What?s Happening to Your DNA Data?: Genetic Testing Services Abound, but Consumers Opting to Use Them Should Be Aware of the Pitfalls.

PubMed

Grifantini, Kristina

2017-01-01

Over the last decade, technology advances in the field of genetics have led to cheaper and more accurate testing. Public interest in personal genetics has grown thanks to media coverage and high-profile stories, such as actress Angelina Jolie's decision to undergo a double mastectomy as a preventative measure against breast cancer when she learned she carries the BRCA1 mutation (relating to breast cancer type 1 susceptibility).

High-risk individuals' perceptions of reproductive genetic testing for CDH1 mutations.

PubMed

Hallowell, Nina; Badger, Shirlene; Richardson, Sue; Caldas, Carlos; Hardwick, Richard H; Fitzgerald, Rebecca C; Lawton, Julia

2017-10-01

Reproductive genetic testing- PreNatal Diagnosis (PND) and Preimplantation Genetic Diagnosis (PGD)-for CDH1 mutations associated with Hereditary Diffuse Gastric Cancer (HDGC)is available in the UK. This qualitative interview study examined high-risk individuals' (n = 35) views of CDH1 reproductive genetic testing. Interviewees generally regarded reproductive genetic testing as an acceptable form of HDGC risk management. However, some were concerned that their genetic risks required them to plan reproduction and anticipated difficulties communicating this to reproductive partners. Individuals had a preference for PGD over PND because it avoided the need for a termination of pregnancy. However, those who had not yet had children expressed concerns about having to undergo IVF procedures and worries about their effectiveness and the need for embryo selection in PGD. It is suggested that high-risk individuals are provided with access to reproductive genetic counselling.

Differences in attitudes toward genetic testing among the public, patients, and health-care professionals in Korea.

PubMed

Eum, Heesang; Lee, Mangyeong; Yoon, Junghee; Cho, Juhee; Lee, Eun Sook; Choi, Kui Son; Lee, Sangwon; Jung, So-Youn; Lim, Myong Cheol; Kong, Sun-Young; Chang, Yoon Jung

2018-06-18

With further advances in medical genetics, genetic tests to determine predisposition to disease are becoming viable for a growing number of diseases. Accordingly, it has also become important to identify various viewpoints on genetic testing. The aims of this study were to examine awareness of and attitudes toward genetic testing among the general public (public), cancer patients (patients), and health-care professionals (clinicians and researchers) in Korea. The present survey was conducted from November 2016 to February 2017. The public and patients were surveyed via face-to-face interviews conducted by trained interviewers. Health-care professionals were surveyed via self-administered questionnaires. In total, 1500 individuals from the general public, 1500 cancer patients, 113 clinicians, and 413 researchers were surveyed. Most respondents from the public and patients had previously heard about genetic testing (public, 89.4%; patients, 92.7%, p < 0.01). Differences in attitudes toward genetic testing among the public, patients, and professionals were noted, although most respondents in the present study were aware of genetic testing. Most of the cancer patients tended to overestimate the potential benefit of genetic testing, whereas clinicians expressed concerns for genetic testing. Providing correct information to people who are scheduled to undergo or order genetic testing could help in making an informed decision thereon.

Psychosocial aspects of genetic testing.

PubMed

Cameron, Linda D; Muller, Cecile

2009-03-01

With rapid advances in genetic testing for disease susceptibility, behavioral medicine faces significant challenges in identifying likely patterns of use, how individuals interpret test results, and psychosocial and health impacts of testing. We review recent research on these psychosocial aspects of genetic testing for disease risk. Individuals exhibit limited sensitivity in their perceptions of genetic risk information, and mental representations of disease risk appear to guide testing perceptions and behavioral responses. Motivations to undergo testing are complex, and efforts to develop decision aids are underway. Findings on psychological and behavioral impacts of genetic testing vary markedly, with some evidence of minimal or positive effects and other evidence indicating negative consequences that may be undetectable using common measures of general well being. Recent evidence suggests that genetic risk information can motivate health behavior change. Research demonstrates wide-ranging influences of testing on family dynamics, and use of genetic testing with children is of increasing concern. More research is needed to determine how to structure health communications and counseling to motivate informed use, promote positive responses, and optimize behavior change. Given the ramifications of genetic information for families, personalized genomics will demand a shift toward a family-based healthcare model.

Attitudes of Patients With Cancer About Personalized Medicine and Somatic Genetic Testing

PubMed Central

Gray, Stacy W.; Hicks-Courant, Katherine; Lathan, Christopher S.; Garraway, Levi; Park, Elyse R.; Weeks, Jane C.

2012-01-01

Purpose: Dramatic advances in genomic technology stand to revolutionize cancer care; however, little is known about patients' understanding and acceptance of personalized medicine and widespread genetic testing (GT). Patients and Methods: We conducted a formative, semi-structured interview study with a random sample of patients with lung, colorectal, and breast cancers to assess awareness of personalized medicine and GT and attitudes about somatic GT. Willingness to undergo GT was elicited through hypothetic scenarios. Results: Sixty-nine patients participated; 71% were women; 42% were black; median age was 59 years; and 42% had an education level ≥ college. We found that a majority of patients either were not aware of the term “personalized medicine” or defined it in unexpected ways. Although many patients identified relevant benefits of somatic testing (eg, informs treatment), many patients also expressed significant concerns (ie, psychological harm and discrimination). A majority of patients expressed a willingness to undergo somatic (predictive, 96%, prognostic, 93%) and germline (cancer risk without incidental information, 87%; cancer risk with incidental information, 81%; pharmacogenetic, 91%) testing; however, far fewer patients expressed a willingness to undergo full genome sequencing (62%). Reluctance was attributed to concerns over incidental findings, information overload, and the lack of a clear benefit. Conclusion: Many patients relayed misunderstandings about somatic testing and a reluctance to undergo full sequencing; oncologists must carefully consider how they present testing to patients so that concerns over discrimination and psychological harm do not hinder test uptake. More work is needed to identify effective ways to communicate complex genomic concepts to patients and research participants. PMID:23598841

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project.

PubMed

Cutting, Elizabeth M; Overby, Casey L; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R; Beitelshees, Amber L

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease.

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project

PubMed Central

Cutting, Elizabeth M.; Overby, Casey L.; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R.; Beitelshees, Amber L.

2015-01-01

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease. PMID:26958179

Attitudes toward direct-to-consumer advertisements and online genetic testing among high-risk women participating in a hereditary cancer clinic.

PubMed

Perez, Giselle K; Cruess, Dean G; Cruess, Stacy; Brewer, Molly; Stroop, Jennifer; Schwartz, Robin; Greenstein, Robert

2011-07-01

Genetic testing for the breast cancer genes 1/2 (BRCA 1/2) has helped women determine their risk of developing breast and ovarian cancer. As interest in genetic testing has grown, companies have created strategies to disseminate information about testing, including direct-to-consumer advertising (DTCA) and online genetic testing. This study examined attitudes toward DTCA and online testing for BRCA among 84 women at a high-risk clinic as well as additional factors that may be associated with these attitudes, such as personal and familial cancer history, cancer worry and risk perception, and history with genetic testing/counseling. Results showed that the majority of the women held favorable attitudes toward DTCA for BRCA testing but did not support online testing. Factors such as familial ovarian cancer, cancer worry, and satisfaction with genetic counseling/testing were associated with positive attitudes toward DTCA, whereas personal breast cancer history was related to negative attitudes. The findings suggest that women may view DTCA as informational but rely on physicians for help in their decision to undergo testing, and also suggest that cancer history may affect women's acceptance of DTCA and genetic testing.

Modern Advances in Genetic Testing: Ethical Challenges and Training Implications for Current and Future Psychologists

PubMed Central

Richmond-Rakerd, Leah S.

2014-01-01

The ethical implications for psychological practice of genetic testing are largely unexplored. Predictive testing can have a significant impact on health and well-being, and increasing numbers of individuals with knowledge of their risk for various disorders are likely to present for psychotherapy. In addition, more people will struggle with the decision of whether to obtain information regarding their genetic material. Psychologists will need to have the appropriate knowledge and clinical skills to effectively counsel this population. This article highlights the relevant ethical issues surrounding psychological treatment of individuals pursuing or considering undergoing genetic testing. These issues are extended to psychologists working in research, education, and policy domains. Recommendations for graduate training programs to facilitate current and future practitioner competence are also discussed. PMID:24707160

Genetic Testing and Post-Testing Decision Making among BRCA-Positive Mutation Women: A Psychosocial Approach.

PubMed

Hesse-Biber, Sharlene; An, Chen

2016-10-01

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.

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders.

PubMed

Fonda Allen, Jill; Stoll, Katie; Bernhardt, Barbara A

2016-02-01

Genetic carrier screening, prenatal screening for aneuploidy, and prenatal diagnostic testing have expanded dramatically over the past 2 decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients' values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. Copyright © 2016 Elsevier Inc. All rights reserved.

A Qualitative Study of Anticipated Decision Making around Type 2 Diabetes Genetic Testing: The Role of Scientifically Concordant and Discordant Expectations

PubMed Central

Carmichael, Alicia G.; Hulswit, Bailey B.; Moe, Emily J.; Jayaratne, Toby Epstein; Yashar, Beverly M.

2016-01-01

Type 2 diabetes mellitus (T2DM) genetic testing is undergoing clinical trials to measure the efficacy of genetic counseling for behavior-based risk reduction. The expectations patients bring to the testing process may play an important role in individual outcomes. We conducted a qualitative exploration of anticipated decision-making and expectations around T2DM genetic testing. Semi-structured interviews were completed with Mexican Americans (n = 34), non-Hispanic Black Americans (n = 39), and non-Hispanic White Americans (n = 39) at risk for T2DM. Transcripts were analyzed for themes. Most participants would accept T2DM genetic testing in order to motivate risk-reducing behaviors or apprise family members of their risk. Participants who would decline testing wished to avoid emotional distress or believed the test would not reveal new risk information. Non-Hispanic Whites and those with college education declined genetic testing more often than other groups. Those without college education were more likely to have testing expectations that were discordant with current science, such as conflating genetic testing with common ‘blood tests.’ Understanding expectations and decision-making factors around T2DM genetic testing will better prepare healthcare professionals to counsel their patients. This may lead to a higher efficacy of T2DM genetic testing and counseling. PMID:27465809

A Qualitative Study of Anticipated Decision Making around Type 2 Diabetes Genetic Testing: the Role of Scientifically Concordant and Discordant Expectations.

PubMed

Carmichael, Alicia G; Hulswit, Bailey B; Moe, Emily J; Jayaratne, Toby Epstein; Yashar, Beverly M

2017-06-01

Type 2 diabetes mellitus (T2DM) genetic testing is undergoing clinical trials to measure the efficacy of genetic counseling for behavior-based risk reduction. The expectations patients bring to the testing process may play an important role in individual outcomes. We conducted a qualitative exploration of anticipated decision-making and expectations around T2DM genetic testing. Semi-structured interviews were completed with Mexican Americans (n = 34), non-Hispanic Black Americans (n = 39), and non-Hispanic White Americans (n = 39) at risk for T2DM. Transcripts were analyzed for themes. Most participants would accept T2DM genetic testing in order to motivate risk-reducing behaviors or apprise family members of their risk. Participants who would decline testing wished to avoid emotional distress or believed the test would not reveal new risk information. Non-Hispanic Whites and those with college education declined genetic testing more often than other groups. Those without college education were more likely to have testing expectations that were discordant with current science, such as conflating genetic testing with common 'blood tests.' Understanding expectations and decision-making factors around T2DM genetic testing will better prepare healthcare professionals to counsel their patients. This may lead to a higher efficacy of T2DM genetic testing and counseling.

Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media.

PubMed

Shamonki, Mousa I; Jin, Helen; Haimowitz, Zachary; Liu, Lian

2016-11-01

To assess whether preimplantation genetic screening (PGS) is possible by testing for free embryonic DNA in spent IVF media from embryos undergoing trophectoderm biopsy. Prospective cohort analysis. Academic fertility center. Seven patients undergoing IVF and 57 embryos undergoing trophectoderm biopsy for PGS. On day 3 of development, each embryo was placed in a separate media droplet. All biopsied embryos received a PGS result by array comparative genomic hybridization. Preimplantation genetic screening was performed on amplified DNA extracted from media and results were compared with PGS results for the corresponding biopsy. [1] Presence of DNA in spent IVF culture media. [2] Correlation between genetic screening result from spent media and corresponding biopsy. Fifty-five samples had detectable DNA ranging from 2-642 ng/μL after a 2-hour amplification. Six samples with the highest DNA levels underwent PGS, rendering one result with a derivative log ratio SD (DLRSD) of <0.85 (a quality control metric of oligonucleotide array comparative genomic hybridization). The fluid sample and trophectoderm results were identical demonstrating (45XY, -13). Three samples were reamplified 1 hour later and tested showing improving DLRSD. One of the three samples with a DLRSD of 0.85 demonstrated (46XY), consistent with the biopsy. Overnight DNA amplification showed DNA in all samples. We demonstrate two novel findings: the presence of free embryonic DNA in spent media and a result that is consistent with trophectoderm biopsy. Improvements in DNA collection, amplification, and testing may allow for PGS without biopsy in the future. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Development and validation of a brief screening instrument for psychosocial risk associated with genetic testing: a pan-Canadian cohort study

PubMed Central

Esplen, Mary Jane; Cappelli, Mario; Wong, Jiahui; Bottorff, Joan L; Hunter, Jon; Carroll, June; Dorval, Michel; Wilson, Brenda; Allanson, Judith; Semotiuk, Kara; Aronson, Melyssa; Bordeleau, Louise; Charlemagne, Nicole; Meschino, Wendy

2013-01-01

Objectives To develop a brief, reliable and valid instrument to screen psychosocial risk among those who are undergoing genetic testing for Adult-Onset Hereditary Disease (AOHD). Design A prospective two-phase cohort study. Setting 5 genetic testing centres for AOHD, such as cancer, Huntington's disease or haemochromatosis, in ambulatory clinics of tertiary hospitals across Canada. Participants 141 individuals undergoing genetic testing were approached and consented to the instrument development phase of the study (Phase I). The Genetic Psychosocial Risk Instrument (GPRI) developed in Phase I was tested in Phase II for item refinement and validation. A separate cohort of 722 individuals consented to the study, 712 completed the baseline package and 463 completed all follow-up assessments. Most participants were female, at the mid-life stage. Individuals in advanced stages of the illness or with cognitive impairment or a language barrier were excluded. Interventions Phase I: GPRI items were generated from (1) a review of the literature, (2) input from genetic counsellors and (3) phase I participants. Phase II: further item refinement and validation were conducted with a second cohort of participants who completed the GPRI at baseline and were followed for psychological distress 1-month postgenetic testing results. Primary and secondary outcome measures GPRI, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Brief Symptom Inventory (BSI) and Impact of Event Scale (IES). Results The final 20-item GPRI had a high reliability—Cronbach's α at 0.81. The construct validity was supported by high correlations between GPRI and BSI and IES. The predictive value was demonstrated by a receiver operating characteristic curve of 0.78 plotting GPRI against follow-up assessments using HAM-D and HAM-A. Conclusions With a cut-off score of 50, GPRI identified 84% of participants who displayed distress postgenetic testing results, supporting its potential usefulness in a clinical setting. PMID:23485718

A Value-Based Medicine cost-utility analysis of genetic testing for neovascular macular degeneration.

