; Michon, Sara-Claude; Andersen, Peter M; Wuu, Joanne
Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS. © 2016 American Academy of Neurology.
Ahmed, Farid E
... their background knowledge on the effectiveness of tests, and of course, laboratory personnel of all levels who are involved in carrying out tests. The chapters on molecular and immunological methods are authoritative and detailed in their scope and application. They are ably supported for the less-experienced reader by the basic inTeam struction provided ...
Wood, Sarah G.; Hart, Sara A.; Little, Callie W.; Phillips, Beth M.
Past research suggests that reading comprehension test performance does not rely solely on targeted cognitive processes such as word reading, but also on other nontarget aspects such as test anxiety. Using a genetically sensitive design, we sought to understand the genetic and environmental etiology of the association between test anxiety and…
In direct-to-consumer (DTC) genetic testing, laboratory-based genetic services are offered directly to the public without an independent healthcare professional being involved. The committee of the Southern African Society for Human Genetics (SASHG) appeals to the public and clinicians to be cautious when considering ...
Anette eBauer Ellingsen
Full Text Available The thermostable direct hemolysin (TDH and/or TDH-related hemolysin (TRH genes are carried by most virulent Vibrio parahaemolyticus serovars. In Norway, trh+ V. parahaemolyticus constitute 4.4% and 4.5 % of the total number of V. parahaemolyticus isolated from blue mussel (Mytilus edulis and water, respectively. The trh gene is located in a region close to the gene cluster for urease production (ure. This region was characterized in V. parahaemolyticus strain TH3996 and it was found that a nickel transport operon (nik was located between the first gene (ureR and the rest of the ure cluster genes. The organization of the trh-ureR-nik-ure gene cluster in the Norwegian trh+ isolates was unknown. In this study, we explore the gene organization within the trh-ureR-nik-ure cluster for these isolates. PCR analyses revealed that the genes within the trh-ureR-nik-ure gene cluster of Norwegian trh+ isolates were organized in a similar fashion as reported previously for TH33996. Additionally, the phylogenetic relationship among these trh+ isolates was investigated using Multilocus Sequence Typing (MLST. Analysis by MLST or ureR-trh sequences generated two different phylogenetic trees for the same strains analyzed, suggesting that ureR-trh genes have been acquired at different times in Norwegian V. parahaemolyticus isolates. MLST results revealed that some pathogenic and non-pathogenic V. parahaemolyticus isolates in Norway appear to be highly genetically related.
Riedijk, S R; de Snoo, F A; van Dijk, S; Bergman, W; van Haeringen, A; Silberg, S; van Elderen, T M T; Tibben, A
Since p16-Leiden presymptomatic testing for hereditary melanoma has become available in the Netherlands, the benefits and risks of offering such testing are evaluated. The current paper investigated why the non-participants were reluctant to participate in genetic testing. Sixty six eligible individuals, who were knowledgeable about the test but had not participated in genetic testing by January 2003, completed a self-report questionnaire assessing motivation, anxiety, family dynamics, risk knowledge and causal attributions. Non-participants reported anxiety levels below clinical significance. A principal components analysis on reasons for non-participation distinguished two underlying motives: emotional and rational motivation. Rational motivation for non-participation was associated with more accurate risk knowledge, the inclination to preselect mutation carriers within the family and lower scores on anxiety. Emotional motivation for non-participation was associated with disease misperceptions, hesitation to communicate unfavourable test results within the family and higher scores on anxiety. Rational and emotional motivation for non-participation in the genetic test for hereditary melanoma was found. Emotionally motivated individuals may be reluctant to disseminate genetic risk information. Rationally motivated individuals were better informed than emotionally motivated individuals. It is suggested that a leaflet is added to the invitation letter to enhance informed decision-making about genetic testing.
Marie A Chaix; Gregor Andelfinger; Paul Khairy
Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.
Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213
The primary objective of this workshopÂ was to discuss in detail the state- of-the-art of progeny testing. All aspects, from setting objectives through data collection and analysis, was be covered. We all know progeny testing is a highly technical phase of our tree improvement programs. Each task is critical and must be performed accurately and within a prescribed time...
Michie, S; Bobrow, M; Marteau, T M
To determine whether, following predictive genetic testing for familial adenomatous polyposis (FAP), children or adults receiving positive results experience clinically significant levels of anxiety or depression, and whether children receiving positive results experience higher levels of anxiety or depression than adults receiving positive results. Two studies, one cross sectional and one prospective. 208 unaffected subjects (148 adults and 60 children) at risk for FAP who have undergone genetic testing since 1990. anxiety, depression; independent variables: test results, demographic measures, psychological resources (optimism, self-esteem). Study 1. In children receiving positive results, mean scores for anxiety and depression were within the normal range. There was a trend for children receiving positive results to be more anxious and depressed than those receiving negative results. In adults, mean scores for anxiety were within the normal range for those receiving negative results, but were in the clinical range for those receiving positive results, with 43% (95% CI 23-65) of the latter having scores in this range. Regardless of test result, adults were more likely to be clinically anxious if they were low in optimism or self-esteem. Children receiving positive or negative results did not experience greater anxiety or depression than adults. Study 2. For children receiving a positive test result, mean scores for anxiety, depression, and self-esteem were unchanged over the year following the result, while mean anxiety scores decreased and self-esteem increased after receipt of a negative test result over the same period of time. Children, as a group, did not show clinically significant distress over the first year following predictive genetic testing. Adults were more likely to be clinically anxious if they received a positive result or were low in optimism or self-esteem, with interacting effects. The association between anxiety, self-esteem, and optimism
Carlos R. Souza-Dias
Full Text Available Purpose: To investigate the veracity of Jampolsky's statement that Bielschowsky's head tilt test is inverted if performed with the patient in the upside-down position and to interpret its neuromuscular mechanism. Methods: We present a series of 10 patients selected from a referred sample who were diagnosed with superior oblique paresis. Hypertropia was measured in the primary position, with the head erect and tilted toward both shoulders with the patient in the erect, supine, and upside-down positions. The last position was achieved by hanging the patient upside-down. Results: As expected, our results showed the veracity of Jampolsky's statement. The forced head tilt difference was inverted or significantly decreased when the test was performed in the upside-down position. Moreover, in all patients, Bielschowsky's phenomenon was neutralized in the supine body position, in which hypertropia with the head erect tended to vanish. In 3 patients, it disappeared completely. Conclusions: This study showed that, in patients with superior oblique paresis, differences in the extent of hypertropia in Bielschowsky's test tended to vanish when the test was performed with the patient in the supine position and invert when it was performed with the patient in the upside-down position.
Community attitudes research regarding genetic issues is important when contemplating the potential value and utilisation of predictive testing for common diseases in mainstream health services. This article aims to report population-based attitudes and discuss their relevance to integrating genetic services in primary health contexts. Men's and women's attitudes were investigated via population-based omnibus telephone survey in Queensland, Australia. Randomly selected adults (n = 1,230) with a mean age of 48.8 years were interviewed regarding perceptions of genetic determinants of health; benefits of genetic testing that predict 'certain' versus 'probable' future illness; and concern, if any, regarding potential misuse of genetic test information. Most (75%) respondents believed genetic factors significantly influenced health status; 85% regarded genetic testing positively although attitudes varied with age. Risk-based information was less valued than certainty-based information, but women valued risk information significantly more highly than men. Respondents reported 'concern' (44%) and 'no concern' (47%) regarding potential misuse of genetic information. This study contributes important population-based data as most research has involved selected individuals closely impacted by genetic disorders. While community attitudes were positive regarding genetic testing, genetic literacy is important to establish. The nature of gender differences regarding risk perception merits further study and has policy and service implications. Community concern about potential genetic discrimination must be addressed if health benefits of testing are to be maximised. Larger questions remain in scientific, policy, service delivery, and professional practice domains before predictive testing for common disorders is efficacious in mainstream health care. Copyright © 2011 S. Karger AG, Basel.
Full Text Available Abstract Background Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Results Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold. However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2% were HIV negative. Conclusion Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.
Baveewo, Steven; Kamya, Moses R; Mayanja-Kizza, Harriet; Fatch, Robin; Bangsberg, David R; Coates, Thomas; Hahn, Judith A; Wanyenze, Rhoda K
Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.
Taylor, Ann T S; Rogers, Jill Cellars
The development of classroom experiments where students examine their own DNA is frequently described as an innovative teaching practice. Often these experiences involve students analyzing their genes for various polymorphisms associated with disease states, like an increased risk for developing cancer. Such experiments can muddy the distinction between classroom investigation and medical testing. Although the goals and issues surrounding classroom genotyping do not directly align with those of clinical testing, instructors can use the guidelines and standards established by the medical genetics community when evaluating the ethics of human genotyping. We developed a laboratory investigation and discussion which allowed undergraduate science students to explore current DNA manipulation techniques to isolate their p53 gene, followed by a dialogue probing the ethical implications of examining their sample for various polymorphisms. Students never conducted genotyping on their samples because of the ethical concerns presented in this paper, so the discussion replaced the actual genetic testing in the class. A science faculty member led the laboratory portion, while a genetic counselor facilitated the discussion of the ethical concepts underlying genetic counseling: autonomy, beneficence, confidentiality, and justice. In their final papers, students demonstrated an understanding of the practice guidelines established by the genetics community and acknowledged the ethical considerations inherent in p53 genotyping. Given the burgeoning market for personalized medicine, teaching undergraduates about the psychosocial and ethical dimensions of human genetic testing is important and timely. Moreover, incorporating a genetic counselor in the classroom discussion provided a rich and dynamic discussion of human genetic testing. Copyright © 2011 Wiley Periodicals, Inc.
Lee, Anthony J; Mitchem, Dorian G; Wright, Margaret J; Martin, Nicholas G; Keller, Matthew C; Zietsch, Brendan P
Popular theory suggests that facial averageness is preferred in a partner for genetic benefits to offspring. However, whether facial averageness is associated with genetic quality is yet to be established. Here, we computed an objective measure of facial averageness for a large sample ( N = 1,823) of identical and nonidentical twins and their siblings to test two predictions from the theory that facial averageness reflects genetic quality. First, we use biometrical modelling to estimate the heritability of facial averageness, which is necessary if it reflects genetic quality. We also test for a genetic association between facial averageness and facial attractiveness. Second, we assess whether paternal age at conception (a proxy of mutation load) is associated with facial averageness and facial attractiveness. Our findings are mixed with respect to our hypotheses. While we found that facial averageness does have a genetic component, and a significant phenotypic correlation exists between facial averageness and attractiveness, we did not find a genetic correlation between facial averageness and attractiveness (therefore, we cannot say that the genes that affect facial averageness also affect facial attractiveness) and paternal age at conception was not negatively associated with facial averageness. These findings support some of the previously untested assumptions of the 'genetic benefits' account of facial averageness, but cast doubt on others.
Arribas-Ayllon, M.; Sarangi, Srikant; Clarke, Angus
Advances in molecular genetics have led to the increasing availability of genetic testing for a variety of inherited disorders. While this new knowledge presents many obvious health benefits to prospective individuals and their families it also raises complex ethical and moral dilemmas for famili......, the assessment of competence and maturity, the ability to engage in shared decision-making through acts of disclosure and choice, are just some of the issues that are examined in detail....... as well as genetic professionals. This book explores the ways in which genetic testing generates not only probabilities of potential futures, but also enjoys new forms of social, individual and professional responsibility. Concerns about confidentiality and informed consent involving children...
Barman, Ludovic; El Graini, Mohammed-Taha; Raisaro, Jean Louis; Ayday, Erman; Hubaux, Jean-Pierre
Recently, several solutions have been proposed to address the complex challenge of protecting individuals’ genetic data during personalized medicine tests. In this short paper, we analyze different privacy threats and propose simple countermeasures for the generic architecture mainly used in the literature. In particular, we present and evaluate a new practical solution against a critical attack of a malicious medical center trying to actively infer raw genetic information of patients.
Several genetic disorders are specific to Jewish heritage; one of the most devastating is Tay-Sachs disease.Tay-Sachs is a fatal hereditary disease, causing progressive neurological problems for which there is no cure. Ethical issues surrounding genetic testing for Tay-Sachs within the Jewish community continue to be complex and multifaceted. A perspective of Tay-Sachs, using rights-based ethics and virtue ethics as a theoretical framework, is explored.
Weinreich, Stephanie S; Bosma, Astrid; Henneman, Lidewij; Rigter, Tessel; Spruijt, Carla M J; Grimbergen, Anneliese J E M A; Breuning, Martijn H; de Koning, Eelco J P; Losekoot, Monique; Cornel, Martina C
Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant for treatment and prognosis in patients with usually early-onset, non-ketotic, insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation carriers. This study describes the first 10 years of genetic testing for MODY in The Netherlands in terms of volume and test positive rate, medical setting, purpose of the test and age of patients tested. Some analyses focus on the most prevalent subtype, HNF1A MODY. Data were retrospectively extracted from a laboratory database. In total, 502 individuals were identified with a pathogenic mutation in HNF4A, GCK or HNF1A between 2001 and 2010. Although mutation scanning for MODY was used at an increasing rate, cascade testing was only used for one relative, on average, per positive index patient. Testing for HNF1A MODY was mostly requested by internists and paediatricians, often from regional hospitals. Primary care physicians and clinical geneticists rarely requested genetic testing for HNF1A MODY. Clinical geneticists requested cascade testing relatively more often than other health professionals. A substantial proportion (currently 29%) of HNF1A MODY probands was at least 40 years old at the time of testing. In conclusion, the number of individuals genetically tested for MODY so far in The Netherlands is low compared with previously predicted numbers of patients. Doctors' valuation of the test and patients' and family members' response to (an offer of) genetic testing on the other hand need to be investigated. Efforts may be needed to develop and implement translational guidelines.
Devos, Steven A; Constandt, Lieve; Tupker, Ron A; Noz, Kathy C; Lucker, Georges P H; Bruynzeel, Derk P; Schuttelaar, Marie-Louise A; Kruyswijk, Mente R J; van Zuuren, Esther J; Vink, Jaqueline; Coenraads, Pieter-Jan; Kiemeney, Lambertus A L M; van der Valk, Pieter G M
Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance-allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong reactions. To improve the appraisal of FM patch-test reactions, we studied the relevance of reactions of different strength. We also studied the predictive value of the following on the relevance of the initial FM patch-test results: patch-test results of a repeated FM test; results of patch tests with balsam of Peru, colophony, and ingredients of the mix; and (history of) atopic dermatitis. One hundred thirty-eight patients who had doubtful positive (?+) or positive (+ to +++) reactions were included in the study. We determined relevance by history taking, location and course of the dermatitis, and additional patch testing. Patients were retested with FM and with each ingredient separately. The relevance of reactions to FM increases with the strength of the reactions. Predictors of relevance are the results of retesting with FM, the results of tests with the ingredients, and a history and/or present symptoms of atopic dermatitis. Retesting with FM and its ingredients may add to the benefit of patch testing.
Full Text Available The low beta of proton or ion beams favors an electrostatic pickup to measure the transverse beam centroid position. Often papers on beam position monitors (BPM are focused on a particular aspect of the problem; however, it is important to consider all various issues of a position measurement system. Based on our experience at the IPHI (high intensity injector proton facility at CEA-Saclay, this paper will address all aspects to design, test, and calibrate a BPM for proton linear accelerators, while emphasizing the determination of the absolute beam position. We present details of the readout electronics, and describe the calibration of the BPM using a test station. For calculation and simulation of the electrical signals we developed a Mathematica script. The error analysis presented, on the basis of six BPMs installed in the high energy section of IPHI, demonstrates the expected accuracy of the position measurement. These studies also identify the parameters that could improve the performance of the beam position control. The experience from these developments is currently being used for the BPM design and test stand dedicated to the Spiral2 accelerator at Ganil-Caen which will deliver heavy ion beams.
J S Pasricha
Full Text Available To evaluate the suitability of some chemicals to act as bases for antigens for patch tests, patch tests were performed with these agents in patients having contact dermatitis. Propylene glycol′used as such produced positive reactions in 25 (50% patients of which 12 were 2 + or more, polyethylene glycol 200 produced positive reactions in 9 (18% cases of which 4 cases were 2 + or more, a mixture of liquid paraffin and hard paraffin gave rise to positive reactions in 10 (10% cases 3 of these being 2 +, a mixture of liquid paraffin and bees wax was positive in 14 (14,Yo cases 3 of these being 2 +, yellow petrolatum was positive in 4 (8% cases, one of which was 2 +, white petrolatum was positive in S (6% cases all of these being + reactions only, and glycerol gave rise to a I + reaction in only one (2% caw. In tropical countries, water should be as base for as many antigens as possible for others, a control test with the b must be included.
The low beta of proton or ion beams favors an electrostatic pickup to measure the transverse beam centroid position. Often papers on beam position monitors (BPM) are focused on a particular aspect of the problem; however, it is important to consider all various issues of a position measurement system. Based on our experience at the IPHI (high intensity injector proton) facility at CEA-Saclay, this paper will address all aspects to design, test, and calibrate a BPM for proton linear accelerators, while emphasizing the determination of the absolute beam position. We present details of the readout electronics, and describe the calibration of the BPM using a test station. For calculation and simulation of the electrical signals we developed a Mathematica script. The error analysis presented, on the basis of six BPMs installed in the high energy section of IPHI, demonstrates the expected accuracy of the position measurement. These studies also identify the parameters that could improve the performance of the beam position control. The experience from these developments is currently being used for the BPM design and test stand dedicated to the Spiral2 accelerator at Ganil-Caen which will deliver heavy ion beams.
Zhan, Xiang; Epstein, Michael P; Ghosh, Debashis
Recently, gene set-based approaches have become very popular in gene expression profiling studies for assessing how genetic variants are related to disease outcomes. Since most genes are not differentially expressed, existing pathway tests considering all genes within a pathway suffer from considerable noise and power loss. Moreover, for a differentially expressed pathway, it is of interest to select important genes that drive the effect of the pathway. In this article, we propose an adaptive association test using double kernel machines (DKM), which can both select important genes within the pathway as well as test for the overall genetic pathway effect. This DKM procedure first uses the garrote kernel machines (GKM) test for the purposes of subset selection and then the least squares kernel machine (LSKM) test for testing the effect of the subset of genes. An appealing feature of the kernel machine framework is that it can provide a flexible and unified method for multi-dimensional modeling of the genetic pathway effect allowing for both parametric and nonparametric components. This DKM approach is illustrated with application to simulated data as well as to data from a neuroimaging genetics study.
Lucon, E.; McCowan, C. N.; Santoyo, R. A.
An investigation has been conducted on the influence of impact machine variables and specimen positioning on characteristic forces and absorbed energies from instrumented Charpy tests. Brittle and ductile fracture behavior has been investigated by testing NIST reference samples of low, high and super-high energy levels. Test machine variables included tightness of foundation, anvil and striker bolts, and the position of the center of percussion with respect to the center of strike. For specimen positioning, we tested samples which had been moved away or sideways with respect to the anvils. In order to assess the influence of the various factors, we compared mean values in the reference (unaltered) and altered conditions; for machine variables, t-test analyses were also performed in order to evaluate the statistical significance of the observed differences. Our results indicate that the only circumstance which resulted in variations larger than 5 percent for both brittle and ductile specimens is when the sample is not in contact with the anvils. These findings should be taken into account in future revisions of instrumented Charpy test standards.
Lucon, E.; McCowan, C. N.; Santoyo, R. A.
An investigation has been conducted on the influence of impact machine variables and specimen positioning on characteristic forces and absorbed energies from instrumented Charpy tests. Brittle and ductile fracture behavior has been investigated by testing NIST reference samples of low, high and super-high energy levels. Test machine variables included tightness of foundation, anvil and striker bolts, and the position of the center of percussion with respect to the center of strike. For specimen positioning, we tested samples which had been moved away or sideways with respect to the anvils. In order to assess the influence of the various factors, we compared mean values in the reference (unaltered) and altered conditions; for machine variables, t-test analyses were also performed in order to evaluate the statistical significance of the observed differences. Our results indicate that the only circumstance which resulted in variations larger than 5 percent for both brittle and ductile specimens is when the sample is not in contact with the anvils. These findings should be taken into account in future revisions of instrumented Charpy test standards.
Teschke, Rolf; Frenzel, Christian; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel
To analyze the validity of applied test criteria and causality assessment methods in assumed Herbalife hepatotoxicity with positive reexposure tests. We searched the Medline database for suspected cases of Herbalife hepatotoxicity and retrieved 53 cases including eight cases with a positive unintentional reexposure and a high causality level for Herbalife. First, analysis of these eight cases focused on the data quality of the positive reexposure cases, requiring a baseline value of alanine aminotransferase (ALT) Herbalife in these eight cases were probable (n = 1), unlikely (n = 4), and excluded (n = 3). Confounding variables included low data quality, alternative diagnoses, poor exclusion of important other causes, and comedication by drugs and herbs in 6/8 cases. More specifically, problems were evident in some cases regarding temporal association, daily doses, exact start and end dates of product use, actual data of laboratory parameters such as ALT, and exact dechallenge characteristics. Shortcomings included scattered exclusion of hepatitis A-C, cytomegalovirus and Epstein Barr virus infection with only globally presented or lacking parameters. Hepatitis E virus infection was considered in one single patient and found positive, infections by herpes simplex virus and varicella zoster virus were excluded in none. Only one case fulfilled positive reexposure test criteria in initially assumed Herbalife hepatotoxicity, with lower CIOMS based causality gradings for the other cases than hitherto proposed.
Mezuk, Briana; Myers, John M; Kendler, Kenneth S
We tested 3 hypotheses-social causation, social drift, and common cause-regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r(2) = -0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model.
Prevalence of Mantoux test positivity among apparently healthy children in Maiduguri, Nigeria. MG Mustapha, AM Garba, AI Rabasa, MS Gimba. Abstract. Background. The impact of tuberculosis (TB) is highest in the developing countries of Asia and Africa, especially among children, in whom the diagnosis is challenging.
Rebolj, Matejka; Pribac, Igor; Lynge, Elsebeth
Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated...
With the identification of the genes responsible for autosomal dominant early-onset familial Alzheimer's disease (FAD genes), there is a considerable interest in the application of this genetic information in medical practice through genetic testing and counseling. Pathogenic mutations in the PSEN1 and PSEN2 genes encoding presenilin-1 and -2, and the APP gene encoding amyloid b precursor protein, account for 18-50% of familial EOAD cases with autosomal dominant pattern of inheritance. A clinical algorithm of genetic testing and counseling proposed for families with AD has been presented here. A screening for mutations in the APP, PSEN1, and PSEN2 genes is available to individuals with AD symptoms and at-risk children or siblings of patients with early-onset disease determined by a known mutation. In an early-onset family, a known mutation in an affected patient puts the siblings and children at a 50% risk of inheriting the same mutation. The goal of genetic testing is to identify at-risk individuals in order to facilitate early and effective treatments in the symptomatic person based on an individual's genotype and strategies to delay the onset of disease in the presymptomatic mutation carriers. However, there are several arguments against the use of genetic testing both presymptomatically (unpredictable psychological consequences of information about a genetic defect for family members) and as a diagnostic tool for the differential diagnosis of dementia in general practice (a risk of errors in an interpretation of mutation penetrance and its secondary effects on family members, especially for novel mutations; the possibility of coexistence of another form of dementia at the presence of a mutation). Currently, APOE genotyping for presymptomatic individuals with a family history of late-onset disease is not recommended. The APOE4 allele may only confer greater risk for disease, but its presence is not conclusive for the development of AD.
Freedman, Barry I; Fletcher, Alison J; Sanghani, Vivek R; Spainhour, Mitzie; Graham, Angelina W; Russell, Gregory B; Cooke Bailey, Jessica N; Iltis, Ana S; King, Nancy M P
Population ancestry-based differences exist in genetic risk for many kidney diseases. Substantial debate remains regarding returning genetic test results to participants. African-Americans (AAs) and European-Americans (EAs) at risk for end-stage kidney disease were queried for views on the value and use of genetic testing in research. A standardized survey regarding attitudes toward genetic testing was administered to 130 individuals (64 AA, 66 EA) with first-degree relatives on dialysis. Fisher's exact test was used to assess differences in participant attitudes between population groups. Mean (SD) age of surveyed AAs and EAs was 45.5 (12.8) and 50.5 (14.4) years, respectively (p = 0.04), with similar familial relationships (p = 0.22). AAs and EAs wished to know their test results if risk could be: (1) reduced by diet or exercise (100 and 98%, p = 0.99); (2) reduced by medical treatment (100 and 98%, p = 0.99), or (3) if no treatments were available (90 and 82%, p = 0.21). If informed they lacked a disease susceptibility variant, 87% of AAs and 88% of EAs would be extremely or pretty likely to inform family members (p = 0.84). If informed they had a disease susceptibility variant, 92% of AAs and 89% of EAs would be extremely or pretty likely to inform their family (p = 0.43). Attitudes toward obtaining and using genetic test results for disease in research contexts were similar in AAs and EAs at risk for end-stage kidney disease. A substantial majority would want information regardless of available treatments and would share the information with the family. These results have important implications for patient care, study design and the informed consent process. © 2013 S. Karger AG, Basel.
Douma, Kirsten F L; Smets, Ellen M A; Allain, Dawn C
Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to gain insight in their perceptions, attitudes and knowledge. Two publically accessible databases were used to invite NGHPs providing cancer genetic services to complete a questionnaire. The survey assessed: sociodemographic attributes, experience in ordering hereditary cancer genetic testing, attitude, knowledge, perception of communication skills (e.g. information giving, decision-making) and educational needs. Of all respondents (N = 49, response rate 11%), most have a positive view of their own information giving (mean = 53.91, range 13-65) and decision making skills (64-77% depending on topic). NGHPs feel responsible for enabling disease and treatment related behavior (89-91%). However, 20-30% reported difficulties managing patients' emotions and did not see management of long-term emotions as their responsibility. Correct answers on knowledge questions ranged between 41 and 96%. Higher knowledge was associated with more confidence in NGHPs' own communication skills (r(s) = .33, p = 0.03). Although NGHPs have a positive view of their communication skills, they perceive more difficulties managing emotions. The association between less confidence in communication skills and lower knowledge level suggests awareness of knowledge gaps affects confidence. NGHPs might benefit from education about managing client emotions. Further research using observation of actual counselling consultations is needed to investigate the skills of this specific group of providers.
Yang, S; Jiang, Y; Jin, Y M; Zhang, J Y; Li, Y
Objective: To observe the clinical characteristics of allergic conjunctivitis, and the correlations with skin prick test results. Methods: A retrospective study. Forty patients with positive skin prick test result were included. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 5 groups. All dates were analyzed for the dependence, normality and homogeneity of variance. Chi-square test, Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlation analysis were performed accordingly. Results: Among 40 patients, 18(45.0%) had a clinical diagnosis of seasonal allergic conjunctivitis, 14(35.0%) had perennial allergic conjunctivitis, 5(12.5%) had vernal keratoconjunctivitis, and 2(5.0%) had atopic keratoconjunctivits, and 1(2.5%) had giant papillary conjunctivitis. There was no significant difference in the number of symptoms and signs score among different types of allergic conjunctivitis, the score of itching and hyperemia had a positive relationship with the number of positive allergens ( r =0.74, Ptest of the allergen, the more symptoms and signs encountered in terms of severity. Conclusion: Seasonal allergic conjunctivitis was the most prevalent disorder, the most important clinical characteristics of allergic conjunctivitis are itching and conjunctival congestion, the main allergens are dust and pollens, patients may be sensitive to multiple allergens. (Chin J Ophthalmol, 2017, 53: 689-693) .
Sijmons, R. H.; Van Langen, I. M.; Sijmons, J. G.
Genetic testing is traditionally preceded by counselling to discuss its advantages and disadvantages with individuals so they can make informed decisions. The new technique of whole genome or exome sequencing, which is currently only used in research settings, can identify many gene mutations,
Nicol, Dianne; Liddicoat, John
Health policy and law reform agencies lack a sound evidence base of the impacts of patents on innovation and access to healthcare to assist them in their deliberations. This paper reports the results of a survey of managers of Australian genetic testing laboratories that asked a series of questions relating to the tests they perform, whether they pay to access patented inventions and whether they have received notifications from patent holders about patents associated with particular tests. Some diagnostics facilities are exposed to patent costs, but they are all located in the private sector. No public hospitals reported paying licence fees or royalties beyond those included in the price of commercial test kits. Some respondents reported having received enforcement notices from patent holders, but almost all related to the widely known breast cancer-associated patents. Respondents were also asked for their views on the most effective mechanisms to protect their ability to provide genetic tests now and in the future. Going to the media, paying licence fees, ignoring patent rights and relying on the government to take action were widely seen as most effective. Litigation and applications for compulsory licences were seen as some of the least effective mechanisms. These results provide an evidence base for development of health policy and law reform. What is known about the topic? The impact of patents on the delivery of genetic testing services remains unclear in Australia. What does this paper add? The survey reported in this paper suggests that, aside from well-known enforcement actions relating to the breast cancer associated patents, there is little evidence that providers of genetic testing services are being exposed to aggressive patent-enforcement practices. What are the implications for practitioners? Although patent-enforcement actions may increase in the future, a range of strategies are available to providers of testing services to protect them against
Ferreira-Gonzalez, Andrea; Teutsch, Steven; Williams, Marc S; Au, Sylvia M; Fitzgerald, Kevin T; Miller, Paul Steven; Fomous, Cathy
As genetic testing technology is integrated into healthcare, increasingly detailed information about individual and population genetic variation is available to patients and providers. Health professionals use genetic testing to diagnose or assess the risk of disease in individuals, families and populations and to guide healthcare decisions. Consumers are beginning to explore personalized genomic services in an effort to learn more about their risk for common diseases. Scientific and technological advances in genetic testing, as with any newly introduced medical technology, present certain challenges to existing frameworks of oversight. In addition, the growing use of genetic testing will require a significant investment in evidence-based assessments to understand the validity and utility of these tests in clinical and personal decisionmaking. To optimize the use of genetic testing in healthcare, all sectors of the oversight system need to be strengthened and yet remain flexible in order to adapt to advances that will inevitably increase the range of genetic tests and methodologies.
Tercyak, Kenneth P.; Mays, Darren; DeMarco, Tiffani A.; Peshkin, Beth N.; Valdimarsdottir, Heiddis B.; Schneider, Katherine A.; Garber, Judy E.; Patenaude, Andrea Farkas
Background Although BRCA1/2 genetic testing is discouraged in minors, mothers may disclose their own results to their children. Factors affecting patients’ disclosure decisions and patient outcomes of disclosure are largely unknown. Methods Mothers (N = 221) of children ages 8-21 enrolled in this prospective study of family communication about cancer genetic testing. Patients underwent BRCA1/2 genetic counseling and testing, and completed standardized behavioral assessments prior to and 1-month following receipt of their results. Results Most patients (62.4%) disclosed BRCA1/2 test results to their child. Patients were more likely to disclose if they received negative or uninformative vs. positive results (OR = 3.11; 95% CI = 1.11 - 8.71; P = .03), their child was ≥ 13 years of age vs. younger (OR = 5.43; 95% CI = 2.18 - 13.53; P Post-decision satisfaction about disclosure was lowest among nondisclosing patients (P information is perceived as beneficial. Satisfaction with disclosure decision-making remains lowest among nondisclosing and conflicted patients. Family communication decision support adjuncts to genetic counseling are needed to help ameliorate these effects. Impact This study describes the prevalence of family communication about maternal BRCA1/2 genetic testing with minor children, and decisions and outcomes of disclosure. PMID:23825307
Paquin, Ryan S; Richards, Adam S; Koehly, Laura M; McBride, Colleen M
Varying perspectives exist regarding the implications of genetic susceptibility testing for common disease, with some anticipating adverse effects and others expecting positive outcomes; however, little is known about the characteristics of people who are most likely to be interested in direct-to-consumer genetic testing. To that end, this study examines the association of individual dispositional differences with health risk perceptions and online information seeking related to a free genetic susceptibility test. Healthy adults enrolled in a large health maintenance organization were surveyed by telephone. Eligible participants (N = 1,959) were given access to a secure website that provided risk and benefit information about a genetic susceptibility test and given the option to be tested. Neuroticism was associated with increased perceptions of disease risk but not with logging on. Those scoring high in conscientiousness were more likely to log on. We found no evidence that neuroticism, a dispositional characteristic commonly linked to adverse emotional response, was predictive of online genetic information seeking in this sample of healthy adults.