PubMed

Brown, Gary C; Brown, Melissa M; Lieske, Heidi B; Lieske, Philip A; Brown, Kathryn S

2015-01-01

There is a dearth of patient, preference-based cost-effectiveness analyses evaluating genetic testing for neovascular age-related macular degeneration (NVAMD). A Value-Based Medicine, 12-year, combined-eye model, cost-utility analysis evaluated genetic testing of Category 3 AMD patients at age 65 for progression to NVAMD. The benefit of genetic testing was predicated upon the fact that early-treatment ranibizumab therapy (baseline vision 20/40-20/80) for NVAMD confers greater patient value than late-treatment (baseline vision ≤20/160). Published genetic data and MARINA Study ranibizumab therapy data were utilized in the analysis. Patient value (quality-of-life gain) and financial value (2012 US real dollar) outcomes were discounted at 3 % annually. Genetic testing-enabled, early-treatment ranibizumab therapy per patient conferred mean 20/40 -1 vision, a 0.845 QALY gain and 14.1 % quality-of-life gain over sham therapy. Late-treatment ranibizumab therapy conferred mean 20/160 +2 vision, a 0.250 QALY gain and 4.2 % quality-of-life gain over sham therapy. The gain from early-treatment over late-treatment was 0.595 QALY (10.0 % quality-of-life gain). The per-patient cost for genetic testing/closer monitoring was $2205 per screened person, $2.082 billion for the 944,000 estimated new Category 3 AMD patients annually. Genetic testing/monitoring costs per early-treatment patient totaled $66,180. Costs per early-treatment patient included: genetic testing costs: $66,180 + direct non-ophthalmic medical costs: -$40,914 + caregiver costs: -$172,443 + employment costs: -$14,098 = a net societal cost saving of $160,582 per early treatment patient. When genetic screening facilitated an incremental 12,965 (8.0 %) of the 161,754, new annual NVAMD patients aged ≥65 in the US to undergo early-treatment ranibizumab therapy, each additional patient treated accrued an overall, net financial gain for society of $160,582. Genetic screening was cost-effective, using World Health Organization criteria, when it enabled an incremental 4.1 % (6634) of 161,754 annual NVAMD patients ≥65 years to receive early-treatment ranibizumab therapy. Genetic screening-enabled, early-treatment ranibizumab therapy for NVAMD is cost-effective if it enables an incremental 4.1 % of the annual US cohort of new-onset NVAMD patients ≥65 to undergo early-treatment with ranibizumab.

Uncertainty in BRCA1 cancer susceptibility testing.

PubMed

Baty, Bonnie J; Dudley, William N; Musters, Adrian; Kinney, Anita Y

2006-11-15

This study investigated uncertainty in individuals undergoing genetic counseling/testing for breast/ovarian cancer susceptibility. Sixty-three individuals from a single kindred with a known BRCA1 mutation rated uncertainty about 12 items on a five-point Likert scale before and 1 month after genetic counseling/testing. Factor analysis identified a five-item total uncertainty scale that was sensitive to changes before and after testing. The items in the scale were related to uncertainty about obtaining health care, positive changes after testing, and coping well with results. The majority of participants (76%) rated reducing uncertainty as an important reason for genetic testing. The importance of reducing uncertainty was stable across time and unrelated to anxiety or demographics. Yet, at baseline, total uncertainty was low and decreased after genetic counseling/testing (P = 0.004). Analysis of individual items showed that after genetic counseling/testing, there was less uncertainty about the participant detecting cancer early (P = 0.005) and coping well with their result (P < 0.001). Our findings support the importance to clients of genetic counseling/testing as a means of reducing uncertainty. Testing may help clients to reduce the uncertainty about items they can control, and it may be important to differentiate the sources of uncertainty that are more or less controllable. Genetic counselors can help clients by providing anticipatory guidance about the role of uncertainty in genetic testing. (c) 2006 Wiley-Liss, Inc.

You want to do what? My mother's choice to have direct-to-consumer genetic testing.

PubMed

Varga, Elizabeth A

2012-06-01

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.

Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts.

PubMed

Geelen, Els; Horstman, Klasien; Marcelis, Carlo L M; Doevendans, Pieter A; Van Hoyweghen, Ine

2012-10-01

Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination.

Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts

PubMed Central

Geelen, Els; Horstman, Klasien; Marcelis, Carlo LM; Doevendans, Pieter A; Van Hoyweghen, Ine

2012-01-01

Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination. PMID:22453290

Personal genome testing in medical education: student experiences with genotyping in the classroom

PubMed Central

2013-01-01

Background Direct-to-consumer (DTC) personal genotyping services are beginning to be adopted by educational institutions as pedagogical tools for learning about human genetics. However, there is little known about student reactions to such testing. This study investigated student experiences and attitudes towards DTC personal genome testing. Methods Individual interviews were conducted with students who chose to undergo personal genotyping in the context of an elective genetics course. Ten medical and graduate students were interviewed before genotyping occurred, and at 2 weeks and 6 months after receiving their genotype results. Qualitative analysis of interview transcripts assessed the expectations and experiences of students who underwent personal genotyping, how they interpreted and applied their results; how the testing affected the quality of their learning during the course, and what were their perceived needs for support. Results Students stated that personal genotyping enhanced their engagement with the course content. Although students expressed skepticism over the clinical utility of some test results, they expressed significant enthusiasm immediately after receiving their personal genetic analysis, and were particularly interested in results such as drug response and carrier testing. However, few reported making behavioral changes or following up on specific results through a healthcare provider. Students did not report utilizing genetic counseling, despite feeling strongly that the 'general public' would need these services. In follow-up interviews, students exhibited poor recall on details of the consent and biobanking agreements, but expressed little regret over their decision to undergo genotyping. Students reported mining their raw genetic data, and conveyed a need for further consultation support in their exploration of genetic variants. Conclusions Personal genotyping may improve students' self-reported motivation and engagement with course material. However, consultative support that is different from traditional genetic counseling will be necessary to support students. Before incorporating personal genotyping into coursework, institutions should lead multi-disciplinary discussion to anticipate issues and incorporate teaching mechanisms that engage the ethical, legal, and social implications of personal genotyping, including addressing those found in this study, to go beyond what is offered by commercial providers. PMID:23510111

Personal genome testing in medical education: student experiences with genotyping in the classroom.

PubMed

Vernez, Simone Lucia; Salari, Keyan; Ormond, Kelly E; Lee, Sandra Soo-Jin

2013-01-01

Direct-to-consumer (DTC) personal genotyping services are beginning to be adopted by educational institutions as pedagogical tools for learning about human genetics. However, there is little known about student reactions to such testing. This study investigated student experiences and attitudes towards DTC personal genome testing. Individual interviews were conducted with students who chose to undergo personal genotyping in the context of an elective genetics course. Ten medical and graduate students were interviewed before genotyping occurred, and at 2 weeks and 6 months after receiving their genotype results. Qualitative analysis of interview transcripts assessed the expectations and experiences of students who underwent personal genotyping, how they interpreted and applied their results; how the testing affected the quality of their learning during the course, and what were their perceived needs for support. Students stated that personal genotyping enhanced their engagement with the course content. Although students expressed skepticism over the clinical utility of some test results, they expressed significant enthusiasm immediately after receiving their personal genetic analysis, and were particularly interested in results such as drug response and carrier testing. However, few reported making behavioral changes or following up on specific results through a healthcare provider. Students did not report utilizing genetic counseling, despite feeling strongly that the 'general public' would need these services. In follow-up interviews, students exhibited poor recall on details of the consent and biobanking agreements, but expressed little regret over their decision to undergo genotyping. Students reported mining their raw genetic data, and conveyed a need for further consultation support in their exploration of genetic variants. Personal genotyping may improve students' self-reported motivation and engagement with course material. However, consultative support that is different from traditional genetic counseling will be necessary to support students. Before incorporating personal genotyping into coursework, institutions should lead multi-disciplinary discussion to anticipate issues and incorporate teaching mechanisms that engage the ethical, legal, and social implications of personal genotyping, including addressing those found in this study, to go beyond what is offered by commercial providers.

Changes in specialists' perspectives on cancer genetic testing, prophylactic surgery and insurance discrimination: then and now.

PubMed

Matloff, Ellen T; Bonadies, Danielle C; Moyer, Anne; Brierley, Karina L

2014-04-01

We surveyed cancer genetics specialists in 1998 to learn what they would do if at 50% risk to carry a BRCA or Lynch syndrome mutation. We chose to repeat our study 14 years later, to examine how perspectives have changed with the extensive data now available. In July 2012 we surveyed the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group via an internet based survey. We found statistically significant increases in the percentage of specialists who: would undergo BRCA testing (p = 0.0006), opt for prophylactic bilateral mastectomy (p =0.0001), opt for prophylactic removal of their uterus and ovaries for Lynch syndrome (p =0.0057 and P = 0.0090, respectively), and bill testing to insurance (p >0.0001). There were also statistically significant decreases in the percentage of participants who would have their colon removed for Lynch syndrome (p = 0.0002) and use an alias when pursuing testing (p > 0.0001). Over the past 14 years there has been a major change in perspective amongst cancer genetic specialists regarding genetic testing, prophylactic surgery and insurance discrimination.

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective.

PubMed

Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

2013-09-01

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.

Knowledge and expectations of women undergoing cancer genetic risk assessment: a qualitative analysis of free-text questionnaire comments.

PubMed

Phelps, C; Wood, F; Bennett, P; Brain, K; Gray, J

2007-08-01

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services.

Interventions to Improve Patient Education Regarding Multifactorial Genetic Conditions: A Systematic Review

PubMed Central

Meilleur, Katherine G.; Littleton-Kearney, Marguerite T.

2009-01-01

The careful education of patients with complex genetic disease is essential. However, healthcare providers often have limited time to spend providing thorough genetic education. Furthermore, the number of healthcare professionals possessing strong genetics training may be inadequate to meet increasing patient demands. Due to such constraints, several interventions have been investigated over the past decade to identify potential resources for the facilitation of this specific type of patient education. This systematic literature review of these interventions for patient education attempts to elucidate the answer to the question: is there sufficient evidence for best practice for delivering genetic information to patients with multifactorial conditions? The various interventions (CD-ROM, group counseling, video/decision aid, and miscellaneous) were analyzed in terms of quality criteria and achievement of specific outcomes and were rated according to the Stetler model for evidence based practice. Seven main outcomes were evaluated: 1. objective and subjective knowledge assessment 2. psychological measures (general anxiety, depression, stress, cancer worry) 3. satisfaction/effectiveness of intervention 4. time spent in counseling (time spent on basic genetic information vs. specific concerns) 5. decision making/intent to undergo genetic testing 6. treatment choice and value of that choice, and, finally 7. risk perception. Overall, the computer interventions resulted in more significant findings that were beneficial than any other category followed by the video category, although the group and miscellaneous categories did not measure all of the outcomes reported by the other two categories. Nevertheless, while these groups had neutral or negative findings in some of the outcomes, the computer intervention group showed significant improvement in genetics knowledge, psychological measures, satisfaction/effectiveness, time spent with counselor, and decision/intent to undergo testing. PMID:19291763

Tumor genome analysis includes germline genome: Are we ready for surprises?

PubMed Central

Catenacci, Daniel VT; Amico, Andrea L; Nielsen, Sarah M; Geynisman, Daniel M; Rambo, Brittany; Carey, George B; Gulden, Cassandra; Fackenthal, Jim; Marsh, Robert D; Kindler, Hedy L; Olopade, Olufunmilayo I

2015-01-01

We sought to describe the spectrum of potential and confirmed germline genomic events incidentally identified during routine medium-throughput somatic tumor DNA sequencing, and to provide a framework for pre- and post-test consent and counseling for patients and families. Targeted tumor-only next-generation sequencing (NGS) had been used to evaluate for possible druggable genomic events obtained from consecutive new patients with metastatic gastroesophageal, hepatobiliary or colorectal cancer seen at the University of Chicago. A panel of medical oncologists, cancer geneticists and genetic counselors retrospectively grouped these patients (N = 111) based on probability of possessing a potentially inherited mutation in a cancer susceptibility gene, both prior to and after incorporating tumor-only NGS results. High-risk patients (determined from NGS results) were contacted and counseled in person by a genetic counselor (N = 21). When possible and indicated, germline genetic testing was offered. Of 8 evaluable high-risk patients, 7 underwent germline testing. Three (37.5%) had confirmed actionable germline mutations (all in the BRCA2 gene). NGS offers promise, but poses significant challenges for oncologists who are ill prepared to handle incidental findings that have clinical implications for at risk family members. In this relatively small cohort of patients undergoing tumor genomic testing for gastrointestinal malignancies, we incidentally identified 3 BRCA2 mutations carriers. This report underscores the need for oncologists to develop a framework for pre- and post-test communication of risks to patients undergoing routine tumor-only sequencing. What's new? High-throughput, ‘next-generation sequencing’ (NGS) allows millions of DNA strands to be sequenced in parallel. NGS is increasingly used to test tumors for mutations that may guide therapy. Sometimes, however, this testing can reveal mutations that are known to be inherited, which means that family members are also at increased risk for cancer. How should this information be presented? This article underscores the need for oncologists to develop a framework for pre- and post-test communication and counseling regarding risk for patients undergoing tumor-only sequencing. PMID:25123297

Attitudes towards cannabis use and genetic testing for schizophrenia.