Antoñanzas, Fernando; Rodríguez-Ibeas, R; Hutter, M F; Lorente, R; Juárez, C; Pinillos, M
We review the published economic evaluation studies applied to genetic technologies in the EU to know the main diseases addressed by these studies, the ways the studies were conducted and to assess the efficiency of these new technologies. The final aim of this review was to understand the possibilities of the economic evaluations performed up to date as a tool to contribute to decision making in this area. We have reviewed a set of articles found in several databases until March 2010. Literature searches were made in the following databases: PubMed; Euronheed; Centre for Reviews and Dissemination of the University of York-Health Technology Assessment, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database; and Scopus. The algorithm was "(screening or diagnosis) and genetic and (cost or economic) and (country EU27)". We included studies if they met the following criteria: (1) a genetic technology was analysed; (2) human DNA must be tested for; (3) the analysis was a real economic evaluation or a cost study, and (4) the articles had to be related to any EU Member State. We initially found 3,559 papers on genetic testing but only 92 articles of economic analysis referred to a wide range of genetic diseases matched the inclusion criteria. The most studied diseases were as follows: cystic fibrosis (12), breast and ovarian cancer (8), hereditary hemochromatosis (6), Down's syndrome (7), colorectal cancer (5), familial hypercholesterolaemia (5), prostate cancer (4), and thrombophilia (4). Genetic tests were mostly used for screening purposes, and cost-effectiveness analysis is the most common type of economic study. The analysed gene technologies are deemed to be efficient for some specific population groups and screening algorithms according to the values of their cost-effectiveness ratios that were below the commonly accepted threshold of 30,000€. Economic evaluation of genetic technologies matters but the number of published studies is still
To add an article against the misuse of a reproductive technology and a genetic engineering, theSwiss Federal Constitution was revised in 1992 through an initiative in 1987. On the basis of thisarticle of the constitution, the Reproductive Medicine Act and the Stem Cell Research Act wereenacted in turns; then, the Federal Law on the Genetic Testing of Humans was enacted in October2004. This paper treats a process of the revision of the constitution in 1992 and the enactment of thelaw in 2004....
Full Text Available Genetic markers have been used at Institute of Field and Vegetable Crops in Novi Sad for a number of years, both for seed quality control and for research purposes. The Laboratory for Seed Testing was the first in the former Yugoslavia to use the method of control of hybrid seed genetic purity based on enzymatic polymorphism. This paper presents the application of protein markers, isozymes, seed storage proteins and DNA markers for evaluation of seed and breeding materials of various agricultural crops in Serbia.
Hanoch, Yaniv; Miron-Shatz, Talya; Rolison, Jonathan J; Ozanne, Elissa
The majority of women (71%) who undergo BRCA1/2 testing-designed to identify genetic mutations associated with increased risk of cancer-receive results that are termed 'ambiguous' or 'uninformative negative'. How women interpret these results and the association with numerical ability was examined. In this study, 477 women at increased risk for breast and ovarian cancer were recruited via the Cancer Genetics Network. They were presented with information about the four different possible BRCA1/2 test results-positive, true negative, ambiguous and uninformative negative-and asked to indicate which of six options represents the best response. Participants were then asked which treatment options they thought a woman receiving the results should discuss with her doctor. Finally, participants completed measures of objective and subjective numeracy. Almost all of the participants correctly interpreted the positive and negative BRCA1/2 genetic test results. However, they encountered difficulties interpreting the uninformative and ambiguous BRCA1/2 genetic test results. Participants were almost equally likely to think either that the woman had learned nothing from the test result or that she was as likely to develop cancer as the average woman. Highly numerate participants were more likely to correctly interpret inconclusive test results (ambiguous, OR = 1.62; 95% CI [1.28, 2.07]; p psychological ramifications of genetic testing, healthcare professionals should consider devoting extra effort to ensuring proper comprehension of ambiguous and uninformative negative test results by women. Copyright © 2014 John Wiley & Sons, Ltd.
... their family history of cancer. Depending on a woman’s family history, the doctor or nurse may then use a ... against routine genetic counseling or BRCA testing of women whose family history is not associated with an increased risk for ...
Hariansyah, A. R.; Raharjo, A.; Zainuri, A.; Parwoto, Y.; Prasetiyo, D.; Prastowo, S.; Widyas, N.
Bali cattle (Bos javanicus) is Indonesian indigenous cattle with having superior genetics potential on fitness traits in tropical environment and low feed quality. Bali Cattle Breeding Center Pulukan Indonesia conducted progeny test per annum in order to select bulls using offspring’s phenotype. This paper aimed to estimate the genetic parameters of yearling weight in Bali cattle progeny test populations and to observe the variation between periods in the above breeding center. Data were collected from the year of 2013 to 2014. There were four bulls (3 tests, 1 AI control) in 2013 and five bulls (4 tests, 1 AI) in 2014. Thirty breeding females were allocated per paddock per bull and allowed to mate naturally. In total 80 and 104 offspring’s records were obtained from 2013 and 2014 data, respectively. We built half-sib family model to estimate the additive genetic variance due to the sire and later estimate the breeding value (EBV) of each sire. Results showed that in 2013 the heritability (h2) for yearling weight was 0.19 while in 2014 was 0.79. In both years, tested bulls had higher EBV compared to the control bulls. The remarkable difference of heritability between years was due to the variations among bull candidates which might differ every year with regards to their origins. The fact that the EBV of tested bulls were higher than the control bulls gave us insight that despite the conservation policy and the continuous departure of Bali cattle bulls outside the Island, the population could still maintain its genetic quality.
Hocaoğlu, Arzu Babayiğit; Erge, Duygu Olmez; Anal, Ozden; Makay, Balahan; Uzuner, Nevin; Karaman, Ozkan
The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis.
This article contains a discussion paper on the use of exotic species and genetically modified organisms in aquaculture and enhanced fisheries, together with a summary of ICLARM's (International Center for Living Aquatic Resources Management, Philippines) current position on this important topic.
Christiansen, Camilla Worm; Gerdes, Anne-Marie Axø
Direct-to-consumer genetic tests are sold over the internet to consumers all over the world - including Denmark. No regulation of these tests has been introduced neither in Denmark nor in Europe, even though they have been on the market since 2007. Such tests have several advantages, but indeed also a long list of potential disadvantages, which are most often ignored, and among these is insufficient training of general practitioners in performing the necessary counselling but also the risk of increased expenses to unnecessary follow-up consultations.
Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J
Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p testing (all p testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.
Huang, Ming-Yi; Huston, Sally A; Perri, Matthew
The purpose of this study was to assess consumer preferences for predictive genetic testing for Alzheimer disease in the United States. A rating conjoint analysis was conducted using an anonymous online survey distributed by Qualtrics to a general population panel in April 2011 in the United States. The study design included three attributes: Accuracy (40%, 80%, and 100%), Treatment Availability (Cure is available/Drug for symptom relief but no cure), and Anonymity (Anonymous/Not anonymous). A total of 12 scenarios were used to elicit people's preference, assessed by an 11-point scale. The respondents also indicated their highest willingness-to-pay (WTP) for each scenario through open-ended questions. A total of 295 responses were collected over 4 days. The most important attribute for the aggregate model was Accuracy, contributing 64.73% to the preference rating. Treatment Availability and Anonymity contributed 20.72% and 14.59%, respectively, to the preference rating. The median WTP for the highest-rating scenario (Accuracy 100%, a cure is available, test result is anonymous) was $100 (mean = $276). The median WTP for the lowest-rating scenario (40% accuracy, no cure but drugs for symptom relief, not anonymous) was zero (mean = $34). The results of this study highlight attributes people find important when making the hypothetical decision to obtain an AD genetic test. These results should be of interests to policy makers, genetic test developers and health care providers.
Xu, C; Lang-Muritano, M; Phan-Hug, F; Dwyer, A A; Sykiotis, G P; Cassatella, D; Acierno, J; Mohammadi, M; Pitteloud, N
Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Rubel, M A; Werner-Lin, A; Barg, F K; Bernhardt, B A
To assess how participants receiving abnormal prenatal genetic testing results seek information and understand the implications of results, 27 US female patients and 12 of their male partners receiving positive prenatal microarray testing results completed semi-structured phone interviews. These interviews documented participant experiences with chromosomal microarray testing, understanding of and emotional response to receiving results, factors affecting decision-making about testing and pregnancy termination, and psychosocial needs throughout the testing process. Interview data were analyzed using a modified grounded theory approach. In the absence of certainty about the implications of results, understanding of results is shaped by biomedical expert knowledge (BEK) and cultural expert knowledge (CEK). When there is a dearth of BEK, as in the case of receiving results of uncertain significance, participants rely on CEK, including religious/spiritual beliefs, "gut instinct," embodied knowledge, and social network informants. CEK is a powerful platform to guide understanding of prenatal genetic testing results. The utility of culturally situated expert knowledge during testing uncertainty emphasizes that decision-making occurs within discourses beyond the biomedical domain. These forms of "knowing" may be integrated into clinical consideration of efficacious patient assessment and counseling.
Fanshawe, Thomas R; Prevost, A Toby; Roberts, J Scott; Green, Robert C; Armstrong, David; Marteau, Theresa M
This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer's disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed epsilon4-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in epsilon4-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving epsilon4-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and epsilon4-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an epsilon4 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates.
Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ
These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external
Zhu, Chang-feng; Peng, Jing
To find the longitudinal genetic effects on mandibular position in mixed dentition. The sample used in this study consisted of lateral cephalograms of eighty-nine pairs of female twins in Beijing. With a mixed longitudinal method, the effective twins were 183 pairs(monozygous 110 pairs and dizygous 73 ones). The genetic and environmental effects on mandibular position were analyzed by statistical methods in female twins from six to twelve years old. Statistical comparisons revealed significant (Pchin is the most subjective to environment change, then the mandibular angle, and the condyle is the least. Using N and S as references, the environmental influence on heights showed different order from the most to least changeable: The mandibular angle, the condyle and the chin. In later stage of our observation, the mandibular morphology and growth type might be family inherited. For environmental influences plays important roles on mandibular position, these findings can be used in orthodontic treatment planning.
Andréa Wiszmeg; Susanne Lundin; Eva Torkelson; Niclas Hagen; Cecilia Lundberg
A qualitative pilot study on the attitudes of some citizens in southern Sweden toward predictive genetic testing – and a quantitative nation wide opinion poll targeting the same issues, was initiated by the Cultural Scientific Research Team of BAGADILICO. The latter is an international biomedical research environment on neurological disease at Lund University. The data of the two studies crystallized through analysis into themes around which the informants’ personal negotiations of opinions a...
Lawson, Victoria; Gharibshahi, Shahram
The diagnosis of inherited neuropathies can be challenging in several ways. First, a hereditary neuropathy must be suspected. Although some family histories are clear with multiple members affected, other families require directed inquiry. Second, even when a hereditary neuropathy is clear, it can be difficult to make a genetic characterization. The field of genotyping is expanding so rapidly, it is difficult to know what tests to order. The authors share their guidelines for the diagnosis of inherited neuropathies. © Thieme Medical Publishers.
Alagrund, Katariina; Orpana, Arto K
The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.
Adedokun, Babatunde O; Yusuf, Bidemi O; Lasisi, J Taye; Jinadu, A A; Sunmonu, M T; Ashanke, A F; Lasisi, O Akeem
Understanding the perceptions of genetic testing by members of the deaf community may help in planning deafness genetics research, especially so in the context of strong adherence to cultural values as found among native Africans. Among Yorubas in Nigeria, deafness is perceived to be caused by some offensive actions of the mother during pregnancy, spiritual attack, and childhood infections. We studied attitudes towards, and acceptance of genetic testing by the deaf community in Nigeria. Structured questionnaires were administered to individuals sampled from the Vocational Training Centre for the Deaf, the religious Community, and government schools, among others. The main survey items elicited information about the community in which the deaf people participate, their awareness of genetic testing, whether or not they view genetic testing as acceptable, and their understanding of the purpose of genetic testing. There were 150 deaf participants (61.3 % males, 38.7 % females) with mean age of 26.7 years ±9.8. A majority of survey respondents indicated they relate only with other members of the deaf community (78 %) and reported believing genetic testing does more good than harm (79.3 %); 57 % expressed interest in genetic testing. Interest in genetic testing for deafness or in genetic testing in pregnancy was not related to whether respondents relate primarily to the deaf or to the hearing community. However, a significantly higher number of male respondents and respondents with low education reported interest in genetic testing.
Tian Lichao; Chen Yuanbo; Sun Zhijia; Tang Bin; Zhou Jianrong; Qi Huirong; Liu Rongguang; Zhang Jian; Yang Guian; Xu Hong
China Spallation Neutron Source (CSNS), one of the Major scientific apparatuses of the national Eleventh Five-Year Plane, is under construction and three spectrumeters will be constructed in the first phase of the project. A 2D position sensitive neutron detector has been constructed for the Multifunctional Reflect spectrumeter (MR) in Institute of High Energy Physics (IHEP). The basic operation principle of the detector and the test on the residual stress diffractometer of Chinese Advanced Research Reactor (CARR) in China Institute of Atomic Energy (CIAE) is introduced in this paper. The results show that it has a good position resolution of l.18 mm (FWHM) for the neutrons of l.37 A and 2D imaging ability, which is consistent with the theory. It can satisfy the requirements of MR and lays the foundation for the construction of larger neutron detectors. (authors)
Lui, Kung-Jong; Chang, Kuang-Chao
In studies of screening accuracy, we may commonly encounter the data in which a confirmatory procedure is administered to only those subjects with screen positives for ethical concerns. We focus our discussion on simultaneously testing equality of sensitivity and specificity between two binary screening tests when only subjects with screen positives receive the confirmatory procedure. We develop four asymptotic test procedures and one exact test procedure. We derive sample size calculation formula for a desired power of detecting a difference at a given nominal [Formula: see text]-level. We employ Monte Carlo simulation to evaluate the performance of these test procedures and the accuracy of the sample size calculation formula developed here in a variety of situations. Finally, we use the data obtained from a study of the prostate-specific-antigen test and digital rectal examination test on 949 Black men to illustrate the practical use of these test procedures and the sample size calculation formula.
Douma, Kirsten F. L.; Smets, Ellen M. A.; Allain, Dawn C.
Non-genetic health professionals (NGHPs) have insufficient knowledge of cancer genetics, express educational needs and are unprepared to counsel their patients regarding their genetic test results. So far, it is unclear how NGHPs perceive their own communication skills. This study was undertaken to
Cornelia Di Gaetano
Full Text Available The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5 when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.
Musleh, Mohammud; Ashworth, Jane; Black, Graeme; Hall, Georgina
Childhood cataract (CC) has an incidence of 3.5 per 10,000 by age 15 years. Diagnosis of any underlying cause is important to ensure effective and prompt management of multisystem complications, to facilitate accurate genetic counselling and to streamline multidisciplinary care. Next generation sequencing (NGS) has been shown to be effective in providing an underlying diagnosis in 70% of patients with CC in a research setting. This project aimed to integrate NGS testing in CC within six months of presentation and increase the rate of diagnosis. A retrospective case note review was undertaken to define the baseline efficacy of current care in providing a precise diagnosis. Quality improvement methods were used to integrate and optimize NGS testing in clinical care and measure the improvements made. The percentage of children receiving an NGS result within six months increased from 26% to 71% during the project period. The mean time to NGS testing and receiving a report decreased and there was a reduction in variation over the study period. Several patients and families had a change in management or genetic counselling as a direct result of the diagnosis given by the NGS test. The current recommended investigation of patients with bilateral CC is ineffective in identifying a diagnosis. Quality Improvement methods have facilitated successful integration of NGS testing into clinical care, improving time to diagnosis and leading to development of a new care pathway.
Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H
Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.
Lima, Paulo Ricardo Martins; Paiva, Samuel Rezende; Cobuci, Jaime Araujo; Braccini Neto, José; Machado, Carlos Henrique Cavallari; McManus, Concepta
The objective of this study was to characterize Nelore cattle on central performance tests in pasture, ranked by the visual classification method EPMURAS (structure, precocity, muscle, navel, breed, posture, and sexual characteristics), and to estimate genetic and phenotypic correlations between these parameters, including visual as well as production traits (initial and final weight on test, weight gain, and weight corrected for 550 days). The information used in the study was obtained on 21,032 Nelore bulls which were participants in the central performance test at pasture of the Brazilian Association for Zebu Breeders (ABCZ). Heritabilities obtained were from 0.19 to 0.50. Phenotypic correlations were positive from 0.70 to 0.97 between the weight traits, from 0.65 to 0.74 between visual characteristics, and from 0.29 to 0.47 between visual characteristics and weight traits. The genetic correlations were positive ranging from 0.80 to 0.98 between the characteristics of structure, precocity and musculature, from 0.13 to 0.64 between the growth characteristics, and from 0.41 to 0.97 between visual scores and weight gains. Heritability and genetic correlations indicate that the use of visual scores, along with the selection for growth characteristics, can bring positive results in selection of beef cattle for rearing on pasture.
Funk, W Chris; Murphy, Melanie A
Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.
Carere, Deanna Alexis; Kraft, Peter; Kaphingst, Kimberly A; Roberts, J Scott; Green, Robert C
The aim of this study was to measure changes to genetics knowledge and self-efficacy following personal genomic testing (PGT). New customers of 23andMe and Pathway Genomics completed a series of online surveys. We measured genetics knowledge (nine true/false items) and genetics self-efficacy (five Likert-scale items) before receipt of results and 6 months after results and used paired methods to evaluate change over time. Correlates of change (e.g., decision regret) were identified using linear regression. 998 PGT customers (59.9% female; 85.8% White; mean age 46.9 ± 15.5 years) were included in our analyses. Mean genetics knowledge score was 8.15 ± 0.95 (out of 9) at baseline and 8.25 ± 0.92 at 6 months (P = 0.0024). Mean self-efficacy score was 29.06 ± 5.59 (out of 35) at baseline and 27.7 ± 5.46 at 6 months (P reported lower self-efficacy following PGT. Change in self-efficacy was positively associated with health-care provider consultation (P = 0.0042), impact of PGT on perceived control over one's health (P consumers in response to receiving complex genetic information.Genet Med 18 1, 65-72.
Baum, Amber E; Solberg, Leah C; Churchill, Gary A; Ahmadiyeh, Nasim; Takahashi, Joseph S; Redei, Eva E
Inbred Wistar-Kyoto rats consistently display hypoactivity in tests of emotional behavior. We used them to test the hypothesis that the genetic factors underlying the behavioral decision-making process will vary in different environmental contexts. The contexts used were the open-field test (OFT), a novel environment with no explicit threats present, and the defensive-burying test (DB), a habituated environment into which a threat has been introduced. Rearing, a voluntary behavior was measured in both tests, and our study was the first to look for genetic loci affecting grooming, a relatively automatic, stress-responsive stereotyped behavior. Quantitative trait locus analysis was performed on a population of 486 F2 animals bred from reciprocal inter-crosses. The genetic architectures of DB and OFT rearing, and of DB and OFT grooming, were compared. There were no common loci affecting grooming behavior in both tests. These different contexts produced the stereotyped behavior via different pathways, and genetic factors seem to influence the decision-making pathways and not the expression of the behavior. Three loci were found that affected rearing behavior in both tests. However, in both contexts, other loci had greater effects on the behavior. Our results imply that environmental context's effects on decision-making vary depending on the category of behavior.
Severin, Franziska; Borry, Pascal; Cornel, Martina C
Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set...... testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit......, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.190....
A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.
Marjanović, Ivan V; Selak-Djokić, Biljana; Perić, Stojan; Janković, Milena; Arsenijević, Vladimir; Basta, Ivana; Lavrnić, Dragana; Stefanova, Elka; Stević, Zorica
Discovering novel mutations in C9orf72, FUS, ANG, and TDP-43 genes in ALS patients arises necessities for better clinical characterizations of these subjects. The aim is to determine clinical and cognitive profile of genetically positive Serbian ALS patients. 241 ALS patients were included in the study (17 familiar and 224 apparently sporadic). The following genes were analyzed: SOD1, C9orf72, ANG, FUS, and TDP-43. An extensive battery of classic neuropsychological tests was used in 27 ALS patients (22 SOD1 positive and 5 SOD1 negative) and 82 healthy controls (HCs). Overall 37 (15.4%) of 241 ALS patients carried mutations in tested genes-among 17 familiar ALS patients 16 (94.1%) were positive and among 224 apparently sporadic 21 (9.4%) had causative mutation. Mutations in SOD1 gene were the most common, representing 27 (73.0%) of all genetically positive ALS patients. The main clinical characteristics of SOD1 positive patients were: spinal onset in lower extremities, common sphincter and sensitive disturbances, and dysexecutive syndrome. Within SOD1 positive patients, we noticed somewhat earlier onset in patients with A145G, sensory and sphincter disturbances were dominant in patients with L144F, while D90A patients had significant sensory involvement. SOD1 negative group consisted of ten (27.0%) patients (six C9orf72, two ANG, one TDP-43, and one patient baring triple FUS, C9orf72 expansion, and ANG variants). Bulbar involvement and more extensive neuropsychological impairment (including executive, visuospatial, and memory difficulties) were the main features of SOD1 negative cohort. Our results suggest that meaningful clinical suspicion of certain ALS genotype might be made based on thorough clinical evaluation of patients.
... contractor, to have the potential to significantly affect the environment, public health and safety, or... evidence of the use of illegal drugs of employees in testing designated positions identified in this... section shall provide for random tests at a rate equal to 30 percent of the total number of employees in...
Peter, Richard; Richter, Andreas; Thistle, Paul
We examine public policy toward the use of genetic information by insurers. Individuals engage in unobservable primary prevention and have access to different prevention technologies. Thus, insurance markets are affected by moral hazard and adverse selection. Individuals can choose to take a genetic test to acquire information about their prevention technology. Information has positive decision-making value, that is, individuals may adjust their behavior based on the result of the test. However, testing also exposes individuals to uncertainty over the available insurance contract, so-called classification risk, which lowers the value of information. In our analysis we distinguish between four different policy regimes, determine the value of information under each regime and associated equilibrium outcomes on the insurance market. We show that the policy regimes can be Pareto ranked, with a duty to disclose being the preferred regime and an information ban the least preferred one. Copyright © 2017 Elsevier B.V. All rights reserved.
De Iorio Maria
Full Text Available Abstract Background Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. Results We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. Conclusions The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible.
Full Text Available Schizophrenia etiology is thought to involve an interaction between genetic and environmental factors during postnatal brain development. However, there is a fundamental gap in our understanding of the molecular mechanisms by which environmental factors interact with genetic susceptibility to trigger symptom onset and disease progression. In this review, we summarize the most recent findings implicating oxidative stress as one mechanism by which environmental insults, especially early life social stress, impact the development of schizophrenia. Based on a review of the literature and the results of our own animal model, we suggest that environmental stressors such as social isolation render parvalbumin-positive interneurons vulnerable to oxidative stress. We previously reported that social isolation stress exacerbates many of the schizophrenia-like phenotypes seen in a conditional genetic mouse model of schizophrenia in which NMDARs are selectively ablated in half of cortical and hippocampal interneurons during early postnatal development (Belforte et al., 2010. We have since revealed that this social isolation-induced effect is caused by impairments in the antioxidant defense capacity in the parvalbumin-positive interneurons in which NMDARs are ablated. We propose that this effect is mediated by the down-regulation of PGC-1α, a master regulator of mitochondrial energy metabolism and anti-oxidant defense, following the deletion of NMDARs (Jiang et al, 2013. Other potential molecular mechanisms underlying redox dysfunction upon gene and environmental interaction will be discussed, with a focus on the unique properties of parvalbumin-positive interneurons.
Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha
To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.
Heikkinen, Anna Maria; Raivisto, Teija; Kettunen, Kaisa; Kovanen, Leena; Haukka, Jari; Pakbaznejad Esmaeili, Elmira; Elg, Jessica; Gieselmann, Dirk-Rolf; Rathnayake, Nilminie; Ruokonen, Hellevi; Tervahartiala, Taina; Sorsa, Timo
In periodontitis, genetics and smoking play important roles in host immune system response. The aim of this study is to determine whether the genetic background of initial periodontitis and caries could be detected using an active matrix metalloproteinase (aMMP)-8 chairside test in Finnish adolescents. Forty-seven participants gave approval for analysis of both oral fluid collection and DNA. An aMMP-8 chairside test was performed on participants (adolescents aged 15 to 17 years), and full-mouth clinical parameters of oral health were assessed including periodontal, oral mucosal, and caries status in Eastern Finland from 2014 to 2015. DNA was extracted from oral fluid samples and genotyped for 71 polymorphisms in 29 candidate genes for periodontitis. Results were analyzed using a logistic regression model. P values were corrected for multiple testing using false discovery rate (<0.05). aMMP-8 chairside test positivity and three or more ≥4 mm pockets were associated with vitamin D receptor (VDR) (rs2228570, P = 0.002, q = 0.04) and MMP3 (rs520540, rs639752, rs679620, P = 0.0009, 0.003, 0.003, q = 0.04, respectively). None of the other single-nucleotide polymorphisms studied showed a significant association with the aMMP-8 chairside test and at least one caries lesion positivity. Genetic polymorphisms of MMP3 and VDR are linked to initial periodontitis in Finnish adolescents, and the aMMP-8 chairside test can eventually detect initial periodontitis in young patients with predisposing genetic background.
Cohen, Stephanie A; Tucker, Megan E
A previous study of genetic counselors (GCs) in the state of Indiana identified movement out of clinical positions within the past 2 years. The aims of this study were to determine if this trend is nationwide and identify reasons why GCs are leaving their positions and factors that might help employers attract and retain GCs. An email was sent to members of the American Board of Genetic Counseling with a link to an online confidential survey. There were 939 responses (23.5% response rate). Overall, 52% of GCs report being highly satisfied in their current position, although almost two thirds think about leaving and one third had changed jobs within the past 2 years. Of those who had changed jobs (n = 295), 74.9% had been working in a hospital/clinic setting but only 46.3% currently do, demonstrating a major shift out of the clinic (p < 0.001). The top three reasons cited for leaving a position were work environment/institutional climate, salary/benefits, and a lack of feeling valued/recognized as a professional. These results confirm that GCs are moving out of clinical positions and document elements of job satisfaction. We suggest points for employers to consider when trying to recruit or retain GCs.
Hann, Katie E J; Freeman, Madeleine; Fraser, Lindsay; Waller, Jo; Sanderson, Saskia C; Rahman, Belinda; Side, Lucy; Gessler, Sue; Lanceley, Anne
Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and
Full Text Available Background: Cystic fibrosis (CF is an autosomal recessive disease caused by mutations in gene encoding cystic fibrosis transmembrane regulator (CFTR protein. Over 1400 mutations found in the gene contribute to the complexity of the CF phenotypes ranging from a classic multiorgan disease commonly involving respiratory, gastrointestinal and reproductive tract to mild and monosymptomatic presentations. Pilocarpine iontophoresis is considered as standard diagnostic test for CF, but it often fails in atypical forms of CF.Methods: In order to provide an additional diagnostic test to assure the diagnosis and provide patients with a proper medical care, we performed a genetic testing on 16 adults suspected to have atypical form of CF. Following counselling, parents of patients with possible homozygote variant of mutations were tested. On a personal request testing was also performed in an adult sibling of a patient with two known mutations to investigate possible carrier hood. The allele specific polymerase chain reaction method (PCR was used to detect 29 most common mutations in the cftr gene.Results: The diagnosis was proved in 3 individuals, a homozygote for Δ F508, and two compound heterozygotes Δ F508/R1162X and Δ F508/3849+10kbC>T. In three cases only one mutation was found: I148T, 2789+5G>A and Δ F508 in a heterozygote form.Conclusions: The genetic testing for CF is a valuable diagnostic tool in atypical forms of CF. Exclusion of possible differential diagnosis is warranted because of a variable CF phenotype. In cases where only one or no mutation was detected a necessity of whole gene sequencing is indicated to exclude rare mutations and polymorphisms that could be implicated in the pathogenesis of atypical CF.
Cascella, R; Strafella, C; Longo, G; Manzo, L; Ragazzo, M; De Felici, C; Gambardella, S; Marsella, L T; Novelli, G; Borgiani, P; Sangiuolo, F; Cusumano, A; Ricci, F; Giardina, E
PurposeThe goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.Patients and methodsThe study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age >55 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).Results and conclusionThe combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.
Kurbatova, O L; Pobedonostseva, E Iu; Prokhorovskaia, V D; Kholod, O N; Evsiukov, A N; Bogomolov, V V; Voronkov, Iu I; Filatova, L M; Larina, O N; Sidorenko, L A; Morgun, V V; Kasparanskiĭ, R R; Altukhov, Iu P
Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.
Full Text Available For test-sheet composition systems, it is important to adaptively compose test sheets with diverse conceptual scopes, discrimination and difficulty degrees to meet various assessment requirements during real learning situations. Computation time and item exposure rate also influence performance and item bank security. Therefore, this study proposes an Adaptive Test Sheet Generation (ATSG mechanism, where a Candidate Item Selection Strategy adaptively determines candidate test items and conceptual granularities according to desired conceptual scopes, and an Aggregate Objective Function applies Genetic Algorithm (GA to figure out the approximate solution of mixed integer programming problem for the test-sheet composition. Experimental results show that the ATSG mechanism can efficiently, precisely generate test sheets to meet the various assessment requirements than existing ones. Furthermore, according to experimental finding, Fractal Time Series approach can be applied to analyze the self-similarity characteristics of GA’s fitness scores for improving the quality of the test-sheet composition in the near future.
Wade, Christopher H; Wilfond, Benjamin S
Several companies utilize direct-to-consumer (DTC) advertising for genetic tests and some, but not all, bypass clinician involvement by offering DTC purchase of the tests. This article examines how DTC marketing strategies may affect genetic counselors, using available cardiovascular disease susceptibility tests as an illustration. The interpretation of these tests is complex and includes consideration of clinical validity and utility, and the further complications of gene-environment interactions and pleiotropy. Although it is unclear to what extent genetic counselors will encounter clients who have been exposed to DTC marketing strategies, these strategies may influence genetic counseling interactions if they produce directed interest in specific tests and unrealistic expectations for the tests' capacity to predict disease. Often, a client's concern about risk for cardiovascular diseases is best addressed by established clinical tests and a family history assessment. Ethical dilemmas may arise for genetic counselors who consider whether to accept clients who request test interpretation or to order DTC-advertised tests that require a clinician's authorization. Genetic counselors' obligations to care for clients extend to interpreting DTC tests, although this obligation may be fulfilled by referral or consultation with specialists. Genetic counselors do not have an obligation to order DTC-advertised tests that have minimal clinical validity and utility at a client's request. This can be a justified restriction on autonomy based on consideration of risks to the client, the costs, and the implications for society. Published 2006 Wiley-Liss, Inc.
Sussner, Katarina M; Thompson, Hayley S; Jandorf, Lina; Edwards, Tiffany A; Forman, Andrea; Brown, Karen; Kapil-Pair, Nidhi; Bovbjerg, Dana H; Schwartz, Marc D; Valdimarsdottir, Heiddis B
Rising health disparities are increasingly evident in relation to use of genetic services (including genetic counseling and testing) for breast cancer risk, with women of African descent less likely to use genetic services compared with Whites. Meanwhile, little is known regarding potential within-group acculturation and psychological differences underlying perceived barriers to genetic testing among women of African descent. Hypothesized contributions of acculturation factors and breast cancer-specific distress to perceived barriers to genetic testing were examined with a statistical analysis of baseline data from 146 women of African descent (56% US born and 44% foreign born) meeting genetic breast cancer risk criteria and participating in a larger longitudinal study that included the opportunity for free genetic counseling and testing. Perceived barriers assessed included: (1) anticipation of negative emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related worry, and (5) family-related guilt associated with genetic testing. In multivariate analyses, being foreign born was a significant predictor of anticipated negative emotional reactions about genetic testing (beta=0.26; SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms) were positively related to anticipated negative emotional reactions (beta=0.02; SE=0.005; p=barriers to genetic testing among women of African descent. The potential utility of culturally tailored genetic counseling services taking into account such influences and addressing emotional and psychological concerns of women considering genetic testing for breast cancer should be investigated.