PubMed

Schiffman, Jason; Lawrence, Ryan E; Demro, Caroline; Appelbaum, Paul S; Dixon, Lisa B

2016-06-01

Within schizophrenia, genetic factors contribute greatly to risk, yet genetic testing for the disorder is not available. For some individuals with specific genotypes, cannabis use may increase risk of schizophrenia. It is possible that genetic tests could be offered in the future to inform individuals of the risk of schizophrenia if they use cannabis. Previous research, however, provides little guidance on how young adults might respond to such tests. We assessed a group of young adults (n = 83) to determine how the perceived magnitude of increased risk for schizophrenia in the presence of cannabis use influences decisions to undergo genetic testing, as well as subsequent attitudes and intentions towards cannabis use. Participants were significantly more likely to indicate willingness to get tested if the results identified a 10% risk versus a 2% risk of schizophrenia. Participants also indicated that if the results of their test reflected increased risk due to cannabis use, it would be more important to avoid cannabis in the 10% risk scenario as compared to the 2% risk scenario. These findings remained consistent among a subset of participants who indicated cannabis use. Results suggest that cannabis users and non-users were positively influenced in terms of intentions to change behaviour based on the magnitude of risk conveyed by genetic testing. These findings provide an initial step towards understanding young people's attitudes towards genetic testing and may help prepare interventions specifically tailored around cannabis use reduction for people at risk for schizophrenia. © 2014 Wiley Publishing Asia Pty Ltd.

Attitudes towards cannabis use and genetic testing for schizophrenia

PubMed Central

Schiffman, Jason; Lawrence, Ryan E.; Demro, Caroline; Appelbaum, Paul S.; Dixon, Lisa

2014-01-01

Aim Within schizophrenia, genetic factors contribute greatly to risk, yet genetic testing for the disorder is not available. For some individuals with specific genotypes, cannabis use may increase risk of schizophrenia. It is possible that genetic tests could be offered in the future to inform individuals of the risk of schizophrenia if they use cannabis. Previous research, however, provides little guidance on how young adults might respond to such tests. Methods We assessed a group of young adults (n = 83) to determine how the perceived magnitude of increased risk for schizophrenia in the presence of cannabis use influences decisions to undergo genetic testing, as well as subsequent attitudes and intentions towards cannabis use. Results Participants were significantly more likely to indicate willingness to get tested if the results identified a 10% risk versus a 2% risk of schizophrenia. Participants also indicated that if the results of their test reflected increased risk due to cannabis use, it would be more important to avoid cannabis in the 10% risk scenario as compared to the 2% risk scenario. These findings remained consistent among a subset of participants who indicated cannabis use. Conclusions Results suggest that cannabis users and non-users were positively influenced in terms of intentions to change behavior based on the magnitude of risk conveyed by genetic testing. These findings provide an initial step towards understanding young people’s attitudes towards genetic testing and may help prepare interventions specifically tailored around cannabis use reduction for people at risk for schizophrenia. PMID:24957110

Online Module for Carrier Screening in Ashkenazi Jewish Individuals Compared with In-Person Genetics Education: A Randomized Controlled Trial.

PubMed

Fan, Chia Wei; Castonguay, Lysanne; Rummell, Sonja; Lévesque, Sébastien; Mitchell, John J; Sillon, Guillaume

2018-04-01

To increase accessibility to genetics services for low-urgency patients seeking Ashkenazi Jewish (AJ) carrier screening, we designed an interactive computer (IC) module that provides pre-test genetics education and allows genetics professionals to order the test without meeting the patients beforehand. We compared this module with in-person genetic counseling (GC) using a randomized trial. AJ individuals were randomized to undergo genetics education via the IC module (n = 26) or GC (n = 28). We compared post-interventional genetics knowledge, perceived genetic risk, and anxiety between the two groups, after accounting for pre-interventional scores, using ANCOVA. Wilcoxon Rank-Sum test was used to compare post-interventional satisfaction. Post-interventional genetics knowledge, risk perception, or anxiety were not significantly different between the two groups after accounting for baseline scores (p = 0.50-0.54), although the data are inconclusive regarding the module's non-inferiority at a 5% margin. Post-intervention satisfaction scores were generally higher in the GC group than the IC module group. Our IC module has the potential to improve access to clinical genetics services for patients and staff, but it is not suitable for all AJ patients and cannot completely replace the benefits of in-person consultations.

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective

PubMed Central

Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

2013-01-01

Background/aims 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. Methods 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. Results 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). Conclusions 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. PMID:23813418

Adopted Individuals' Views on the Utility and Value of Expanded Carrier Screening.

PubMed

Spencer, Sara; Ewing, Sarah; Calcagno, Kathryn; O'Neill, Suzanne

2018-03-30

Adoptees may not have family medical history and ethnicity information. Carrier screening assesses reproductive risk. Expanded carrier screening (ECS) screens for many genetic conditions regardless of a patient's knowledge of family history and ethnicity. This study aimed to better understand the opinions and attitudes of adopted individuals on the use of ECS in determining a patient's reproductive genetic risks. Specifically, the study assessed how adopted individuals feel that results of ECS may be useful to them and whether adoptees feel that meeting with a genetics professional in the process of undergoing ECS would be useful. Adult adoptees (N = 124) were recruited online. Their opinions on ECS were explored. The majority reported they had never been offered carrier screening (92%). The majority of adoptees wanted ECS (76%). Neither the amount of contact with biological relatives nor having medical knowledge about biological relatives was significantly associated with adoptees' desire to pursue ECS. There was a significant positive correlation between adoptees of higher education levels and the amount they would pay for ECS (p = 0.004). The majority of participants (95%) indicated a genetics professional would be helpful when undergoing ECS. The findings suggest this population may want ECS and support from genetics healthcare professionals. Advocacy for genetic counseling and testing for adoptees appears justifiable.

Current directions in behavioral medicine research on genetic testing for disease susceptibility: introduction to the special section.

PubMed

Sherman, Kerry A; Cameron, Linda D

2015-10-01

The aim of this special section is to showcase research contributing to our understanding of factors influencing decisions to undergo genetic testing and the impact of the genetic testing process on health-related behaviors of tested individuals. The first two articles report studies investigating factors associated with interest in genetic testing and acceptance of test results (Sherman et al. in J Behav Med doi: 10.1007/s10865-015-9630-9 , 2015; Taber et al. in J Behav Med doi: 10.1007/s10865-015-9642-5 , 2015b). The next two papers address the unique contribution of genetic risk information to understanding risk beyond genetic counseling alone (Heiniger et al. in J Behav Med doi 10.1007/s10865-015-9632-7 , 2015; Taber et al. in J Behav Med doi: 10.1007/s10865-015-9648-z , 2015a). The final three articles investigate the effects of genetic risk information on beliefs about disease control and prevention (Aspinwall et al. in J Behav Med doi: 10.1007/s10865-015-9631-8 , 2015; Kelly et al. in J Behav Med doi 10.1007/s10865-014-9613-2 , 2014; Myers et al. in J Behav Med doi: 10.1007/s10865-015-9626-5 , 2015). Collectively, the special section of papers highlights the diverse ways in which behavioural medicine contributes to our understanding of genetic testing for disease risk, and points to the value of further research to better understand ways in which individuals perceive, interpret and respond to genetic risk information.

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

PubMed

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

Modeling the dyadic effects of parenting, stress, and coping on parent-child communication in families tested for hereditary breast-ovarian cancer risk.

PubMed

Hamilton, Jada G; Mays, Darren; DeMarco, Tiffani; Tercyak, Kenneth P

2016-10-01

Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy. BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoing BRCA genetic testing and their untested co-parents (N = 102 parenting dyads), we examined how maternal and co-parent characteristics independently and conjointly influenced the overall quality of parent-child communication with minor children. Statistical associations were tested in accordance with the Actor-Partner Interdependence Model. Significant Actor effects were observed among mothers, such that open parent-child communication prior to genetic testing was positively associated with open communication 6 months following receipt of genetic test results; and among co-parents, more open parent-child communication at baseline and greater perceived quality of the parenting relationship were associated with more open parent-child communication at follow-up. Partner effects were also observed: co-parents' baseline communication and confidence in their ability to communicate with their minor children about genetic testing was positively associated with open maternal parent-child communication at follow-up. These results demonstrate that for families facing the prospect of cancer genetic testing, perceptions and behaviors of both members of child-rearing couples have important implications for the overall quality of communication with their minor children, including communication about cancer risk.

Modeling the dyadic effects of parenting, stress, and coping on parent–child communication in families tested for hereditary breast-ovarian cancer risk

PubMed Central

Hamilton, Jada G.; Mays, Darren; DeMarco, Tiffani; Tercyak, Kenneth P.

2016-01-01

Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy. BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoing BRCA genetic testing and their untested co-parents (N = 102 parenting dyads), we examined how maternal and co-parent characteristics independently and conjointly influenced the overall quality of parent–child communication with minor children. Statistical associations were tested in accordance with the Actor–Partner Interdependence Model. Significant Actor effects were observed among mothers, such that open parent–child communication prior to genetic testing was positively associated with open communication 6 months following receipt of genetic test results; and among co-parents, more open parent–child communication at baseline and greater perceived quality of the parenting relationship were associated with more open parent–child communication at follow-up. Partner effects were also observed: co-parents’ baseline communication and confidence in their ability to communicate with their minor children about genetic testing was positively associated with open maternal parent– child communication at follow-up. These results demonstrate that for families facing the prospect of cancer genetic testing, perceptions and behaviors of both members of child-rearing couples have important implications for the overall quality of communication with their minor children, including communication about cancer risk. PMID:26848859

Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations

PubMed Central

King, Kathryn S.; Prodanov, Tamara; Kantorovich, Vitaly; Fojo, Tito; Hewitt, Jacqueline K.; Zacharin, Margaret; Wesley, Robert; Lodish, Maya; Raygada, Margarita; Gimenez-Roqueplo, Anne-Paule; McCormack, Shana; Eisenhofer, Graeme; Milosevic, Dragana; Kebebew, Electron; Stratakis, Constantine A.; Pacak, Karel

2011-01-01

Purpose To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence. Patients and Methods From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations. Results Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location. Conclusion The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation. PMID:21969497

Understanding patient and provider perceptions and expectations of genomic medicine

PubMed Central

Hall, Michael J; Forman, Andrea; Montgomery, Susan; Rainey, Kim; Daly, Mary B

2014-01-01

Advances in genome sequencing technology have fostered a new era of clinical genomic medicine. Genetic counselors, who have begun to support patients undergoing multi-gene panel testing for hereditary cancer risk, will review brief clinical vignettes, and discuss early experiences with clinical genomic testing. Their experiences will frame a discussion about how current testing may challenge patient understanding and expectations toward the evaluation of cancer risk and downstream preventive behaviors. PMID:24992205

Genetic testing for BRCA1: effects of a randomised study of knowledge provision on interest in testing and long term test uptake; implications for the NICE guidelines.

PubMed

Hall, Julia; Gray, Susan; A'Hern, Roger; Shanley, Susan; Watson, Maggie; Kash, Kathryn; Croyle, Robert; Eeles, Rosalind

2009-01-01

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 < 0.0001). Provision of educational information did not affect level of interest. Knowledge about breast cancer susceptibility genes was poor. According to the NICE guidelines regarding eligibility for BRCA1 and BRCA2 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.

Hemochromatosis and Iron Overload Screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults.

PubMed

McLaren, Christine E; Barton, James C; Adams, Paul C; Harris, Emily L; Acton, Ronald T; Press, Nancy; Reboussin, David M; McLaren, Gordon D; Sholinsky, Phyliss; Walker, Ann P; Gordeuk, Victor R; Leiendecker-Foster, Catherine; Dawkins, Fitzroy W; Eckfeldt, John H; Mellen, Beverly G; Speechley, Mark; Thomson, Elizabeth

2003-02-01

The HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively. Participants undergo testing for serum iron measures and common mutations of the hemochromatosis gene ( ) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload. Of the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male. Information from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis.

[Views of Icelandic women towards genetic counseling - and testing of BRCA2 mutations].

PubMed

Jonsdottir, Thordis; Valdimarsdottir, Heiddis; Tryggvadottir, Laufey; Lund, Sigrun Helga; Thordardottir, Marianna; Magnusson, Magnus Karl; Valdimarsdottir, Unnur

2018-01-01

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 (p<0.0001) and were less afraid of the consequence of being a mutation carrier (p<0.0001) compared to those with little or no family history. Regardless of family history, half (49%) worried that results from genetic testing could influence their health insurance. Almost all, or 97% of the women, were positive or very positive toward using existing genetic information obtained through scientific work, to inform affected indi-viduals of their mutation status. Conclusion Icelandic women are positive towards genetic counseling 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.

TANTAMOUNT TO FRAUD?: EXPLORING NON-DISCLOSURE OF GENETIC INFORMATION IN LIFE INSURANCE APPLICATIONS AS GROUNDS FOR POLICY RESCISSION.

PubMed

Prince, Anya E R

2016-01-01

Many genetic counselors recommend that individuals secure desired insurance policies, such as life insurance, prior to undergoing predictive genetic testing. It has been argued, however, that this practice is "tantamount to fraud" and that failure to disclose genetic test results, or conspiring to secure a policy before testing, opens an individual up to legal recourse. This debate traps affected individuals in a Catch-22. If they apply for life insurance and disclose a genetic test result, they may be denied. If they apply without disclosing the information, they may have committed fraud. The consequences of life insurance fraud are significant: If fraud is found on an application, a life insurer can rescind the policy, in some cases even after the individual has passed away. Such a rescission could leave family members or beneficiaries without the benefits of the life insurance policy payment after the individual's death and place them in in economic difficulty. Although it is clear that lying in response to a direct question about genetic testing would be tantamount to fraud, few, if any, life insurance applications currently include broad questions about genetic testing. This paper investigates whether non-disclosure of unasked for genetic information constitutes fraud and explores varying types of insurance questions that could conceivably be interpreted as seeking genetic information. Life insurance applicants generally have no duty to disclose unasked for information, including genetic information, on an application. However, given the complexities of genetic information, individuals may be exposed to fraud and rescission of their life insurance policy despite honest attempts to truthfully and completely answer all application questions.

Attitudes of women of advanced maternal age undergoing invasive prenatal diagnosis and the impact of genetic counselling

PubMed Central

Godino, Lea; Pompilii, Eva; D'Anna, Federica; Morselli-Labate, Antonio M; Nardi, Elena; Seri, Marco; Rizzo, Nicola; Pilu, Gianluigi; Turchetti, Daniela

2016-01-01

Despite the increasing availability and effectiveness of non-invasive screening for foetal aneuploidies, most women of advanced maternal age (AMA) still opt for invasive tests. A retrospective cross-sectional survey was performed on women of AMA undergoing prenatal invasive procedures, in order to explore their motivations and the outcome of preliminary genetic counselling according to the approach (individual or group) adopted. Of 687 eligible women, 221 (32.2%) participated: 117 had received individual counselling, while 104 had attended group sessions. The two groups did not differ by socio-demographic features. The commonest reported reason to undergo invasive tests was AMA itself (67.4%), while only 10.4% of women mentioned the opportunity of making informed choices. The majority perceived as clear and helpful the information received at counselling, and only 12.7% had doubts left that, however, often concerned non-pertinent issues. The impact of counselling on risk perception and decisions was limited: a minority stated their perceived risk of foetal abnormalities had either increased (6.8%) or reduced (3.6%), and only one eventually declined invasive test. The 52.6% of women expressed a preference toward individual counselling, which also had a stronger impact on perceived risk reduction (P=0.003). Nevertheless, group counselling had a more favourable impact on both clarity of understanding and helpfulness (P=0.0497 and P=0.035, respectively). The idea that AMA represents an absolute indication for invasive tests appears deeply rooted; promotion of non-invasive techniques may require extensive educational efforts targeted to both the general population and health professionals. PMID:26014424

Understanding patient and provider perceptions and expectations of genomic medicine.

PubMed

Hall, Michael J; Forman, Andrea D; Montgomery, Susan V; Rainey, Kim L; Daly, Mary B

2015-01-01

Advances in genome sequencing technology have fostered a new era of clinical genomic medicine. Genetic counselors, who have begun to support patients undergoing multi-gene panel testing for hereditary cancer risk, will review brief clinical vignettes, and discuss early experiences with clinical genomic testing. Their experiences will frame a discussion about how current testing may challenge patient understanding and expectations toward the evaluation of cancer risk and downstream preventive behaviors. © 2014 Wiley Periodicals, Inc.

Awareness, attitudes and perspectives of direct-to-consumer genetic testing in Greece: a survey of potential consumers.

PubMed

Mavroidopoulou, Vasiliki; Xera, Ellie; Mollaki, Vasiliki

2015-09-01

Direct-to-consumer genetic testing (DTCGT) is now offered by numerous companies. The present survey aimed to explore awareness, interest, reasons to take and refuse DTCGT, and understanding of results amongst 725 higher education students in Greece. A third of the responders were aware of DTCGT and interest was dependent on cost. More than 60% of the participants would undergo DTCGT to learn more about their health, to warn their children, so that their doctor can monitor their health and change their lifestyle. Nevertheless, they would prefer to consult their doctor first and expressed concerned about their personal data. After receiving results from a hypothetical DTC genetic test predicting higher risk for colon cancer, 59.5% of the responders thought that they could understand the results but 46.1% believed that the results have diagnostic value. In total, 83.6% of the participants would ask their doctor to explain the results and 70.4% would discuss results with their family. In conclusion, the majority of higher education students in Greece appreciate the benefits of genetic testing but with the involvement of their doctor. A physician's participation in the process and informing the public about the true value of genetic testing, are crucial to avoid misinterpretation of DTCGT results.

Genetic risk assessment for women with epithelial ovarian cancer: referral patterns and outcomes in a university gynecologic oncology clinic.

PubMed

Petzel, Sue V; Vogel, Rachel Isaksson; Bensend, Tracy; Leininger, Anna; Argenta, Peter A; Geller, Melissa A

2013-10-01

Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04-8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referral, personal/family cancer history, demographics, and genetic test results. Groups were compared using chi-squared and Fisher's exact test for categorical variables and t-tests for continuous variables. The study population consisted of 376 women with ovarian cancer, 72 (19 %) of who were referred for genetic counseling/testing, primarily during surveillance. Of those referred, 42 (58 %) had personal or family genetic counseling and 34 (47 %) were ultimately tested or identified due to known family mutation. Family history and prior cancer were associated with referral. Family history, living in a larger community, higher-stage disease, and serous histology were associated with undergoing genetic counseling. Risk assessment identified 20 BRCA1/2 (5.3 %) and 1 HNPCC (0.3 %) mutation carriers. Based on recent estimates that 11.7-16.6 % of women with ovarian cancer are BRCA carriers and 2 % are HNPCC carriers, results suggest under-identification of carriers and under-utilization of genetic services by providers and patients. Interventions to increase medical providers' referrals, even in a specialized oncology clinic, are necessary and may include innovations in educating these providers using web-based methods. Ease of referral by the introduction of an electronic cancer genetic referral form represents another new direction that may increase genetic risk assessment for high-risk women with ovarian cancer.

Understanding of BRCA1/2 genetic tests results: the importance of objective and subjective numeracy.

PubMed

Hanoch, Yaniv; Miron-Shatz, Talya; Rolison, Jonathan J; Ozanne, Elissa

2014-10-01

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 < 0.001; uninformative, OR = 1.40; 95% CI [1.10, 1.80]). Given the medical and 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.

Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis

PubMed Central

Ormondroyd, Elizabeth; Donnelly, Louise; Moynihan, Clare; Savona, Cornelie; Bancroft, Elizabeth; Evans, D Gareth; Eeles, Rosalind; Lavery, Stuart; Watson, Maggie

2012-01-01

The scope of conditions for which preimplantation genetic diagnosis (PGD) is licensed has recently been expanded in the United Kingdom to include genetic predisposition to adult-onset cancer. This qualitative interview study explores reproductive decision making, knowledge of and attitudes to reproductive genetic testing (prenatal diagnosis and PGD) with 25 women aged 18–45 years who received a positive BRCA test in the United Kingdom before having children. In this cohort of younger women, BRCA testing was motivated by risk management decisions; for some, BRCA status has affected their later decisions about having children. The perceived severity of hereditary breast/ovarian cancer (HBOC) influences thoughts about passing on the mutation to children and willingness to consider reproductive genetic testing, but most participants do not believe HBOC is a condition for which pregnancy termination is justified. PGD is considered more acceptable and advantageous because it would prevent transmission to future generations, but women have concerns about selecting embryos and the fact that they and affected family members would not have been selected. Women would also be deterred by the need to undergo in vitro fertilisation (IVF) and ovarian stimulation for PGD. Awareness of reproductive testing options was very variable among the cohort. The findings highlight the complexities of reproductive decision making for young women who knowingly carry a BRCA mutation, and the dilemmas inherent to reproductive genetic testing when the condition being tested for also affects a prospective parent. Counselling and psychological support for BRCA-positive women and couples concerning reproductive options are strongly indicated. PMID:21811309

Genetic Causes of Recurrent Pregnancy Loss.

PubMed

Page, Jessica M; Silver, Robert M

2016-09-01

Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted.

Genetic Test Reporting and Counseling for Melanoma Risk in Minors May Improve Sun Protection Without Inducing Distress.

PubMed

Stump, Tammy K; Aspinwall, Lisa G; Kohlmann, Wendy; Champine, Marjan; Hauglid, Jamie; Wu, Yelena P; Scott, Emily; Cassidy, Pamela; Leachman, Sancy A

2018-01-19

Genetic testing of minors is advised only for conditions in which benefits of early intervention outweigh potential psychological harms. This study investigated whether genetic counseling and test reporting for the CDKN2A/p16 mutation, which confers highly elevated melanoma risk, improved sun protection without inducing distress. Eighteen minors (M age  = 12.4, SD = 1.9) from melanoma-prone families completed measures of protective behavior and distress at baseline, 1 week (distress only), 1 month, and 1 year following test disclosure. Participants and their mothers were individually interviewed on the psychological and behavioral impact of genetic testing 1 month and 1 year post-disclosure. Carriers (n = 9) and noncarriers (n = 9) reported significantly fewer sunburns and a greater proportion reported sun protection adherence between baseline and 1 year post-disclosure; results did not vary by mutation status. Anxiety symptoms remained low post-disclosure, while depressive symptoms and cancer worry decreased. Child and parent interviews corroborated these findings. Mothers indicated that genetic testing was beneficial (100%) because it promoted risk awareness (90.9%) and sun protection (81.8%) without making their children scared (89.9%); several noted their child's greater independent practice of sun protection (45.4%). In this small initial study, minors undergoing CDKN2A/p16 genetic testing reported behavioral improvements and consistently low distress, suggesting such testing may be safely implemented early in life, allowing greater opportunity for risk-reducing lifestyle changes.

An economic model of amniocentesis choice.

PubMed

Fajnzylber, Eduardo; Hotz, V Joseph; Sanders, Seth G

2010-03-01

Medical practitioners typically utilize the following protocol when advising pregnant women about testing for the possibility of genetic disorders with their fetus: Pregnant women over the age of 35 should be tested for Down syndrome and other genetic disorders, while for younger women, such tests are discouraged (or not discussed) as the test can cause a pregnancy to miscarry. The logic appears compelling. The rate at which amniocentesis causes a pregnancy to miscarry is constant while the rate of genetic disorder rises substantially over a woman's reproductive years. Hence the potential benefit from testing - being able to terminate a fetus that is known to have a genetic disorder - rises with maternal age. This article argues that this logic is incomplete. While the benefits to testing do rise with age, the costs rise as well. Undergoing an amniocentesis always entails the risk of inducing a miscarriage of a healthy fetus. However, these costs are lower at early ages, because there is a higher probability of being able to replace a miscarried fetus with a healthy birth at a later age. We develop and calibrate a dynamic model of amniocentesis choice to explore this tradeoff. For parameters that characterize realistic age patterns of chromosomal abnormalities, fertility rates and miscarriages following amniocentesis, our model implies a falling, rather than rising, rate of amniocentesis as women approach menopause.

Breast cancer genetic testing awareness, attitudes and intentions of Latinas living along the US-Mexico border: a qualitative study.

PubMed

Chalela, Patricia; Pagán, José A; Su, Dejun; Muñoz, Edgar; Ramirez, Amelie G

2012-01-01

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 genetic risk susceptibility information to Latinas to help them make informed testing decisions.

The Right to Know and the Right Not to Know Revisited: Part One.

PubMed

Brownsword, Roger; Wale, Jeff

2017-01-01

Prompted by developments in human genetics, a recurrent bioethical question concerns a person's 'right to know' and 'right not to know' about genetic information held that is intrinsically related to or linked to them. In this paper, we will revisit the claimed rights in relation to two particular test cases. One concerns the rights of the 500,000 participants in UK Biobank (UKB) whose biosamples, already having been genotyped, will now be exome sequenced, and the other concerns the rights of pregnant women (and their children) who undergo non-invasive prenatal testing (NIPT)-a simple blood test that can reveal genetic information about both a foetus and its mother. This two-part paper is in four principal sections. First, we sketch the relevant features of our two test cases. Secondly, we consider the significance of recent legal jurisprudence in the UK and Singapore. Thirdly, we consider how, the jurisprudence apart, the claimed rights might be grounded. Fourthly, we consider the limits on the rights. We conclude with some short remarks about the kind of genetically aware society that we might want to be and how far there is still an opportunity meaningfully to debate the claimed rights.

Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: a naturally-occurring experiment.

PubMed

Mouchawar, Judy; Hensley-Alford, Sharon; Laurion, Suzanne; Ellis, Jennifer; Kulchak-Rahm, Alanna; Finucane, Melissa L; Meenan, Richard; Axell, Lisen; Pollack, Rebecca; Ritzwoller, Debra

2005-03-01

To describe the impact of Myriad Genetics, Inc.'s direct-to-consumer advertising (DTC-ad) campaign on cancer genetic services within two Managed Care Organizations, Kaiser Permanente Colorado (KPCO), Denver, Colorado, where the ad campaign occurred, and Henry Ford Health System (HFHS), Detroit, Michigan, where there were no advertisements. The main outcome measures were the changes in number and pretest mutation probability of referrals approved for cancer genetic services at KPCO and HFHS during the campaign versus the year prior, and mutation probability of those undergoing testing. At KPCO, referrals increased 244% during the DTC-ad compared to the same time period a year earlier (P value<0.001). The proportion of referrals at high pretest probability of a mutation (10% or greater) dropped from 69% the previous year to 48% during the campaign (P value<0.001). There was no significant change in pretest mutation probability among women who underwent testing between the two time periods. HFHS reported no significant change between the two time periods for numbers or mutation probability of referrals, or for mutation probability of women tested. The DTC-ad caused significant increase in demand for cancer genetic services. In the face of potential future DTC-ad for inherited cancer risk, providers and payers need to consider the delivery of genetic services and genetic education for persons of all risk levels.

Living at Risk: Concealing Risk and Preserving Hope in Huntington Disease

PubMed Central

Sims, Sharon L.; Swenson, Melinda M.; Harrison, Joan M.; Moskowitz, Carol; Stepanov, Nonna; Suter, Gregory W.; Westphal, Beryl J.

2013-01-01

Much of the qualitative research on Huntington disease has focused on the genetic testing aspects of HD. The overall purpose of this qualitative study was to gather information about the everyday experience of living with the risk of developing Huntington disease in a sample of individuals at risk for HD who have chosen not to pursue genetic testing. Data for this article was obtained from unstructured, open-ended qualitative interviews of a sample of people participating in the PHAROS study. PHAROS, the Prospective Huntington At-Risk Observational Study, is a multi-site study that aims to establish whether experienced clinicians can reliably determine the earliest clinical symptoms of Huntington disease in individuals at 50% risk for HD who have chosen not to undergo genetic testing. Interviews were conducted at six PHAROS research sites across the United States. In this paper, the research team used qualitative description to construct and explore two main themes: (1) careful concealment of risk as an act of self-preservation and (2) preserving hope. PMID:17943424

Identification of cognitive profiles among women considering BRCA1/2 testing through the utilisation of cluster analytic techniques.

PubMed

Roussi, Pagona; Sherman, Kerry A; Miller, Suzanne M; Hurley, Karen; Daly, Mary B; Godwin, Andrew; Buzaglo, Joanne S; Wen, Kuang-Yi

2011-10-01

Based on the cognitive-social health information processing model, we identified cognitive profiles of women at risk for breast and ovarian cancer. Prior to genetic counselling, participants (N = 171) completed a study questionnaire concerning their cognitive and affective responses to being at genetic risk. Using cluster analysis, four cognitive profiles were generated: (a) high perceived risk/low coping; (b) low value of screening/high expectancy of cancer; (c) moderate perceived risk/moderate efficacy of prevention/low informativeness of test result; and (d) high efficacy of prevention/high coping. The majority of women in Clusters One, Two and Three had no personal history of cancer, whereas Cluster Four consisted almost entirely of women affected with cancer. Women in Cluster One had the highest number of affected relatives and experienced higher levels of distress than women in the other three clusters. These results highlight the need to consider the psychological profile of women undergoing genetic testing when designing counselling interventions and messages.

The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis.