Full Text Available Kazutaka Noda, Masatomi Ikusaka, Yoshiyuki Ohira, Toshihiko Takada, Tomoko TsukamotoDepartment of General Medicine, Chiba University Hospital, Chiba, JapanObjective: Patient medical history is important for making a diagnosis of causes of dizziness, but there have been no studies on the diagnostic value of individual items in the history. This study was performed to identify and validate useful questions for suspecting a diagnosis of benign paroxysmal positional vertigo (BPPV.Methods: Construction and validation of a disease prediction model was performed at the outpatient clinic in the Department of General Medicine of Chiba University Hospital. Patients with dizziness were enrolled (145 patients for construction of the disease prediction model and 61 patients for its validation. This study targeted BPPV of the posterior semicircular canals only with a positive Dix–Hallpike test (DHT + BPPV to avoid diagnostic ambiguity. Binomial logistic regression analysis was performed to identify the items that were useful for diagnosis or exclusion of DHT + BPPV.Results: Twelve patients from the derivation set and six patients from the validation set had DHT + BPPV. Binomial logistic regression analysis selected a "duration of dizziness ≤15 seconds" and "onset when turning over in bed" as independent predictors of DHT + BPPV with an odds ratio (95% confidence interval of 4.36 (1.18–16.19 and 10.17 (2.49–41.63, respectively. Affirmative answers to both questions yielded a likelihood ratio of 6.81 (5.11–9.10 for diagnosis of DHT + BPPV, while negative answers to both had a likelihood ratio of 0.19 (0.08–0.47.Conclusion: A "duration of dizziness ≤15 seconds" and "onset when turning over in bed" were the two most important questions among various historical features of BPPV.Keywords: benign paroxysmal positional vertigo, likelihood ratio, diagnosis, screening, prediction rules
The Test Storage Ring (TSR) for heavy ions, currently under design and construction at the Max Planck Institute for Nuclear Physics in Heidelberg, requires an extensive beam diagnostics system in order to enable it to operate without friction. This thesis concerns the beam position determination sub-system of this diagnostics system which is intended to determine the beam center of gravity of a bunched beam inside the cross section of the beam tube in a non-destructive manner. An electrostatic pickup is used to sense the location of the beam; the mode of operation of this device will be explained in detail. The signals go to a preamplifier from where they are then sent via a multiplex system to the measuring unit. This point also represents the interface to the computer system that controls the TSR. The prototype developed here was tested with the aid of a particle beam, as well as with other measurement methods. Resolutions of better than 1 mm about the center have been measured. In order to achieve or even improve such resolutions later in actual operation, it is possible to determine the properties of the preamplifiers with the aid of calibration signals and to take these into account in the course of the signal evaluation in the computer. The differences between the individual electrodes of a given pickup must also be compensated. These procedures and their associated electronic circuits are also described in this paper
Bråred Christensson, Johanna; Andersen, Klaus E; Bruze, Magnus; Johansen, Jeanne D; Garcia-Bravo, Begoña; Gimenez Arnau, Ana; Goh, Chee-Leok; Nixon, Rosemary; White, Ian R
R-Limonene is a common fragrance terpene found in domestic and industrial products. R-Limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a recent multicentre study, 5.2% (range 2.3-12.1%) of 2900 patients showed a positive patch test reaction to oxidized R-limonene. To study the exposure to limonene among consecutive dermatitis patients reacting to oxidized R-limonene in an international setting, and to assess the relevance of the exposure for the patients' dermatitis. Oxidized R-limonene 3.0% (containing limonene hydroperoxides at 0.33%) in petrolatum was tested in 2900 consecutive dermatitis patients in Australia, Denmark, the United Kingdom, Singapore, Spain, and Sweden. A questionnaire assessing exposure to limonene-containing products was completed. Overall, exposure to products containing limonene was found and assessed as being probably relevant for the patients' dermatitis in 36% of the limonene-allergic patients. In Barcelona and Copenhagen, > 70% of the patients were judged to have had an exposure to limonene assessed as relevant. Oxidized R-limonene is a common fragrance allergen, and limonene was frequently found in the labelling on the patients' products, and assessed as relevant for the patients' dermatitis. A large number of domestic and occupational sources for contact with R-limonene were identified. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Borry, Pascal; Howard, Heidi C; Sénécal, Karine; Avard, Denise
More and more companies are advertising and selling genetic tests directly to consumers. Considering the ethical, legal, and psychological concerns surrounding genetic testing in minors, a study of companies' websites was performed in order to describe and analyze their policies with respect to this issue. Of the 29 companies analyzed, 13 did not provide any information about this matter, eight companies allowed genetic testing upon parental request, four companies stated that their website is not directed to children under 18 years, and four companies suggested that in order to be tested, applicants should have reached the age of legal majority. If private companies offer genetic tests which are also offered in a clinical setting, can they be expected to adhere to the existing clinical guidelines with regard to these tests? If so, a certain ambiguity exists. Many companies are emphasizing in their disclaimers that their services are not medical services and should not be used as a basis for making medical decisions. Nonetheless, it remains debatable whether genetic testing in minors would be appropriate in this context. In line with the Advisory Committee on Genetic Testing, the Human Genetics Commission addressed the problem of non-consensual testing and recommended not to supply genetic testing services directly to those under the age of 16 or to those not able to make a competent decision regarding testing.
Miah, Andy; Rich, Emma
This paper explores the prospect of genetic tests for performance in physical activity and sports practices. It investigates the terminology associated with genetics, testing, selection and ability as a means towards a socio-ethical analysis of its value within sport, education and society. Our argument suggests that genetic tests need not even be…
... particular tests; and (3) facilitating genetic and genomic data-sharing for research and new scientific...; Comment Request Information Program on the Genetic Testing Registry AGENCY: National Institutes of Health... currently valid OMB control number. Proposed Collection: Title: The Genetic Testing Registry; Type of...
Full Text Available Background. External impingement tests are considered as being particularly reliable for identifying subacromial and coracoid shoulder impingement mechanisms. The purpose of the present study was to evaluate if these tests are likely to provoke an internal shoulder impingement mechanism which, in cases of a pathologic condition, can lead to a positive test result. Method. In 37 subjects, the mechanical contact between the glenoid rim and the rotator cuff (RC was measured quantitatively and qualitatively in external impingement test positions using an open MRI system. Results. Mechanical contact of the supraspinatus with the posterosuperior glenoid was present in 30 subjects in the Neer test. In the Hawkins test, the subscapularis was in contact with the anterosuperior glenoid in 33 subjects and the supraspinatus in 18. In the horizontal impingement test, anterosuperior contact of the supraspinatus with the glenoid was identified in 35 subjects. Conclusion. The Neer, Hawkins, and horizontal impingement tests are likely to provoke the mechanism of an internal shoulder impingement. A posterosuperior internal impingement mechanism is being provoked predominately in the Neer test. The Hawkins test narrows the distance between the insertions of the subscapularis and supraspinatus and the anterosuperior labrum, which leads to an anterosuperior impingement mechanism.
Laegsgaard, Mett Marri; Mors, Ole
as a guide in this field, but the optimal utilization of genetic testing has also been recognized to depend on knowledge of the potential consumers' attitudes. To provide knowledge to inform the public debate on mental illness and genetics, and the future conducting of psychiatric genetic testing....... Psychiatric and somatic genetic testing attracted the same amounts of accept. General attitudes toward access to psychiatric genetic testing and information revealed substantial support for bioethical principles of autonomy and privacy. However, questions describing more specific situations revealed......Psychiatric genetic research may eventually render possible psychiatric genetic testing. Whereas all genetic knowledge has certain characteristics raising ethical, legal, and social issues, psychiatric genetic knowledge adds more controversial issues. Ethical principles have been proposed...
Kalina J. Michalska
Full Text Available Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging, hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (rs53576 and rs1042778 in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex, anterior cingulate cortex and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.
Marseguerra, Marzio; Zio, Enrico; Cipollone, Maurizio
The experimental determination of the failure time probability distribution of highly reliable components, such as those used in nuclear and aerospace applications, is intrinsically difficult due to the lack, or scarce significance, of failure data which can be collected during the relatively short test periods. A possibility to overcome this difficulty is to resort to the so-called degradation tests, in which measurements of components' degradation are used to infer the failure time distribution. To design such tests, parameters like the number of tests to be run, their frequency and duration, must be set so as to obtain an accurate estimate of the distribution statistics, under the existing limitations of budget. The optimisation problem which results is a non-linear one. In this work, we propose a method, based on multi-objective genetic algorithms for determining the values of the test parameters which optimise both the accuracy in the estimate of the failure time distribution percentiles and the testing costs. The method has been validated on a degradation model of literature
Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew
Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity. A wider literature search was performed to provide a fuller assessment of the pharmacogenetic test and variants were matched to FDA recommendations. Additional evidence from CPIC guidelines, PharmGKB, and Dutch Pharmacogenetics Working Group was reviewed to determine current clinical practice. The value of the tests across ethnic groups was determined, including information on linkage disequilibrium between the tested SNP and causal pharmacogenetic variant, where relevant. 23andMe offers 12 pharmacogenetic tests to their UK customers, some of which are in standard clinical practice, and others which are less widely applied. The clinical validity and clinical utility varies extensively between tests. The variants tested are likely to have different degrees of sensitivity due to different risk allele frequencies and linkage disequilibrium patterns across populations. The clinical relevance depends on the ethnicity of the individual and variability of pharmacogenetic markers. Further research is required to determine causal variants and provide more complete assessment of drug response and side effects. 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful
Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin
The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.
Imudia, Anthony N; Plosker, Shayne
Preimplantation genetic testing (PGT) of oocytes and embryos is the earliest form of prenatal testing. PGT requires in vitro fertilization for embryo creation. In the past 25 years, the use of PGT has increased dramatically. The indications of PGT include identification of embryos harboring single-gene disorders, chromosomal structural abnormalities, chromosomal numeric abnormalities, and mitochondrial disorders; gender selection; and identifying unaffected, HLA-matched embryos to permit the creation of a savior sibling. PGT is not without risks, limitations, or ethical controversies. This review discusses the techniques and clinical applications of different forms of PGT and the debate surrounding its associated uncertainty and expanded use. Copyright © 2016 Elsevier Inc. All rights reserved.
Preimplantation genetic diagnosis (PGD) was introduced as an alternative to prenatal diagnosis: embryos cultured in vitro were analysed for a monogenic disease and only disease-free embryos were transferred to the mother, to avoid the termination of pregnancy with an affected foetus. It soon transpired that human embryos show a great deal of acquired chromosomal abnormalities, thought to explain the low success rate of IVF - hence preimplantation genetic testing for aneuploidy (PGT-A) was developed to select euploid embryos for transfer. Areas covered: PGD has followed the tremendous evolution in genetic analysis, with only a slight delay due to adaptations for diagnosis on small samples. Currently, next generation sequencing combining chromosome with single-base pair analysis is on the verge of becoming the golden standard in PGD and PGT-A. Papers highlighting the different steps in the evolution of PGD/PGT-A were selected. Expert commentary: Different methodologies used in PGD/PGT-A with their pros and cons are discussed.
Marketing of genetic testing, although similar to direct-to-consumer advertising of prescription drugs, raises additional concerns and considerations. These include issues of limited knowledge among patients and health care providers of available genetic tests, difficulty in interpretation of genetic testing results, lack of federal oversight of companies offering genetic testing, and issues of privacy and confidentiality. Until all of these considerations are addressed, direct or home genetic testing should be discouraged because of the potential harm of a misinterpreted or inaccurate result.
Full Text Available Abstract:The objective of this study was to compare the findings of the bedside head impulse test (HIT, passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA. In 16 patients with CA and bilaterally pathological bedside HIT, VOR gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses. Those with normal calorics showed a slightly reduced HIT gain (mean±SD: 0.73±0.15. In those with pathological calorics, gains 80ms and 100 ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111±62 ms after onset of the HIT than in those with normal calorics. (191±17 ms, p=0.0064 We indentified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA.
Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L
The terms 'false-positive' and 'false-negative' are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results. This larger universe, while not solely comprised of technically 'true' or 'false' positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms 'potentially inappropriate' positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation. Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error. Clinical UDT interpretation is a complicated task requiring knowledge of recent prescription, over-the-counter and herbal drug administration, drug metabolism and analytical sensitivities and specificities.
Hietala, M; Hakonen, A; Aro, A R
evaluated attitudes toward gene tests in general and also respondents' preparedness to undergo gene tests for predictive testing, carrier detection, prenatal diagnosis, and selective abortion, in theoretical situations. The results of the study indicate that both the Finnish population in general and family...... members of AGU patients have a favorable attitude toward genetic testing. However, a commonly expressed reason against testing was that test results might lead to discrimination in employment or insurance policies. Based on the responses, we predict that future genetic testing programs will most probably...
Rolison, Jonathan J; Hanoch, Yaniv; Miron-Shatz, Talya
Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.
Full Text Available A 62 year-old caucasian male was admitted in our pulmonary hypertension expert center with initial diagnosis of pulmonary veno-occlusive disease for validation and specific treatment approach. Routine examinations revealed no apparent cause of pulmonary hypertension. Patient was referred for a thorax contrast enhanced multi-slice computed tomography which revealed extensive bilateral thrombi in pulmonary lower lobe arteries, pleading for chronic post embolic lesions. A right heart catheterization and pulmonary angiography confirmed the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH. Following the local regulations, the patient underwent thrombophilia screening including molecular genetic testing, with positive findings for heterozygous for VCORK1 -1639G>A gene single nucleotide polymorphism, PAI-1 4G/5G and factor II G20210A gene. With heterozygous genetic profile of 3 mutations he has a genetic predisposition for developing a thrombophilic disease which could be involved in the etiology of CTEPH. Familial screening was extended to descendants; the unique son was tested with positive results for the same three genes. Supportive pulmonary hypertension drug therapy was initiated together with patient self-monitoring management of oral anticoagulation therapy. For optimal control of targeted anticoagulation due to a very high risk of thrombotic state the patient used a point-of-care device (CoaguChek®XS System, Roche Diagnostics for coagulation self-monitoring.
Wasson, Katherine; Cook, E David; Helzlsouer, Kathy
The development of genetic tests marketed and sold direct-to-consumers (DTC) via the internet raises moral concerns and debate about their appropriateness and ethical and clinical significance. These tests are offered for a wide range of diseases and conditions, and the mutations have variable penetrance and associated risk. A number of these tests lack data on their accuracy and reliability, making interpretation of results difficult. DTC genetic testing is undertaken outside the context of the physician-patient relationship and may lack appropriate individual and family genetic counseling, leaving the consumer vulnerable to potential harms, such as misinterpretation of results, including false positive or false reassurance, with limited or no benefits. Beauchamp and Childress's four principles of biomedical ethics provide a framework for analyzing the ethical issues raised by DTC genetic testing. We argue that the potential harms outweigh the potential benefits of such tests, that respect for autonomy should be limited in light of potential harm from DTC testing, and that the availability of genetic testing over the internet may be considered unfair and unjust and affect resource allocation by placing an unfair burden on primary care physicians. In light of the moral issues posed by these tests, practical responses are suggested in the areas of consumer education, medical education, and interaction with commercial companies.
Wiberg, A; Granstam, A; Ingvast, S; Härkönen, T; Knip, M; Korsgren, O; Skog, O
In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3·3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52·6 (range 21–74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases. PMID:26313035
Wallace, R A
No guidelines exist for assessment of aetiology of intellectual disability in adults with intellectual disability by adult physicians, although robust guidelines exist for paediatric populations. It was speculated that the paediatric guidelines would also be suitable for adults. In rural/regional setting with limited clinical genetics, to perform a quality assurance evaluation on genetics assessment of aetiology of developmental disability in adults attending a dedicated healthcare clinic for adults with intellectual disability, compared results with paediatric standards, speculates if these seem appropriate for adults and speculates on a role for clinical genetics services. Retrospective chart audit of eligible patients looking at genetic clinical assessment, tests selected (molecular karyotype, G banding, metabolics), and yields of positive results. The results were compared with the recommended paediatric guidelines. Of 117 eligible adult patients, ideal genetic history was incomplete for 40% of patients without Down syndrome because of physician cause and lack of information. The number of abnormal genetic results increased from 46% to 66%, mainly from the molecular karyotype, though not all may have been clinically relevant. The improved yield from this test was similar to that in paediatric studies. Use of G banding and metabolic testing could be refined. Improvement can be made in clinical genetic assessment, but results generally support use of molecular karyotyping as first tier testing of cause of unknown intellectual disability in adults, as in the case for paediatric populations. The study highlights a necessary complementary role for clinical geneticists to interpret abnormal results. © 2016 Royal Australasian College of Physicians.
Wolfe, Kate; Stueber, Kerstin; McQuillin, Andrew; Jichi, Fatima; Patch, Christine; Flinter, Frances; Strydom, André; Bass, Nick
Background: An increasing number of genetic causes of intellectual disabilities (ID) are identifiable by clinical genetic testing, offering the prospect of bespoke patient management. However, little is known about the practices of psychiatrists and their views on genetic testing. Method: We undertook an online survey of 215 psychiatrists, who…
V.N. Giri (Veda); Knudsen, K.E. (Karen E.); Kelly, W.K. (William K.); Abida, W. (Wassim); G.L. Andriole (Gerald); C.H. Bangma (Chris); Bekelman, J.E. (Justin E.); Benson, M.C. (Mitchell C.); A. Blanco (Amie); Burnett, A. (Arthur); Catalona, W.J. (William J.); Cooney, K.A. (Kathleen A.); M.R. Cooperberg (Matthew); D. Crawford (David); Den, R.B. (Robert B.); Dicker, A.P. (Adam P.); S. Eggener (Scott); N.E. Fleshner (Neil); Freedman, M.L. (Matthew L.); F. Hamdy (Freddie); Hoffman-Censits, J. (Jean); Hurwitz, M.D. (Mark D.); Hyatt, C. (Colette); Isaacs, W.B. (William B.); Kane, C.J. (Christopher J.); Kantoff, P. (Philip); R.J. Karnes (Jeffrey); Karsh, L.I. (Lawrence I.); Klein, E.A. (Eric A.); Lin, D.W. (Daniel W.); Loughlin, K.R. (Kevin R.); Lu-Yao, G. (Grace); Malkowicz, S.B. (S. Bruce); Mann, M.J. (Mark J.); Mark, J.R. (James R.); McCue, P.A. (Peter A.); Miner, M.M. (Martin M.); Morgan, T. (Todd); Moul, J.W. (Judd W.); Myers, R.E. (Ronald E.); Nielsen, S.M. (Sarah M.); Obeid, E. (Elias); Pavlovich, C.P. (Christian P.); Peiper, S.C. (Stephen C.); D.F. Penson (David F.); D.P. Petrylak (Daniel P); Pettaway, C.A. (Curtis A.); R. Pilarski (Robert); P. Pinto (Peter); Poage, W. (Wendy); Raj, G.V. (Ganesh V.); R. Rebbeck (Timothy); M. Robson (Mark); Rosenberg, M.T. (Matt T.); Sandler, H. (Howard); A.O. Sartor (Oliver); Schaeffer, E. (Edward); Schwartz, G.F. (Gordon F.); Shahin, M.S. (Mark S.); N.D. Shore (Neal); Shuch, B. (Brian); Soule, H.R. (Howard R.); S.A. Tomlins (Scott A); Trabulsi, E.J. (Edouard J.); Uzzo, R. (Robert); Griend, D.J.V. (Donald J. Vander); P.C. Walsh (Patrick); Weil, C.J. (Carol J.); Wender, R. (Richard); Gomella, L.G. (Leonard G.)
textabstractPurpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling,
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.
Mai, Phuong L; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S; Wideroff, Louise; Graubard, Barry I
Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000-2005 and 2005-2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (pinteraction=0.03) or with a usual place of care (pinteraction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25-39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. Published by Elsevier Inc.
Full Text Available Extraversion is a personality trait which has been systematically related to positive affect and well-being. One of the mechanisms that may account for these positive outcomes is the ability to regulate the responses to positive, as well as negative, moods. Prior research has found that extraverts' higher positive mood maintenance could explain their higher levels of positive affect. However, research exploring differences between extraverts and introverts in negative mood regulation has yielded mixed results. The aim of the current study was explore the role of different facets of mood regulation displayed by extraverts, ambiverts, and introverts. After been exposed to a sad vs. happy mood induction, participants underwent a mood regulation task. Extraverts and ambiverts exhibited higher positive mood regulation than introverts, but similar mood repair. Thus, this research highlights the importance of positive mood regulation in the psychological functioning of extraverts, and opens new conceptualizations for developing interventions for introverts to improve their positive mood regulation and, hence, overall positive affect and well-being.
... Options Talking to Family Family Stories Diseases Genetic Counseling for Hereditary Breast and Ovarian Cancer Recommend on ... mutation, your doctor may refer you for genetic counseling. Understanding and dealing with a strong family health ...
Li, L; Qiu, L; Wu, M
Objective: To analyze patients' tendency towards genetics counseling and tests based on a prospective cohort study on hereditary ovarian cancer. Methods: From February 2017 to June 2017, among 220 cases of epithelial ovarian cancer in Peking Union Medical College Hospital, we collected epidemiological, pathological and tendency towards genetics counseling and tests via medical records and questionnaire.All patients would get education about hereditary ovarian cancer by pamphlets and WeChat.If they would receive further counseling, a face to face interview and tests will be given. Results: Among all 220 patients, 10 (4.5%) denied further counseling.For 210 patients receiving genetic counseling, 170 (81%) accepted genetic tests.In multivariate analysis, risk factors relevant to acceptance of genetic tests included: being charged by physicians of gynecologic oncology for diagnosis and treatment, receiving counseling in genetic counseling clinics, and having family history of breast cancer.For patients denying genetic tests, there were many subjective reasons, among which, "still not understanding genetic tests" (25%) and "unable bear following expensive targeting medicine" . Conclusions: High proportion patients of epithelial ovarian cancer would accept genetic counseling and tests.Genetic counseling clinics for gynecologic oncology would further improve genetic tests for patients.
Morahan, Grant; Mehta, Munish; James, Ian
Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1...... diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions....
Lamy, T; Jarne, P; Laroche, F; Pointier, J-P; Huth, G; Segard, A; David, P
An increasing number of studies are simultaneously investigating species diversity (SD) and genetic diversity (GD) in the same systems, looking for 'species- genetic diversity correlations' (SGDCs). From negative to positive SGDCs have been reported, but studies have generally not quantified the processes underlying these correlations. They were also mostly conducted at large biogeographical scales or in recently degraded habitats. Such correlations have not been looked for in natural networks of connected habitat fragments (metacommunities), and the underlying processes remain elusive in most systems. We investigated these issues by studying freshwater snails in a pond network in Guadeloupe (Lesser Antilles). We recorded SD and habitat characteristics in 232 ponds and assessed GD in 75 populations of two species. Strongly significant and positive SGDCs were detected in both species. Based on a decomposition of SGDC as a function of variance-covariance of habitat characteristics, we showed that connectivity (opportunity of water flow between a site and the nearest watershed during the rainy season) has the strongest contribution on SGDCs. More connective sites received both more alleles and more species through immigration resulting in both higher GD and higher SD. Other habitat characteristics did not contribute, or contributed negatively, to SGDCs. This is true of the desiccation frequency of ponds during the dry season, presumably because species markedly differ in their ability to tolerate desiccation. Our study shows that variation in environmental characteristics of habitat patches can promote SGDCs at metacommunity scale when the studied species respond homogeneously to these environmental characteristics. © 2013 John Wiley & Sons Ltd.
... recommending an HIV regimen. Testing for sexually transmitted diseases (STDs) Coinfection with another STD can cause HIV infection to advance faster and increase the risk of HIV transmission to a sexual partner. STD testing makes it possible to detect ...
Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS
Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...
Aspinwall, Lisa G; Taber, Jennifer M; Leaf, Samantha L; Kohlmann, Wendy; Leachman, Sancy A
CDKN2A/p16 mutations confer 76% lifetime risk of melanoma and up to 17% lifetime risk of pancreatic cancer. Our objective was to determine the short- and long-term impact of CDKN2A/p16 genetic counseling and test reporting on psychological distress, cancer worry, and perceived costs and benefits of testing. Prospective changes in anxiety, depression, and cancer worry following CDKN2A/p16 counseling and test reporting were evaluated at multiple assessments over 2 years among 60 adult members of melanoma-prone families; 37 participants completed the 2-year follow-up. Quantitative and qualitative assessments of the costs and benefits of testing were carried out. Outcomes were evaluated among unaffected noncarriers (n = 27), unaffected carriers (n = 15), and affected carriers (n = 18). Reported anxiety and depression were low. For carriers and noncarriers, anxiety decreased significantly throughout the 2-year period, whereas depression and melanoma worry showed short-term decreases. Worry about pancreatic cancer was low and decreased significantly. In all groups, test-related distress and uncertainty were low, regret was absent, and positive experiences were high. All participants (>93% at each assessment) reported at least one perceived benefit of genetic testing; only 15.9% listed any negative aspect. Carriers reported increased knowledge about melanoma risk and prevention (78.3%) and increased prevention and screening behaviors for self and family (65.2%). Noncarriers reported increased knowledge (95.2%) and emotional benefits (71.4%). Among US participants familiar with their hereditary melanoma risk through prior epidemiological research participation, CDKN2A/p16 genetic testing provides multiple perceived benefits to both carriers and noncarriers without inducing distress in general or worry about melanoma or pancreatic cancer. Copyright © 2011 John Wiley & Sons, Ltd.
Vrecar, Irena; Peterlin, Borut; Teran, Natasa; Lovrecic, Luca
Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues. Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing. Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia. Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared.
Chalela, Patricia; Pagán, José A; Su, Dejun; Muñoz, Edgar; Ramirez, Amelie G
Genetic testing for breast cancer may facilitate better-informed decisions regarding cancer prevention, risk reduction, more effective early detection, and better determination of risk for family members. Despite these potential benefits, significant portions of the US population-particularly Latinas-lack awareness of genetic testing for breast cancer susceptibility. Among women who are tested, less than 4% are Latina. To uncover reasons for Latinas' low participation, this study explores awareness, attitudes and behavioral intentions to undergo genetic testing among average-risk Latinas along the Texas-Mexico border. Eight focus groups were conducted with 58 Latinas aged 19-69 living in Hidalgo County, a largely Latino region of South Texas. Focus group discussions were digitally recorded, transcribed and analyzed using qualitative content analysis to assess, categorize and interpret them. Two experienced study team members analyzed transcripts to identify major concepts grouped into theme categories. Participants mostly had less than a high-school education (43%), spoke primarily Spanish (52%), were of Mexican-American origin (90%) and had a family income of $30,000 or less (75%). Focus groups found that most participants had positive attitudes and strong interest in genetic testing, yet lacked general awareness and knowledge about genetic testing, its risks, benefits, and limitations. Participants also identified several key cultural-based influencers, such as family, religious beliefs and fear of testing. The delivery of culturally adapted risk information is needed to increase and ensure Latinas' understanding of breast cancer genetic testing during their decision-making processes. Key Latino values-religiosity, importance of family and the influential role of health care providers in health decisions-should also be considered when designing interventions targeting this specific group. Further research is needed to identify effective ways to communicate
Jeong, Hyeonsoo; Song, Ki-Duk; Seo, Minseok; Caetano-Anollés, Kelsey; Kim, Jaemin; Kwak, Woori; Oh, Jae-Don; Kim, EuiSoo; Jeong, Dong Kee; Cho, Seoae; Kim, Heebal; Lee, Hak-Kyo
Natural and artificial selection following domestication has led to the existence of more than a hundred pig breeds, as well as incredible variation in phenotypic traits. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Here we investigate the relationship between genomic composition and this phenotypic trait by scanning for signatures of positive selection in whole-genome sequencing data. We generated genomes of 10 Berkshire pigs at a total of 100.6 coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of 11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million SNVs and 3.4 million Indels in the mapped regions. We identified several associated genes related to lipid metabolism, intramuscular fatty acid deposition, and muscle fiber type which attribute to pork quality (TG, FABP1, AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also conducted to detect breed specific genetic variation. In addition, de novo short sequence read assembly strategy identified several candidate genes (SLC25A14, IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. Results revealed several candidate genes involved in Berkshire meat quality; most of these genes are involved in lipid metabolism and intramuscular fat deposition. These results can provide a basis for future research on the genomic characteristics of Berkshire pigs.
Kayupova, N.A.; Svyatova, G.S.; Abildinova, G.Zh.
Up to present, there is no one positive opinion about the effect of a small amount of ionizing radiation doses on the genetic system of a human being. In connection with it, the all-round medical and genetic researches conducted by a united methodical basis and intended to study general mutagen and teratogen radiation effects are of a certain significance. With that end in view, the medical and genetic testing of a number of rural population around Semipalatinsk test-site (STS) was conducted. The all-round methods of medical and genetic consequences evaluation were developed, and 'active revealing of the congenital fetation disease (CFD)' method was submitted for consideration. Aside from analysis of the general genetic and demographic data, outcomes of more than 160.000 confinements were studied, and a high frequency rate of the CFD of 'the strict recording' (6.11 per 1000 new-born children in areas of extreme radiation hazard) was discovered, that surely exceeded the similar index for the monitored areas (2.92 per 1000 new-born children). A higher frequency rate of the Down's syndrome and numerous CFD (1.66 and 1.07 per 1000 new-born children accordingly) were revealed as well. As a result of the cytogenetic monitoring of the tested population, it was ascertained that a total frequency rate of the aberrant cell emergence was equal to 4.9 per 100 cells, that is 3.9 times as much than the similar index for the monitored area. A high frequency rate of the markers induced by radiation was discovered, which proved the increased mutagen effect of the environment. Biological presentation of the radiation effect on population was conducted in two methods of the biological monitoring, and according to the frequency rate of the chromosomal aberrations in lymphocytes of peripheral blood, that are induced by radiation, and electro paramagnetic resonance of teeth enamel (Kazakhstan national Nuclear Center). The results of the medical and genetic research conducted were an
Patch, C.; Sequeiros, J.; Cornel, M.C.
The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and
Sanderson, Saskia C; Wardle, Jane; Humphries, Steve E
Human genetics research is increasingly concerned with multifactorial conditions such as diabetes and heart disease, which are influenced not only by genetic but also lifestyle factors such as diet and smoking. Although the results of 'lifestyle-genetic' tests using this information could conceivably motivate lifestyle changes in the future, companies are already selling such tests and related lifestyle advice commercially. Some academics and lobby groups have condemned the companies for selling these tests in advance of scientific support. Others are concerned that the tests may not motivate lifestyle improvements, instead causing distress in people receiving adverse test results and complacency in those receiving reassuring results. There is currently no regulatory oversight of genetic test utility, despite consensus in the Public Health Genomics community that clinical utility (including psychological and behavioural impact) of all emerging genetic tests should be evaluated before being introduced for individual use. Clearly, empirical data in this area is much needed, to inform understanding of the potential utility of these tests, and of whether stricter regulation of commercial exploitation is needed. In this article, we review the current situation regarding lifestyle-genetic tests, and discuss the challenges inherent in conducting this kind of behavioural research in the genomics era. Copyright 2008 S. Karger AG, Basel.
Bonython, Wendy Elizabeth; Arnold, Bruce Baer
Loi recently proposed a libertarian right to direct to consumer genetic testing (DTCGT)- independent of autonomy or utility-reflecting Cohen's work on self-ownership and Hohfeld's model of jural relations. Cohen's model of libertarianism dealt principally with self-ownership of the physical body. Although Loi adequately accounts for the physical properties of DNA, DNA is also an informational substrate, highly conserved within families. Information about the genome of relatives of the person undergoing testing may be extrapolated without requiring direct engagement with their personal physical copy of the genome, triggering rights and interests of relatives that may differ from the rights and interests of others, that is, individual consumers, testing providers and regulators. Loi argued that regulatory interference with exercise of the right required justification, whereas prima facie exercise of the right did not. Justification of regulatory interference could include 'conflict with other people's rights', 'aggressive' use of the genome and 'harming others'. Harms potentially experienced by relatives as a result of the individual's exercise of a right to test include breach of genetic privacy, violation of their right to determine when, and if, they undertake genetic testing and discrimination. Such harms may justify regulatory intervention, in the event they are recognised; motives driving 'aggressive' use of the genome may also be relevant. Each of the above criteria requires clarification, as potential redundancies and tensions exist between them, with different implications affecting different groups of rights holders. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Minear, Mollie A; Alessi, Stephanie; Allyse, Megan; Michie, Marsha; Chandrasekharan, Subhashini
Noninvasive prenatal genetic testing (NIPT) for chromosomal aneuploidy involving the analysis of cell-free fetal DNA became commercially available in 2011. The low false-positive rate of NIPT, which reduces unnecessary prenatal invasive diagnostic procedures, has led to broad clinician and patient adoption. We discuss the ethical, legal, and social issues raised by rapid and global dissemination of NIPT. The number of women using NIPT is anticipated to expand, and the number of conditions being tested for will continue to increase as well, raising concerns about the routinization of testing and negative impacts on informed decision making. Ensuring that accurate and balanced information is available to all pregnant women and that access to NIPT is equitable will require policy guidance from regulators, professional societies, and payers. Empirical evidence about stakeholders' perspectives and experiences will continue to be essential in guiding policy development so that advances in NIPT can be used effectively and appropriately to improve prenatal care.
different from one derived from mixture analysis [46.3%(95% Bayesian credibility interval 36.5%-55.8%)]. Positive ... Health Organization (WHO) report of the World's top. 22 high ..... World re- port 2009. WHO/HTM/TB/2009.411. Geneva: World.
Liver enzymes-alanine and aspartate aminotransferases and alkaline phosphatase (AST, ALT and ALP), bilirubin and serum proteins were determined using standard laboratory methods and these parameters were used to evaluate the liver function of human immunodeficiency virus (HIV)- positive patients receiving ...
Augusta, Petr; Augustová, Petra
Roč. 54, č. 2 (2018), s. 289-303 ISSN 0023-5954 Institutional support: RVO:67985556 Keywords : stability * multidimensional systems * positive polynomials * fast Fourier transforms * numerical algorithm Subject RIV: BC - Control Systems Theory OBOR OECD: Automation and control systems Impact factor: 0.379, year: 2016 https://www.kybernetika.cz/content/2018/2/289/paper.pdf
Devos, S.A.; Constandt, L.; Tupker, R.A.; Noz, K.C.; Lucker, G.P.H.; Bruynzeel, D.P.; Schuttelaar, M.L.; Kruyswijk, M.R.; Zuuren, E.J. van; Vink, J.; Coenraads, P.J.; Kiemeney, L.A.L.M.; Valk, P.G.M. van der
BACKGROUND: Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance-allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong
Devos, S.A.; Constandt, L.; Tupker, R.A.; Noz, K.C.; Lucker, G.P.H.; Bruynzeel, D.P.; Schuttelaar, M.L.A.; Kruyswijk, M.R.J.; van Zuuren, E.J.; Vink, J.; Coenraads, P.J.; Kiemeney, L.A.L.M.; van der Valk, P.G.M.