PubMed

Duncan, Rony E; Gillam, Lynn; Savulescu, Julian; Williamson, Robert; Rogers, John G; Delatycki, Martin B

2010-03-01

Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely offered to young people during early adolescence. While this is not controversial, due to the medical benefit conferred by the test, it is nonetheless challenging as a consequence of the stage of life of the young people, and the simultaneous involvement of multiple family members. Despite these challenges, it is possible to ensure that the test is offered in such a way that it actively acknowledges and facilitates young people's developing autonomy and psychosocial well-being. In this paper we present findings from ten in-depth interviews with young people who have undergone predictive genetic testing for FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17 years at the time of their predictive test; aged 12-25 years at the time of their research interview). We present five themes that emerged from the interviews which highlight key ethical challenges associated with such testing. These are: (1) the significance of the test; (2) young people's lack of involvement in the decision to be tested; (3) young people's limited understanding; (4) provision of the blood test at the first visit; and (5) group testing of family members. We draw on these themes to make eight recommendations for future practice. Together, these recommendations highlight the importance of providing developmentally appropriate care to young people undergoing predictive genetic testing for FAP.

The withdrawal from oncogenetic counselling and testing for hereditary and familial breast and ovarian cancer. A descriptive study of an Italian sample.

PubMed

Caruso, Anita; Vigna, Cristina; Maggi, Gabriella; Sega, Fabio Massimo; Cognetti, Francesco; Savarese, Antonella

2008-11-24

Oncogenetic counselling is seldom followed through, even when individuals are eligible according to the test criteria. The basic variables which influence the decision to undergo the genetic counselling process are: risk perception, expected benefit or limitations of genetic testing, general psychological distress or cancer-specific distress, lack of trust in one's emotional reactions when faced with negative events, expected level of family support and communications within the family. The aim of this study was to describe the psychosocial variables of an Italian sample that forgoes genetic counselling. From May 2002 to December 2006 a psychological questionnaire was sent out to one hundred and six subjects, who freely requested a first genetic informative consultation, and never asked to have a second visit and the family tree drawn up in order to inquire about their eligibility for genetic testing. Statistical analysis was performed by Pearson chi-square test, t-test and Spearman RHO coefficient. The survey presents a lack of emotional cohesion and structured roles and rules within the family system and a positive correlation between the number of children, anxiety and risk perception. The main reasons for giving up on counselling were a sense that testing was a waste of time and the inability to emotionally handle the negative consequences of the test outcome. The subjects who maintained that test and an early diagnosis were a "waste of time" experienced more anxiety. The study revealed the importance to ac knowledging the whole persona and their family system as well as provide information highlighting usefulness of early diagnosis.

A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees.

PubMed

Bohl, Daniel D; Telles, Connor J; Ruiz, Ferrin K; Badrinath, Raghav; DeLuca, Peter A; Grauer, Jonathan N

2016-04-01

Retrospective cohort. To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.

An investigation of the factors effecting high-risk individuals’ decision-making about prophylactic total gastrectomy and surveillance for hereditary diffuse gastric cancer (HDGC)

PubMed Central

Hallowell, Nina; Badger, Shirlene; Richardson, Sue; Caldas, Carlos; Hardwick, Richard H.; Fitzgerald, Rebecca C.; Lawton, Julia

2018-01-01

Because Hereditary Diffuse Gastric Cancer (HDGC) has an early onset and poor prognosis, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative interviews were carried out with 35 high-risk individuals from the Familial Gastric Cancer Study in the UK. Twenty-seven had previously undergone PTG and eight had been identified as carrying a pathogenic CDH1 mutation but had declined surgery at the time of interview. The interviews explored the experience of decision-making and factors influencing risk-management decisions. The data suggest that decisions to proceed with PTG are influenced by a number of potentially competing factors: objective risk confirmation by genetic testing and/or receiving a positive biopsy; perceived familial cancer burden and associated risk perceptions; perceptions of post-surgical life; an increasing inability to tolerate endoscopic procedures; a concern that surveillance could miss a cancer developing and individual’s life stage. These findings have implications for advising this patient group. PMID:27256430

Choosing between possible lives: legal and ethical issues in preimplantation genetic diagnosis.

PubMed

Scott, Rosamund

2006-01-01

This article critically appraises the current legal scope of the principal applications of preimplantation genetic diagnosis (PGD). This relatively new technique, which is available to some parents undergoing in vitro fertilization (IVF) treatment, aims to ensure that a child is not born with a seemingly undesirable genetic condition. The question addressed here is whether there should be serious reasons to test for genetic conditions in embryos in order to be able to select between them. The Human Fertilisation and Embryology Authority and the Human Genetics Commission have decided that there should be such reasons by broadly aligning the criteria for PGD with those for selective abortion. This stance is critically explored, as are its implications for the possible use of PGD to select either against or for marginal features or for significant traits. The government is currently reviewing the legal scope and regulation of PGD.

Psychosocial factors associated with the uptake of contralateral prophylactic mastectomy among BRCA1/2 mutation noncarriers with newly-diagnosed breast cancer

PubMed Central

Hamilton, Jada G.; Genoff, Margaux C.; Salerno, Melissa; Amoroso, Kimberly; Boyar, Sherry R.; Sheehan, Margaret; Fleischut, Megan Harlan; Siegel, Beth; Arnold, Angela G.; Salo-Mullen, Erin E.; Hay, Jennifer L.; Offit, Kenneth; Robson, Mark E.

2017-01-01

Purpose Women who are newly diagnosed with breast cancer may consider contralateral prophylactic mastectomy (CPM) to reduce their future risk of cancer in their unaffected breast. Pre-surgical BRCA1/2 genetic testing can provide valuable risk information to guide this choice. However, little is understood about why BRCA1/2 mutation noncarriers, who are generally not at substantially elevated risk of contralateral disease, select CPM. Methods We examined the uptake of CPM among breast cancer patients identified as BRCA1/2 mutation noncarriers (n=92) as part of a larger prospective study of the impact of pre-surgical BRCA1/2 testing. Data obtained from self-report questionnaires and patient medical records were used to examine associations between theoretically-relevant background and psychosocial factors and BRCA1/2 mutation noncarriers’ decisions to undergo CPM. Results Among BRCA1/2 mutation noncarriers, 25% (n=23) elected to undergo CPM. Psychosocial factors including a self-reported physician recommendation for CPM, greater perceived contralateral breast cancer risk, and greater perceived benefits of CPM were all significantly associated with the uptake of CPM. Conclusions A sizeable minority of BRCA1/2 mutation noncarriers choose to undergo CPM after learning their mutation status through pre-surgical genetic testing. BRCA1/2 mutation noncarriers’ cognitive perceptions and social influences appear to be important in shaping their decisions regarding CPM. This work highlights the importance of several psychosocial factors in influencing patients’ surgical decisions. Future research is needed that examines the formation of BRCA1/2 mutation noncarriers’ beliefs regarding their disease and available treatment options, and that characterizes the physician-patient communication that occurs in this complex decision-making context. PMID:28150129

Psychosocial factors associated with the uptake of contralateral prophylactic mastectomy among BRCA1/2 mutation noncarriers with newly diagnosed breast cancer.

PubMed

Hamilton, Jada G; Genoff, Margaux C; Salerno, Melissa; Amoroso, Kimberly; Boyar, Sherry R; Sheehan, Margaret; Fleischut, Megan Harlan; Siegel, Beth; Arnold, Angela G; Salo-Mullen, Erin E; Hay, Jennifer L; Offit, Kenneth; Robson, Mark E

2017-04-01

Women who are newly diagnosed with breast cancer may consider contralateral prophylactic mastectomy (CPM) to reduce their future risk of cancer in their unaffected breast. Pre-surgical BRCA1/2 genetic testing can provide valuable risk information to guide this choice. However, little is understood about why BRCA1/2 mutation noncarriers, who are generally not at substantially elevated risk of contralateral disease, select CPM. We examined the uptake of CPM among breast cancer patients identified as BRCA1/2 mutation noncarriers (n = 92) as part of a larger prospective study of the impact of pre-surgical BRCA1/2 testing. Data obtained from self-report questionnaires and patient medical records were used to examine associations between theoretically relevant background and psychosocial factors and BRCA1/2 mutation noncarriers' decisions to undergo CPM. Among BRCA1/2 mutation noncarriers, 25% (n = 23) elected to undergo CPM. Psychosocial factors including a self-reported physician recommendation for CPM, greater perceived contralateral breast cancer risk, and greater perceived benefits of CPM were all significantly associated with the uptake of CPM. A sizeable minority of BRCA1/2 mutation noncarriers choose to undergo CPM after learning their mutation status through pre-surgical genetic testing. BRCA1/2 mutation noncarriers' cognitive perceptions and social influences appear to be important in shaping their decisions regarding CPM. This work highlights the importance of several psychosocial factors in influencing patients' surgical decisions. Future research is needed that examines the formation of BRCA1/2 mutation noncarriers' beliefs regarding their disease and available treatment options, and that characterizes the physician-patient communication that occurs in this complex decision-making context.

Psychological effects of amniocentesis on women and their spouses: importance of the testing period and genetic counseling.

PubMed

Kukulu, Kamile; Buldukoglu, Kadriye; Keser, Ibrahim; Keser, Ilkay; Simşek, Mehmet; Mendilcioğlu, Inanç; Lüleci, Güven

2006-03-01

To evaluate both women's and their spouses' reasons for undergoing amniocentesis, their concerns relating to the procedure as well as their psychological reactions and coping mechanisms during the testing period. Eighty-five women undergoing amniocentesis and their spouses took part in the study. The couples completed a questionnaire that provided demographic data and insights into their experiences of amniocentesis. Age was the main reason for undergoing amniocentesis. When they first learned that they were going to undergo amniocentesis, women were more concerned about the potential danger to their fetus than their spouses. Most of participants believed that their pregnancy would continue after amniocentesis. However, they also stated that they were prepared for an abortion. Uncertainty and tension were two significant emotions experienced by couples while waiting for the test results. For the majority of women (80%) and men (42.3%) the strongest support was provided by their spouses during this period. In summary, we can conclude that the test did have a major psychological impact on both women and their spouses, but did not have a negative impact on their coping mechanisms. The psychological impact of amniocentesis on women and their spouses does not constitute a major obstacle to their ability to cope. However, a certain number of couples reported feelings of uncertainty, tension and anxiety about fetal injury. We strongly suggest that counseling should be given to high-risk families and that prenatal/antenatal care units must be established.

An economic model of amniocentesis choice

PubMed Central

Fajnzylber, Eduardo; Hotz, V. Joseph; Sanders, Seth G.

2010-01-01

Medical practitioners typically utilize the following protocol when advising pregnant women about testing for the possibility of genetic disorders with their fetus: Pregnant women over the age of 35 should be tested for Down syndrome and other genetic disorders, while for younger women, such tests are discouraged (or not discussed) as the test can cause a pregnancy to miscarry. The logic appears compelling. The rate at which amniocentesis causes a pregnancy to miscarry is constant while the rate of genetic disorder rises substantially over a woman’s reproductive years. Hence the potential benefit from testing – being able to terminate a fetus that is known to have a genetic disorder – rises with maternal age. This article argues that this logic is incomplete. While the benefits to testing do rise with age, the costs rise as well. Undergoing an amniocentesis always entails the risk of inducing a miscarriage of a healthy fetus. However, these costs are lower at early ages, because there is a higher probability of being able to replace a miscarried fetus with a healthy birth at a later age. We develop and calibrate a dynamic model of amniocentesis choice to explore this tradeoff. For parameters that characterize realistic age patterns of chromosomal abnormalities, fertility rates and miscarriages following amniocentesis, our model implies a falling, rather than rising, rate of amniocentesis as women approach menopause. PMID:21516255

Military Health Care Dilemmas and Genetic Discrimination: A Family's Experience with Whole Exome Sequencing.

PubMed

Helm, Benjamin M; Langley, Katherine; Spangler, Brooke B; Schrier Vergano, Samantha A

2015-01-01

Whole-exome sequencing (WES) has increased our ability to analyze large parts of the human genome, bringing with it a plethora of ethical, legal, and social implications. A topic dominating discussion of WES is identification of "secondary findings" (SFs), defined as the identification of risk in an asymptomatic individual unrelated to the indication for the test. SFs can have considerable psychosocial impact on patients and families, and patients with an SF may have concerns regarding genomic privacy and genetic discrimination. The Genetic Information Nondiscrimination Act of 2008 (GINA) currently excludes protections for members of the military. This may cause concern in military members and families regarding genetic discrimination when considering genetic testing. In this report, we discuss a case involving a patient and family in which a secondary finding was discovered by WES. The family members have careers in the U.S. military, and a risk-predisposing condition could negatively affect employment. While beneficial medical management changes were made, the information placed exceptional stress on the family, who were forced to navigate career-sensitive "extra-medical" issues, to consider the impacts of uncovering risk-predisposition, and to manage the privacy of their genetic information. We highlight how information obtained from WES may collide with these issues and emphasize the importance of genetic counseling for anyone undergoing WES.

Evidence that personal genome testing enhances student learning in a course on genomics and personalized medicine.

PubMed

Salari, Keyan; Karczewski, Konrad J; Hudgins, Louanne; Ormond, Kelly E

2013-01-01

An emerging debate in academic medical centers is not about the need for providing trainees with fundamental education on genomics, but rather the most effective educational models that should be deployed. At Stanford School of Medicine, a novel hands-on genomics course was developed in 2010 that provided students the option to undergo personal genome testing as part of the course curriculum. We hypothesized that use of personal genome testing in the classroom would enhance the learning experience of students. No data currently exist on how such methods impact student learning; thus, we surveyed students before and after the course to determine its impact. We analyzed responses using paired statistics from the 31 medical and graduate students who completed both pre-course and post-course surveys. Participants were stratified by those who did (N = 23) or did not (N = 8) undergo personal genome testing. In reflecting on the experience, 83% of students who underwent testing stated that they were pleased with their decision compared to 12.5% of students who decided against testing (P = 0.00058). Seventy percent of those who underwent personal genome testing self-reported a better understanding of human genetics on the basis of having undergone testing. Further, students who underwent personal genome testing demonstrated an average 31% increase in pre- to post-course scores on knowledge questions (P = 3.5×10(-6)); this was significantly higher (P = 0.003) than students who did not undergo testing, who showed a non-significant improvement. Undergoing personal genome testing and using personal genotype data in the classroom enhanced students' self-reported and assessed knowledge of genomics, and did not appear to cause significant anxiety. At least for self-selected students, the incorporation of personal genome testing can be an effective educational tool to teach important concepts of clinical genomic testing.

Information needs of mothers regarding communicating BRCA1/2 cancer genetic test results to their children.

PubMed

Tercyak, Kenneth P; Peshkin, Beth N; Demarco, Tiffani A; Patenaude, Andrea Farkas; Schneider, Katherine A; Garber, Judy E; Valdimarsdottir, Heiddis B; Schwartz, Marc D

2007-01-01

Mothers who participate in genetic testing for hereditary breast/ovarian cancer risk must decide if, when, and how to ultimately share their BRCA1 and BRCA2 (BRCA1/2) test results with their minor-age children. One of the primary aides for mothers in making this decision is cancer genetic counseling. However, counseling is limited in how well it can educate mothers about such decisions without the availability of resources that are specific to family communication and genetic testing per se. In an effort to fill this gap and identify mothers most likely to benefit from such resources, surveys were conducted with 187 mothers undergoing BRCA1/2 testing who had children 8-21 years old. Data were collected weeks after genetic testing but prior to mothers' learning of their test results; quantitative assessments of informational resource needs (i.e., speaking with previous BRCA1/2 testing participants who are parents regarding their experiences, reading educational literature about options and what to expect, speaking with a family counselor, attending a family support group, and self-nominated other resources), testing motivations, decision making vigilance, and decisional conflict regarding communicating test results to children were included. Mothers' most-to-least frequently cited information resource needs were: literature (93.4%), family counseling (85.8%), prior participants (79.0%), support groups (53.9%), and other (28.9%; e.g., pediatricians and psychologists). Seventy-eight percent of mothers were interested in accessing three or more resources. In multivariate regression analyses, testing motivations (beta = 0.35, p = 0.03), decision-making vigilance (beta = 0.16, p = 0.00), and decisional conflict (beta = 0.10, p = 0.00) were associated with mothers' need level; mothers with a greater interest in testing to learn about their children's risks, those with more vigilant decision-making styles, and those with higher decisional conflict had the greatest need. In conjunction with enhanced genetic counseling focusing on family disclosure, educational literature, and psychosocial support may promote improved outcomes.

Sending family history questionnaires to patients before a colonoscopy improves genetic counseling for hereditary colorectal cancer.

PubMed

Kessels, Koen; Eisinger, Joey D; Letteboer, Tom G; Offerhaus, G Johan A; Siersema, Peter D; Moons, Leon M G

2017-06-01

To investigate whether sending a family history questionnaire to patients prior to undergoing colonoscopy results in an increased availability of family history and better genetic counseling. A questionnaire was mailed to patients before they underwent outpatient colonoscopy at a university hospital in 2013. These patients' additional characteristics and referral for genetic evaluation were retrieved from the electronic medical records. Patients undergoing inpatient coloboscopy, with confirmed hereditary colorectal cancer (CRC) or inflammatory bowel disease were excluded. All study patients from 2010 to 2013 were matched with the database of the genetics department to determine who consulted a geneticist. A total of 6163 patients underwent colonoscopy from 2010 to 2013. Of 1421 who underwent colonoscopy in 2013, 53 (3.7%) consulted a geneticist, while 75 (1.6%) of 4742 patients undergoing colonoscopy between 2010 and 2012 did so (P < 0.01). A total of 974 patients undergoing colonoscopy in 2013 were included to evaluate the completed questionnaire. Of these, 282 (29.0%) completed the questionnaire. Family history was not recorded in the electronic medical records of 393 (40.3%). In 129 (32.8%), family history was obtained from the completed questionnaire. In 2013, 49 (60.5%) out of 81 patients referred for genetic counseling were referred based on their family history. Eight (9.9%) patients were referred based on the completed questionnaire. Screening for hereditary CRC in a population undergoing outpatient colonoscopy with a questionnaire sent by mail resulted in an increased availability of family histories and genetic counseling. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Current surgical management of carotid body tumors.

PubMed

Davila, Victor J; Chang, James M; Stone, William M; Fowl, Richard J; Bower, Thomas C; Hinni, Michael L; Money, Samuel R

2016-12-01

Carotid body tumors (CBTs) are rare. Management guidelines may include genetic testing for succinate dehydrogenase (SDH) mutations. We performed an institutional review of the surgical management of CBT. A retrospective analysis (1994-2015) of CBT excisions at our institution was performed. Data obtained included demographics, genetic testing (if performed), intraoperative details, postoperative morbidity, and long-term outcomes. Data from the first CBT excision were included in patients with bilateral tumors. Genetic testing was routinely offered in patients with a family history of CBT or multiple paragangliomas. A total of 183 CBTs (124 female [67.7%]) were excised. A neck mass was present in 106 patients (57.9%), 24 patients (12.1%) presented with tenderness or neck pain, and 3 (1.6%) presented with cranial nerve dysfunction. Computed tomography (57.9%) or magnetic resonance imaging (51.3%) were the most commonly used imaging modalities. Preoperative angiography was performed in 73 patients (39.8%), and 62 of them (84.5%) underwent embolization or internal carotid balloon occlusion testing, or both. Mean tumor diameter was 3.2 cm (range, 0.6-7.2 cm). There were 71 (38.8%), 75 (41%), and 37 (20.2%) Shamblin type 1, 2, and 3 tumors, respectively. Average operating time was 224 minutes (range, 52-696 minutes). Average blood loss was 143.9 mL (range, 10-2000 mL). Arterial reconstruction with an interposition graft was required in 10, and patch angioplasty was performed in four. Cranial nerve injury was permanent in 10 (5.5%), and the rate of stroke was 1% (n = 2). A total of 382 lymph nodes were excised, and all were benign. There were no deaths ≤30 days. Only one patient presented with malignant disease 2 years after CBT excision, and this patient did not undergo genetic testing. Thirty-four (18.6%) had a family history of CBT. SDH testing was performed in 18 patients, and 17 tested positive. Positive genetic testing had a correlation with earlier age at operation (P < .0001). Mean age at diagnosis of patients with SDH mutations was 38.0 years, and patients without known SDH mutations presented at a mean age of 50.3 years. In patients with SDH mutations, tumor diameter, operating time, blood loss, and distribution of Shamblin type 1, 2, and 3 lesions were not significantly different compared with the control group. CBT can be treated with minimal morbidity and mortality; however, the subgroup of patients with positive SDH mutations may represent a variant group of younger patients. Vascular surgeons should be aware of genetic testing to identify patients and family members who should undergo additional preoperative testing and monitoring for other paragangliomas. Concomitant lymph node dissection does not appear to add value in absence of clinic suspicion for malignancy. Copyright © 2016. Published by Elsevier Inc.

HIPAA's Individual Right of Access to Genomic Data: Reconciling Safety and Civil Rights.

PubMed

Evans, Barbara J

2018-01-04

In 2014, the United States granted individuals a right of access to their own laboratory test results, including genomic data. Many observers feel that this right is in tension with regulatory and bioethical standards designed to protect the safety of people who undergo genomic testing. This commentary attributes this tension to growing pains within an expanding federal regulatory program for genetic and genomic testing. The Genetic Information Nondiscrimination Act of 2008 expanded the regulatory agenda to encompass civil rights and consumer safety. The individual access right, as it applies to genomic data, is best understood as a civil-rights regulation. Competing regulatory objectives-safety and civil rights-were not successfully integrated during the initial rollout of genomic civil-rights regulations after 2008. Federal law clarifies how to prioritize safety and civil rights when the two come into conflict, although with careful policy design, the two need not collide. This commentary opens a dialog about possible solutions to advance safety and civil rights together. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Duchenne Muscular Dystrophy: a Survey of Perspectives on Carrier Testing and Communication Within the Family.

PubMed

Hayes, Brenna; Hassed, Susan; Chaloner, Jae Lindsay; Aston, Christopher E; Guy, Carrie

2016-06-01

Carrier testing is widely available for multiple genetic conditions, and several professional organizations have created practice guidelines regarding appropriate clinical application and the testing of minors. Previous research has focused on carrier screening, predictive testing, and testing for X-linked conditions. However, family perspectives on carrier testing for X-linked lethal diseases have yet to be described. In this study, we explored communication within the family about carrier testing and the perspectives of mothers of sons with an X-linked lethal disease, Duchenne muscular dystrophy (DMD). Twenty-five mothers of sons with DMD participated in an anonymous online survey. Survey questions included multiple choice, Likert scale, and open ended, short answer questions. Analysis of the multiple choice and Likert scale questions revealed that most mothers preferred a gradual style of communication with their daughters regarding risk status. In addition, most participants reported having consulted with a genetic counselor and found it helpful. Comparisons between groups, analyzed using Fisher's exact tests, found no differences in preferred style due to mother's carrier status or having a daughter. Thematic analysis was conducted on responses to open ended questions. Themes identified included the impact of family implications, age and maturity, and a desire for autonomy regarding the decision to discuss and undergo carrier testing with at-risk daughters, particularly timing of these discussions. Implications for genetic counseling practice are discussed.

Genetic testing in nephrotic syndrome--challenges and opportunities.

PubMed

Gbadegesin, Rasheed A; Winn, Michelle P; Smoyer, William E

2013-03-01

Monogenic nephrotic syndrome (nephrotic syndrome caused by a single gene defect) is responsible for only a small percentage of cases of nephrotic syndrome, but information from studies of the unique cohort of patients with this form of the disease has dramatically improved our understanding of the disease pathogenesis. The use of genetic testing in the management of children and adults with nephrotic syndrome poses unique challenges for clinicians in terms of who to test and how to use the information obtained from testing in the clinical setting. In our view, not enough data exist at present to justify the routine genetic testing of all patients with nephrotic syndrome. Testing is warranted, however, in patients with congenital nephrotic syndrome (onset at 0-3 months), infantile nephrotic syndrome (onset at 3-12 months), a family history of nephrotic syndrome, and those in whom nephrotic syndrome is associated with other congenital malformations. The family and/or the patient should be given complete and unbiased information on the potential benefits and risks associated with therapy, including the reported outcomes of treatment in patients with similar mutations. Based on the data available in the literature so far, intensive immunosuppressive treatment is probably not indicated in monogenic nephrotic syndrome if complete or partial remission has not been achieved within 6 weeks of starting treatment. We advocate that family members of individuals with genetic forms of nephrotic syndrome undergo routine genetic testing prior to living-related kidney transplantation. Prospective, multicentre studies are needed to more completely determine the burden of disease caused by monogenic nephrotic syndrome, and randomized controlled trials are needed to clarify the presence or absence of clinical responses of monogenic nephrotic syndrome to available therapies.

Key messages for communicating information about BRCA1 and BRCA2 to women with breast or ovarian cancer: Consensus across health professionals and service users.

PubMed

Jacobs, Chris; Pichert, Gabriella; Harris, Jackie; Tucker, Kathy; Michie, Susan

2017-11-01

Genetic testing of cancer predisposing genes will increasingly be needed in oncology clinics to target cancer treatment. This Delphi study aimed to identify areas of agreement and disagreement between genetics and oncology health professionals and service users about the key messages required by women with breast/ovarian cancer who undergo BRCA1/BRCA2 genetic testing and the optimal timing of communicating key messages. Participants were 16 expert health professionals specialising in oncology/genetics and 16 service users with breast/ovarian cancer and a pathogenic BRCA1/BRCA2 variant. Online questionnaires containing 53 inductively developed information messages were circulated to the groups separately. Participants rated each message as key/not key on a Likert scale and suggested additional messages. Questionnaires were modified according to the feedback and up to 3 rounds were circulated. Consensus was reached when there was ≥75% agreement. Thirty key messages were agreed by both groups with 7 of the key messages agreed by ≥95% of participants: dominant inheritance, the availability of predictive testing, the importance of pretest discussion, increased risk of breast and ovarian cancer, and the option of risk-reducing mastectomy and bilateral salpingo-oophorectomy. Both groups agreed that key messages should be communicated before genetic testing and once a pathogenic variant has been identified. There was a high level of agreement within and between the groups about the information requirements of women with breast/ovarian cancer about BRCA1/BRCA2. These key messages will be helpful in developing new approaches to the delivery of information as genetic testing becomes further integrated into mainstream oncology services. Copyright © 2017 John Wiley & Sons, Ltd.

Improved genetic counseling in Alport syndrome by new variants of COL4A5 gene.

PubMed

Fernandez-Rosado, Francisco; Campos, Ana; Alvarez-Cubero, Maria Jesus; Ruiz, Ana; Entrala-Bernal, Carmen

2015-07-01

There are current requirements of using genetic databases for offering a better genetic assistance to patients of some syndromes, especially those with X-linked heredity patterns (like Alport Syndrome) for the high probability of having descendants affected by the disease. We describe the first reported case of COL4A5 gene missense c.1499 G>T mutation in a 16-year-old girl confirmed to be affected by Alport Syndrome after genetic counseling. Next Generation Sequencing procedures let discover this mutation and offer an accurate clinical treatment to this patient. Current scientific understanding of genetic syndromes suggests the high importance of updated databases and the inclusion of Variant of Unknown Significance related to clinical cases. All of this updating could enable patients to have a better opportunity of diagnosis and having genetic and clinical counseling. This event is even more important in women planning to start a family to have correct genetic counseling regarding the risk posed to offspring, and allowing the decision to undergo prenatal testing. © 2015 Asian Pacific Society of Nephrology.

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome.

PubMed

Katz, L H; Burton-Chase, A M; Advani, S; Fellman, B; Polivka, K M; Yuan, Y; Lynch, P M; Peterson, S K

2016-03-01

Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper gastrointestinal endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer (EC) and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for EC and only one-third advised relatives to have genetic counseling. Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of nondiagnostic germline mutation testing among patients with LLS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome

PubMed Central

Katz, Lior H.; Burton-Chase, Allison M.; Advani, Shailesh; Fellman, Bryan; Polivka, Katrina M.; Yuan, Ying; Lynch, Patrick M.; Peterson, Susan K.

2016-01-01

Background Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Methods Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Results Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper GI endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for endometrial cancer and only one-third advised relatives to have genetic counseling. Conclusions Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of non-diagnostic germline mutation testing among patients with LLS. PMID:26272410

Initial Results of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

PubMed

Howarth, Dt R; Lum, Sharon S; Esquivel, Pamela; Garberoglio, Carlos A; Senthil, Maheswari; Solomon, Naveenraj L

2015-10-01

Multigene panel testing for hereditary cancer risk has recently become commercially available; however, the impact of its use on patient care is undefined. We sought to evaluate results from implementation of panel testing in a multidisciplinary cancer center. We performed a retrospective review of consecutive patients undergoing genetic testing after initiating use of multigene panel testing at Loma Linda University Medical Center. From February 13 to August 25, 2014, 92 patients were referred for genetic testing based on National Comprehensive Cancer Network guidelines. Testing was completed in 90 patients. Overall, nine (10%) pathogenic mutations were identified: five BRCA1/2, and four in non-BRCA loci. Single-site testing identified one BRCA1 and one BRCA2 mutation. The remaining mutations were identified by use of panel testing for hereditary breast and ovarian cancer. There were 40 variants of uncertain significance identified in 34 patients. The use of panel testing more than doubled the identification rate of clinically significant pathogenic mutations that would have been missed with BRCA testing alone. The large number of variants of uncertain significance identified will require long-term follow-up for potential reclassification. Multigene panel testing provides additional information that may improve patient outcomes.