BACKGROUND: Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance-allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong
Noh, Jaekwang; Ko, Hak Hyun; Yun, Yeomin; Choi, Young Sook; Lee, Sang Gon; Shin, Sue; Han, Kyou Sup; Song, Eun Young
We evaluated the performance and false positive rate of Mediace RPR test (Sekisui, Japan), a newly introduced nontreponemal test using a chemistry autoanalyzer. The sensitivity of Mediace RPR test was analyzed using sera from 50 patients with syphilis in different stages (8 primary, 7 secondary, and 35 latent), 14 sera positive with fluorescent treponemal antibody absorption (FTA-ABS) IgM, and 74 sera positive with conventional rapid plasma regain (RPR) card test (Asan, Korea) and also positive with Treponema pallidum hemagglutination (TPHA) test or FTA-ABS IgG test. The specificity was analyzed on 108 healthy blood donors. We also performed RPR card test on 302 sera that had been tested positive with Mediace RPR test and also performed TPHA or FTA-ABS IgG test to analyze the false positive rate of Mediace RPR test. A cutoff value of 0.5 R.U. (RPR unit) was used for Mediace RPR test. Mediace RPR test on syphilitic sera of different stages (primary, secondary, and latent stages) and FTA-ABS IgM positive sera showed a sensitivity of 100%, 100%, 82.9% and 100%, respectively. Among the 74 sera positive with conventional RPR card test and TPHA or FTA-ABS IgG test, 55 were positive with Mediace test. The specificity of Mediace RPR test on blood donors was 97.2%. Among the 302 sera positive with Mediace RPR test, 137 sera (45.4%) were negative by RPR card and TPHA/FTA-ABS IgG tests. Although the sensitivities of Mediace RPR were good for primary and secondary syphilis, due to its high negative rate of Mediace RPR over the conventional RPR positive samples, further studies are necessary whether it can replace conventional nontreponemal test for screening purpose. Moreover, in view of the high false positive rate, positive results by Mediace RPR test should be confirmed with treponemal tests.
Full Text Available Abstract Background With a growing number of genetic tests becoming available to the health and consumer markets, genetic health care providers in Canada are faced with the challenge of developing robust decision rules or guidelines to allocate a finite number of public resources. The objective of this study was to gain Canadian genetic health providers' perspectives on factors and criteria that influence and shape resource allocation decisions for publically funded predictive genetic testing in Canada. Methods The authors conducted semi-structured interviews with 16 senior lab directors and clinicians at publically funded Canadian predictive genetic testing facilities. Participants were drawn from British Columbia, Alberta, Manitoba, Ontario, Quebec and Nova Scotia. Given the community sampled was identified as being relatively small and challenging to access, purposive sampling coupled with snowball sampling methodologies were utilized. Results Surveyed lab directors and clinicians indicated that predictive genetic tests were funded provincially by one of two predominant funding models, but they themselves played a significant role in how these funds were allocated for specific tests and services. They also rated and identified several factors that influenced allocation decisions and patients' decisions regarding testing. Lastly, participants provided recommendations regarding changes to existing allocation models and showed support for a national evaluation process for predictive testing. Conclusion Our findings suggest that largely local and relatively ad hoc decision making processes are being made in relation to resource allocations for predictive genetic tests and that a more coordinated and, potentially, national approach to allocation decisions in this context may be appropriate.
Collins, Veronica R; Meiser, Bettina; Ukoumunne, Obioha C; Gaff, Clara; St John, D James; Halliday, Jane L
To fully assess predictive genetic testing programs, it is important to assess outcomes over periods of time longer than the 1-year follow-up reported in the literature. We conducted a 3-year study of individuals who received predictive genetic test results for previously identified familial mutations in Australian Familial Cancer Clinics. Questionnaires were sent before attendance at the familial cancer clinic and 2 weeks, 4 months, 1 year, and 3 years after receiving test results. Psychological measures were included each time, and preventive behaviors were assessed at baseline and 1 and 3 years. Psychological measures were adjusted for age, gender, and baseline score. The study included 19 carriers and 54 non-carriers. We previously reported an increase in mean cancer-specific distress in carriers at 2 weeks with a return to baseline levels by 12 months. This level was maintained until 3 years. Non-carriers showed sustained decreases after testing with a significantly lower level at 3 years compared with baseline (P depression and anxiety scores did not differ between carriers and non-carriers and, at 3 years, were similar to baseline. All carriers and 7% of non-carriers had had a colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological screening in the previous 2 years. Prophylactic surgery was rare. This report of long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis colorectal cancer mutations.
Full Text Available A qualitative pilot study on the attitudes of some citizens in southern Sweden toward predictive genetic testing – and a quantitative nation wide opinion poll targeting the same issues, was initiated by the Cultural Scientific Research Team of BAGADILICO. The latter is an international biomedical research environment on neurological disease at Lund University. The data of the two studies crystallized through analysis into themes around which the informants’ personal negotiations of opinions and emotions in relation to the topic centred: Concept of Risk,‘Relations and Moral Multi-layers, Worry, Agency and Autonomy, Authority, and Rationality versus Emotion. The studies indicate that even groups of people that beforehand are non-engaged in the issue, harbour complex and ambivalent emotions and opinions toward questions like this. A certain kind of situation bound pragmatism that with difficulty could be shown by quantitative methods alone emerges. This confirms our belief that methodological consideration of combining quantitative and qualitative methods is crucial for gaining a more complex representation of attitudes, as well as for problematizing the idea of a unified public open to inquiry.
Pang, Jing; Martin, Andrew C; Bates, Timothy R; Hooper, Amanda J; Bell, Damon A; Burnett, John R; Norman, Richard; Watts, Gerald F
The aim of this study was to evaluate the clinical outcome of parent-child testing for familial hypercholesterolaemia (FH) employing genetic testing and the likely additional cost of treating each child. Parent-child testing for gene variants causative of FH was carried out according to Australian guidelines. The number of new cases detected, the low-density lipoprotein (LDL)-cholesterol that best predicted a mutation and the proportional reduction in LDL-cholesterol following statin treatment was evaluated. Treatment costs were calculated as the cost per mmol/L reduction in LDL-cholesterol. A total of 126 adult patients, known to have a pathogenic mutation causative of FH, and their children were studied. From 244 children identified, 148 (60.7%) were genetically screened; 84 children were identified as mutative positive (M+) and 64 as mutative negative. Six of the M+ children were already on statin treatment; 40 were subsequently treated with low-dose statins, with LDL-cholesterol falling significantly by 38% (P < 0.001). The estimated cost per mmol/L reduction of LDL-cholesterol of a child receiving statins from ages 10 to 18 years is AU$1361, which can potentially be cost-effective. An LDL-cholesterol threshold of 3.5 mmol/L had a sensitivity of 92.8% and specificity of 96.6% for the detection of a mutation. Genetic testing of children of affected parents with FH is an effective means of detecting new cases of FH. Cascade testing can enable early statin therapy with significant reductions in LDL-cholesterol concentration. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).
Marceau, Kristine; Knopik, Valerie S.; Neiderhiser, Jenae M.; Lichtenstein, Paul; Spotts, Erica L.; Ganiban, Jody M.; Reiss, David
In the present study we examined how genotype-environment correlation processes differ as a function of adolescent age. We tested whether adolescent age moderates genetic and environmental influences on positivity and negativity in mother-adolescent and father-adolescent relationships using parallel samples of twin parents from the Twin and Offspring Study in Sweden and twin/sibling adolescents from the Nonshared Environment in Adolescent Development Study. We inferred differences in the role of passive and non-passive genotype-environment correlation based on biometric moderation findings. Findings indicated that non-passive rGE played a stronger role for positivity in mother- and father- adolescent relationships in families with older adolescents than families with younger adolescents, and that passive rGE played a stronger role for positivity in the mother-adolescent relationship in families with younger adolescents than in families with older adolescents. Implications of these findings for the timing and targeting of interventions on family relationships are discussed. PMID:25924807
A.C.J.W. Janssens (Cécile); M.J. Khoury (Muin Joseph)
textabstractMultifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is
Strandberg, B.; Kjær, C.
The report contains the proceedings from the conference Genetically Modified Organisms in Nordic Habitats - Sustainable Use or Loss of Diversity? in Helsinki, 1998......The report contains the proceedings from the conference Genetically Modified Organisms in Nordic Habitats - Sustainable Use or Loss of Diversity? in Helsinki, 1998...
Arnos, Kathleen S.
Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in…
Full Text Available Clinical genetic testing (CGT of children with autism spectrum disorder (ASD may have positive and negative effects. Knowledge about parents’ attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents’ attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child’s ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49–67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child’s future and cause family conflicts. Parents against CGT (9% were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children’s ASD diagnosis had a weak positive association with parent’s positive attitudes to CGT (p-values range from <0.001 to 0.975. Parents prefer that CGT is offered to those having a child with ASD (65%, when the child’s development deviates from normal (48%, or before pregnancy (36%. A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation.
Johannessen, Jarle; Nærland, Terje; Hope, Sigrun; Torske, Tonje; Høyland, Anne Lise; Strohmaier, Jana; Heiberg, Arvid; Rietschel, Marcella; Djurovic, Srdjan; Andreassen, Ole A
Clinical genetic testing (CGT) of children with autism spectrum disorder (ASD) may have positive and negative effects. Knowledge about parents' attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents' attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child's ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49-67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child's future and cause family conflicts. Parents against CGT (9%) were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children's ASD diagnosis had a weak positive association with parent's positive attitudes to CGT ( p -values range from <0.001 to 0.975). Parents prefer that CGT is offered to those having a child with ASD (65%), when the child's development deviates from normal (48%), or before pregnancy (36%). A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation.
Noda, Kazutaka; Ikusaka, Masatomi; Ohira, Yoshiyuki; Takada, Toshihiko; Tsukamoto, Tomoko
Kazutaka Noda, Masatomi Ikusaka, Yoshiyuki Ohira, Toshihiko Takada, Tomoko TsukamotoDepartment of General Medicine, Chiba University Hospital, Chiba, JapanObjective: Patient medical history is important for making a diagnosis of causes of dizziness, but there have been no studies on the diagnostic value of individual items in the history. This study was performed to identify and validate useful questions for suspecting a diagnosis of benign paroxysmal positional vertigo (BPPV).Methods: Constr...
Sanderson, Saskia C.; Wardle, Jane; Humphries, Steve E.
Human genetics research is increasingly concerned with multifactorial conditions such as diabetes and heart disease, which are influenced not only by genetic but also lifestyle factors such as diet and smoking. Although the results of ‘lifestyle-genetic’ tests using this information could conceivably motivate lifestyle changes in the future, companies are already selling such tests and related lifestyle advice commercially. Some academics and lobby groups have condemned the companies for sell...
Woon, See-Tarn; Ameratunga, Rohan
New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs). Since 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014. We undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity. Thorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.
von Euler-Chelpin, My Catarina; Risør, Louise Madeleine; Thorsted, Brian Larsen
Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests...
In Europe, there is a wide variety of genetic tests that various private companies offer to patients or to consumers. More and more people have become curious about their genetic predisposition and susceptibility. Most public health-care systems, however, are not adequately prepared for responding to these new demands and to the results of these genetic tests as, quite often, there is no available therapy for the identified genetic condition. This discrepancy between the newly emerging expectations and the insufficient responses contributes to a further rift between the public and private sectors of health care. Individual genetic test results may also trigger the need for personalized medicine and may open up a competition between the two fields in offering further genetic tests and medical exams. Pro-active patients may need a different kind of information on genetic tests and their implications. In this context, how should the public health system deal with the challenges of private testing? Will private genetic testing transform health care from a solidarity-based system to an individualistic one? In this paper, I would like to explore the emerging legal and ethical issues related to genetic testing and the relevant legal framework that has developed so far. In the conclusion, I will examine the possibilities of further legal development.
Full Text Available In Europe, there is a wide variety of genetic tests that various private companies offer to patients or to consumers. More and more people have become curious about their genetic predisposition and susceptibility. Most public health-care systems, however, are not adequately prepared for responding to these new demands and to the results of these genetic tests as, quite often, there is no available therapy for the identified genetic condition. This discrepancy between the newly emerging expectations and the insufficient responses contributes to a further rift between the public and private sectors of health care. Individual genetic test results may also trigger the need for personalized medicine and may open up a competition between the two fields in offering further genetic tests and medical exams. Pro-active patients may need a different kind of information on genetic tests and their implications. In this context, how should the public health system deal with the challenges of private testing? Will private genetic testing transform health care from a solidarity-based system to an individualistic one? In this paper, I would like to explore the emerging legal and ethical issues related to genetic testing and the relevant legal framework that has developed so far. In the conclusion, I will examine the possibilities of further legal development.
Direct-to-consumer (DTC) genetic tests have aroused controversy. Critics have argued many of the tests are not backed by scientific evidence, misguide their customers and should be regulated more stringently. Proponents suggest that finding out genetic susceptibilities for diseases could encourage healthier behaviours and makes the results of genetics research available to the public. This paper reviews the state of play in DTC genetic testing, focusing on tests identifying susceptibilities for lifestyle-related diseases. It will start with mapping the market for the tests. The paper will review (1) research on the content of the online marketing of DTC tests, (2) studies on the effects of DTC genetic tests on customers and (3) academic and policy proposals on how to regulate the tests. Current studies suggest that the marketing of DTC genetic tests often exaggerates their predictive powers, which could misguide consumers. However, research indicates that the tests do not seem to have major negative effects (worry and confusion) but neither do they engender positive effects (lifestyle change) on current users. Research on regulation of the tests has most commonly suggested regulating the marketing claims of the companies. In conclusion, the risks and benefits of DTC genetic tests are less significant than what has been predicted by critics and proponents, which will be argued reflects broader historical trends transforming health and medicine.
Barlow-Stewart, Kristine; Taylor, Sandra D; Treloar, Susan A; Stranger, Mark; Otlowski, Margaret
To undertake a systematic process of verification of consumer accounts of alleged genetic discrimination. Verification of incidents reported in life insurance and other contexts that met the criteria of genetic discrimination, and the impact of fear of such treatment, was determined, with consent, through interview, document analysis and where appropriate, direct contact with the third party involved. The process comprised obtaining evidence that the alleged incident was accurately reported and determining whether the decision or action seemed to be justifiable and/or ethical. Reported incidents of genetic discrimination were verified in life insurance access, underwriting and coercion (9), applications for worker's compensation (1) and early release from prison (1) and in two cases of fear of discrimination impacting on access to genetic testing. Relevant conditions were inherited cancer susceptibility (8), Huntington disease (3), hereditary hemochromatosis (1), and polycystic kidney disease (1). In two cases, the reversal of an adverse underwriting decision to standard rate after intervention with insurers by genetics health professionals was verified. The mismatch between consumer and third party accounts in three life insurance incidents involved miscommunication or lack of information provision by financial advisers. These first cases of verified genetic discrimination make it essential for policies and guidelines to be developed and implemented to ensure appropriate use of genetic test results in insurance underwriting, to promote education and training in the financial industry, and to provide support for consumers and health professionals undertaking challenges of adverse decisions.
Lowery, Jan T; Byers, Tim; Axell, Lisen; Ku, Lisa; Jacobellis, Jillian
To assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer. Telephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low or =10%). High-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.
Spörndly-Nees, Søren; Dåsberg, Brian; Nielsen, Rasmus Oestergaard
Lower limb injuries are a large problem in athletes. However, there is a paucity of knowledge on the relationship between alignment of the medial longitudinal arch (MLA) of the foot and development of such injuries. A reliable and valid test to quantify foot type is needed to be able to investiga...
Tannert, Line K; Falkencrone, Sidsel; Mortz, Charlotte G
Background: Diagnostic workup of penicillin allergy comprises skin testing with penicillins, and patients are deemed allergic if skin test is positive. However, the literature suggests that skin test-positive patients may be challenge-negative, indicating that the skin test may be falsely positive....... Objective: To investigate real-time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin. Methods: Skin microdialysis was performed in 21 penicillin-allergic patients with positive skin test, 13 non-allergic volunteers...... serving as negative controls, and 7 grass pollen-allergic patients serving as positive controls. Histamine was measured by microdialysis after skin test with penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of the patients. Results: Only 10/21 patients (47.6%) were skin test...
Patrinos, George P; Baker, Darrol J; Al-Mulla, Fahd; Vasiliou, Vasilis; Cooper, David N
Genomic medicine seeks to exploit an individual's genomic information in the context of guiding the clinical decision-making process. In the post-genomic era, a range of novel molecular genetic testing methodologies have emerged, allowing the genetic testing industry to grow at a very rapid pace. As a consequence, a considerable number of different private diagnostic testing laboratories now provide a wide variety of genetic testing services, often employing a direct-to-consumer (DTC) business model to identify mutations underlying (or associated with) common Mendelian disorders, to individualize drug response, to attempt to determine an individual's risk of a multitude of complex (multifactorial) diseases, or even to determine a person's identity. Recently, we have noted a novel trend in the provision of private molecular genetic testing services, namely saliva and buccal swab collection kits (for deoxyribonucleic acid (DNA) isolation) being offered for sale over the counter by pharmacies. This situation is somewhat different from the standard DTC genetic testing model, since pharmacists are healthcare professionals who are supposedly qualified to give appropriate advice to their clients. There are, however, a number of issues to be addressed in relation to the marketing of DNA collection kits for genetic testing through pharmacies, namely a requirement for regulatory clearance, the comparative lack of appropriate genetics education of the healthcare professionals involved, and most importantly, the lack of awareness on the part of both the patients and the general public with respect to the potential benefits or otherwise of the various types of genetic test offered, which may result in confusion as to which test could be beneficial in their own particular case. We believe that some form of genetic counseling should ideally be integrated into, and made inseparable from, the genetic testing process, while pharmacists should be obliged to receive some basic
Given the importance of MDs, detection of genetic predisposition is potentially attractive ... burden for affected individuals and families: disease is often early onset and ... to detection of BRCA-related breast cancer in a local public health sector.
Borry, Pascal; van Hellemondt, Rachel E; Sprumont, Dominique; Jales, Camilla Fittipaldi Duarte; Rial-Sebbag, Emmanuelle; Spranger, Tade Matthias; Curren, Liam; Kaye, Jane; Nys, Herman; Howard, Heidi
An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.
Meisel Susanne F
Full Text Available Abstract Background Genetic testing for risk of weight gain is already available over the internet despite uncertain benefits and concerns about adverse emotional or behavioral effects. Few studies have assessed the effect of adding genetic test feedback to weight control advice, even though one of the proposed applications of genetic testing is to stimulate preventive action. This study will investigate the motivational effect of adding genetic test feedback to simple weight control advice in a situation where weight gain is relatively common. Methods/design First-year university students (n = 800 will be randomized to receive either 1 their personal genetic test result for a gene (FTO related to weight gain susceptibility in addition to a leaflet with simple weight control advice (‘Feedback + Advice’ group, FA, or 2 only the leaflet containing simple weight control advice (‘Advice Only’ group, AO. Motivation to avoid weight gain and active use of weight control strategies will be assessed one month after receipt of the leaflet with or without genetic test feedback. Weight and body fat will be measured at baseline and eight months follow-up. We will also assess short-term psychological reactions to the genetic test result. In addition, we will explore interactions between feedback condition and gene test status. Discussion We hope to provide a first indication of the clinical utility of weight-related genetic test feedback in the prevention context. Trial registration Current controlled trials ISRCTN91178663
DeLisi, Lynn E
This review outlines the positive and negative aspects of DNA testing and provides an account of the issues particularly relevant to schizophrenia. Modern technology has changed the field of medicine so rapidly that patients and their families have become much more independent in their healthcare decisions than in the previous decade. Simply by finding information on the Internet, they gain knowledge about disease diagnosis, treatment options and their side-effects. No medical field likely has been more affected and more controversial than that of genetics. It is now possible to sequence the individual human genome and detect single nucleotide variations, microdeletions and duplications within it. Commercial companies have sprung up in a similar manner to the software or electronic industries and have begun to market direct-to-consumer DNA testing. Much of this may be performed to satisfy curiosity about one's ancestry; but commercially available results that appear incidentally can also be distributed to the consumer. Ethicists, genetics researchers, clinicians and government agencies are currently in discussion about concerns raised about commercially available DNA testing, while at the same time recognizing its value in some instances to be able to predict very serious disabilities.
Tiller, Jane; Otlowski, Margaret; Lacaze, Paul
Under current Australian regulation, life insurance companies can require applicants to disclose all genetic test results, including results from research or direct-to-consumer tests. Life insurers can then use this genetic information in underwriting and policy decisions for mutually rated products, including life, permanent disability, and total income protection insurance. Over the past decade, many countries have implemented moratoria or legislative bans on the use of genetic information ...
Vashlishan Murray, Amy B; Carson, Michael J; Morris, Corey A; Beckwith, Jon
Marketers of genetic tests often openly or implicitly misrepresent the utility of genetic information. Scientists who are well aware of the current limitations to the utility of such tests are best placed to publicly counter misrepresentations of the science. Copyright © 2010 Elsevier Ltd. All rights reserved.
Vlahovich, Nicole; Hughes, David C; Griffiths, Lyn R; Wang, Guan; Pitsiladis, Yannis P; Pigozzi, Fabio; Bachl, Nobert; Eynon, Nir
There has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease. This review provides an overview of the current status of genetic testing for the purposes of exercise prescription and injury prevention. As such there are a variety of potential uses for genetic testing, including identification of risks associated with participation in sport and understanding individual response to particular types of exercise. However, there are many challenges remaining before genetic testing has evidence-based practical applications; including adoption of international standards for genomics research, as well as resistance against the agendas driven by direct-to-consumer genetic testing companies. Here we propose a way forward to develop an evidence-based approach to support genetic testing for exercise prescription and injury prevention. Based on current knowledge, there is no current clinical application for genetic testing in the area of exercise prescription and injury prevention, however the necessary steps are outlined for the development of evidence-based clinical applications involving genetic testing.
de Paor, Aisling
With rapid scientific and technological advances, the past few years has witnessed the emergence of a new genetic era and a growing understanding of the genetic make-up of human beings. These advances have propelled the introduction of companies offering direct to consumer (DTC) genetic testing, which facilitates the direct provision of such tests to consumers, (for example, via the internet). Although DTC genetic testing offers benefits by enhancing consumer accessibility to such technology, promoting proactive healthcare and increasing genetic awareness, it presents a myriad of challenges, from an ethical, legal and regulatory perspective. As DTC genetic testing usually eliminates the need for a medical professional in accessing genetic tests, this lack of professional guidance and counselling may result in misinterpretation and confusion regarding results. In addition, an evident concern relates to the scientific validity and quality of these tests. A further problem arising is the lack or inadequacy of regulation in this field. Despite the increasing accessibility of DTC genetic testing, this legislative vacuum is apparent in Ireland, where there is no concrete legislation. This article explores the main ethical, legal and regulatory issues arising with the advent of rapid advances in DTC genetic testing in Ireland. Further, with inevitable future advances in genetic science, as well as increasing internet accessibility, the challenges presented are likely to become more amplified. In consideration of the ethical and legal challenges, this paper highlights the regulation of DTC genetic testing as a growing concern in Ireland, recognising its importance to both the scientific community as well as in respect of enhancing consumer confidence in such technologies.
Pivetti, Monica; Montali, Lorenzo; Simonetti, Giorgia
This study explores the underlying values and beliefs that guide women's reasoning on prenatal genetic test (PGT) uptake, as framed by their own words, during a group discussion, in a Catholic country such as Italy. Women's reasoning was explored by means of five focus group consisting of seven pregnant women and 13 new mothers. The focus group material content was analysed using the Nudist software. The discourse around PGT was rooted into four frames of reference: The usefulness dimension was used to express the positions in favour of PGT, whereas morality, risk and trust were used to express negative evaluations on such a technology. Participants advocated for themselves the choice of being tested, besides giving some credit to the partner's opinion. Moreover, participants reported little knowledge on PGT. The research shed some light on the frames of reference used by participants to build their positions on PGT uptake, confirming the public's ability to translate scientific accounts into personally meaningful information. A more complete understanding of the reasons for decisions to test would help counsellors to better communicate with women and couples, and to better assist them to make a better informed testing decision. © 2012 John Wiley & Sons, Ltd.
Palmer, Christina G. S.; Boudreault, Patrick; Baldwin, Erin E.; Sinsheimer, Janet S.
Using a prospective, longitudinal study design, this paper addresses the impact of genetic counseling and testing for deafness on deaf adults and the Deaf community. This study specifically evaluated the effect of genetic counseling and Connexin-26 and Connexin-30 genetic test results on participants' deaf identity and understanding of their genetic test results. Connexin-26 and Connexin-30 genetic testing was offered to participants in the context of linguistically and culturally appropriate genetic counseling. Questionnaire data collected from 209 deaf adults at four time points (baseline, immediately following pre-test genetic counseling, 1-month following genetic test result disclosure, and 6-months after result disclosure) were analyzed. Four deaf identity orientations (hearing, marginal, immersion, bicultural) were evaluated using subscales of the Deaf Identity Development Scale-Revised. We found evidence that participants understood their specific genetic test results following genetic counseling, but found no evidence of change in deaf identity based on genetic counseling or their genetic test results. This study demonstrated that culturally and linguistically appropriate genetic counseling can improve deaf clients' understanding of genetic test results, and the formation of deaf identity was not directly related to genetic counseling or Connexin-26 and Connexin-30 genetic test results. PMID:25375116
Petrik, Dustin T.; Simpson, Barry; Kijas, James W.; Clawson, Michael L.; Chitko-McKown, Carol G.; Harhay, Gregory P.; Leymaster, Kreg A.
In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks. PMID:23408992
Michael P Heaton
Full Text Available In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV in the U.S., and Visna/Maedi virus (VMV elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154 has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V and the extracellular domains (E31Q, I74F, and I102T of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes. The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.
Geransar, Rose; Einsiedel, Edna
Commercialization of genetic technologies is expanding the horizons for the marketing and sales of genetic tests direct-to-consumers (DTCs). This study assesses the information provision and access requirements that are in place for genetic tests that are being advertised DTC over the Internet. Sets of key words specific to DTC genetic testing were entered into popular Internet search engines to generate a list of 24 companies engaging in DTC advertising. Company requirements for physician mediation, genetic counseling arrangements, and information provision were coded to develop categories for quantitative analysis within each variable. Results showed that companies offering risk assessment and diagnostic testing were most likely to require that testing be mediated by a clinician, and to recommend physician-arranged counseling. Companies offering enhancement testing were less likely to require physician mediation of services and more likely to provide long-distance genetic counseling. DTC advertisements often provided information on disease etiology; this was most common in the case of multifactorial diseases. The majority of companies cited outside sources to support the validity of claims about clinical utility of the tests being advertised; companies offering risk assessment tests most frequently cited all information sources. DTC advertising for genetic tests that lack independent professional oversight raises troubling questions about appropriate use and interpretation of these tests by consumers and carries implications for the standards of patient care. These implications are discussed in the context of a public healthcare system.
Hilliard, R.K.; Johnson, R.P.
The first Specialists' Meeting on sodium fire technology sponsored by the International Working Group on Fast Reactors (IWGFR) was held in Richland, Washington in 1972. The group concluded that the state-of-technology at that time was inadequate to support the growing LMFBR industry. During the second IWGFR Specialists' Meeting on sodium fires, held in Cadarache, France in 1978, a large quantity of technical information was exchanged and areas were identified where additional work was needed. Advances in several important areas of sodium fire technology have been made in the United States since that time, including improved computer codes, design of a sodium fire protection system for the CRBRP, measurement of water release from heated concrete, and testing and modeling of the sodium-concrete reaction. Research in the U.S. related to sodium fire technology is performed chiefly at the Energy Systems Group of Rockwell International (including Atomics International), the Hanford Engineering Development Laboratory (HEDL), and the Sandia National Laboratories (SNL). The work at the first two laboratories is sponsored by the U.S. Department of Energy, while that at the latter is sponsored by the U.S. Nuclear Regulatory Commission. Various aspects of sodium fire related work is also performed at several other laboratories. The current status of sodium fire technology in the U.S. is summarized in this report
Uhlmann, Wendy R; Schwalm, Katie; Raymond, Victoria M
Obtaining genetic testing insurance authorizations for patients is a complex, time-involved process often requiring genetic counselor (GC) and physician involvement. In an effort to mitigate this complexity and meet the increasing number of genetic testing insurance authorization requests, GCs formed a novel partnership with an industrial engineer (IE) and a patient services associate (PSA) to develop a streamlined work flow. Eight genetics clinics and five specialty clinics at the University of Michigan were surveyed to obtain benchmarking data. Tasks needed for genetic testing insurance authorization were outlined and time-saving work flow changes were introduced including 1) creation of an Excel password-protected shared database between GCs and PSAs, used for initiating insurance authorization requests, tracking and follow-up 2) instituting the PSAs sending GCs a pre-clinic email noting each patients' genetic testing insurance coverage 3) inclusion of test medical necessity documentation in the clinic visit summary note instead of writing a separate insurance letter and 4) PSAs development of a manual with insurance providers and genetic testing laboratories information. These work flow changes made it more efficient to request and track genetic testing insurance authorizations for patients, enhanced GCs and PSAs communication, and reduced tasks done by clinicians.
Resende, Juliana Alves; Fontes, Cláudia Oliveira; Ferreira-Machado, Alessandra Barbosa; Nascimento, Thiago César; Silva, Vânia Lúcia; Diniz, Cláudio Galuppo
Although most Brazilian dairy products meet high technological standards, there are quality issues regarding milk production, which may reduce the final product quality. Several microbial species may contaminate milk during manufacture and handling. If antimicrobial usage remains uncontrolled in dairy cattle, the horizontal transfer of antimicrobial resistance genes in foodstuffs may be of particular concern for both food producers and dairy industry. This study focused on the evaluation of putative Gram positive cocci in Minas cheese and of antimicrobial and biocide resistance genes among the isolated bacteria. Representative samples of 7 different industrially trademarked Minas cheeses (n = 35) were processed for selective culture and isolation of Gram positive cocci. All isolated bacteria were identified by DNA sequencing of the 16S rRNA gene. Antimicrobial resistance genes were screened by PCR. Overall, 208 strains were isolated and identified as follows: Enterococcus faecalis (47.6%), Macrococcus caseolyticus (18.3%), Enterococcus faecium (11.5%), Enterococcus caseliflavus (7.7%), Staphylococcus haemolyticus (7.2%), Staphylococcus aureus (4.3%), Staphylococcus epidermidis (2.9%), and Enterococcus hirae (0.5%). The genetic markers mecA (78.0%) and smr (71.4%) were the most prevalent, but others were also detected, such as blaZ (65.2%), msrA (60.9%), msrB (46.6%), linA (54.7%), and aacA-aphD (47.6%). The occurrence of opportunist pathogenic bacteria harboring antimicrobial resistance markers in the cheese samples are of special concern, since these bacteria are not considered harmful contaminating agents according to the Brazilian sanitary regulations. However, they are potentially pathogenic bacteria and the cheese may be considered a reservoir for antimicrobial resistance genes available for horizontal transfer through the food chain, manufacturing personnel and consumers. © 2018 Institute of Food Technologists®.
Witt, Magdalena M; Witt, Michał P
Medical confidentiality in clinical genetics poses an important question about its scope, which would be in line with professional ethics and simple honesty. It is already known that the maintenance of absolute anonymity, bearing in mind the current progress of genetic techniques, is virtually impossible. On the other hand, our insight into the information contained in the human genome is increasing. This mini-review presents the authors' standpoint regarding this complex and difficult issue.
Hüttner, Marion; Nakao, Minoru; Wassermann, Torsten; Siefert, Ludwig; Boomker, Joop D F; Dinkel, Anke; Sako, Yasuhito; Mackenstedt, Ute; Romig, Thomas; Ito, Akira
Echinococcus felidis had been described in 1937 from African lions, but was later included in Echinococcus granulosus as a subspecies or a strain. In the absence of any genetic characterization, most previous records of this taxon from a variety of large African mammals remained unconfirmed due to the lack of diagnostic criteria and the possible confusion with the sympatric E. granulosus sensu stricto, Echinococcus ortleppi and Echinococcus canadensis. In this study, we obtained taeniid eggs from lion feces in Uganda and amplified DNA from individual eggs. Mitochondrial and nuclear DNA sequences showed similarities with those of other Echinococcus spp., but high values of percentage divergence of mitochondrial genes indicated the presence of a distinct species. In a second step, we compared this material with the preserved specimens of adult E. granulosus felidis, which had been identified morphologically approximately 40 years ago in South Africa. All DNA fragments (<200 bp) that could be amplified from the adults showed 100% similarity with the Ugandan material. In the phylogenetic tree of Echinococcus which was constructed from the mitochondrial genes, E. felidis is positioned as a sister taxon of E. granulosus sensu stricto. The data obtained will facilitate the development of diagnostic tools necessary to study the epidemiology of this enigmatic parasite.
Cooper, Tara E.; Krause, David J.
Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176
Bardakjian, Tanya M; Helbig, Ingo; Quinn, Colin; Elman, Lauren B; McCluskey, Leo F; Scherer, Steven S; Gonzalez-Alegre, Pedro
To determine the diagnostic yield of different genetic test modalities in adult patients with neurological disorders, we evaluated all adult patients seen for genetic diagnostic evaluation in the outpatient neurology practice at the University of Pennsylvania between January 2016 and April 2017 as part of the newly created Penn Neurogenetics Program. Subjects were identified through our electronic medical system as those evaluated by the Program's single clinical genetic counselor in that period. A total of 377 patients were evaluated by the Penn Neurogenetics Program in different settings and genetic testing recommended. Of those, 182 (48%) were seen in subspecialty clinic setting and 195 (52%) in a General Neurogenetics Clinic. Genetic testing was completed in over 80% of patients in whom it was recommended. The diagnostic yield was 32% across disease groups. Stratified by testing modality, the yield was highest with directed testing (50%) and array comparative genomic hybridization (45%), followed by gene panels and exome testing (25% each). In conclusion, genetic testing can be successfully requested in clinic in a large majority of adult patients. Age is not a limiting factor for a genetic diagnostic evaluation and the yield of clinical testing across phenotypes (almost 30%) is consistent with previous phenotype-focused or research-based studies. These results should inform the development of specific guidelines for clinical testing and serve as evidence to improve reimbursement by insurance payers.