Factors influencing intrafamilial communication of hereditary breast and ovarian cancer genetic information

PubMed Central

Nycum, Gillian; Avard, Denise; Knoppers, Bartha M

2009-01-01

What factors influence intrafamilial communication of hereditary breast and ovarian cancer (HBOC) genetic risk information? Such information can have health implications for individuals who undergo genetic testing, but it can also have implications for their blood relatives. This literature review adopts an ecological model to summarize factors at the individual, familial, and community levels, as well as cross cutting factors relating to the complexity of HBOC genetic information and responsibilities that this information can give rise to. These factors are complex and may result in conflicting senses of responsibility. Faced with the task of communicating HBOC genetic information, the response may be to attempt to balance the potential negative impact of the information on the well-being of the informee (eg, can s/he handle this information?) against the potential health benefit that the knowledge could result in. This balancing represents an effort to reconcile conflicting approaches to protecting family members, and is a moral dilemma. This review sheds light on the factors that contribute to resolve this dilemma. PMID:19319160

Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees.

PubMed

Baptista, Natalie M; Christensen, Kurt D; Carere, Deanna Alexis; Broadley, Simon A; Roberts, J Scott; Green, Robert C

2016-09-01

American adult adoptees may possess limited information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study. The PGen Study surveyed new 23andMe and Pathway Genomics customers before and 6 months after receiving PGT results. Exploratory analyses compared adoptees' and nonadoptees' PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and postdisclosure actions using logistic regression models. Of 1,607 participants, 80 (5%) were adopted. As compared with nonadoptees, adoptees were more likely to cite limited knowledge of family health history (OR = 10.1; 95% CI = 5.7-19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6-4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated health-care utilization or health-behavior change. PGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history.Genet Med 18 9, 924-932.

Impact of Huntington Disease Gene-Positive Status on Pre-Symptomatic Young Adults and Recommendations for Genetic Counselors.

PubMed

Gong, Ping; Fanos, Joanna H; Korty, Lauren; Siskind, Carly E; Hanson-Kahn, Andrea K

2016-12-01

Huntington disease (HD) is an autosomal dominant, progressive neurodegenerative disorder for which there is no cure. Predictive testing for HD is available to asymptomatic at-risk individuals. Approximately half of the population undergoing predictive testing for HD consists of young adults (≤35 years old). Finishing one's education, starting a career, engaging in romantic relationships and becoming a parent are key milestones of young adulthood. We conducted a qualitative study to explore how testing gene-positive for HD influences young adults' attainment of these milestones, and to identify major challenges that pre-symptomatic young adults face to aid the development of targeted genetic counseling. Results of our study demonstrate that 1) knowing one's gene-positive status results in an urgency to reach milestones and positively changes young adults' approach to life; 2) testing positive influences young adults' education and career choices, romantic relationships, and family planning; 3) young adults desire flexible and tailored genetic counseling to address needs and concerns unique to this population. Findings of this study contribute to the understanding of the impact of predictive testing for HD on young adults, and highlight issues unique to this population that call for further research, intervention and advocacy.

Direct to consumer genetic testing and the libertarian right to test.

PubMed

Bonython, Wendy Elizabeth; Arnold, Bruce Baer

2017-08-20

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.

Large, Prospective Analysis of the Reasons Patients Do Not Pursue BRCA Genetic Testing Following Genetic Counseling.

PubMed

Hayden, Sommer; Mange, Sarah; Duquette, Debra; Petrucelli, Nancie; Raymond, Victoria M

2017-08-01

Genetic counseling (GC) and genetic testing (GT) identifies high-risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high-risk individuals, and demonstrate the value of pre-GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA-related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT. From 2008 to 2012, 10,726 patients underwent GC; 3476 (32.4%) did not pursue GT. Primary reasons included: not the best test candidate (28.1%), not clinically indicated (23.3%), and insurance/out of pocket cost concerns (13.6%). Patient disinterest was the primary reason for declining in 17.1%. Insurance/out of pocket cost concerns were the primary reason for not testing in 13.4% of untested individuals with private insurance. Among untested individuals with breast and/or ovarian cancer, 22.5% reported insurance/out of pocket cost concerns as the primary reason for not testing and 6.6% failed to meet Medicare criteria. In a five-year time period, nearly one-third of patients who underwent BRCA GC did not pursue GT. GT was not indicated in almost half of patients. Insurance/out of pocket cost concerns continue to be barriers.

Medium-based noninvasive preimplantation genetic diagnosis for human α-thalassemias-SEA.

PubMed

Wu, Haitao; Ding, Chenhui; Shen, Xiaoting; Wang, Jing; Li, Rong; Cai, Bing; Xu, Yanwen; Zhong, Yiping; Zhou, Canquan

2015-03-01

To develop a noninvasive medium-based preimplantation genetic diagnosis (PGD) test for α-thalassemias-SEA. The embryos of α-thalassemia-SEA carriers undergoing in vitro fertilization (IVF) were cultured. Single cells were biopsied from blastomeres and subjected to fluorescent gap polymerase chain reaction (PCR) analysis; the spent culture media that contained embryo genomic DNA and corresponding blastocysts as verification were subjected to quantitative-PCR (Q-PCR) detection of α-thalassemia-SEA. The diagnosis efficiency and allele dropout (ADO) ratio were calculated, and the cell-free DNA concentration was quantitatively assessed in the culture medium. The diagnosis efficiency of medium-based α-thalassemias-SEA detection significantly increased compared with that of biopsy-based fluorescent gap PCR analysis (88.6% vs 82.1%, P < 0.05). There is no significant difference regarding ADO ratio between them. The optimal time for medium-based α-thalassemias-SEA detection is Day 5 (D5) following IVF. Medium-based α-thalassemias-SEA detection could represent a novel, quick, and noninvasive approach for carriers to undergo IVF and PGD.

Ovariectomy results in inbred strain-specific increases in anxiety-like behavior in mice

PubMed Central

Schoenrock, Sarah Adams; Oreper, Daniel; Young, Nancy; Ervin, Robin Betsch; Bogue, Molly A.; Valdar, William; Tarantino, Lisa M.

2017-01-01

Women are at an increased risk for developing affective disorders during times of hormonal flux, including menopause when the ovaries cease production of estrogen. However, while all women undergo menopause, not all develop an affective disorder. Increased vulnerability can result from genetic predisposition, environmental factors and gene by environment interactions. In order to investigate interactions between genetic background and estrogen depletion, we performed bilateral ovariectomy, a surgical procedure that results in estrogen depletion and is thought to model the post-menopausal state, in a genetically defined panel of 37 inbred mouse strains. Seventeen days post-ovariectomy, we assessed behavior in two standard rodent assays of anxiety- and depressive-like behavior, the open field and forced swim tests. We detected a significant interaction between ovariectomy and genetic background on anxiety-like behavior in the open field. No strain specific effects of ovariectomy were observed in the forced swim assay. However, we did observe significant strain effects for all behaviors in both the open field and forced swim tests. This study is the largest to date to look at the effects of ovariectomy on behavior and provides evidence that ovariectomy interacts with genetic background to alter anxiety-like behavior in an animal model of menopause. PMID:27693591

The impact of receiving predictive genetic information about Lynch syndrome on individual colonoscopy and smoking behaviors

PubMed Central

Kim, Joanne Soo-Min; Coyte, Peter C.; Cotterchio, Michelle; Keogh, Louise A.; Flander, Louisa B.; Gaff, Clara; Laporte, Audrey

2016-01-01

Background This study investigated whether receiving the results of predictive genetic testing for Lynch syndrome—indicating the presence or absence of an inherited predisposition to various cancers, including colorectal cancer—was associated with change in individual colonoscopy and smoking behaviours, which could prevent colorectal cancer. Methods The study population included individuals with no previous diagnosis of colorectal cancer, whose families had already-identified deleterious mutations in the mismatch repair or EPCAM genes. Hypotheses were generated from a simple health economics model and tested against individual-level panel data from the Australasian Colorectal Cancer Family Registry. Results The empirical analysis revealed evidence consistent with some of the hypotheses, with a higher likelihood of undergoing colonoscopy in those who discovered their genetic predisposition to colorectal cancer and a lower likelihood of quitting smoking in those who discovered their lack thereof. Conclusion Predictive genetic information about Lynch syndrome was associated with change in individual colonoscopy and smoking behaviours but not necessarily in ways to improve population health. Impact The study findings suggest that the impact of personalized medicine on disease prevention is intricate, warranting further analyses to determine the net benefits and costs. PMID:27528600

Assessment of demand for prenatal diagnostic testing using willingness to pay.

PubMed

Caughey, Aaron B; Washington, A Eugene; Gildengorin, Virginia; Kuppermann, Miriam

2004-03-01

To investigate the demand for invasive prenatal diagnostic testing (amniocentesis and chorionic villous sampling) in a racially/ethnically diverse group of pregnant women of all ages in the San Francisco Bay Area by using estimates of willingness to pay for these procedures. We surveyed 447 women of varying ages, ethnicity, and socioeconomic levels to assess their desire to undergo and willingness to pay for invasive prenatal testing for chromosomal disorders. Each woman was asked what she would be willing to pay for invasive diagnostic testing up to the full cost of the procedure. We also asked several demographic and attitudinal questions. Overall, 49% of the women indicated an interest in undergoing invasive prenatal diagnostic testing. Women aged 35 years and older were more likely to desire testing as compared with women aged less than 35 years (72% versus 36%, P <.001). Of the women aged less than 35 years who desired testing, 31% indicated that they would be willing to pay the full price of $1,300, whereas 73% were willing to pay a portion of the cost. Maternal age of 35 years or greater (odds ratio [OR] 3.3; 95% confidence interval [CI] 2.0, 5.6) and willingness to have an elective abortion (OR 2.8; 95% CI 1.6, 4.9) were significant predictors of desire to undergo prenatal diagnostic testing after controlling for income, race/ethnicity, and education. Maternal age of 35 years or greater (OR 3.5; 95% CI 1.59, 7.88) and having an income greater than $35,000 (OR 2.3; 95% CI 1.02, 5.26) were significant predictors of willingness to pay the full price of testing. A substantial proportion of women of all ages indicate a desire to undergo and a willingness to pay for prenatal diagnostic testing. Variations in willingness to pay are correlated with both socioeconomic and attitudinal differences in addition to age. Guidelines regarding use of prenatal genetic diagnosis should be expanded to offer testing to all women, not just those deemed at increased risk. II-2

[Present status and tasks for genetic testing and risk-reducing surgery in patients with hereditary breast and ovarian cancer].

PubMed

Arai, Masami; Taki, Keiko; Iwase, Haruko; Takizawa, Ken; Nishimura, Seiichiro; Iwase, Takuji

2012-04-01

In Japan, awareness of hereditary breast and ovarian cancer (HBOC) has gradually increased among health care workers and the general population. We focus on two current topics: genetic testing and risk-reducing surgery for HBOC. Genetic testing for BRCA1 and BRCA2, the genes responsible for HBOC, is performed to diagnose HBOC. PCR-direct sequencing is a standard method used for BRCA1/2 mutation analysis. Recently, genetic rearrangement of BRCA1 was reported in a Japanese patient with HBOC. Therefore, MLPA tests are also being included in routine genetic testing for the disease. The result of "uncertain significance, " which indicates unclear pathogenic significance, is obtained in about 3% of all patients who undergo BRCA1/2 genetic tests. Furthermore, novel candidate genes for HBOC, such as RAD51C, PALB2, and BRIP1, were recently identified. Prophylactic surgical intervention for HBOC includes procedures such as risk-reducing bilateral salpingo-oophorectomy (RRSO) and risk-reducing mastectomy(RRM). In Japan, RRSO is performed in very few patients at present. Increasing evidence from overseas indicates that RRSO contributes to a decreased incidence of ovarian/breast cancers and lowers overall mortality. Therefore, a system for performing RRSO was established in our institute. RRSO was approved to be performed as a clinical examination by our Institutional Review Board. The clinical significance of ipsilateral complete mastectomy and RRM remains unclear. Based on the NCCN guidelines, conservative mastectomy with radiation therapy is relatively contraindicated in patients with HBOC. However, several studies have reported that conservative mastectomy with radiation the rapydoes not increase the incidence of recurrent or metachronous breast cancers in the ipsilateral breast of mutation-positive patients when compared to mutation-negative or control patients. However, more aggressive malignancies seem to be included in the mutation-positive group(especially BRCA1 -mutation-positive cases). RRM clearly reduced the incidence of breast cancers. RRM may also be allowed as a treatment option for HBOC in Japan.

Strategies for identifying new prions in yeast

PubMed Central

MacLea, Kyle S

2011-01-01

The unexpected discovery of two prions, [URE3] and [PSI+], in Saccharomyces cerevisiae led to questions about how many other proteins could undergo similar prion-based structural conversions. However, [URE3] and [PSI+] were discovered by serendipity in genetic screens. Cataloging the full range of prions in yeast or in other organisms will therefore require more systematic search methods. Taking advantage of some of the unique features of prions, various researchers have developed bioinformatic and experimental methods for identifying novel prion proteins. These methods have generated long lists of prion candidates. The systematic testing of some of these prion candidates has led to notable successes; however, even in yeast, where rapid growth rate and ease of genetic manipulation aid in testing for prion activity, such candidate testing is laborious. Development of better methods to winnow the field of prion candidates will greatly aid in the discovery of new prions, both in yeast and in other organisms, and help us to better understand the role of prions in biology. PMID:22052351

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

PubMed

Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

2013-11-01

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005.

Sperm retrieval rate and pregnancy rate in infertile couples undergoing in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia in Hong Kong.