Peter D Paré
Full Text Available The human genome project promised a revolution in health care – the development of ‘personalized medicine’, where knowledge of an individual’s genetic code enables the prediction of risk for specific diseases and the potential to alter that risk based on preventive measures and lifestyle modification. The present brief review provides a report card on the progress toward that goal with respect to respiratory disease. Should generalized population screening for genetic risk factors for respiratory disease be instituted? Or not?
Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A
This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.
Caulfield, Timothy; McGuire, Amy L
Direct-to-consumer (DTC) genetic testing has attracted a great amount of attention from policy makers, the scientific community, professional groups, and the media. Although it is unclear what the public demand is for these services, there does appear to be public interest in personal genetic risk information. As a result, many commentators have raised a variety of social, ethical, and regulatory issues associated with this emerging industry, including privacy issues, ensuring that DTC companies provide accurate information about the risks and limitations of their services, the possible adverse impact of DTC genetic testing on healthcare systems, and concern about how individuals may interpret and react to genetic risk information.
Wehenkel, C.; Corral-Rivas, J. J.; Castellanos-Bocaz, H. A.; Pinedo-Alvarez, A.
The concepts of genetic diversity and naturalness are well known as measures of conservation values and as descriptors of state or condition. A lack of research evaluating the relationship between genetic diversity and naturalness in biological communities, along with the possible implications in terms of evolutionary aspects and conservation management, make this subject particularly important as regards forest tree communities.We therefore examined the following hypothesis: the genetic dive...
Egglestone, Corin; Morris, Anne; O'Brien, Ann
Direct-to-consumer (DTC) genetic tests can be purchased over the internet. Some companies claim to provide relative genetic risks for various diseases and thus encourage healthy behaviour. There are concerns that exposure to such information may actually discourage healthy behaviour or increase health anxiety. An online survey was conducted (n = 275). Respondents were composed of individuals who had purchased a DTC genetic test and received their results (consumers, n = 189), as well as individuals who were either awaiting test results or considering purchasing a test (potential consumers, n = 86). Consumers were asked if their health behaviour or health anxiety had changed after receiving their results. Respondents' current health behaviour and health anxiety were queried and compared. In total, 27.3 % of consumers claimed a change in health behaviour, all either positive or neutral, with no reported cessation of any existing health behaviour. A change in health anxiety was claimed by 24.6 % of consumers, 85.3 % of which were a reduction. Consumers had significantly better health behaviour scores than potential consumers (p = 0.02), with no significant difference in health anxiety. This study points towards an association between receipt of DTC genetic test results and increased adoption of healthy behaviours for a minority of consumers based on self-report, with more mixed results in relation to health anxiety.
Background. Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene (FMR-1) gene. Objectives. To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders ...
Nutrigenetics has been used for decades to prevent rare monogenic disorders such as phenylketonuria. Gene-diet interaction can now also be targeted to prevent or reduce the risk of many chronic conditions long before clinical manifestation. This multidisciplinary approach unites conventional medicine with genetics and ...
The thought of genetically engineered (GE) trees might conjure images of mutant trees with unnatural and invasive tendencies, but there is much more to the story. GE trees are a new reality that, like it or not, will probably be part of the future of forestry. The basic inclination of most Forest Guild stewards is to reject GE trees as violating our principle to...
Meulenkamp, Tineke M.; Tibben, Aad; Mollema, Eline D.; Van Langen, Irene M.; Wiegman, Albert; De Wert, Guido M.; De Beaufort, Inez D.; Wilde, Arthur A. M.; Smets, Ellen M. A.
We studied the experiences of children identified by family screening who were found to be a mutation carrier for a genetic cardiovascular disease (Long QT Syndrome (LQTS), Hypertrophic Cardiomyopathy (HCM), Familial Hypercholesterolemia (FH)). We addressed the (a) manner in which they perceive
National Research Council Staff
... on Scientific Evaluation of the Introduction of Genetically Modified Microoganisms and Plants into the Environment Board on Biology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1989 i Copyrightthe cannot be not from book, paper however, version for formatting, original authoritative the typesetting-s...
Flett, Gordon L.; Blankstein, Kirk R.; Hewitt, Paul L.
The current study examined the associations among trait dimensions of perfectionism, test performance, and levels of positive and negative affect after taking a test. A sample of 92 female university students completed the Multidimensional Perfectionism Scale one week prior to an actual class test. Measures of positive affect and negative affect…
Van der Zande, Paul; Akkerman, Sanne F.; Brekelmans, Mieke; Waarlo, Arend Jan; Vermunt, Jan D.
Contemporary genomics research will impact the daily practice of biology teachers who want to teach up-to-date genetics in secondary education. This article reports on a research project aimed at enhancing biology teachers' expertise for teaching genetics situated in the context of genetic testing. The increasing body of scientific knowledge concerning genetic testing and the related consequences for decision-making indicate the societal relevance of an educational approach based on situated learning. What expertise do biology teachers need for teaching genetics in the personal health context of genetic testing? This article describes the required expertise by exploring the educational practice. Nine experienced teachers were interviewed about the pedagogical content, moral and interpersonal expertise areas concerning how to teach genetics in the personal health context of genetic testing, and the lessons of five of them were observed. The findings showed that the required teacher expertise encompasses specific pedagogical content expertise, interpersonal expertise and a preference for teacher roles and teaching approaches for the moral aspects of teaching in this context. A need for further development of teaching and learning activities for (reflection on) moral reasoning came to the fore. Suggestions regarding how to apply this expertise into context-based genetics education are discussed.
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest 'opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.
Yoshida, Kunihiro; Tamai, Mariko; Kubota, Takeo; Kawame, Hiroshi; Amano, Naoji; Ikeda, Shu-ichi; Fukushima, Yoshimitsu
Predictive genetic testing for hereditary neuromuscular diseases is a delicate issue for individuals at risk and their families, as well as for medical staff because these diseases are often late-onset and intractable. Therefore careful pre- and post-test genetic counseling and psychosocial support should be provided along with such genetic testing. The Division of Clinical and Molecular Genetics was established at our hospital in May 1996 to provide skilled professional genetic counseling. Since its establishment, 14 individuals have visited our clinic to request predictive genetic testing for hereditary neuromuscular diseases (4 for myotonic dystrophy, 6 for spinocerebellar ataxia, 3 for Huntington's disease, and 1 for Alzheimer's disease). The main reasons for considering testing were to remove uncertainty about the genetic status and to plan for the future. Nine of 14 individuals requested testing for making decisions about a forthcoming marriage or pregnancy (family planning). Other reasons raised by the individuals included career or financial planning, planning for their own health care, and knowing the risk for their children. At the first genetic counseling session, all of the individuals expressed hopes of not being a gene carrier and of escaping from fear of disease, and seemed not to be mentally well prepared for an increased-risk result. To date, 7 of the 14 individuals have received genetic testing and only one, who underwent predictive genetic testing for spinocerebellar ataxia, was given an increased-risk result. The seven individuals including the one with an increased-risk result, have coped well with their new knowledge about their genetic status after the testing results were disclosed. None of them has expressed regret. In pre-test genetic counseling sessions, we consider it quite important not only to determine the psychological status of the individual, but also to make the individual try to anticipate the changes in his/her life upon
Rebolj, Matejka; Pribac, Igor; Frederiksen, Maria Eiholm
Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing...... will probably replace cytology in future primary cervical screening. However, HPV testing is associated with more frequent false-positive tests compared to cytology. False-positive tests are defined as positive screening tests which are not subsequently confirmed with high-grade CIN. Several authors have...
Vassy, Jason L; O'Brien, Kelsey E; Waxler, Jessica L; Park, Elyse R; Delahanty, Linda M; Florez, Jose C; Meigs, James B; Grant, Richard W
Type 2 diabetes genetic risk testing might motivate at-risk patients to adopt diabetes prevention behaviors. However, the influence of literacy and numeracy on patient response to diabetes genetic risk is unknown. The authors investigated the association of health literacy, genetic literacy, and health numeracy with patient responses to diabetes genetic risk. and Measurements Overweight patients at high phenotypic risk for type 2 diabetes were recruited for a clinical trial of diabetes genetic risk testing. At baseline, participants predicted how their motivation for lifestyle modification to prevent diabetes might change in response to hypothetical scenarios of receiving "high" and "low" genetic risk results. Responses were analyzed according to participants' health literacy, genetic literacy, and health numeracy. Two-thirds (67%) of participants (n = 175) reported very high motivation to prevent diabetes. Despite high health literacy (92% at high school level), many participants had limited health numeracy (30%) and genetic literacy (38%). Almost all (98%) reported that high-risk genetic results would increase their motivation for lifestyle modification. In contrast, response to low-risk genetic results varied. Higher levels of health literacy (P = 0.04), genetic literacy (P = 0.02), and health numeracy (P = 0.02) were associated with an anticipated decrease in motivation for lifestyle modification in response to low-risk results. While patients reported that high-risk genetic results would motivate them to adopt healthy lifestyle changes, response to low-risk results varied by patient numeracy and literacy. However, anticipated responses may not correlate with true behavior change. If future research justifies the clinical use of genetic testing to motivate behavior change, it may be important to assess how patient characteristics modify that motivational effect.
David C Whitcomb
Full Text Available Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1 gene, the cystic fibrosis transmembrane conductance regulator (CFTR gene, and the pancreatic secretory trypsin inhibitor (PSTI or serine protease inhibitor, Kazal type 1 (SPINK1 gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of the PRSS1 gene, which can be readily identified by genetic testing. Mutations of the CFTR gene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of the SPINK1 (or PSTI gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of the PRSS1 and SPINK1 genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests that SPINK1 is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.
Rubinstein, Wendy S; Maglott, Donna R; Lee, Jennifer M; Kattman, Brandi L; Malheiro, Adriana J; Ovetsky, Michael; Hem, Vichet; Gorelenkov, Viatcheslav; Song, Guangfeng; Wallin, Craig; Husain, Nora; Chitipiralla, Shanmuga; Katz, Kenneth S; Hoffman, Douglas; Jang, Wonhee; Johnson, Mark; Karmanov, Fedor; Ukrainchik, Alexander; Denisenko, Mikhail; Fomous, Cathy; Hudson, Kathy; Ostell, James M
The National Institutes of Health Genetic Testing Registry (GTR; available online at http://www.ncbi.nlm.nih.gov/gtr/) maintains comprehensive information about testing offered worldwide for disorders with a genetic basis. Information is voluntarily submitted by test providers. The database provides details of each test (e.g. its purpose, target populations, methods, what it measures, analytical validity, clinical validity, clinical utility, ordering information) and laboratory (e.g. location, contact information, certifications and licenses). Each test is assigned a stable identifier of the format GTR000000000, which is versioned when the submitter updates information. Data submitted by test providers are integrated with basic information maintained in National Center for Biotechnology Information's databases and presented on the web and through FTP (ftp.ncbi.nih.gov/pub/GTR/_README.html).
The purpose of this study is to evaluate the clinical usefulness of exercise (Ex) ECG test with sublingual nitroglycerin (NTG) and Ex cardiac scintigraphy in differentiating false positive responses from true positive responses of Ex ECG test. We examined 7 pts (age : 46+-7 years) with true positive Ex ECG test (TP) and 8 pts (age : 55+-10 years) with false positive Ex ECG test (FP). TP had significant coronary artery disease and FP did not. Ex test was done by multistage ergometer test. In 5 pts of TP and all pts of FP, Ex cardiac scintigraphy was performed. In TP, Ex cardiac scintigraphy revealed reversible perfusion deficit, but not in FP. NTG was administered 3 minutes before Ex test was started. Ex test with NTG was terminated at the same load as Ex test without NTG. Pressure-rate products at the end point of Ex test did not show significant difference between Ex test without NTG and that with NTG (TP: 203x10 2 , 213x10 2 , FP: 196x10 2 , 206x10 2 , respectively). In 7 pts of FP, ST depression in Ex test without NTG was not improved in Ex test with NTG. On the other hand, in all pts of TP, ST depression seen in Ex test without NTG, was not observed in Ex test with NTG. It may be concluded that Ex cardiac scintigraphy is diagnostic for differentiation of false positive responses from true positive responses of Ex ECG test, as well as Ex ECG test with NTG is. (author)
Phillips, B.J.; Kranz, E.; Elias, P.S.
As part of a programme of short-term tests used to detect possible genetic toxicity in irradiated foodstuffs, cultured Chinese hamster ovary cells were exposed to extracts and digests of irradiated and unirradiated dates, fish and chicken and subjected to tests for cytotoxicity, sister chromatid exchange induction and mutation to thioguanine resistance. The results showed no evidence of genetic toxicity induced in food by irradiation. The general applicability of cell culture tests to the detection of mutagens in food is discussed. (author)
Maqueda, Mercedes; Sánchez-Hidalgo, Marina; Fernández, Matilde; Montalbán-López, Manuel; Valdivia, Eva; Martínez-Bueno, Manuel
This review highlights the main genetic features of circular bacteriocins, which require the co-ordinated expression of several genetic determinants. In general terms, it has been demonstrated that the expression of such structural genes must be combined with the activity of proteins involved in
Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten
According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Patch, Christine; Sequeiros, Jorge; Cornel, Martina C
The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and the appropriate regulatory and policy response. How these concerns are interpreted and addressed is an ongoing debate. If the possibility of using the discoveries from genomic science to improve health is to be realised without losing public confidence, then improvements in the evaluation and mechanisms for control of supply of tests may be as important as the science itself.
Cooper, Gregory S; Markowitz, Sanford D; Chen, Zhengyi; Tuck, Missy; Willis, Joseph E; Berger, Barry M; Brenner, Dean E; Li, Li
There is uncertainty as to the appropriate follow-up of patients who test positive on multimarker stool DNA (sDNA) testing and have a colonoscopy without neoplasia. To determine the prevalence of missed colonic or occult upper gastrointestinal neoplasia in patients with an apparent false positive sDNA. We prospectively identified 30 patients who tested positive with a commercially available sDNA followed by colonoscopy without neoplastic lesions. Patients were invited to undergo repeat sDNA at 11-29 months after the initial test followed by repeat colonoscopy and upper endoscopy. We determined the presence of neoplastic lesions on repeat evaluation stratified by results of repeat sDNA. Twelve patients were restudied. Seven patients had a negative second sDNA test and a normal second colonoscopy and upper endoscopy. In contrast, 5 of 12 subjects had a persistently positive second sDNA test, and 3 had positive findings, including a 3-cm sessile transverse colon adenoma with high-grade dysplasia, a 2-cm right colon sessile serrated adenoma with dysplasia, and a nonadvanced colon adenoma (p = 0.045). These corresponded to a positive predictive value of 0.60 (95% CI 0.17-1.00) and a negative predictive value of 1.00 (95% CI 1.00-1.00) for the second sDNA test. In addition, the medical records of all 30 subjects with apparent false positive testing were reviewed and no documented cases of malignant tumors were recorded. Repeat positive sDNA testing may identify a subset of patients with missed or occult colorectal neoplasia after negative colonoscopy for an initially positive sDNA. High-quality colonoscopy with careful attention to the right colon in patients with positive sDNA is critically important and may avoid false negative colonoscopy.
Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P
Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
This report covers the development of a three channel Hall effect position sensing system for the commutation of a three phase dc torquer motor. The effort consisted of the evaluation, modification and re-packaging of a commercial position sensor and the design of a target configuration unique to this application. The resulting design meets the contract requirements and, furthermore, the test results indicate not only the practicality and versatility of the design, but also that there may be higher limits of resolution and accuracy achievable.
Hall, Julia; Gray, Susan; A'Hern, Roger; Shanley, Susan; Watson, Maggie; Kash, Kathryn; Croyle, Robert; Eeles, Rosalind
Interest in searching for mutations in BRCA1 and BRCA2 is high. Knowledge regarding these genes and the advantages and limitations of genetic testing is limited. It is unknown whether increasing knowledge about breast cancer genetic testing alters interest in testing. Three hundred and seventy nine women (260 with a family history of breast cancer; 119 with breast cancer) from The Royal Marsden NHS Foundation Trust were randomised to receive or not receive written educational information on cancer genetics. A questionnaire was completed assessing interest in BRCA1 testing and knowledge on breast cancer genetics and screening. Actual uptake of BRCA1 testing is reported with a six year follow-up. Eighty nine percent of women at risk of breast cancer and 76% of women with breast cancer were interested in BRCA1 testing (P testing, the families of 66% of the at risk group and 13% of the women with breast cancer would be eligible for testing (probability of BRCA1 mutation >or=20%). Within six years of randomisation, genetic testing was actually undertaken on 12 women, only 10 of whom would now be eligible, on the NICE guidelines. There is strong interest in BRCA1 testing. Despite considerable ignorance of factors affecting the inheritance of breast cancer, education neither reduced nor increased interest to undergo testing. The NICE guidelines successfully triage those with a high breast cancer risk to be managed in cancer genetics clinics.
CDC’s Response to Zika FOR MEN: A POSITIVE ZIKA VIRUS TEST What does it mean for me? You’ ... Zika test result, which means that you have Zika virus. Zika is spread through mosquito bites and through ...
Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus
Genetic testing and (non)disclosure of genetic information present ethical and moral dilemmas for the management of parental responsibility vis-à-vis the child's autonomy. Ethical guidelines aimed at professionals currently seek to defer childhood testing where there is no clear medical or psychosocial benefit. This version of autonomy is derived from a bioethical paradigm which brackets the individual rights and capacities of the child. In this paper we focus on situated parental accounts of responsibility/autonomy to understand the complex forms of relational work -i.e. the micropolitics of balancing rights and responsibilities - involving a range of inherited genetic disorders. Interviews (n= 20) were conducted with parents whose genetic condition may have had consequences for their children. Using rhetorical discourse analysis, we show how parents draw upon a number of rhetorical/discoursal devices to produce accounts where genetic responsibility is actually or potentially transmitted to the child. We identify three kinds of accounting practice: (1) aligned responsibility; (2) deferred responsibility; and (3) misaligned responsibility. Each of these practices demonstrates how parents position themselves responsibly by foregrounding figures and events onto which the child's autonomy is selectively mapped. Rather than simple representations, we regard these accounts as complex moral performances that seek alignment with broader bioethical discourses.
Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.
Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479
Anderson, Emily E; Wasson, Katherine
The stories in this volume shed light on the potential of narrative inquiry to fill gaps in knowledge, particularly given the mixed results of quantitative research on patient views of and experiences with genetic and genomic testing. Published studies investigate predictors of testing (particularly risk perceptions and worry); psychological and behavioral responses to testing; and potential impact on the health care system (e.g., when patients bring DTC genetic test results to their primary care provider). Interestingly, these themes did not dominate the narratives published in this issue. Rather, these narratives included consistent themes of expectations and looking for answers; complex emotions; areas of contradiction and conflict; and family impact. More narrative research on patient experiences with genetic testing may fill gaps in knowledge regarding how patients define the benefits of testing, changes in psychological and emotional reactions to test results over time, and the impact of testing on families.
Koenekoop, R.K.; Lopez, I.; Hollander, A.I. den; Allikmets, R.; Cremers, F.P.M.
Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular
Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M.; Papatheodorou, Efstathios; Ware, James S.; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R.; Crawford, Jackie; Love, Donald R.; Pua, Chee J.; Soh, Bee Y.; Bhalshankar, Jaydutt D.; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G.; van der Werf, Christian; Wijeyeratne, Yanushi D.; Mellor, Greg; Till, Jan; Cohen, Marta C.; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A. M.; Cook, Stuart A.; Bezzina, Connie R.; Sheppard, Mary N.; Behr, Elijah R.
Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and
van der Zande, P.A.M.|info:eu-repo/dai/nl/304827363
Learners in Dialogue; this thesis aims at the exploration of teacher expertise for teachers who want to teach genetics in the context of genetic testing and at finding ways to foster teacher learning concerning this expertise. Recent developments in the field of genomics will impact the daily
Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M
BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy...
Full Text Available Bridget Kiely, Sujit Vettam, Andrew Adesman Division of Developmental and Behavioral Pediatrics, Department of Pediatrics, Steven and Alexandra Cohen Children’s Medical Center of New York, New Hyde Park, NY, USA Purpose: Several professional societies recommend that genetic testing be routinely included in the etiologic workup of children with developmental disabilities. The aim of this study was to determine the rate at which genetic testing is performed in this population, based on data from a nationally representative survey.Methods: Data were analyzed from the Survey of Pathways to Diagnosis and Services, a telephone-based survey of parents and guardians of US school-age children with current or past developmental conditions. This study included 3,371 respondents who indicated that their child had an autism spectrum disorder (ASD, intellectual disability (ID, and/or developmental delay (DD at the time of survey administration. History of genetic testing was assessed based on report by the parent/s. Children were divided into the following five mutually exclusive condition groups: ASD with ID; ASD with DD, without ID; ASD only, without ID or DD; ID without ASD; and DD only, without ID or ASD. Logistic regression was used to assess the demographic correlates of genetic testing, to compare the rates of genetic testing across groups, and to examine associations between genetic testing and use of other health-care services.Results: Overall, 32% of this sample had a history of genetic testing, including 34% of all children with ASD and 43% of those with ID. After adjusting for demographics, children with ASD + ID were more than seven times as likely as those with ASD only, and more than twice as likely as those who had ID without ASD, to have undergone genetic testing. Prior specialist care (developmental pediatrician or neurologist and access to all needed providers within the previous year were associated with higher odds of genetic testing
Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E
Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these laboratories, the European Molecular Genetics Quality Network has organized a yearly external quality assessment (EQA) scheme for molecular genetic testing of HD for over 10 years. EQA compares a laboratory's output with a fixed standard both for genotyping and reporting of the results to the referring physicians. In general, the standard of genotyping is very high but the clarity of interpretation and reporting of the test result varies more widely. This emphasizes the need for best practice guidelines for this disorder. We have therefore developed these best practice guidelines for genetic testing for HD to assist in testing and reporting of results. The analytical methods and the potential pitfalls of molecular genetic testing are highlighted and the implications of the different test outcomes for the consultand and his or her family members are discussed.
Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M
The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Questionnaires were completed with 200 participants. Responses indicated that participants' perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning.
Douma, Kirsten F L; Aaronson, Neil K; Vasen, Hans F A; Verhoef, Senno; Gundy, Chad M; Bleiker, Eveline M A
Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.
Acmg Board Of Directors
Disclaimer: These recommendations are designed primarily as an educational resource for medical geneticists and other health-care providers, to help them provide quality medical genetic services. Adherence to these recommendations does not necessarily assure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these recommendations.Genet Med advance online publication 05 January 2017.
Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter
Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.
Zimmermann, F.K.; von Borstel, R.C.; von Halle, E.S.; Parry, J.M.; Siebert, D.; Zetterberg, G.; Barale, R.; Loprieno, N.
This review article with over 200 references summarizes the results of mutation screening tests with 492 chemicals using saccharomyces cerevisiae as the test organism. In addition, an extensive description of S. cerevisiae as a test organism is given. Yeast can be used to study genetic effects both in mitotic and in meiotic cells because it can be cultured as a stable haploid or a stable diploid. The most commonly used genetic endpoint has been mitotic recombination either as mitotic crossing-over or mitotic gene conversion. Data were available on tests with 492 chemicals, of which 249 were positive, as reported in 173 articles or reports. The genetic test/carcinogenicity accuracy was 0.74, based on the carcinogen listing established in the gene-tox program. The yeast tests supplement the bacterial tests for detecting agents that act via radical formation, antibacterial drugs, and other chemicals interfering with chromosome segregation and recombination processes.
Andersen, Sune Bangsbøll; Vejborg, Ilse; von Euler-Chelpin, My
women experiencing a negative screening test, regardless of whether the false positive statement was given following assessment or following surgery. The benign to malignant biopsy ratio, comparing the type B false positives to the true positives, was by the fifth round well below the desirable level...
Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L
To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.
Li, Min; Piao, Jianhua; Yang, Xiaoguang
To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.
Conrad, Melissa D; Kissinger, Patricia; Schmidt, Norine; Martin, David H; Carlton, Jane M
Recently developed genotyping tools allow better understanding of Trichomonas vaginalis population genetics and epidemiology. These tools have yet to be applied to T vaginalis collected from HIV+ populations, where understanding the interaction between the pathogens is of great importance due to the correlation between T vaginalis infection and HIV transmission. The objectives of the study were twofold: first, to compare the genetic diversity and population structure of T vaginalis collected from HIV+ women with parasites from reference populations; second, to use the genetic markers to perform a case study demonstrating the usefulness of these techniques in investigating the mechanisms of repeat infections. Repository T vaginalis samples from a previously described treatment trial were genotyped at 11 microsatellite loci. Estimates of genetic diversity and population structure were determined using standard techniques and compared with previously reported estimates of global populations. Genotyping data were used in conjunction with behavioural data to evaluate mechanisms of repeat infections. T vaginalis from HIV+ women maintain many of the population genetic characteristics of parasites from global reference populations. Although there is evidence of reduced diversity and bias towards type 1 parasites in the HIV+ population, the populations share a two-type population structure and parasite haplotypes. Genotyping/behavioural data suggest that 36% (12/33) of repeat infections in HIV+ women can be attributed to treatment failure. T vaginalis infecting HIV+ women is not genetically distinct from T vaginalis infecting reference populations. Information from genotyping can be valuable for understanding mechanisms of repeat infections.
Ramirez, Amelie G; Chalela, Patricia; Gallion, Kipling J; Muñoz, Edgar; Holden, Alan E; Burhansstipanov, Linda; Smith, Selina A; Wong-Kim, Evaon; Wyatt, Stephen W; Suarez, Lucina
This study examined interest in and attitudes toward genetic testing in 5 different population groups. The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences. Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to "follow doctor recommendations" (p=0.017), "concern for effects on family" (p=0.044), "distrust of modern medicine" (p=0.036), "cost" (p=0.025), and "concerns about communication of results to others" (p=0.032). There was a significant inverse relationship between interest and genetic testing cost (p<0.050), with the exception of Latinas, who showed the highest level of interest regardless of increasing cost. Cost may be an important barrier to obtaining genetic testing services, and participants would benefit by genetic counseling that incorporates the unique cultural values and beliefs of each group to create an individualized, culturally competent program. Further research about attitudes toward genetic testing is needed among Asian Americans, Native Americans, and Appalachians for whom data are severely lacking. Future study of the different Latina perceptions toward genetic testing are encouraged.
Bollinger, Juli Murphy; Green, Robert C; Kaufman, David
The first regulatory rulings by the U.S. Food and Drug Administration on direct-to-consumer (DTC) genetic testing services are expected soon. As the process of regulating these and other genetic tests moves ahead, it is important to understand the preferences of DTC genetic testing customers about the regulation of these products. An online survey of customers of three DTC genetic testing companies was conducted 2-8 months after they had received their results. Participants were asked about the importance of regulating the companies selling DTC genetic tests. Most of the 1,046 respondents responded that it would be important to have a nongovernmental (84%) or governmental agency (73%) monitor DTC companies' claims to ensure the consistency with scientific evidence. However, 66% also felt that it was important that DTC tests be available without governmental oversight. Nearly, all customers favored a policy to ensure that insurers and law enforcement officials could not access their information. Although many DTC customers want access to genetic testing services without restrictions imposed by the government regulation, most also favor an organization operating alongside DTC companies that will ensure that the claims made by the companies are consistent with sound scientific evidence. This seeming contradiction may indicate that DTC customers want to ensure that they have unfettered access to high-quality information. Additionally, policies to help ensure privacy of data would be welcomed by customers, despite relatively high confidence in the companies.
Chen, Hao; Guan, Weipeng; Li, Simin; Wu, Yuxiang
To improve the precision of indoor positioning and actualize three-dimensional positioning, a reversed indoor positioning system based on visible light communication (VLC) using genetic algorithm (GA) is proposed. In order to solve the problem of interference between signal sources, CDMA modulation is used. Each light-emitting diode (LED) in the system broadcasts a unique identity (ID) code using CDMA modulation. Receiver receives mixed signal from every LED reference point, by the orthogonality of spreading code in CDMA modulation, ID information and intensity attenuation information from every LED can be obtained. According to positioning principle of received signal strength (RSS), the coordinate of the receiver can be determined. Due to system noise and imperfection of device utilized in the system, distance between receiver and transmitters will deviate from the real value resulting in positioning error. By introducing error correction factors to global parallel search of genetic algorithm, coordinates of the receiver in three-dimensional space can be determined precisely. Both simulation results and experimental results show that in practical application scenarios, the proposed positioning system can realize high precision positioning service.
Linda J. Herbert
Full Text Available It has been well-established that some adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD are at increased risk for cigarette smoking. Current research on the genetic basis of this association could ultimately translate into genetic tests capable of identifying smoking-prone adolescents with ADHD. In this study we examined 81 ADHD affected adolescents’ (age 13–21 interest in genetic testing for nicotine addiction susceptibility. Fifty-seven percent of adolescents indicated a fair amount of interest or more in testing. Most adolescents indicated that the personal information revealed from testing would be either useful (29% or interesting (37%. Implications for genetically-informed smoking prevention and cessation interventions in high risk adolescents with ADHD are discussed.
Oostrom, I.I.H. van; Meijers-Heijboer, H.; Duivenvoorden, H.J.; Brocker-Vriends, A.H.; Asperen, C.J. van; Sijmons, R.H.; Seynaeve, C.; Gool, A.R. van; Klijn, J.G.M.; Tibben, A.
This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis
van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Bröcker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; van Gool, A. R.; Klijn, J. G. M.; Tibben, A.
This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis
van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.
This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis
Cai, T.; Lin, X.; Carroll, R. J.
the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least
... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...
Boonstra, Philip S; Gruber, Stephen B; Raymond, Victoria M
Anticipation, manifested through decreasing age of onset or increased severity in successive generations, has been noted in several genetic diseases. Statistical methods for genetic anticipation range from a simple use of the paired t-test for age of onset restricted to affected parent-child pairs......, and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare...... the issue of multiplex ascertainment and its effect on the different methods. We then focus on exploring genetic anticipation in Lynch syndrome and analyze new data on the age of onset in affected parent-child pairs from families seen at the University of Michigan Cancer Genetics clinic with a mutation...
Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E
Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...
Manzini, Arianna; Vears, Danya F
Predictive genetic testing for susceptibility to psychiatric conditions is likely to become part of standard practice. Because the onset of most psychiatric diseases is in late adolescence or early adulthood, testing minors could lead to early identification that may prevent or delay the development of these disorders. However, due to their complex aetiology, psychiatric genetic testing does not provide the immediate medical benefits that current guidelines require for testing minors. While several authors have argued non-medical benefits may play a crucial role in favour of predictive testing for other conditions, little research has explored such a role in psychiatric disorders. This paper outlines the potential non-medical benefits and harms of psychiatric genetic testing in minors in order to consider whether the non-medical benefits could ever make such testing appropriate. Five non-medical themes arise in the literature: psychological impacts, autonomy/self-determination, implications of the biomedical approach, use of financial and intellectual resources, and discrimination. Non-medical benefits were prominent in all of them, suggesting that psychiatric genetic testing in minors may be appropriate in some circumstances. Further research needs to empirically assess these potential non-medical benefits, incorporate minors in the debate, and include normative reflection to evaluate the very purposes and motivations of psychiatric genetic testing in minors.
Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.
Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081
Berti, A; Yacoub, M R; Skov, Per Stahl
the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2......Summary: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate...... with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0...
Khawaja, Anthony P; Viswanathan, Ananth C
Following a dramatic reduction in the cost of genotyping technology in recent years, there have been significant advances in the understanding of the genetic basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient activity in the UK hospital eye service and are a huge burden for the National Health Service. A potential benefit of genetic testing is personalised glaucoma management, allowing direction of our limited healthcare resources to the glaucoma patients who most need it. Our review aims to summarise recent discoveries in the field of glaucoma genetics and to discuss their potential clinical utility. While genome-wide association studies have now identified over ten genes associated with primary open-angle glaucoma (POAG), individually, variants in these genes are not predictive of POAG in populations. There are data suggesting some of these POAG variants are associated with conversion from ocular hypertension to POAG and visual field progression among POAG patients. However, these studies have not been replicated yet and such genetic testing is not currently justified in clinical care. In contrast, genetic testing for inherited early-onset disease in relatives of POAG patients with a known genetic mutation is of clear benefit; this can support either regular review to commence early treatment when the disease develops, or discharge from ophthalmology services of relatives who do not carry the mutation. Genetic testing for POAG at a population level is not currently justified.
Greenberg, Marisa; Smith, Rachel A
Genetic test results reveal not only personal information about a person's likelihood of certain medical conditions but also information about the person's genetic relatives. Given the familial nature of genetic information, one's obligation to protect family members may be a motive for disclosing genetic test results, but this claim has not been methodically tested. Existing models of disclosure decision making presume self-interested motives, such as seeking social support, instead of other-interested motives, like familial obligation. This study investigated young adults' (N = 173) motives to share a genetic-based health condition, alpha-1 antitrypsin deficiency, after reading a hypothetical vignette. Results show that social support and familial obligation were both reported as motives for disclosure. In fact, some participants reported familial obligation as their primary motivator for disclosure. Finally, stronger familial obligation predicted increased likelihood of disclosing hypothetical genetic test results. Implications of these results were discussed in reference to theories of disclosure decision-making models and the practice of genetic disclosures.
Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan
The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. PMID:26582191
Zhang, Di; Ng, Vincent H; Wang, Zhaochen; Zhai, Xiaomei; Lie, Reidar K
The application of genetic technologies in China, especially in the area of prenatal genetic testing, is rapidly increasing in China. In the wealthy regions of China, prenatal genetic testing is already very widely adopted. We argue that the government should actively promote prenatal genetic testing to the poor areas of the country. In fact, the government should prioritize resources first to make prenatal genetic testing a standard routine care with an opt-out model in these area. Healthcare professions would be required to inform pregnant women about the availability of genetic testing and provide free testing on a routine basis unless the parents choose not to do so. We argue that this proposal will allow parents to make a more informed decision about their reproductive choices. Secondarily, this proposal will attract more healthcare professionals and other healthcare resources to improve the healthcare infrastructures in the less-developed regions of the country. This will help to reduce the inequity of accessing healthcare services between in different regions of China. We further argue that this policy proposal is not practicing eugenics. © 2015 John Wiley & Sons Ltd.
Sun, Koun-Tem; Chen, Yu-Jen; Tsai, Shu-Yen; Cheng, Chien-Fen
In educational measurement, the construction of parallel test forms is often a combinatorial optimization problem that involves the time-consuming selection of items to construct tests having approximately the same test information functions (TIFs) and constraints. This article proposes a novel method, genetic algorithm (GA), to construct parallel…
Stegeman, Inge; de Wijkerslooth, Thomas R.; Stoop, Esther M.; van Leerdam, Monique; van Ballegooijen, M.; Kraaijenhagen, Roderik A.; Fockens, Paul; Kuipers, Ernst J.; Dekker, Evelien; Bossuyt, Patrick M.
Differences in the risk of a false negative or a false positive fecal immunochemical test (FIT) across subgroups may affect optimal screening strategies. We evaluate whether subgroups are at increased risk of a false positive or a false negative FIT result, whether such variability in risk is
Shi Xueming; Wu Hongchun; Sun Shouhua; Liu Shuiqing
The in-core fuel management optimization model based on the genetic algorithm has been established. An encode/decode technique based on the assemblies position is presented according to the characteristics of HFETR. Different reproduction strategies have been studied. The expert knowledge and the adaptive genetic algorithms are incorporated into the code to get the optimized loading patterns that can be used in HFETR
Full Text Available Abstract Background Concerns about the general psychological impact of genetic testing have been raised. In the Environmental Triggers of Type 1 Diabetes (MIDIA study, genetic testing was performed for HLA-conferred type 1 diabetes susceptibility among Norwegian newborns. The present study assessed whether mothers of children who test positively suffer from poorer mental health and well-being after receiving genetic risk information about their children. Methods The study was based on questionnaire data from the Norwegian Mother and Child Cohort (MoBa study conducted by the Norwegian Institute of Public Health. Many of the mothers in the MoBa study also took part in the MIDIA study, in which their newborn children were tested for HLA-conferred genetic susceptibility for type 1 diabetes. We used MoBa questionnaire data from the 30th week of pregnancy (baseline and 6 months post-partum (3-3.5 months after disclosure of test results. We measured maternal symptoms of anxiety and depression (SCL-8, maternal self-esteem (RSES, and satisfaction with life (SWLS. The mothers also reported whether they were seriously worried about their child 6 months post-partum. We compared questionnaire data from mothers who had received information about having a newborn with high genetic risk for type 1 diabetes (N = 166 with data from mothers who were informed that their baby did not have a high-risk genotype (N = 7224. The association between genetic risk information and maternal mental health was analysed using multiple linear regression analysis, controlling for baseline mental health scores. Results Information on genetic risk in newborns was found to have no significant impact on maternal symptoms of anxiety and depression (p = 0.9, self-esteem (p = 0.2, satisfaction with life (p = 0.2, or serious worry about their child (OR = 0.98, 95% CI 0.64-1.48. Mental health before birth was strongly associated with mental health after birth. In addition, an increased
Full Text Available The purpose of this study was to identify attitudes and perceptions of willingness to participate in genetic testing for type 2 diabetes (T2D risk prediction in the general population. Adults (n = 598 were surveyed on attitudes about utilizing genetic testing to predict future risk of T2D. Participants were recruited from public libraries (53%, online registry (37% and a safety net hospital emergency department (10%. Respondents were 37 ± 11 years old, primarily White (54%, female (69%, college educated (46%, with an annual income ≥$25,000 (56%. Half of participants were interested in genetic testing for T2D (52% and 81% agreed/strongly agreed genetic testing should be available to the public. Only 57% of individuals knew T2D is preventable. A multivariate model to predict interest in genetic testing was adjusted for age, gender, recruitment location and BMI; significant predictors were motivation (high perceived personal risk of T2D [OR = 4.38 (1.76, 10.9]; family history [OR = 2.56 (1.46, 4.48]; desire to know risk prior to disease onset [OR = 3.25 (1.94, 5.42]; and knowing T2D is preventable [OR = 2.11 (1.24, 3.60], intention (if the cost is free [OR = 10.2 (4.27, 24.6]; and learning T2D is preventable [OR = 5.18 (1.95, 13.7] and trust of genetic testing results [OR = 0.03 (0.003, 0.30]. Individuals are interested in genetic testing for T2D risk which offers unique information that is personalized. Financial accessibility, validity of the test and availability of diabetes prevention programs were identified as predictors of interest in T2D testing.
Buch, Line Hjortø; Sørensen, Morten Kargo; Berg, Peer
We tested the following hypotheses: (i) breeding schemes with genomic selection are superior to breeding schemes without genomic selection regarding annual genetic gain of the aggregate genotype (ΔGAG), annual genetic gain of the functional traits and rate of inbreeding per generation (ΔF), (ii......) a positive interaction exists between the use of genotypic information and a short generation interval on ΔGAG and (iii) the inclusion of an indicator trait in the selection index will only result in a negligible increase in ΔGAG if genotypic information about the breeding goal trait is known. We examined......, greater contributions of the functional trait to ΔGAG and lower ΔF than the two breeding schemes without genomic selection. Thus, the use of genotypic information may lead to more sustainable breeding schemes. In addition, a short generation interval increases the effect of using genotypic information...
A recent addition to the debate about the benefits and harms of direct-to-consumer (DTC) advertising of medicines and pharmaceuticals is a growing critique of DTC marketing and sale of genetic tests. Academic and policy literatures exploring this issue have, however, tended to focus on the sale of genetic tests, paying rather less attention to the particular implications of advertising. The globalization of broadcast media and ever increasing access to the Internet mean that public exposure to advertising for medical technologies is a reality that national regulatory bodies will be hard pressed to constrain. Working through a case study detailing Myriad Genetics' 2002 pilot advertising campaign for their BRACAnalysis genetic susceptibility test for hereditary breast and ovarian cancer, this paper highlights some of the diverse and often overlooked and unregulated approaches to DTC advertising, and the associated social, ethical and policy implications.
Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong
It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online. PMID:28736464
Rogers, Jill Cellars; Taylor, Ann T S
Educating undergraduates about current genetic testing and genomics can involve novel and creative teaching practices. The higher education literature describes numerous pedagogical approaches in the laboratory designed to engage science and liberal arts students. Often these experiences involve students analyzing their own genes for various polymorphisms, some of which are associated with disease states such as an increased risk for developing cancer. While the literature acknowledges possible ethical ramifications of such laboratory exercises, authors do not present recommendations or rubrics for evaluating whether or not the testing is, in fact, ethical. In response, we developed a laboratory investigation and discussion which allowed undergraduate science students to explore current DNA manipulation techniques to isolate their p53 gene, followed by a dialogue probing the ethical implications of examining their sample for various polymorphisms. Students never conducted genotyping on their samples because of ethical concerns, so the discussion served to replace actual genetic testing in the class. A basic scientist led the laboratory portion of the assignment. A genetic counselor facilitated the discussion, which centered around existing ethical guidelines for clinical genetic testing and possible challenges of human genotyping outside the medical setting. In their final papers, students demonstrated an understanding of the practice guidelines established by the genetics community and acknowledged the ethical considerations inherent in p53 genotyping. Given the burgeoning market for personalized medicine, teaching undergraduates about the psychosocial and ethical dimensions of human gene testing seems important and timely, and introduces an additional role genetic counselors can play in educating consumers about genomics.
Friesen, Phoebe; Lawrence, Ryan E; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa
Genetic tests for schizophrenia could introduce both risks and benefits. Little is known about the hopes and expectations of young adults at clinical high-risk for psychosis concerning genetic testing for schizophrenia, despite the fact that these youth could be among those highly affected by such tests. We conducted semistructured interviews with 15 young adults at clinical high-risk for psychosis to ask about their interest, expectations, and hopes regarding genetic testing for schizophrenia. Most participants reported a high level of interest in genetic testing for schizophrenia, and the majority said they would take such a test immediately if it were available. Some expressed far-reaching expectations for a genetic test, such as predicting symptom severity and the timing of symptom onset. Several assumed that genetic testing would be accompanied by interventions to prevent schizophrenia. Participants anticipated mixed reactions on finding out they had a genetic risk for schizophrenia, suggesting that they might feel both a sense of relief and a sense of hopelessness. We suggest that genetic counseling could play an important role in counteracting a culture of genetic over-optimism and helping young adults at clinical high-risk for psychosis understand the limitations of genetic testing. Counseling sessions could also invite individuals to explore how receiving genetic risk information might impact their well-being, as early evidence suggests that some psychological factors help individuals cope, whereas others heighten distress related to genetic test results.
Andersen, Klaus Ejner; Christensen, Lars Porskjaer; Vølund, Aage
and possibly reproduce this association with the use of TRUE((R)) test data and supplementary tests with fragrance mix ingredients from the Department of Dermatology, Odense University Hospital. MATERIALS AND METHODS: Six thousand one hundred and fifteen consecutive eczema patients tested from 1995 to 2007......BACKGROUND: Both epoxy resin (diglycidyl ether of bisphenol A) and fragrance mix I are included in the European baseline series of contact allergens. A significant association between positive reactions to epoxy resin and fragrance mix has been reported by others. OBJECTIVE: To investigate...... were included, and test results from all patients tested with fragrance mix ingredients were analysed. RESULTS: One hundred and forty-five (2.4%) were positive to epoxy resin and 282 (4.6%) were positive to fragrance mix I. Nineteen were positive to both giving an odds ratio of 3.3, which...
Lamoril, Jérôme; Bogard, Marc
Since the development of new human genome sequencing technologies at the beginning of the 2000, commercial companies have developped direct to consumer genomic services, which means without medical prescription. From 2007 to 2013, many companies have offered services assesing associated risk with human public health in the world especially in the United States. This kind of company is forbidden in France. From 2009 to 2013, in United States, under the pressure of national or state health administrations, these companies have been progressively forbidden. However, in certain parts of the world, companies are still offering such services. The latter raise many different questions such as ethical, juridical, medical, scientific, educative, professional one. Many studies and debates have demonstrated their limit and the lack of usefulness and advantage in the field of human health for the time being. The commercialization of this type of services has arrived all too soon et is not yet ripe. In our time of globalization, with the lack of international rules controlling direct access to genetic services in the field of human health, there is an urgent need to regulate. International administrations and politicians must act fast. Inevitably, under the pressure of lobbies and citizens, companies (multinational or not) will develop especially as 1) new sequencing technologies evolve rapidly, 2) are cheaper from year to year, 3) scientific and medical knowledges are progressing quickly, 4) services are spreading faster through the web and other networks.
Shiloh, S; Koehly, L; Jenkins, J; Martin, J; Hadley, D
The emotional effects of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) provided within a counseling program were assessed among 253 individuals. Assessments were scheduled at baseline before testing, and again after 6 and 12 months post-test. Negative emotional reactions were evaluated using the Revised Impact of Event Scale and the Center for Epidemiological Studies-Depression Scale. Monitoring coping style was assessed at baseline using the Miller Behavioral Style Scale. Mean reductions were indicated in distress and depression levels within the first 6 months after counseling and testing. High monitors were generally more distressed than low monitors, specifically if they had indeterminate or positive results. Genetic counseling and testing for HNPCC do not result in long-term distress for most people. Of the variables investigated, only time and coping style have main effects on emotional reactions, and the impacts of mutation status are moderated by coping style. Psychological interventions, aimed to alleviate adverse emotional effects, were suggested for certain participants, i.e. recipients of positive or indeterminate results who are high monitors.
Seisebaev, A.T.; Bakhtin, M.M.; Zhapbasov, R.Zh.
For an objective assessment of nuclear test consequences for the environment it is necessary, together with the investigation of radiation situation, to study live biological systems, particularly the genetic effects of chronic ionizing radiation. The long staying of plants and animals on the territories with the elevated radiation background level can lead to the change of organism genetic system. In this connection the monitoring of chronically exposed natural populations is of particular interest and can serve as the objective indicator of the scale of natural biota genetic damage. Basing on the results obtained during plant and animal studies one can indirectly assess the hazard of people genetic damage. Besides, studying the mutational process on natural populations exposed to the chronic ionizing radiation one can reveal new regularities, which are impossible to be detected in the laboratory conditions, and new aspects of radiation genetics. The issue of radiation adaptation of organisms affected by the various doses of ionizing radiation is very acute. The prerequisite of organism adaptation to the certain radiation background is genetic heterogeneity of individuals comprising the population and selection of radiation-induced individuals, which are the carriers of the mutation of high radioresistance. The uniqueness of the Semipalatinsk Test site and the necessity of long-term investigations of the nuclear test consequences for the environment demand the elaboration of principles for organization and utilization of natural population genetic monitoring. Radiation-genetic monitoring is the long-term observation of palpitation gene pool conditions, assessment and forecast of their spatial and time alteration, determination of limits of changes admitted under the condition of environmental radioactive contamination. It includes a series of the main research directions and has quite certain methodological peculiarities. In this paper we discuss the tasks of
Torres, A K; Escartín, N; Monzó, C; Guzmán, C; Ferrer, I; González-Muñoz, C; Peña, P; Monzó, V; Marcaida, G; Rodríguez-López, R
To describe the populational distribution of the UGT1A1*28 variant (genetic variant code rs8175347) located in the promotor of the UGT gene and correlate its genotypes with the results of the fasting test, as well as its relationship with the biochemical disorder of Gilbert's syndrome (GS) in a Valencian population. We studied the prevalence of the genotypes (TA) 6/6 (TA) 6/7 and (TA) 7/7 of the deleterious variant rs8175347 in 144 patients with hyperbilirubinemia, 38 of whom had previously undergone the fasting test to diagnose GS, and in 150 control patients. By analysing the genomic region of the TATA box of the UGT1A1 gene promotor using Sanger sequencing, we established the correlation between the rs8175347 genotypes and the fasting test results and with the patients' biochemical disorders. The rate of heterozygosity of allele (TA) 7 in the control population was 32% and increased to 87.59% among the patients with suspected GS. The rate of genotype TA 7/7 was 81.94% among the patients with hyperbilirubinemia, compared with 11.33% in the control patients. The fasting test showed a 15.79% rate of false negatives and a 5.26% rate of false positives. The high frequency of allele (TA) 7 among the Valencian control population, almost double the 5% reported for European control patients, confirms the high rate of GS reported in the Spanish population, without observing significant differences between the geographical ends of the country. The efficacy and reliability of the fasting test for the diagnosis of GS is questionable. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn
Philip C Hill
Full Text Available Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT test could identify tuberculosis (TB contacts with boosting of immunity to non-tuberculous mycobacterial exposure.We conducted tuberculin and ELISPOT tests in 1665 TB contacts: 799 were tuberculin test negative and were offered a repeat test after three months. Those with tuberculin test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72% contacts had a repeat tuberculin test; 176 (25% had test conversion, which increased with exposure to a case (p = 0.002, increasing age (p = 0.0006 and BCG scar (p = 0.06. 114 tuberculin test converters had ELISPOT results: 16(14% were recruitment positive/follow-up positive, 9 (8% positive/negative, 34 (30% negative/positive, and 55 (48% were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin test converters (p = 0.038. Estimates of boosting ranged from 32%-41% of skin test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment.We estimate that approximately one third of tuberculin skin test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with tuberculin test conversion that would benefit most from prophylactic treatment.
Yoo, J. Y.; Kim, J. H.; Hu, H.; Lee, J. S.; Kim, J. I.
The reliability and accuracy of the information on control rod position are very important to the reactor safety and the design of the core protection system. A survey on the RSPT(Reed Switch Position Transmitter) type control rod position indication system and its actual implementation in the exiting nuclear power plants in Korea was performed first. The prototype of control rod position indicator having the high performance for the ballscrew type CEDM was developed on the basis of RSPT technology identified through the survey. The characteristics of control rod position indicator was defined and documented through design procedure and preliminary performance test
Frameworks of Choice verkent de culturele en politieke aspecten van voorspellende en genetische tests. Het boek analyseert de sociale, culturele, en economische gevolgen voor het individu na een voorspellende of genetische screening. Margaret Sleeboom-Faulkner geeft een genuanceerd beeld van de
Wang, C-W; Hui, E C
With the progress in cancer genetics and assisted reproductive technologies, it is now possible for cancer gene mutation carriers not only to reduce cancer mortality through the targeting of surveillance and preventive therapies, but also to avoid the birth of at-risk babies through the choice of different means of reproduction. Thus, the incidence of hereditary cancer syndromes may be decreased in the future. The integration of cancer genetic testing and assisted reproductive technologies raises certain ethical, legal and social issues beyond either genetic testing or assisted reproductive technology itself. In this paper, the reproductive decisions/choices of at-risk young couples and the ethical, legal and social concerns of prenatal genetic testing and preimplantation genetic diagnosis for susceptibility to hereditary cancer syndromes are discussed. Specifically, three ethical principles related to the integration of cancer genetic testing and assisted reproductive technologies, i.e. informed choice, beneficence to children and social justice, and their implications for the responsible translation of these medical techniques into common practice of preventive medicine are highlighted.
Apathy, Nate C; Menser, Terri; Keeran, Lindsay M; Ford, Eric W; Harle, Christopher A; Huerta, Timothy R
Direct-to-consumer genetic tests for inherited disease risks have gained recent approvals from the Food and Drug Administration, and interest in these tests has continued to grow. Broad use of these tests coupled with planning and discussion with health providers regarding genetic risks and potential protective behavior changes have been proposed as preventive tools to reduce health disparities and improve equity in health outcomes. However, awareness of direct-to-consumer genetic testing has historically demonstrated differences by education, income, and race; these disparities could jeopardize potential benefits by limiting access and use. The national survey data from the Health Information National Trends Survey was analyzed to understand how overall awareness of direct-to-consumer genetic testing and disparities in awareness across sociodemographic groups have changed since 2007. The findings showed persistent disparities, as well as a widening gap in awareness between Hispanics and non-Hispanic whites (OR 2007 =1.52, OR 2014 =0.58, p change =0.0056), despite overall increases in awareness over time. Given these findings, policies regulating direct-to-consumer genetic tests should prioritize equitable distribution of benefits by including provisions that counteract prevailing disparities in awareness. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Korf, B R
The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.
Polak, Jonathan; Odili, Ogheneruona; Craver, Mary Ashleigh; Mayen, Anthony; Purrman, Kyle; Rahman, Asem; Sang, Charlie Joseph; Cook, Paul P
Abstract Background Testing for Clostridium difficile infection (CDI) commonly involves checking for the presence of toxins A and B by enzyme immunoassay (EIA) or nucleic acid amplification (NAA). The former is very specific, but not very sensitive. The latter is very sensitive. Beginning in 2011, our hospital incorporated an algorithm that involved testing liquid stool specimens for glutamate dehydrogenase (GDH) and toxin by EIA. For discrepant results, the stool specimen was tested for the ...
Direct-to-consumer genetic testing (DTC-GT) has sparked much controversy and undergone dramatic changes in its brief history. Debates over appropriate health policies regarding DTC-GT would benefit from empirical research on its benefits, harms, and limitations. We review the recent literature (2011-present) and summarize findings across (1) content analyses of DTC-GT websites, (2) studies of consumer perspectives and experiences, and (3) surveys of relevant health care providers. Findings suggest that neither the health benefits envisioned by DTC-GT proponents (e.g., significant improvements in positive health behaviors) nor the worst fears expressed by its critics (e.g., catastrophic psychological distress and misunderstanding of test results, undue burden on the health care system) have materialized to date. However, research in this area is in its early stages and possesses numerous key limitations. We note needs for future studies to illuminate the impact of DTC-GT and thereby guide practice and policy regarding this rapidly evolving approach to personal genomics. PMID:24058877
Liu, Shiguo; Yu, Xiaoxia; Xu, Quanchen; Cui, Jiajia; Yi, Mingji; Zhang, Xinhua; Ge, Yinlin; Ma, Xu
Recently, a genome-wide association study has indicated associations between single nucleotide polymorphisms in the Collagen Type XXVII Alpha 1 gene (COL27A1) and Tourette syndrome in several ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of Tourette syndrome, the associations between polymorphisms in COL27A1 and Tourette syndrome were assessed in Chinese trios. PCR-directed sequencing was used to evaluate the genetic contributions of three SNPs in COL27A1(rs4979356, rs4979357 and rs7868992) using haplotype relative risk (HRR) and transmission disequilibrium tests (TDT) with a total of 260 Tourette syndrome trios. The family-based association was significant between Tourette syndrome and rs4979356 (TDT: χ2 = 4.804, P = 0.033; HRR = 1.75, P = 0.002; HHRR = 1.32, P = 0.027), and transmission disequilibrium was suspected for rs4979357 (TDT: χ2 = 3.969, P = 0.053; HRR = 1.84, P = 0.001; HHRR = 1.29, P = 0.044). No statistically significant allele transfer was found for rs7868992 (TDT: χ2 = 2.177, P = 0.158). Although the TDT results did not remain significant after applying the conservative Bonferroni correction (p = 0.005), the significant positive HRR analysis confirmed the possibility of showing transmission disequilibrium, which provides evidence for an involvement of COL27A1in the development of TS. However, these results need to be verified with larger datasets from different populations.
Mona H Fenstad
Full Text Available BACKGROUND: Preeclampsia is a serious pregnancy complication, demonstrating a complex pattern of inheritance. The elucidation of genetic liability to preeclampsia remains a major challenge in obstetric medicine. We have adopted a positional cloning approach to identify maternal genetic components, with linkages previously demonstrated to chromosomes 2q, 5q and 13q in an Australian/New Zealand familial cohort. The current study aimed to identify potential functional and structural variants in the positional candidate gene TNFSF13B under the 13q linkage peak and assess their association status with maternal preeclampsia genetic susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: The proximal promoter and coding regions of the positional candidate gene TNFSF13B residing within the 13q linkage region was sequenced using 48 proband or founder individuals from Australian/New Zealand families. Ten sequence variants (nine SNPs and one single base insertion were identified and seven SNPs were successfully genotyped in the total Australian/New Zealand family cohort (74 families/480 individuals. Borderline association to preeclampsia (p = 0.0153 was observed for three rare SNPs (rs16972194, rs16972197 and rs56124946 in strong linkage disequilibrium with each other. Functional evaluation by electrophoretic mobility shift assays showed differential nuclear factor binding to the minor allele of the rs16972194 SNP, residing upstream of the translation start site, making this a putative functional variant. The observed genetic associations were not replicated in a Norwegian case/control cohort (The Nord-Trøndelag Health Study (HUNT2, 851 preeclamptic and 1,440 non-preeclamptic women. CONCLUSION/SIGNIFICANCE: TNFSF13B has previously been suggested to contribute to the normal immunological adaption crucial for a successful pregnancy. Our observations support TNFSF13B as a potential novel preeclampsia susceptibility gene. We discuss a possible role for TNFSF13B in
Varga, Elizabeth A
As a genetic counselor, I had mixed opinions when my mother told me of her intent to undergo genomewide, SNP-based direct-to-consumer (DTC) genetic testing. I cautioned her that results could be misleading, could increase anxiety and were often of limited clinical validity or utility. I warned of the possibility of learning unintended health information and expressed concerns about how the information might be used by a private company. I told her about the variability in results among companies. Yet, she persisted in her desire, reminding me that she was an informed consumer. After reviewing her goals and understanding of the information she might receive, she elected to proceed. Despite my insistence that I would not be her personal genetic counselor, when the results came back, I found myself immersed in her genetic data. In this manuscript, I will examine how this personal experience challenged my perceptions of DTC testing.
Mutation by 60 Co γ irradiation was studied in five different histidine-requiring auxotrophs of Salmonella typhimurium. The strains TA98 (sensitive to frameshift) and TA100 (sensitive to base-pair substitution) were irradiated (10-84 Gy and 45-317 Gy, respectively) and revertants were counted. TA98 exhibited radiation-induced revertants, 2.8 fold of spontaneous revertants, although no significant increase was detected in TA100. Then, three other frameshift-sensitive strains TA1537, TA1538 and TA94 were irradiated in a dose of 61-167 Gy. Only in TA94, revertants increased 3.5 fold. Since spontaneous revertants are known to be independent of cell density, a decrease of bacterial number by γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation as a mutagenetic agent. The mutagenicity of dinitropyrene, a mutagen widely existing in food, and dismutagenicity of boiling water insoluble fraction of Hizikia fusiforme, edible marine alga, were tested on γ induced revertant formation in TA98 and TA94. Dinitropyrene synergistically increased γ induced revertants and Hizikia insoluble fraction reduced the synergistic effect of dinitropyrene dependently on the concentration. (author)
Verhagen, L. M.; Hermans, P. W. M.; Warris, A.; de Groot, R.; Maes, M.; Villalba, J. A.; del Nogal, B.; van den Hof, S.; Mughini Gras, L.; van Soolingen, D.; Pinelli, E.; de Waard, J. H.
The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in
Malik, S.; Imran, M.; Hanif, A.; Bilal, M.
Breast cancer is the most common malignancy among Asian women including Pakistan where recurrent mutations among certain sub-ethnic groups predisposing to breast cancer have recently been established. Study Design: The current retrospective study involves identification of genetic and non-genetic risk factors in 27 specific mutation positive females out of a. total of 100 females diagnosed with breast cancer, representing a sample from the Punjabi ethnic population of the city of Lahore. The study has been carried out by telephonic communication with the mutation positive patients or their relatives. Results: Out of the total 27% patients positive for specific BRCA mutations, 23% were positive for BRCAI mutations and 4% for BRCA2. Among a total of 100 breast cancer patients the BRCAI-IVS14, lG>A mutation was identified in 5 Punjabi ethnic females with Rajput sub ethnicity, BRCAI-3889delAG in 10 (8 with Mughal and 2 with Khan sub ethnicity), BRCAI-2080insA in 8 (Rajput sub ethnics) and BRCA2-3337C>T in 4 (Minhas sub ethnic) subjects. Two BRCAI mutations, namely 3889delAG and 2080insA were found to coexist in only one study case (with Mughal sub ethnicity). All the mutation positive breast cancers had unilateral ductal carcinoma. Of the 23 cases positive for screened BRCAI mutations, 17 were diagnosed for breast cancer at a relatively early age (age<40) and 6 were diagnosed at late age (age<41) whereas all cases positive for single BRCA2 mutation under consideration were diagnosed at late age. Furthermore, 24 of 27 patients with specific BRCA mutations had a positive family history of breast cancer. The high prevalence of the screened BRCA mutations in certain Punjabi sub-ethnicities indicates the importance of counseling. It is suggested that consanguinity may be a risk factor for recurrent population specific mutations. Hormonal factors including use of oral contraceptives, polycystic ovaries, central obesity, nulliparity, late age at first pregnancy, lack of
Arad, Michael; Monserrat, Lorenzo; Haron-Khun, Shiraz; Seidman, Jonathan G; Seidman, Christine E; Arbustini, Eloisa; Glikson, Michael; Freimark, Dov
Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM. To analyze the impact of genetic diagnosis on the clinical management of HCM. Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation. Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation. Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.
Sattler, Tine; Sekulic, Damir; Hadzic, Vedran; Uljevic, Ognjen; Dervisevic, Edvin
Vertical jumping is known to be important in volleyball, and jumping performance tests are frequently studied for their reliability and validity. However, most studies concerning jumping in volleyball have dealt with standard rather than sport-specific jumping procedures and tests. The aims of this study, therefore, were (a) to determine the reliability and factorial validity of 2 volleyball-specific jumping tests, the block jump (BJ) test and the attack jump (AJ) test, relative to 2 frequently used and systematically validated jumping tests, the countermovement jump test and the squat jump test and (b) to establish volleyball position-specific differences in the jumping tests and simple anthropometric indices (body height [BH], body weight, and body mass index [BMI]). The BJ was performed from a defensive volleyball position, with the hands positioned in front of the chest. During an AJ, the players used a 2- to 3-step approach and performed a drop jump with an arm swing followed by a quick vertical jump. A total of 95 high-level volleyball players (all men) participated in this study. The reliability of the jumping tests ranged from 0.97 to 0.99 for Cronbach's alpha coefficients, from 0.93 to 0.97 for interitem correlation coefficients and from 2.1 to 2.8 for coefficients of variation. The highest reliability was found for the specific jumping tests. The factor analysis extracted one significant component, and all of the tests were highly intercorrelated. The analysis of variance with post hoc analysis showed significant differences between 5 playing positions in some of the jumping tests. In general, receivers had a greater jumping capacity, followed by libero players. The differences in jumping capacities should be emphasized vis-a-vis differences in the anthropometric measures of players, where middle hitters had higher BH and body weight, followed by opposite hitters and receivers, with no differences in the BMI between positions.
Wu, Baolin; Guan, Weihua
Acar and Sun (2013, Biometrics 69, 427-435) presented a generalized Kruskal-Wallis (GKW) test for genetic association studies that incorporated the genotype uncertainty and showed its robust and competitive performance compared to existing methods. We present another interesting way to derive the GKW test via a rank linear model. © 2014, The International Biometric Society.
Wu, Baolin; Guan, Weihua
Acar and Sun (2013, Biometrics, 69, 427-435) presented a generalized Kruskal-Wallis (GKW) test for genetic association studies that incorporated the genotype uncertainty and showed its robust and competitive performance compared to existing methods. We present another interesting way to derive the GKW test via a rank linear model.
Julie Anne Quinlivan
Full Text Available Introduction: The advent of human genome project has lead to genetic tests that identify high-risk states for certain cancers. Many are privately marketed on the Internet. Despite the availability of tests, limited data has evaluated factors that lead to test uptake. The aim of the present study was to explore the attitudes of a cohort of new mothers towards uptake of a genetic cancer test with a 50% predictive value of cancer.Methods: A cross-sectional survey was undertaken. The project targeted women who had recently given birth at an Australian tertiary referral hospital. Women were asked about a theoretical blood test that detected an increased risk for the development of cancer. Attitudes and knowledge questionnaires were completed. Results: Of 232 consecutive women approached, 32 declined, giving a response rate of 86.2%. Only 63 (31.5% women stated they would have the test. Absence of religious belief, higher level of education, better knowledge of terms used in genetics, an absence of concern over emotional, employment and insurance discrimination and previous acceptance of Down syndrome screening in pregnancy were each associated with significantly higher rate of test uptake in univariate analysis (all pConclusion: Concern over discrimination and having made a prior decision to have genetic testing were the principal factors associated with decision-making.
Christiaans, Imke; van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.
Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with sudden cardiac death. predictive genetic counseling and testing are performed using adapted Huntington guidelines, that is, psychosocial care and time for reflection are not obligatory and the test result can be
Bowen, D J; Harris, J; Jorgensen, C M; Myers, M F; Kuniyuki, A
Direct-to-consumer marketing of genetic tests is beginning to appear in select markets, and little independent evaluation has been conducted on the effects of this marketing on consumer attitudes or behavior. The purpose of this paper is to identify the effects of socioeconomic status on women's reactions to such a campaign, including knowledge of the test, perceptions of personal risk, communications with others about the test, and interest in pursuing the test. The only United States provider of genetic testing for breast and ovarian cancer susceptibility (BRCA1/2 testing) conducted a pilot marketing campaign that targeted women aged 25-54 and their health care providers in 2 cities, Atlanta, Ga., and Denver, Colo. The design for the evaluation was a post campaign consumer survey, based on a cross-sectional stratified random sample of women in the 2 intervention sites and 2 comparison sites. The campaign had no differential impact by socioeconomic status. However, there was a consistent relationship between socioeconomic status and several outcome variables, including knowledge of the test, beliefs about the test, and desire to know about genetic risk. These data indicate that socioeconomic status may play a role in uptake of genetic services, regardless of response to a media campaign. Copyright 2009 S. Karger AG, Basel.
Full Text Available Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA strains (Nichols, DAL-1, Mexico A, SS14, 4 T. p. ssp. pertenue (TPE strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc, 1 T. p. ssp. endemicum (TEN strain (Bosnia A and one strain (Cuniculi A of Treponema paraluisleporidarum ecovar Cuniculus (TPLC were examined with respect to the presence of nucleotide intrastrain heterogeneous sites.The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5, DAL-1 (n = 4, and SS14 (n = 7, TPE strain Samoa D (n = 1, and TEN strain Bosnia A (n = 5. Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K, in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY, in genes involved in cell structure (murC, translation (prfA, general and DNA metabolism (putative SAM dependent methyltransferase, topA, and in seven hypothetical genes.Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.
Čejková, Darina; Strouhal, Michal; Norris, Steven J; Weinstock, George M; Šmajs, David
Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14), 4 T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), 1 T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were examined with respect to the presence of nucleotide intrastrain heterogeneous sites. The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n = 4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n = 5). Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K), in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY), in genes involved in cell structure (murC), translation (prfA), general and DNA metabolism (putative SAM dependent methyltransferase, topA), and in seven hypothetical genes. Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.
Michelle R. Lent
Full Text Available This study explored attitudes toward hypothetical genetic testing for posttraumatic stress disorder (PTSD and addiction among veterans. We surveyed a random sample of community-based veterans (n = 700 by telephone. One year later, we asked the veterans to provide a DNA sample for analysis and 41.9% of them returned the DNA samples. Overall, most veterans were not interested in genetic testing neither for PTSD (61.7% nor for addiction (68.7%. However, bivariate analyses suggested there was an association between having the condition of interest and the likelihood of genetic testing on a 5-point scale (p < 0.001 for PTSD; p = 0.001 for alcohol dependence. While ordinal regressions confirmed these associations, the models with the best statistical fit were bivariate models of whether the veteran would likely test or not. Using logistic regressions, significant predictors for PTSD testing were receiving recent mental health treatment, history of a concussion, younger age, having PTSD, having alcohol dependence, currently taking opioids for pain, and returning the DNA sample during the follow-up. For addiction testing, significant predictors were history of concussion, younger age, psychotropic medication use, having alcohol dependence, and currently taking opioids for pain. Altogether, 25.9% of veterans reported that they would have liked to have known their genetic results before deployment, 15.6% reported after deployment, and 58.6% reported they did not want to know neither before nor after deployment. As advancements in genetic testing continue to evolve, our study suggests that consumer attitudes toward genetic testing for mental disorders are complex and better understanding of these attitudes and beliefs will be crucial to successfully promote utilization.
Rhebergen, Martijn D F; Visser, Maaike J; Verberk, Maarten M; Lenderink, Annet F; van Dijk, Frank J H; Kezic, Sanja; Hulshof, Carel T J
We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well.
Oncogenetic consultations and predictive BRCA1/2 testing are intertwined processes and the specific impact of these genetic tests if performed alone through direct-to-consumer offers remains unknown. Noteworthy, the expectations of patients vary with their own status, whether they are affected or not by breast cancer at the time genetic testing is performed. The prescription of genetic tests for BCRA mutations has doubled in France between 2003 and 2009. There is a consensus on the fact that genetic results disclosure led to a significant increase in the knowledge and understanding that the patients have of the genetic risk and also changed the medical follow-up of these patients. Evaluating the psychological burden of tests disclosure did not reveal any major distress in patients who are followed by high-quality multidisciplinary teams. Longitudinal cohorts studies have now evaluated the perception and behaviour of these patients, and observed sociodemographic as well as geographic and psychosocial differences both in the acceptation of prophylactic strategies such as surgery, and time to surgery. © 2011 médecine/sciences - Inserm / SRMS.
Lee, Hwa Jeen; Park, Seungman; Kang, Hyoung Jin; Jun, Jong Kwan; Lee, Jung Ae; Lee, Dong Soon; Park, Sung Sup; Seong, Moon-Woo
Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.
Tiller, Jane; Otlowski, Margaret; Lacaze, Paul
Under current Australian regulation, life insurance companies can require applicants to disclose all genetic test results, including results from research or direct-to-consumer tests. Life insurers can then use this genetic information in underwriting and policy decisions for mutually rated products, including life, permanent disability, and total income protection insurance. Over the past decade, many countries have implemented moratoria or legislative bans on the use of genetic information by life insurers. The Australian government, by contrast, has not reviewed regulation since 2005 when it failed to ensure implementation of recommendations made by the Australian Law Reform Commission. In that time, the Australian life insurance industry has been left to self-regulate its use of genetic information. As a result, insurance fears in Australia now are leading to deterred uptake of genetic testing by at-risk individuals and deterred participation in medical research, both of which have been documented. As the potential for genomic medicine grows, public trust and engagement are critical for successful implementation. Concerns around life insurance may become a barrier to the development of genomic health care, research, and public health initiatives in Australia, and the issue should be publicly addressed. We argue a moratorium on the use of genetic information by life insurers should be enacted while appropriate longer term policy is determined and implemented.
Full Text Available Under current Australian regulation, life insurance companies can require applicants to disclose all genetic test results, including results from research or direct-to-consumer tests. Life insurers can then use this genetic information in underwriting and policy decisions for mutually rated products, including life, permanent disability, and total income protection insurance. Over the past decade, many countries have implemented moratoria or legislative bans on the use of genetic information by life insurers. The Australian government, by contrast, has not reviewed regulation since 2005 when it failed to ensure implementation of recommendations made by the Australian Law Reform Commission. In that time, the Australian life insurance industry has been left to self-regulate its use of genetic information. As a result, insurance fears in Australia now are leading to deterred uptake of genetic testing by at-risk individuals and deterred participation in medical research, both of which have been documented. As the potential for genomic medicine grows, public trust and engagement are critical for successful implementation. Concerns around life insurance may become a barrier to the development of genomic health care, research, and public health initiatives in Australia, and the issue should be publicly addressed. We argue a moratorium on the use of genetic information by life insurers should be enacted while appropriate longer term policy is determined and implemented.
Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A
A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Parameshwar V Pandit
Full Text Available A class of distribution-free tests based on convex combination of two U-statistics is considered for testing independence against positive quadrant dependence. The class of tests proposed by Kochar and Gupta (1987 and Kendall’s test are members of the proposed class. The performance of the proposed class is evaluated in terms of Pitman asymptotic relative efficiency for Block- Basu (1974 model and Woodworth family of distributions. It has been observed that some members of the class perform better than the existing tests in the literature. Unbiasedness and consistency of the proposed class of tests have been established.
Visser, M. J.; Rhebergen, M. D. F.; Kezic, S.; van Dijk, F. J. H.; Willems, D. L.; Verberk, M. M.
Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are
Chalmers, Peter N; Cvetanovich, Gregory L; Kupfer, Noam; Wimmer, Markus A; Verma, Nikhil N; Cole, Brian J; Romeo, Anthony A; Nicholson, Gregory P
While Jobe's test is widely used, it does not isolate supraspinatus activity. Our purpose was to examine the electromyographic (EMG) activity within the supraspinatus and deltoid with resisted abduction to determine the shoulder position that best isolates the activity of the supraspinatus. We performed EMG analysis of the supraspinatus, anterior head of the deltoid, and middle head of the deltoid in 10 normal volunteers. We measured EMG activity during resisted shoulder abduction in the scapular plane to both manual resistance and a standardized load in varying degrees of abduction and rotation. To determine which position best isolates supraspinatus activity, the ratio of supraspinatus to deltoid activity (S:D) was calculated for each position. Results were analyzed with a repeated-measures analysis of variance with Bonferroni correction. The posterior deltoid was excluded as it serves mostly to extend and externally rotate. Our study confirmed Jobe's findings of maximal supraspinatus activity at 90° of abduction. However, decreasing abduction significantly increased S:D for both resisted manual testing and testing against a standardized load (P = .002 and .001, respectively). The greatest S:D ratio (4.6 ± 3.4 for standardized load testing) was seen at the "champagne toast" position, i.e., 30° of abduction, mild external rotation, 30° of flexion, and 90° of elbow flexion. The smallest ratio (0.8 ± 0.6) was seen at Jobe's position. Testing of abduction strength in the champagne toast position, i.e., 30° of abduction, mild external rotation, and 30° of flexion, better isolates the activity of the supraspinatus from the deltoid than Jobe's "empty can" position. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Naylor, Rochelle N; John, Priya M; Winn, Aaron N; Carmody, David; Greeley, Siri Atma W; Philipson, Louis H; Bell, Graeme I; Huang, Elbert S
OBJECTIVE To evaluate the cost-effectiveness of a genetic testing policy for HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients 25-40 years old with a MODY prevalence of 2%. RESEARCH DESIGN AND METHODS We used a simulation model of type 2 diabetes complications based on UK Prospective Diabetes Study data, modified to account for the natural history of disease by genetic subtype to compare a policy of genetic testing at diabetes diagnosis versus a policy of no testing. Under the screening policy, successful sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a glycosylated hemoglobin reduction of -1.5% compared with usual care. GCK-MODY received no therapy. Main outcome measures were costs and quality-adjusted life years (QALYs) based on lifetime risk of complications and treatments, expressed as the incremental cost-effectiveness ratio (ICER) (USD/QALY). RESULTS The testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of 205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the ICER would be ~50,000 USD. If MODY prevalence was >30%, the testing policy was cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER of ~50,000 USD. CONCLUSIONS Our simulated model suggests that a policy of testing for MODY in selected populations is cost-effective for the U.S. based on contemporary ICER thresholds. Higher prevalence of MODY in the tested population or decreased testing costs would enhance cost-effectiveness. Our results make a compelling argument for routine coverage of genetic testing in patients with high clinical suspicion of MODY.
Full Text Available In the previous two parts of educational manuscript series in Emergency, we explained some screening characteristics of diagnostic tests including accuracy, sensitivity, specificity, and positive and negative predictive values. In the 3rd part we aimed to explain positive and negative likelihood ratio (LR as one of the most reliable performance measures of a diagnostic test. To better understand this characteristic of a test, it is first necessary to fully understand the concept of sensitivity and specificity. So we strongly advise you to review the 1st part of this series again. In short, the likelihood ratios are about the percentage of people with and without a disease but having the same test result. The prevalence of a disease can directly influence screening characteristics of a diagnostic test, especially its sensitivity and specificity. Trying to eliminate this effect, LR was developed. Pre-test probability of a disease multiplied by positive or negative LR can estimate post-test probability. Therefore, LR is the most important characteristic of a test to rule out or rule in a diagnosis. A positive likelihood ratio > 1 means higher probability of the disease to be present in a patient with a positive test. The further from 1, either higher or lower, the stronger the evidence to rule in or rule out the disease, respectively. It is obvious that tests with LR close to one are less practical. On the other hand, LR further from one will have more value for application in medicine. Usually tests with 0.1 < LR > 10 are considered suitable for implication in routine practice.
Tannert, Line Kring; Mørtz, Charlotte G; Skov, Per Stahl
INTRODUCTION: According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. OBJECTIVE: To investigate the clinical relevance...... of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. METHODS: A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged......-IgE measured (T0), and then skin tested and had s-IgE measured 4 weeks later (T1). RESULTS: Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T0. Positive ST result or positive s-IgE alone did not predict...
von Euler-Chelpin, My; Kuchiki, Megumi; Vejborg, Ilse
of misclassification, i.e. women who were actually false-negatives instead of false-positives. METHOD: We used data from the Copenhagen Mammography Screening Programme, Denmark. The study population was the 295 women, out of 4743 recalled women from a total of 58,003 participants, with a false-positive test during...... the women with misclassified tests had been excluded, there was an excess risk of breast cancer of 27% (RR=1.27, 95% confidence interval (CI), 1.11-1.46) among the women with a false-positive test compared to women with only negative tests. Women with a false-positive test determined at assessment had...... an excess risk of 27%, while false-positives determined at surgery had an excess risk of 30%. CONCLUSIONS: The results indicate that the increased risk is not explained only by misclassification. The excess risk remains for false-positives determined at assessment as well as at surgery, which favours some...
Schaefer, K. U.; Kurtzhals, J. A.; Kager, P. A.; Gachihi, G. S.; Gramiccia, M.; Kagai, J. M.; Sherwood, J. A.; Muller, A. S.
The leishmanin skin test (LST) was applied in 26 clusters of an average of 97 individuals in Baringo District, Kenya. These clusters were centered around recent cases of visceral leishmaniasis (VL). Of 2,411 individuals tested, 254 (10.5%, 155 males and 99 females) had a positive reaction. Among
Brock, Inger; Ruhwald, Morten; Lundgren, Bettina
Although tuberculosis (TB) is a minor problem in Denmark, severe and complicated cases occur in HIV positive. Since the new M. tuberculosis specific test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the patients in our clinic have been screened for the presence of latent...
Brock, Inger; Ruhwald, Morten; Lundgren, Bettina
BACKGROUND: Although tuberculosis (TB) is a minor problem in Denmark, severe and complicated cases occur in HIV positive. Since the new M. tuberculosis specific test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the patients in our clinic have been screened...
Kostka, Marion P.; Galassi, John P.
The study compared modified versions of systematic desensitization and covert positive reinforcement to a no-treatment control condition in the reduction of test anxiety. On an anagrams performance test, the covert reinforcement and control groups were superior to the desensitization group. (Author)
In recent years, genome-wide association studies (GWAS) and gene-expression profiling have generated a large number of valuable datasets for assessing how genetic variations are related to disease outcomes. With such datasets, it is often of interest to assess the overall effect of a set of genetic markers, assembled based on biological knowledge. Genetic marker-set analyses have been advocated as more reliable and powerful approaches compared with the traditional marginal approaches (Curtis and others, 2005. Pathways to the analysis of microarray data. TRENDS in Biotechnology 23, 429-435; Efroni and others, 2007. Identification of key processes underlying cancer phenotypes using biologic pathway analysis. PLoS One 2, 425). Procedures for testing the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least-squares kernel machines and linear mixed models. Biometrics 63, 1079-1088; Liu and others, 2008. Estimation and testing for the effect of a genetic pathway on a disease outcome using logistic kernel machine regression via logistic mixed models. BMC bioinformatics 9, 292-2; Wu and others, 2010. Powerful SNP-set analysis for case-control genome-wide association studies. American Journal of Human Genetics 86, 929) have been proposed as powerful alternatives to the standard Rao score test (Rao, 1948. Large sample tests of statistical hypotheses concerning several parameters with applications to problems of estimation. Mathematical Proceedings of the Cambridge Philosophical Society, 44, 50-57). The advantages of these EB-based tests are most apparent when the markers are correlated, due to the reduction in the degrees of freedom. In this paper, we propose an adaptive score test which up- or down-weights the contributions from each member of the marker-set based on the Z-scores of
Lantos, Paul M; Branda, John A; Boggan, Joel C; Chudgar, Saumil M; Wilson, Elizabeth A; Ruffin, Felicia; Fowler, Vance; Auwaerter, Paul G; Nigrovic, Lise E
Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Lawrence, Ryan E; Friesen, Phoebe; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa
Genetic tests for schizophrenia may introduce risks and benefits. Among young adults at clinical high-risk for psychosis, little is known about their concerns and how they assess potential risks. We conducted semi-structured interviews with 15 young adults at clinical high-risk for psychosis to ask about their concerns. Participants expressed concerns about test reliability, data interpretation, stigma, psychological harm, family planning, and privacy. Participants' responses showed some departure from the ethics literature insofar as participants were primarily interested in reporting their results to people to whom they felt emotionally close, and expressed little consideration of biological closeness. Additionally, if tests showed an increased genetic risk for schizophrenia, four clinical high-risk persons felt obligated to tell an employer and another three would "maybe" tell an employer, even in the absence of clinical symptoms. These findings suggest opportunities for clinicians and genetic counselors to intervene with education and support.
Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz
was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case–control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism......Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...
Full Text Available Patients with Lynch syndrome (LS have a significantly increased risk of developing colorectal cancer (CRC and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing
Schneider, Susanne A; Klein, Christine
Genetic testing holds many promises in movement disorders, but also pitfalls that require careful consideration for meaningful results. These include the primary indication for testing in the first place, concerns regarding the implications of symptomatic, presymptomatic, and susceptibility testing, the mutation frequency in the gene of interest, the general lack of neuroprotective treatment options for neurodegenerative movement disorders, the prognosis of the condition diagnosed, and patient confidentiality concerns. Furthermore, new technical achievements and the available technical expertise, feasibility of specific gene testing, and its coverage through a health insurance carrier should be considered. Guidelines for testing have been established by some disease societies to advise clinicians and in parallel legal regulations are being adjusted at a national and international level. We review these and other critical points and recent developments regarding genetic testing in the field of movement disorders.
Forrest, Laura; Delatycki, Martin; Curnow, Lisette; Gen Couns, M; Skene, Loane; Aitken, Maryanne
The aim of this study was to investigate the uptake of genetic testing by at-risk family members for four genetic conditions: chromosomal translocations, fragile X syndrome, Huntington disease, and spinal muscular atrophy. A clinical audit was undertaken using genetics files from Genetic Health Services Victoria. Data were extracted from the files regarding the number of at-risk family members and the proportion tested. Information was also collected about whether discussion of at-risk family members and family communication during the genetic consultation was recorded. The proportion of at-risk family members who had genetic testing ranged from 11% to 18%. First-degree family members were most frequently tested and the proportion of testing decreased by degree of relatedness to the proband. Smaller families were significantly more likely to have genetic testing for all conditions except Huntington disease. Female at-risk family members were significantly more likely to have testing for fragile X syndrome. The majority of at-risk family members do not have genetic testing. Family communication is likely to influence the uptake of genetic testing by at-risk family members and therefore it is important that families are supported while communicating to ensure that at-risk family members are able to make informed decisions about genetic testing.
Benjamin John Landis
Full Text Available Human cardiovascular malformations (CVMs frequently have a genetic contribution. Through the application of novel technologies such as next generation sequencing, DNA sequence variants associated with CVMs are being identified at a rapid pace. While clinicians are now able to offer testing with next generation sequencing gene panels or whole exome sequencing to any patient with a CVM, the interpretation of genetic variation remains problematic. Variable phenotypic expression, reduced penetrance, inconsistent phenotyping methods, and the lack of high throughput functional testing of variants, contribute to these challenges. This article elaborates critical issues that impact the decision to broadly implement clinical molecular genetic testing in CVMs. Major benefits of testing include establishing a genetic diagnosis, facilitating cost-effective screening of family members who may have subclinical disease, predicting recurrence risk in offspring, enabling early diagnosis and anticipatory management of CV and non-CV disease phenotypes, predicting long term outcomes, and facilitating the development of novel therapies aimed at disease improvement or prevention. Limitations include financial cost, psychosocial cost, and ambiguity of interpretation of results. Multiplex families and patients with syndromic features are two groups where disease causation could potentially be firmly established. However, these account for the minority of the overall CVM population, and there is increasing recognition that genotypes previously associated with syndromes also exist in patients who lack non-CV findings. In all circumstances, ongoing dialogue between cardiologists and clinical geneticists will be needed to accurately interpret genetic testing and improve these patients’ health. This may be most effectively implemented by the creation and support of CV genetics services at centers committed to pursuing testing for patients.
Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan
The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Gottlieb, Sami L; Stoner, Bradley P; Zaidi, Akbar A; Buckel, Christina; Tran, Molly; Leichliter, Jami S; Berman, Stuart M; Markowitz, Lauri E
Few data exist on potential harms of chlamydia screening. We assessed the psychosocial impact of receiving a positive Chlamydia trachomatis test result. We prospectively studied women ≥16 years of age undergoing chlamydia testing in 2 Midwestern family planning clinics. We surveyed women at baseline and about 1 month after receiving test results, using 9 validated psychosocial scales/subscales and chlamydia-specific questions. Changes in scale scores were calculated for each woman. Mean percent changes in scores for chlamydia-positive and -negative women were compared using a t test. We enrolled 1807 women (response rate, 84%). Of the 1688 women with test results, 149 (8.8%) tested positive. At follow-up, chlamydia-positive women (n = 71) had a 75% increase in anxiety about sexual aspects of their life on the Multidimensional Sexual Self-Concept Questionnaire (P < 0.001), significantly greater than the 26% increase among 280 randomly selected chlamydia-negative women (P = 0.02). There were no differences for the other 8 scales/subscales, including general measures of anxiety, depression, and self-esteem. Chlamydia-positive women were more likely than chlamydia-negative women to be "concerned about chlamydia" (80% vs. 40%, P < 0.001) and to report breaking up with a main partner (33% vs. 11%, P < 0.001) at follow-up. Women testing positive reported a range of chlamydia-specific concerns. Chlamydia-positive women had significant increases in anxiety about sex and concern about chlamydia, but did not have marked changes in more general measures of psychosocial well-being about 1 month after diagnosis. Chlamydia diagnoses were associated with some disruption of relationships with main partners. Chlamydia-specific concerns may guide counseling messages to minimize psychosocial impact.
Acar, Elif F.; Sun, Lei
Motivated by genetic association studies of SNPs with genotype uncertainty, we propose a generalization of the Kruskal-Wallis test that incorporates group uncertainty when comparing k samples. The extended test statistic is based on probability-weighted rank-sums and follows an asymptotic chi-square distribution with k-1 degrees of freedom under the null hypothesis. Simulation studies confirm the validity and robustness of the proposed test in finite samples. Application to a genome-wide asso...
Li, Li; Zhang, Yunwei; Chen, Ling
In order to solve the problem of selecting positioning technology for inspection robot in underground pipeline environment, the wireless network signal strength and GPS positioning signal testing are carried out in the actual underground pipeline environment. Firstly, the strength variation of the 3G wireless network signal and Wi-Fi wireless signal provided by China Telecom and China Unicom ground base stations are tested, and the attenuation law of these wireless signals along the pipeline is analyzed quantitatively and described. Then, the receiving data of the GPS satellite signal in the pipeline are tested, and the attenuation of GPS satellite signal under underground pipeline is analyzed. The testing results may be reference for other related research which need to consider positioning in pipeline.
Eisenhofer, Graeme; Klink, Barbara; Richter, Susan; Lenders, Jacques Wm; Robledo, Mercedes
The tremendous advances over the past two decades in both clinical genetics and biochemical testing of chromaffin cell tumours have led to new considerations about how these aspects of laboratory medicine can be integrated to improve diagnosis and management of affected patients. With germline mutations in 15 genes now identified to be responsible for over a third of all cases of phaeochromocytomas and paragangliomas, these tumours are recognised to have one of the richest hereditary backgrounds among all neoplasms. Depending on the mutation, tumours show distinct differences in metabolic pathways that relate to or even directly impact clinical presentation. At the same time, there has been improved understanding about how catecholamines are synthesised, stored, secreted and metabolised by chromaffin cell tumours. Although the tumours may not always secrete catecholamines it has become clear that almost all continuously produce and metabolise catecholamines. This has not only fuelled changes in laboratory medicine, but has also assisted in recognition of genotype-biochemical phenotype relationships important for diagnostics and clinical care. In particular, differences in catecholamine and energy pathway metabolomes can guide genetic testing, assist with test interpretation and provide predictions about the nature, behaviour and imaging characteristics of the tumours. Conversely, results of genetic testing are important for guiding how routine biochemical testing should be employed and interpreted in surveillance programmes for at-risk patients. In these ways there are emerging needs for modern laboratory medicine to seamlessly integrate biochemical and genetic testing into the diagnosis and management of patients with chromaffin cell tumours.
As increasing evidence suggests that multiple correlated genetic variants could jointly influence the outcome, a multilocus test that aggregates association evidence across multiple genetic markers in a considered gene or a genomic region may be more powerful than a single-marker test for detecting susceptibility loci. We propose a multilocus test, AdaJoint, which adopts a variable selection procedure to identify a subset of genetic markers that jointly show the strongest association signal, and defines the test statistic based on the selected genetic markers. The P-value from the AdaJoint test is evaluated by a computationally efficient algorithm that effectively adjusts for multiple-comparison, and is hundreds of times faster than the standard permutation method. Simulation studies demonstrate that AdaJoint has the most robust performance among several commonly used multilocus tests. We perform multilocus analysis of over 26,000 genes/regions on two genome-wide association studies of pancreatic cancer. Compared with its competitors, AdaJoint identifies a much stronger association between the gene CLPTM1L and pancreatic cancer risk (6.0 × 10(-8)), with the signal optimally captured by two correlated single-nucleotide polymorphisms (SNPs). Finally, we show AdaJoint as a powerful tool for mapping cis-regulating methylation quantitative trait loci on normal breast tissues, and find many CpG sites whose methylation levels are jointly regulated by multiple SNPs nearby.
Full Text Available Abstract Application of test-day models for the genetic evaluation of dairy populations requires the solution of large mixed model equations. The size of the (covariance matrices required with such models can be reduced through the use of its first eigenvectors. Here, the first two eigenvectors of (covariance matrices estimated for dairy traits in first lactation were used as covariables to jointly estimate genetic parameters of the first three lactations. These eigenvectors appear to be similar across traits and have a biological interpretation, one being related to the level of production and the other to persistency. Furthermore, they explain more than 95% of the total genetic variation. Variances and heritabilities obtained with this model were consistent with previous studies. High correlations were found among production levels in different lactations. Persistency measures were less correlated. Genetic correlations between second and third lactations were close to one, indicating that these can be considered as the same trait. Genetic correlations within lactation were high except between extreme parts of the lactation. This study shows that the use of eigenvectors can reduce the rank of (covariance matrices for the test-day model and can provide consistent genetic parameters.
Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara
Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNALysUUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm5s2U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm5s2U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.
Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R
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...
Williams-Jones, Bryn; Burgess, Michael M
Decisions about funding health services are crucial to controlling costs in health care insurance plans, yet they encounter serious challenges from intellectual property protection--e.g., patents--of health care services. Using Myriad Genetics' commercial genetic susceptibility test for hereditary breast cancer (BRCA testing) in the context of the Canadian health insurance system as a case study, this paper applies concepts from social contract theory to help develop more just and rational approaches to health care decision making. Specifically, Daniel's and Sabin's "accountability for reasonableness" is compared to broader notions of public consultation, demonstrating that expert assessments in specific decisions must be transparent and accountable and supplemented by public consultation.
Weitzel, J N
Few advances in medical science have yielded as much publicity and controversy as discoveries in genetics. Moving quickly from the bench to the bedside, genetic testing for inherited susceptibility to breast and ovarian cancer has had a significant impact on our paradigms for decisions about the treatment and prevention of disease. Assessment of cancer risk is developing into a distinct discipline, with rapidly evolving genetic technologies and models for estimating an individual's risk of cancer. Exciting developments in chemoprevention of breast cancer demonstrate the potential to offer a broader range of options for decreasing cancer risk. This article will consider recent advances in the understanding of cancer genetics, and describe the state-of-the-art in terms of management of individuals with inherited susceptibility to breast and ovarian cancer.
Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y
Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Légaré, France; Robitaille, Hubert; Gane, Claire; Hébert, Jessica; Labrecque, Michel; Rousseau, François
Knowledge translation (KT) interventions are attempts to change behavior in keeping with scientific evidence. While genetic tests are increasingly available to healthcare consumers in the clinic, evidence about their benefits is unclear and decisions about genetic testing are thus difficult for all parties. We sought to identify KT interventions that involved decisions about genetic testing in the clinical context and to assess their effectiveness for improving decision making in terms of behavior change, increased knowledge and wellbeing. We searched for trials assessing KT interventions in the context of genetic testing up to March 2014 in all systematic reviews (n = 153) published by two Cochrane review groups: Effective Practice and Organisation of Care (EPOC) and Consumers and Communication. We retrieved 2473 unique trials of which we retained only 28 (1%). Two EPOC reviews yielded two trials of KT interventions: audit and feedback (n = 1) and educational outreach (n = 1). Both targeted health professionals and the KT intervention they assessed was found to be effective. Four Consumers and Communication reviews yielded 26 trials: decision aids (n = 15), communication of DNA-based disease risk estimates (n = 7), personalized risk communication (n = 3) and mobile phone messaging (n = 1). Among these, 25 trials targeted only health consumers or patients and the KT interventions were found to be effective in four trials, partly effective in seven, and ineffective in four. Lastly, only one trial targeted both physicians and patients and was found to be effective. More research on the effectiveness of KT interventions regarding genetic testing in the clinical context may contribute to patients making informed value-based decisions and drawing the maximum benefit from clinical applications of genetic and genomic innovations.
Full Text Available Knowledge translation (KT interventions are attempts to change behavior in keeping with scientific evidence. While genetic tests are increasingly available to healthcare consumers in the clinic, evidence about their benefits is unclear and decisions about genetic testing are thus difficult for all parties.We sought to identify KT interventions that involved decisions about genetic testing in the clinical context and to assess their effectiveness for improving decision making in terms of behavior change, increased knowledge and wellbeing.We searched for trials assessing KT interventions in the context of genetic testing up to March 2014 in all systematic reviews (n = 153 published by two Cochrane review groups: Effective Practice and Organisation of Care (EPOC and Consumers and Communication.We retrieved 2473 unique trials of which we retained only 28 (1%. Two EPOC reviews yielded two trials of KT interventions: audit and feedback (n = 1 and educational outreach (n = 1. Both targeted health professionals and the KT intervention they assessed was found to be effective. Four Consumers and Communication reviews yielded 26 trials: decision aids (n = 15, communication of DNA-based disease risk estimates (n = 7, personalized risk communication (n = 3 and mobile phone messaging (n = 1. Among these, 25 trials targeted only health consumers or patients and the KT interventions were found to be effective in four trials, partly effective in seven, and ineffective in four. Lastly, only one trial targeted both physicians and patients and was found to be effective.More research on the effectiveness of KT interventions regarding genetic testing in the clinical context may contribute to patients making informed value-based decisions and drawing the maximum benefit from clinical applications of genetic and genomic innovations.
Harris, Anna; Kelly, Susan E.; Wyatt, Sally
Despite a growing personal genomics market, little is known about how people engage with the possibilities offered by direct-to-consumer (DTC) genetic testing. In order to help address this gap, this study deploys narrative analysis of YouTube videos posted by individuals who have purchased DTC genetic testing for disease. Genetic testing is said to be contributing to new states of illness, where individuals may become “patients-in-waiting.” In the videos analyzed, we found a new form of storytelling about this ambiguous state of illness, which we refer to as autobiology. Autobiology – the study of, and story about, one's own biology – concerns narratives of sense-making through forms of biological practice, as well as wayfaring narratives which interweave genetic markers and family histories of disease. These autobiologies – part of a broader shift toward public stories about genetics and other healthcare technologies – exhibit playfulness, as well as being bound with consumerist practices. PMID:24772003
Forman, Andrea D; Hall, Michael J
Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.
Niemiec, Emilia; Kalokairinou, Louiza; Howard, Heidi Carmen
A variety of health-related genetic testing is currently advertized directly to consumers. This article provides a timely overview of direct-to-consumer genetic testing (DTC GT) and salient ethical issues, as well as an analysis of the impact of the recently adopted regulation on in vitro diagnostic medical devices on DTC GT. DTC GT companies currently employ new testing approaches, report on a wide spectrum of conditions and target new groups of consumers. Such activities raise ethical issues including the questionable analytic and clinical validity of tests, the adequacy of informed consent, potentially misleading advertizing, testing in children, research uses and commercialization of genomic data. The recently adopted regulation on in vitro diagnostic medical devices may limit the offers of predisposition DTC GT in the EU market.
Gu, Peipei; Niu, Zhendong; Chen, Xuting; Chen, Wei
In recent years, computer-based testing has become an effective method to evaluate students' overall learning progress so that appropriate guiding strategies can be recommended. Research has been done to develop intelligent test assembling systems which can automatically generate test sheets based on given parameters of test items. A good multisubject test sheet depends on not only the quality of the test items but also the construction of the sheet. Effective and efficient construction of test sheets according to multiple subjects and criteria is a challenging problem. In this paper, a multi-subject test sheet generation problem is formulated and a test sheet generating approach based on intelligent genetic algorithm and hierarchical planning (GAHP) is proposed to tackle this problem. The proposed approach utilizes hierarchical planning to simplify the multi-subject testing problem and adopts genetic algorithm to process the layered criteria, enabling the construction of good test sheets according to multiple test item requirements. Experiments are conducted and the results show that the proposed approach is capable of effectively generating multi-subject test sheets that meet specified requirements and achieve good performance.
New insights into the genetics of sport performance lead to new areas of application. One area is the use of genetic tests to identify athletic talent. Athletic performances involve a high number of complex phenotypical traits. Based on the ACCE model (review of Analytic and Clinical validity, Clinical utility, and Ethical, legal and social implications), a critique is offered of the lack of validity and predictive power of genetic tests for talent. Based on the ideal of children's right to an open future, a moral argument is given against such tests on children and young athletes. A possible role of genetic tests in sport is proposed in terms of identifying predisposition for injury. In meeting ACCE requirements, such tests could improve individualised injury prevention and increase athlete health. More generally, limitations of science are discussed in the identification of talent and in the understanding of complex human performance phenotypes. An alternative approach to talent identification is proposed in terms of ethically sensitive, systematic and evidence-based holistic observation over time of relevant phenotypical traits by experienced observers. Talent identification in sport should be based on the primacy of the phenotype.
Testing of chemicals for their genetic activity by applying only one method has the disadvantage, that the results are of limited value. However, a combination of several test systems in such a manner that the apparent difference between the results allows additional conclusions about the pharmacokinetic properties of the substances tested, the correlation between molecular mutations and cytogenetic effects and the possible carcinogenic activity. Three nitrofuran derivatives (nitrofurantoin, carofur and FANFT) tested in six different in vitro and in vivo mutagenicity tests partly showed strong genetic activity without metabolic activation and weak cytogenetic effects. However, polycyclic hydrocarbons needed mammalian metabolism to display their mutagenicity: Dimethylbenzoanthracene and benzo(a)pyrene could be activated by liver microsomes and showed also cytogenetic effects, but phenanthrene was only active in the SCE-test. Out of nine heavy metal salts potassium chromate, potassium dichromate, calcium chromate and cis-dichloro diammine-Pt(II) were effective in at least one genetic and one cytogenetic test. The correlation between mutagenic and the known carcinogenic activity of all test substances was good in the case of the hydrocarbons and the nitrofuran derivatives; the heavy metal salts, however, are of low relevance for the carcinogenicity of the metals itself.
Sarup, Pernille; Loeschcke, Volker
Hormesis, the beneficial effect of a mild stress, has been proposed as a means to prolong the period of healthy ageing as it can increase the average lifespan of a cohort. However, if we want to use hormesis therapeutically it is important that the treatment is beneficial on the individual level and not just on average at the population level. Long lived lines have been shown not to benefit from a, in other lines, hormesis inducing heat treatment in Drosophila melanogaster, D. buzzatii and mice. Also in many experiments hormesis has been reported to occur in one sex only, usually males but not in females. Here we investigated the interaction between the hormetic response and genetic background, sex and duration of a mild heat stress in D. melanogaster, using three replicate lines that have been selected for increased longevity and their respective control lines. We found that genetic background influences the position of the hormetic zone. The implication of this result could be that in a genetically diverse populations a treatment that is life prolonging in one individual could be life shortening in other individuals. However, we did find a hormetic response in all combinations of line and sex in at least one of the experiments which suggests that if it is possible to identify the optimal hormetic dose individually hormesis might become a therapeutic treatment.
Akhtar Rasool Asif
Full Text Available Objective Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods By using fixation index (FST based method, IL-32 (9375 gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and FST. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8 in Codeml program of phylogenetic analysis by maximum liklihood. Results IL-32 is detected under positive selection using the FST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%, bison (91.97%, camel (58.39%, cat (56.59%, buffalo (56.50%, human (56.13%, dog (50.97%, horse (54.04%, and rabbit (53.41% respectively. Conclusion This study provides evidence for IL-32 gene as under significant positive selection in goat.
Shu, D.; Rodricks, B.; Barraza, J.; Sanchez, T.; Kuzay, T.M.
The advent of third generation synchrotron radiation sources, like the Advanced Photon Source (APS), will provide significant increases in brilliance over existing synchrotron sources. The APS x-ray undulators will increase the brilliance in the 3-40 KeV range by several orders of magnitude. Thus, the design of the photon beam position monitor is a challenging engineering task. The beam position monitors must withstand the high thermal load, be able to achieve sub-micron spatial resolution while maintaining their stability, and be compatible with both undulators and wigglers. A preliminary APS prototype photon beam position monitor consisting of a CVD-diamond-based, tungsten-coated blade was tested on the APS/CHESS undulator at the Cornell High Energy Synchrotron Radiation Source (CHESS) and on the NSLS X-13 undulator beamline. Results from these tests, as well as the design of this prototype APS photon beam position monitor, will be discussed in this paper
Shu, D.; Rodricks, B.; Barraza, J.; Sanchez, T.; Kuzay, T.M.
The advent of thirs generation synchrotron sources, like the Advanced Photon Source (APS), will provide significant increases in brilliance over existing synchrotron sources. The APS X-ray undulators will increase the brilliance in the 3-40 keV range by several orders of magnitude. Thus, the design of the photon beam position monitor is a challenging engineering task. The beam position monitors must withstand the high thermal load, be able to achieve submicron spatial resolution while maintaining their stability, and be compatible with both undulators and wigglers. A preliminary APS prototype photon beam position monitor consisting of a CVD-diamond-based, tungsten-coated blade was tested on the APS/CHESS undulator at the Cornell High Energy Synchrotron Radiation Source (CHESS) and on the NSLS X-13 undulator beamline. Results from these tests, as well as the design of this prototype APS photon beam position monitor, will be discussed in this paper. (orig.)
Rota, Ada; Corrò, Michela; Drigo, Ilenia; Bortolami, Alessio; Börjesson, Stefan
Among the coagulase-positive, potentially pathogenic staphylococci, Staphylococcus pseudintermedius has been frequently isolated from bitches' milk. This organism colonizes the mammary gland or causes infection, while S. aureus has been only occasionally reported. The objective of this study was to investigate the occurrence and persistence of coagulase-positive staphylococci in the colostrum and milk of postpartum bitches, either treated or untreated with antimicrobials, and to assess the incidence, antibiotic resistance profile and genetic type of the methicillin-resistant strains. On postpartum D1, D7 and D15, drops of secretion were collected from the mammary glands of 27 postpartum bitches, nine of which were treated with antimicrobials. Coagulase-positive staphylococci were identified, antimicrobial susceptibility and the presence of mecA were tested and the genetic profile of methicillin-resistant strains was assessed. Staphylococcus pseudintermedius was the only coagulase-positive staphylococcus isolated, and its presence was detected in 21 out of 27 bitches and in 66 out of 145 swabs. In a single bitch, it caused puerperal mastitis. In untreated bitches, the frequency of isolation was lower in colostrum than in milk. All of the isolates except one were resistant to at least three antimicrobial classes, while 14 out of 66 S. pseudintermedius strains were methicillin-resistant mecA positive (MRSP) and were isolated from eight bitches housed in the same breeding kennel. A significant association was found between antimicrobial treatment and the presence of MRSP. Six of the 12 typed isolates belonged to spa-type t02 carrying SCCmec II/III, and another six were non-typeable with spa carrying SCCmec IV. The t02-SCCmec II/III isolates were sequence type (ST) 71; four NT-SCCmec IV isolates were ST258 and two were ST369. PFGE showed that isolates from the same dog had identical band patterns, while isolates from different dogs had unique band patterns. MRSP strains
Collins, J; Ryan, L; Truby, H
In the future, it may be possible for individuals to take a genetic test to determine their genetic predisposition towards developing lifestyle-related chronic diseases. A systematic review of the literature was undertaken to identify the factors associated with an interest in having predictive genetic testing for obesity, type II diabetes and heart disease amongst unaffected adults. Ovid Medline, PsycINFO and EMBASE online databases were searched using predefined search terms. Publications meeting the inclusion criteria (English language, free-living adult population not selected as a result of their disease diagnosis, reporting interest as an outcome, not related to a single gene inherited disease) were assessed for quality and content. Narrative synthesis of the results was undertaken. From the 2329 publications retrieved, eight studies met the inclusion criteria and were included in the review. Overall, the evidence base was small but of positive quality. Interest was associated with personal attitudes towards disease risk and the provision of information about genetic testing, shaped by perceived risk of disease and expected outcomes of testing. The role of demographic factors was investigated with largely inconclusive findings. Interest in predictive genetic testing for obesity, type II diabetes or heart disease was greatest amongst those who perceived the risk of disease to be high and/or the outcomes of testing to be beneficial. © 2013 The British Dietetic Association Ltd.
Full Text Available Objective. The study aims at assessing personality tendencies and orientations that could be closely correlated with knowledge, awareness, and interest toward undergoing genetic testing. Methods. A sample of 145 subjects in Italy completed an online survey, investigating demographic data, health orientation, level of perceived knowledge about genetic risk, genetic screening, and personal attitudes toward direct to consumer genetic testing (DTCGT. Results. Results showed that respondents considered genetic assessment to be helpful for disease prevention, but they were concerned that results could affect their life planning with little clinical utility. Furthermore, a very high percentage of respondents (67% had never heard about genetic testing directly available to the public. Data showed that personality tendencies, such as personal health consciousness, health internal control, health esteem, and confidence, motivation to avoid unhealthiness and motivation for healthiness affected the uptake of genetic information and the interest in undergoing genetic testing. Conclusions. Public knowledge and attitudes toward genetic risk and genetic testing among European countries, along with individual personality and psychological tendencies that could affect these attitudes, remain unexplored. The present study constitutes one of the first attempts to investigate how such personality tendencies could motivation to undergo genetic testing and engagement in lifestyle changes.
Schwitulla, J; Brasch, J; Löffler, H; Schnuch, A; Geier, J; Uter, W
As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions. To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS. Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions. Men, patients aged ≥ 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative. The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary. © 2014 British Association of Dermatologists.
Perdrisat, C.F.; Koechner, D.; Majewski, S.; Pourang, R.; Wilson, C.D.; Zorn, C.
Several applications of two Hamamatsu position sensitive photomultiplier tubes to the detection of high energy particles with scintillating fibers are discussed. The PMTs are of the multiwire anode grid design, type R2486 and R4135. These tubes were tested with both single samples and arrays of 2 and 3 mm diameter scintillating fibers. Measurements of position resolution of the PMTs using either the charge digitization or the delay line readout techniques were made. The results indicate an intrinsic inability of the technique to reconstruct the actual position of a fiber on the photocathode when its location falls halfway between two grid wires. A way to overcome this limit is suggested. (orig.)
This document describes the method used to test design criteria for gear actuated ball valves installed in 241-AN-A Valve Pit located at 200E Tank Farms. The purpose of this procedure is to demonstrate the following: Equipment is properly installed, labeled, and documented on As-Built drawings; New Manifold Valves in the 241-AN-A Valve Pit are fully operable using the handwheel of the valve operators; New valve position indicators on the valve operators will show correct valve positions; New valve position switches will function properly; and New valve locking devices function properly.
Linneberg, A; Jørgensen, T; Nielsen, N H
BACKGROUND: It is disputed whether increases in self-reported respiratory allergy represent a true increase or merely increased recognition. We aimed to investigate whether the prevalence of skin-prick-test (SPT)-positive allergic rhinitis had increased in an adult general population in Copenhagen...... (participation rate 74.6%) and 482 (participation rate 53.4%) subjects were examined in 1990 and 1998, respectively. Diagnoses of SPT-positive allergic rhinitis were based on a history of nasal symptoms on exposure to allergens and SPT positivity to allergens. RESULTS: The prevalence of a diagnosis of SPT...
Sargsyan, V.; Schreiber, H.J.; Evtushenko, P.; Schurig, R.
A new type of a cavity BPM proposed for beam position determination along the TESLA linac was tested at the accelerator ELBE in Rossendorf / Dresden. Measurements using an improved BPM (large and stable cross-talk isolation, significantly less energy dissipation, a novel LO signal generation) were performed in single- and multi-bunch regimes. Agreement with expectations was found. The low bunch charge available allowed for preliminary measurements on sensitivity and position resolution, which extrapolated to TESLA would ful l the demands for precise bunch-to-bunch position determination. Possible improvements, in particular on the signal processing scheme, are also discussed. (orig.)
Cox, S. L.; Zlot, A. I.; Silvey, S. K.; Silvey, S. K.
Introduction. Appropriate use of genetic tests for population-based cancer screening, diagnosis of inherited cancers, and guidance of cancer treatment can improve health outcomes. We investigated clinicians’ use and knowledge of eight breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a randomized survey of 2,191 Oregon providers, asking about their experience with fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1, and KRAS. Results. Clinicians reported low confidence in their knowledge of medical genetics; most confident were OB-GYNs and specialists. Clinicians were more likely to have ordered/recommended BRCA and MMR than the other tests, and OB-GYNs were twice as likely to have ordered/recommended BRCA testing than primary care providers. Less than 10% of providers ordered/recommended OncoVue, fecal DNA, CYP2D6, or UGT1A1; less than 30% ordered/recommended tumor gene expression profiles or KRAS. The most common reason for not ordering/recommending these tests was lack of familiarity. Conclusions. Use of appropriate, evidence-based testing can help reduce incidence and mortality of certain cancers, but these tests need to be better integrated into clinical practice. Continued evaluation of emerging technologies, dissemination of findings, and an increase in provider confidence and knowledge are necessary to achieve this end.
Vladutiu, A.O.; Sulewski, J.M.; Pudlak, K.A.; Stull, C.G.
A young woman with amenorrhea had a consistently positive pregnancy test result (serum radioimmunoassay measurement of ..beta..-human chorionic gonadotropin hormone). No fetal or placental tissue was found after uterine curettage and exploratory laparotomy. The false-positive pregnancy test result was due to heterophilic antibovine and antigoat antibodies in the patient's serum. These antibodies interfered with radioimmunoassays using goat antibodies. This case shows that serum heterophilic antibodies can interfere with immunoassays and result in unnecessary diagnostic procedures and/or unnecessary treatment.
Vladutiu, A.O.; Sulewski, J.M.; Pudlak, K.A.; Stull, C.G.
A young woman with amenorrhea had a consistently positive pregnancy test result (serum radioimmunoassay measurement of #betta#-human chorionic gonadotropin hormone). No fetal or placental tissue was found after uterine curettage and exploratory laparotomy. The false-positive pregnancy test result was due to heterophilic antibovine and antigoat antibodies in the patient's serum. These antibodies interfered with radioimmunoassays using goat antibodies. This case shows that serum heterophilic antibodies can interfere with immunoassays and result in unnecessary diagnostic procedures and/or unnecessary treatment
Douma, K.F.L.; Aaronson, N.K.; Vasen, H.F.A.; Verhoef, S.; Gundy, C.M.; Bleiker, E.M.A.
Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA
Genetic counseling and testing for breast cancer have traditionally been offered to eligible patients after completion of their primary treatment. Women with hereditary breast cancer, caused by a germline mutation in the BRCA1 or BRCA2 gene, have an increased risk of contralateral breast cancer and
Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P
Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.
Weinreich, S.S.; Bosma, A.R.; Henneman, L.; Rigter, T.; Spruijt, C.M.J.; Grimbergen, A.J.E.M.; Breuning, M.H.; de Koning, E.J.P.; Losekoot, M.; Cornel, M.C.
Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant for treatment and prognosis in patients with usually early-onset, non-ketotic, insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation carriers. This study describes the first 10 years of
Palmquist, Aunchalee E. L.; Upton, Rachel; Lee, Seungjin; Panter, Abby T.; Hadley, Don W.; Koehly, Laura M.
Objective: To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome. Design: Family-centered, cascade recruitment; baseline assessment of a longitudinal study. Setting: Clinical research setting. Participants: Participants were 390 persons, ages 18 and older, including persons…
Niroomand-Rad, A.; Cumberlin, R.
The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm 3 dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimated doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs
Lindahl, Mats Gunnar
To make meaning of scientific knowledge in such a way that concepts and values of the life-world are not threatened is difficult for students and laymen. Ethics and morals pertaining to the use of genetic tests for hereditary diseases have been investigated and discussed by educators, anthropologists, medical doctors and philosophers giving, at…
Berwouts, Sarah; Fanning, Katrina; Morris, Michael A; Barton, David E; Dequeker, Elisabeth
In the 2000s, a number of initiatives were taken internationally to improve quality in genetic testing services. To contribute to and update the limited literature available related to this topic, we surveyed 910 human molecular genetic testing laboratories, of which 291 (32%) from 29 European countries responded. The majority of laboratories were in the public sector (81%), affiliated with a university hospital (60%). Only a minority of laboratories was accredited (23%), and 26% was certified. A total of 22% of laboratories did not participate in external quality assessment (EQA) and 28% did not use reference materials (RMs). The main motivations given for accreditation were to improve laboratory profile (85%) and national recognition (84%). Nearly all respondents (95%) would prefer working in an accredited laboratory. In accredited laboratories, participation in EQA (Pquality assurance (Pquality implementation score (QIS), we showed that accredited laboratories (average score 92) comply better than certified laboratories (average score 69, Pquality indicators. We conclude that quality practices vary widely in European genetic testing laboratories. This leads to a potentially dangerous situation in which the quality of genetic testing is not consistently assured. PMID:22739339
Finkelman, Matthew; Kim, Wonsuk; Roussos, Louis A.
Much recent psychometric literature has focused on cognitive diagnosis models (CDMs), a promising class of instruments used to measure the strengths and weaknesses of examinees. This article introduces a genetic algorithm to perform automated test assembly alongside CDMs. The algorithm is flexible in that it can be applied whether the goal is to…
Lammens, C.R.M.; Aaronson, N.K.; Wagner, A.; Sijmons, R.H.; Ausems, M.G.E.M.; Vriends, A.H.J.T.; Ruijs, M.W.G.; van Os, T.A.M.; Spruijt, L.; Gómez García, E.B.; Kluijt, I.; Nagtegaal, T.; Verhoef, S.; Bleiker, E.M.A.
Purpose Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome, characterized by a high risk of developing cancer at various sites and ages. To date, limited clinical benefits of genetic testing for LFS have been demonstrated, and there are concerns about the potential adverse psychosocial
...: Written comments should be sent by email to [email protected] . Comments may also be submitted by postal... subject line of the email or postal mailing as ``Genetic Testing Study.'' Because written comments and... wishing to present oral testimony at either hearing must request an opportunity to do so in writing no...
Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa; Guerrini, Renzo; Hämäläinen, Eija; Hartmann, Corinna; Hernandez-Hernandez, Laura; Hjalgrim, Helle; Koeleman, Bobby P C; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R; Leu, Costin; Marini, Carla; McMahon, Jacinta M; Mei, Davide; Møller, Rikke S; Muhle, Hiltrud; Myers, Candace T; Nava, Caroline; Serratosa, Jose M; Sisodiya, Sanjay M; Stephani, Ulrich; Striano, Pasquale; van Kempen, Marjan J A; Verbeek, Nienke E; Usluer, Sunay; Zara, Federico; Palotie, Aarno; Mefford, Heather C; Scheffer, Ingrid E; De Jonghe, Peter; Helbig, Ingo; Suls, Arvid
BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying
Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M
The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. © 2015 by American Society of Clinical Oncology.
Vassy, Jason L; Donelan, Karen; Hivert, Marie-France; Green, Robert C; Grant, Richard W
Genetic testing for chronic disease susceptibility may motivate young adults for preventive behavior change. This nationally representative survey gave 521 young adults hypothetical scenarios of receiving genetic susceptibility results for heart disease, type 2 diabetes, and stroke and asked their (1) interest in such testing, (2) anticipated likelihood of improving diet and physical activity with high- and low-risk test results, and (3) readiness to make behavior change. Responses were analyzed by presence of established disease-risk factors. Respondents with high phenotypic diabetes risk reported increased likelihood of improving their diet and physical activity in response to high-risk results compared with those with low diabetes risk (odds ratio (OR), 1.82 (1.03, 3.21) for diet and OR, 2.64 (1.24, 5.64) for physical activity). In contrast, poor baseline diet (OR, 0.51 (0.27, 0.99)) and poor physical activity (OR, 0.53 (0.29, 0.99)) were associated with decreased likelihood of improving diet. Knowledge of genetic susceptibility may motivate young adults with higher personal diabetes risk for improvement in diet and exercise, but poor baseline behaviors are associated with decreased intention to make these changes. To be effective, genetic risk testing in young adults may need to be coupled with other strategies to enable behavior change.
Kocken, P.L.; Theunissen, M.H.C.; Schönbeck, Y.; Henneman, L.; Janssens, A.C.J.W.; Detmar, S.B.
The objective of this paper is to assess parental beliefs and intentions about genetic testing for their children in a multi-ethnic population with the aim of acquiring information to guide interventions for obesity prevention and management. A cross-sectional survey was conducted in parents of
Kunadiya, Manisha; White, Diane; Dunstan, William A; Hardy, Giles E St J; Andjic, Vera; Burgess, Treena I
Phytophthora cinnamomi is one of the world's most invasive plant pathogens affecting ornamental plants, horticultural crops and natural ecosystems. Accurate diagnosis is very important to determine the presence or absence of this pathogen in diseased and asymptomatic plants. In previous studies, P. cinnamomi species-specific primers were designed and tested using various polymerase chain reaction (PCR) techniques including conventional PCR, nested PCR and quantitative real-time PCR. In all cases, the primers were stated to be highly specific and sensitive to P. cinnamomi. However, few of these studies tested their primers against closely related Phytophthora species (Phytophthora clade 7). In this study, we tested these purported P. cinnamomi-specific primer sets against 11 other species from clade 7 and determined their specificity; of the eight tested primer sets only three were specific to P. cinnamomi. This study demonstrated the importance of testing primers against closely related species within the same clade, and not just other species within the same genus. The findings of this study are relevant to all species-specific microbial diagnosis. © FEMS 2017. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Burton, Sarah K; Withrow, Kara; Arnos, Kathleen S; Kalfoglou, Andrea L; Pandya, Arti
Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening.
Jenkins, Nicholas; Lawton, Julia; Douglas, Margaret; Hallowell, Nina
In this article we explore the concept of inter-embodiment and its potential for advancing sociological research into illness biography and genetic identity. Inter-embodiment theory views embodied knowledge as produced through relations between bodies, as opposed to originating from within the body or as the product of relations between disembodied selves. Drawing on a qualitative study in which we interviewed 38 individuals about their experiences of discovering they had high cholesterol and undergoing genetic testing for familial hypercholesterolaemia (FH), we discuss how their narratives may be understood from an inter-embodiment perspective. The participants frequently talked at length about their family histories of high cholesterol and cardiovascular disease. Through these accounts, we develop the concept of the family corpus in order to highlight the role body networks play in shaping lay constructions of genetic identity and a familial disease biography. The notion of a family corpus, we argue, is useful in understanding why genetic testing for FH was experienced as either biographical re-enforcement or as biographical disruption. We conclude by discussing the implications of our findings for future sociological research into illness biography and genetic identity. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.
A-nongwech, Nattapong; Pruekpramool, Chaninan
The purpose of this research was to develop a Metacognition test in a Genetics Laboratory for undergraduate students. The participants were 30 undergraduate students of a Rajabhat university in Rattanakosin group in the second semester of the 2016 academic year using purposive sampling. The research instrument consisted of 1) Metacognition test and 2) a Metacognition test evaluation form for experts focused on three main points which were an accurate evaluation form of content, a consistency between Metacognition experiences and questions and the appropriateness of the test. The quality of the test was analyzed by using the Index of Consistency (IOC), discrimination and reliability. The results of developing Metacognition test were summarized as 1) The result of developing Metacognition test in a Genetics Laboratory for undergraduate students found that the Metacognition test contained 56 items of open - ended questions. The test composed of 1) four scientific situations, 2) fourteen items of open - ended questions in each scientific situation for evaluating components of Metacognition. The components of Metacognition consisted of Metacognitive knowledge, which were divided into person knowledge, task knowledge and strategy knowledge and Metacognitive experience, which were divided into planning, monitoring and evaluating, and 3) fourteen items of scoring criteria divided into four scales. 2) The results of the item analysis of Metacognition in Genetics Laboratory for undergraduate students found that Index of Consistency between Metacognitive experiences and questions were in the range between 0.75 - 1.00. An accuracy of content equaled 1.00. The appropriateness of the test equaled 1.00 in all situations and items. The discrimination of the test was in the range between 0.00 - 0.73. Furthermore, the reliability of the test equaled 0.97.
Tsai, Ginger J; Cameron, Carrie A; Czerwinski, Jennifer L; Mendez-Figueroa, Hector; Peterson, Susan K; Noblin, Sarah Jane
Recognizing the heterogeneity of the Asian population with regards to acculturation, education, health awareness, and cultural values is vital for tailoring culturally sensitive and appropriate care. Prior studies show that cultural values influence perceptions of genetics within Asian populations. The reputation of the family unit factors into decisions such as pregnancy termination and disclosure of family medical history, and the nondirective model of American genetic counseling may conflict with the historical Asian model of paternalistic health care. Previous studies also provide conflicting evidence regarding correlations between education, acculturation, age, and awareness and perceptions of genetic testing. The aims of this study were to describe attitudes towards prenatal genetics among Southeast and East Asian women living in the United States for varying amounts of time and to explore sociocultural factors influencing those attitudes. Twenty-three Asian women who were members of Asian cultural organizations in the United States were interviewed via telephone about their attitudes towards prenatal genetic counseling, prenatal genetic testing, and termination of pregnancy. Responses were transcribed and coded for common themes using a thematic analysis approach. Four major themes emerged. In general, participants: (1) had diverse expectations for genetic counselors; (2) tended to weigh risks and benefits with regards to genetic testing decisions; (3) had mixed views on termination for lethal and non-lethal genetic conditions; and (4) identified cultural factors which influenced testing and termination such as lack of available resources, societal shame and stigma, and family pressure. These findings may allow prenatal genetic counselors to gain a richer, more nuanced understanding of their Asian patients and to offer culturally tailored prenatal genetic counseling.
Rysgaard Carolyn D
Full Text Available Abstract Background Hepatitis B virus (HBV is a common cause of viral hepatitis with significant health complications including cirrhosis and hepatocellular carcinoma. Assays for hepatitis B surface antigen (HBsAg are the most frequently used tests to detect HBV infection. Vaccination for HBV can produce transiently detectable levels of HBsAg in patients. However, the time course and duration of this effect is unclear. The objective of this retrospective study was to clarify the frequency and duration of transient HBsAg positivity following vaccination against HBV. Methods The electronic medical record at an academic tertiary care medical center was searched to identify all orders for HBsAg within a 17 month time period. Detailed chart review was performed to identify all patients who were administered HBV vaccine within 180 days prior to HBsAg testing and also to ascertain likely cause of weakly positive (grayzone results. Results During the 17 month study period, 11,719 HBsAg tests were ordered on 9,930 patients. There were 34 tests performed on 34 patients who received HBV vaccine 14 days or less prior to HBsAg testing. Of these 34 patients, 11 had grayzone results for HBsAg that could be attributed to recent vaccination. Ten of the 11 patients were renal dialysis patients who were receiving HBsAg testing as part of routine and ongoing monitoring. Beyond 14 days, there were no reactive or grayzone HBsAg tests that could be attributed to recent HBV vaccination. HBsAg results reached a peak COI two to three days following vaccination before decaying. Further analysis of all the grayzone results within the 17 month study period (43 results out of 11,719 tests revealed that only 4 of 43 were the result of true HBV infection as verified by confirmatory testing. Conclusions Our study confirms that transient HBsAg positivity can occur in patients following HBV vaccination. The results suggest this positivity is unlikely to persist beyond 14 days
Tyrrell, J M; Wootton, M; Toleman, M A; Howe, R A; Woodward, M; Walsh, T R
CTX-M genes are the most prevalent ESBL globally, infiltrating nosocomial, community and environmental settings. Wild and domesticated animals may act as effective vectors for the dissemination of CTX-producing Enterobacteriaceae. This study aimed to contextualise blaCTX-M-14-positive, cephalosporin-resistant Enterobacteriaceae human infections and compared resistance and pathogenicity markers with veterinary isolates. Epidemiologically related human (n=18) and veterinary (n=4) blaCTX-M-14-positive E. coli were fully characterised. All were typed by XbaI pulsed field gel electrophoresis and ST. Chromosomal/plasmidic locations of blaCTX-M-14 were deduced by S1-nuclease digestion, and association with ISEcp1 was investigated by sequencing. Conjugation experiments assessed transmissibility of plasmids carrying blaCTX-M-14. Presence of virulence determinants was screened by PCR assay and pathogenicity potential was determined by in vitro Galleria mellonella infection models. 84% of clinical E. coli originated from community patients. blaCTX-M-14 was found ubiquitously downstream of ISEcp1 upon conjugative plasmids (25-150 kb). blaCTX-M-14 was also found upon the chromosome of eight E. coli isolates. CTX-M-14-producing E. coli were found at multiple hospital sites. Clonal commonality between patient, hospitals and livestock microbial populations was found. In vivo model survival rates from clinical isolates (30%) and veterinary isolates (0%) were significantly different (pE. coli involving community patients and farm livestock. blaCTX-M-14 positive human clinical isolates carry a lower intrinsic pathogenic potential than veterinary E. coli highlighting the need for greater veterinary practices in preventing dissemination of MDR E. coli among livestock. Copyright © 2016. Published by Elsevier B.V.
Tang, Haiming; Thomas, Paul D
PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. Here, we describe the PSEP tool, and assess its performance on standard benchmarks for distinguishing disease-associated from neutral variation in humans. On these benchmarks, PSEP outperforms not only previous tools that utilize evolutionary conservation, but also several highly used tools that include multiple other sources of information as well. For predicting pathogenic human variants, the trace back of course starts with a human 'reference' protein sequence, but the PSEP tool can also be applied to predicting deleterious or pathogenic variants in reference proteins from any of the ∼100 other species in the PANTHER database. PANTHER-PSEP is freely available on the web at http://pantherdb.org/tools/csnpScoreForm.jsp Users can also download the command-line based tool at ftp://ftp.pantherdb.org/cSNP_analysis/PSEP/ CONTACT: email@example.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Grant, Richard W; Meigs, James B; Florez, Jose C; Park, Elyse R; Green, Robert C; Waxler, Jessica L; Delahanty, Linda M; O'Brien, Kelsey E
The efficacy of diabetes genetic risk testing to motivate behavior change for diabetes prevention is currently unknown. This paper presents key issues in the design and implementation of one of the first randomized trials (The Genetic Counseling/Lifestyle Change (GC/LC) Study for Diabetes Prevention) to test whether knowledge of diabetes genetic risk can motivate patients to adopt healthier behaviors. Because individuals may react differently to receiving 'higher' vs 'lower' genetic risk results, we designed a 3-arm parallel group study to separately test the hypotheses that: (1) patients receiving 'higher' diabetes genetic risk results will increase healthy behaviors compared to untested controls, and (2) patients receiving 'lower' diabetes genetic risk results will decrease healthy behaviors compared to untested controls. In this paper we describe several challenges to implementing this study, including: (1) the application of a novel diabetes risk score derived from genetic epidemiology studies to a clinical population, (2) the use of the principle of Mendelian randomization to efficiently exclude 'average' diabetes genetic risk patients from the intervention, and (3) the development of a diabetes genetic risk counseling intervention that maintained the ethical need to motivate behavior change in both 'higher' and 'lower' diabetes genetic risk result recipients. Diabetes genetic risk scores were developed by aggregating the results of 36 diabetes-associated single nucleotide polymorphisms. Relative risk for type 2 diabetes was calculated using Framingham Offspring Study outcomes, grouped by quartiles into 'higher', 'average' (middle two quartiles) and 'lower' genetic risk. From these relative risks, revised absolute risks were estimated using the overall absolute risk for the study group. For study efficiency, we excluded all patients receiving 'average' diabetes risk results from the subsequent intervention. This post-randomization allocation strategy was
Full Text Available In order to observe the microbiological status of CMT positive samples, 734 apparently health mammary quarters from buffalo cows were submitted to physical evaluation, strip cup test and CMT. After milk samples inoculation in 10% ovine blood agar base media and in MacConkey agar and incubation under aerobic condition for 72 hours at 37oC, identification was proceeded. According to CMT, 227 quarters (30,93% were positive, among them 73 (32,16% presented 1+ reaction, 53 (23,35% were 2+ and 101 (44,49% were 3+. Microbiological exams of such samples were positive in 147 (64,76% out of 227 CMT positive samples and among the remaining 72 (31,72% were negative and 8 (3,52 were contaminated. In the 147 microbiological positive samples 204 bacteria were found in pure or associated growth and the most frequent agents were: Corynebacterium sp (59,25%; Staphylococcus sp (17,65% among which 86,11% were coagulase negative and 13,89% were coagulase positive; and Micrococcus sp (6,37%. The results revealed that, excluding the eight contaminated samples, 147 (67,12% quarters out of 219 CMT positive could be considered as bacteria-carrier and that even in a smaller percentage false-positive results can cause problems in a sanitary program for mastitis control in dairy buffalo cows.
Siol, V; Lange, A; Prenzler, A; Neubauer, S; Frank, M
Objectives: The present study aims to investigate the interest of young adults in predictive oncological genetic testing and their willingness to pay for such a test. Furthermore, major determinants of the 2 variables of interest were identified. Methods: 348 students of economics from the Leibniz University of Hanover were queried in July 2013 using an extensive questionnaire. Among other things, the participants were asked if they are interested in information about the probability to develop cancer in the future and their willingness to pay for such information. Data were analysed using descriptive statistics and ordinal probit regressions. Additionally marginal effects were calculated. Results: About 50% of the students were interested in predictive oncological genetic testing and were willing to pay for the test. Moreover, the participants who were willing to pay for the test partly attach high monetary values to the information that could so be obtained. The study shows that the interest of the students and their willingness to pay were primarily influenced by individual attitudes and perceptions. Conclusions: The study proves that young adults were interested in predictive genetic testing and appreciate information about their probability of develop cancer someday. © Georg Thieme Verlag KG Stuttgart · New York.
Joseph, Meera; Rab, Faiza; Panabaker, Karen; Nisker, Jeff
Family physicians in Canada as reported in several studies do not recognize the importance of family history in relation to breast/ovarian cancer and thus Canadian women with strong family histories continue to develop early-onset breast cancer without the knowledge of or ability to make choices regarding increased surveillance or preventative strategies. This study explored the feelings of women who learned about their hereditary risk only after their diagnosis younger than 52 years and who eventually tested positive for a BRCA gene mutation. Thirty-four such women were mailed an invitation to participate in this research including a letter of information, consent form, and discussion prompts for their written narrative response. Rigorous mixed method analyses were performed using Charmaz-based qualitative analyses as well as quantitative analyses. Thirteen women (38.2%) responded with narratives for qualitative analysis from which 4 themes were coconstructed as follows: I, types of emotions; II, emotional response; III, coping with emotions; and IV, advice to women at similar risk. Women felt they should have learned about their hereditary risk from their family physician and through public education before their diagnosis. Although not experienced at the time of diagnosis, anger, frustration, and regret were experienced after receiving their BRCA results. These emotions arose from our research participants' lack of opportunity for prior genetic counseling and testing opportunity for genetic counseling and testing. With increased public and physician education, it is hoped that women with significant family histories of breast/ovarian cancer will be identified before diagnosis and given options regarding cancer surveillance and risk reduction strategies.