PubMed

Ko, J Ky; Chai, J; Lee, V Cy; Li, R Hw; Lau, E; Ho, K L; Tam, P C; Yeung, W Sb; Ho, P C; Ng, E Hy

2016-12-01

There are currently no local data on the sperm retrieval and pregnancy rates in in-vitro fertilisation and testicular sperm extraction cycles, especially with regard to the presence of genetic abnormalities. This study aimed to determine the sperm retrieval and pregnancy rates in infertile couples who underwent in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia. This retrospective case series was conducted at a tertiary assisted reproduction unit in Hong Kong. Men with non-obstructive azoospermia who underwent in-vitro fertilisation and testicular sperm extraction between January 2001 and December 2013 were included. The main outcome measures were sperm retrieval and pregnancy rates. During the study period, 89 men with non-obstructive azoospermia underwent in-vitro fertilisation and testicular sperm extraction. Sperm was successfully retrieved in 40 (44.9%) men. There was no statistically significant difference in the sperm retrieval rate of those with karyotypic abnormalities (2/5, 40.0% vs 28/61, 45.9%; P=1.000) and AZFc microdeletion (3/6, 50.0% vs 28/61, 45.9%; P=1.000) compared with those without. Sperms were successfully retrieved in patients who had mosaic Klinefelter syndrome (2/3, 66.7%) but not in the patient with non-mosaic Klinefelter syndrome. No sperms were found in men with AZFa or AZFb microdeletions. Pregnancy test was positive in 15 (16.9%) patients and the clinical pregnancy rate was 13.5% (12/89) per cycle. The clinical pregnancy rate per transfer was 34.3% (12/35). The sperm retrieval rate and clinical pregnancy rate per initiated cycle in men undergoing in-vitro fertilisation and testicular sperm extraction in our unit were 44.9% and 13.5%, respectively. No sperms could be retrieved in the presence of AZFa and AZFb microdeletions, but karyotype and AZFc microdeletion abnormalities otherwise did not predict the success of sperm retrieval in couples undergoing in-vitro fertilisation and testicular sperm extraction. Genetic tests are important prior to testicular sperm extraction for patient selection and genetic counselling.

The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.

PubMed

Grotegut, Chad A; Ngan, Emily; Garrett, Melanie E; Miranda, Marie Lynn; Ashley-Koch, Allison E; Swamy, Geeta K

2017-09-01

Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. The objective of this study was to determine whether genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the oxytocin receptor, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. Pregnant women with a singleton gestation residing in Durham County, NC, were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype-tagging single-nucleotide polymorphisms in OXTR and 7 haplotype-tagging single-nucleotide polymorphisms in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for the association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were used. Race/ethnicity was included in all models because of differences in allele frequencies across populations, and Bonferroni correction for multiple testing was used. DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. Eighteen haplotype-tagging single-nucleotide polymorphisms within OXTR and 7 haplotype-tagging single-nucleotide polymorphisms within GRK6 were examined. Five single-nucleotide polymorphisms in OXTR showed nominal significance with maximal infusion rate of oxytocin, and two single-nucleotide polymorphisms in OXTR were associated with total oxytocin dose received. One single-nucleotide polymorphism in OXTR and two single-nucleotide polymorphisms in GRK6 were associated with duration of labor, one of which met the multiple testing threshold (P = .0014, rs2731664 [GRK6], mean duration of labor, 17.7 hours vs 20.2 hours vs 23.5 hours for AA, AC, and CC genotypes, respectively). Three single-nucleotide polymorphisms, two in OXTR and one in GRK6, showed nominal significance with mode of delivery. Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. With further research, pharmacogenomic approaches may potentially be utilized to develop personalized treatment to improve safety and efficacy outcomes among women undergoing induction of labor. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy

PubMed Central

Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

2013-01-01

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation – ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005. PMID:24225486

Risk Perception and Psychological Distress in Genetic Counselling for Hereditary Breast and/or Ovarian Cancer.

PubMed

Cicero, G; De Luca, R; Dorangricchia, P; Lo Coco, G; Guarnaccia, C; Fanale, D; Calò, V; Russo, A

2017-10-01

Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.

"For all my family's sake, I should go and find out": an Australian report on genetic counseling and testing uptake in individuals at high risk of breast and/or ovarian cancer.

PubMed

Wakefield, Claire E; Ratnayake, Paboda; Meiser, Bettina; Suthers, Graeme; Price, Melanie A; Duffy, Jessica; Tucker, Kathy

2011-06-01

Despite proven benefits, the uptake of genetic counseling and testing by at-risk family members of BRCA1 and BRCA2 mutation carriers remains low. This study aimed to examine at-risk individuals' reported reasons for and against familial cancer clinic (FCC) attendance and genetic testing. Thirty-nine telephone interviews were conducted with relatives of high-risk mutation carriers, 23% (n = 9) of whom had not previously attended an FCC. Interview responses were analyzed using the frameworks of Miles and Huberman. The reasons most commonly reported for FCC attendance were for clarification of risk status and to gain access to testing. While disinterest in testing was one reason for FCC nonattendance, several individuals were unaware of their risk (n = 3) or their eligibility to attend an FCC (n = 2), despite being notified of their risk status through their participation in a large-scale research project. Individuals' reasons for undergoing testing were in line with that reported elsewhere; however, concerns about discrimination and insurance were not reported in nontestees. Current guidelines regarding notifying individuals discovered to be at increased risk in a research, rather than clinical setting, take a largely nondirective approach. However, this study demonstrates that individuals who receive a single letter notifying them of their risk may not understand/value the information they receive.

[Genetic counseling and instruction of marriage for deaf young people: study of 115 cases].

PubMed

Han, Bing; Dai, Pu; Wang, Guo-Jian; Yuan, Yong-Yi; Li, Qi; Zhang, Xin; Kang, Dong-Yang; Han, Dong-Yi

2009-03-17

To invesigate the molecular pathogenesis of deafness among the youth by means of genetic testing so as to provide pre-marriage genetic counseling and instruction for the deaf youth. 217 deaf young people, 126 males and 91 females, aged 18.9 (16 - 26), from Yunnan and Guizhou provinces, underwent history taking, auditory testing, and collection of peripheral blood samples. Genomic DNA and mitochondrial DNA were extracted to undergo sequence analysis of the entire gene GJB2, common point mutation of SLC26A4 gene, and mutation of mtDNA A1555G. Genetic prediction and marriage instruction were provided to each subject based on these results. Twenty-three of the 117 persons (10.5%), 13 males and 10 females, were mtDNA A1555G mutation carriers and they were instructed that they, their maternal relatives, and the offspring of the female carriers, should they be born, should strictly avoid the administration of amino glycoside antibiotics. Twenty eight of the 115 persons (12.9%), were confirmed to carry homozygous or compound GJB2 mutations, 5 individuals (2.3%) carried heterozygous GJB2 mutation, 19 (8.8%) carried homozygous or compound SLC26A4 mutations, and one (0.5%) carried heterozygous SLC26A4 mutation. The suggestion for them was to avoid getting married with deaf partners caused by the same deaf gene or with individuals carrying mutations in the same deaf gene. Meanwhile, suggestions such as avoiding aggressive exercises and head injury were provided to the deaf young people with SLC26A4 mutations. Genetic testing can provide more accurate and useful genetic counseling and instruction to deaf young people for their partner selection and eugenics.

Spontaneous coronary artery dissection and its association with heritable connective tissue disorders.

PubMed

Henkin, Stanislav; Negrotto, Sara M; Tweet, Marysia S; Kirmani, Salman; Deyle, David R; Gulati, Rajiv; Olson, Timothy M; Hayes, Sharonne N

2016-06-01

Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. 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/

Influence of individual differences in disease perception on consumer response to direct-to-consumer genomic testing

PubMed Central

Boeldt, D.L.; Schork, N.J.; Topol, E.J.; Bloss, C.S.

2016-01-01

Individuals who undergo multiplex direct-to-consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow-up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer’s disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services. PMID:24798746

Influence of individual differences in disease perception on consumer response to direct-to-consumer genomic testing.

PubMed

Boeldt, D L; Schork, N J; Topol, E J; Bloss, C S

2015-03-01

Individuals who undergo multiplex direct-to-consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow-up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer's disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer

PubMed Central

Hall, Michael J.; Reid, Julia E.; Burbidge, Lynn A.; Pruss, Dmitry; Deffenbaugh, Amie M.; Frye, Cynthia; Wenstrup, Richard J.; Ward, Brian E.; Scholl, Thomas A.; Noll, Walter W.

2009-01-01

Background In women at increased risk for breast and ovarian cancer, the identification of a BRCA1/2 mutation has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1/2 testing in high-risk women from diverse ancestral backgrounds exists due to variability in prevalence estimates of deleterious (disease-associated) mutations in non-White populations. We examined the prevalence of BRCA1/2 mutations in an ethnically diverse group of women referred for genetic testing. Methods We conducted a cross-sectional analysis to assess the prevalence of BRCA1/2 mutations in a group of non-Ashkenazi Jewish women undergoing genetic testing. Results From 1996-2006, 46,276 women meeting study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of subjects, and recurrent deleterious mutations (prevalence > 2%) were identified in all ancestral groups. Women of non-European descent were younger (45.9 yrs, SD11.6) than European (50.0 yrs, SD11.9)(p<0.001). Women of African (15.6%)[OR 1.3(1.1-1.5)] and Latin American (14.8%)[OR 1.2(1.1-1.4)] ancestries had a significantly higher prevalence of deleterious BRCA1/2 mutations compared to women of Western European ancestry (12.1%), primarily due to an increased prevalence of BRCA1 mutations in these two groups. Non-European ethnicity was strongly associated with having a variant of uncertain significance; however, re-classification decreased variant reporting (12.8%→5.9%), with women of African ancestry experiencing the largest decline (58%). Conclusions Mutation prevalence is high among women referred for clinical BRCA1/2 testing, and risk is similar across diverse ethnicities. BRCA1/2 testing is integral to cancer risk assessment in all high-risk women. PMID:19241424

Adopting Genetics: Motivations and Outcomes of Personal Genomic Testing in Adult Adoptees

PubMed Central

Baptista, Natalie M.; Christensen, Kurt D.; Carere, Deanna Alexis; Broadley, Simon A.; Roberts, J. Scott; Green, Robert C.

2015-01-01

Purpose American adult adoptees may possess limited amounts of information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study. Methods The PGen Study surveyed new 23andMe and Pathway Genomics customers prior to and 6 months after receiving PGT results. Exploratory analyses compared adoptees’ and non-adoptees’ PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and post-disclosure actions using logistic regression models. Results Of 1607 participants, 80 (5%) were adopted. As compared to non-adoptees, adoptees were more likely to cite limited family health history knowledge (OR = 10.1; 95% CI = 5.7–19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6–4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated healthcare utilization or health behavior change. Conclusion PGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history. PMID:26820063

Plant contributions to our understanding of sex chromosome evolution.

PubMed

Charlesworth, Deborah

2015-10-01

A minority of angiosperms have male and female flowers separated in distinct individuals (dioecy), and most dioecious plants do not have cytologically different (heteromorphic) sex chromosomes. Plants nevertheless have several advantages for the study of sex chromosome evolution, as genetic sex determination has evolved repeatedly and is often absent in close relatives. I review sex-determining regions in non-model plant species, which may help us to understand when and how (and, potentially, test hypotheses about why) recombination suppression evolves within young sex chromosomes. I emphasize high-throughput sequencing approaches that are increasingly being applied to plants to test for non-recombining regions. These data are particularly illuminating when combined with sequence data that allow phylogenetic analyses, and estimates of when these regions evolved. Together with comparative genetic mapping, this has revealed that sex-determining loci and sex-linked regions evolved independently in many plant lineages, sometimes in closely related dioecious species, and often within the past few million years. In reviewing recent progress, I suggest areas for future work, such as the use of phylogenies to allow the informed choice of outgroup species suitable for inferring the directions of changes, including testing whether Y chromosome-like regions are undergoing genetic degeneration, a predicted consequence of losing recombination. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Detecting Coevolution in Mammalian Sperm–Egg Fusion Proteins

PubMed Central

CLAW, KATRINA G.; GEORGE, RENEE D.; SWANSON, WILLIE J.

2018-01-01

SUMMARY Interactions between sperm and egg proteins can occur physically between gamete surface-binding proteins, and genetically between gamete proteins that work in complementary pathways in which they may not physically interact. Physically interacting sperm–egg proteins have been functionally identified in only a few species, and none have been verified within mammals. Candidate genes on both the sperm and egg surfaces exist, but gene deletion studies do not support functional interactions between these sperm–egg proteins; interacting sperm–egg proteins thus remain elusive. Cooperative gamete proteins undergo rapid evolution, and it is predicted that these sperm–egg proteins will also have correlated evolutionary rates due to compensatory changes on both the sperm and egg. To explore potential physical and genetic interactions in sperm–egg proteins, we sequenced four candidate genes from diverse primate species, and used regression and likelihood methods to test for signatures of coevolution between sperm–egg gene pairs. With both methods, we found that the egg protein CD9 coevolves with the sperm protein IZUMO1, suggesting a physical or genetic interaction occurs between them. With regression analysis, we found that CD9 and CRISP2 have correlated rates of evolution, and with likelihood analysis, that CD9 and CRISP1 have correlated rates. This suggests that the different tests may reflect different levels of interaction, be it physical or genetic. Coevolution tests thus provide an exploratory method for detecting potentially interacting sperm–egg protein pairs. PMID:24644026

Detecting coevolution in mammalian sperm-egg fusion proteins.

PubMed

Claw, Katrina G; George, Renee D; Swanson, Willie J

2014-06-01

Interactions between sperm and egg proteins can occur physically between gamete surface-binding proteins, and genetically between gamete proteins that work in complementary pathways in which they may not physically interact. Physically interacting sperm-egg proteins have been functionally identified in only a few species, and none have been verified within mammals. Candidate genes on both the sperm and egg surfaces exist, but gene deletion studies do not support functional interactions between these sperm-egg proteins; interacting sperm-egg proteins thus remain elusive. Cooperative gamete proteins undergo rapid evolution, and it is predicted that these sperm-egg proteins will also have correlated evolutionary rates due to compensatory changes on both the sperm and egg. To explore potential physical and genetic interactions in sperm-egg proteins, we sequenced four candidate genes from diverse primate species, and used regression and likelihood methods to test for signatures of coevolution between sperm-egg gene pairs. With both methods, we found that the egg protein CD9 coevolves with the sperm protein IZUMO1, suggesting a physical or genetic interaction occurs between them. With regression analysis, we found that CD9 and CRISP2 have correlated rates of evolution, and with likelihood analysis, that CD9 and CRISP1 have correlated rates. This suggests that the different tests may reflect different levels of interaction, be it physical or genetic. Coevolution tests thus provide an exploratory method for detecting potentially interacting sperm-egg protein pairs. © 2014 Wiley Periodicals, Inc.

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy.

PubMed

Harper, Joyce; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo J; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

2014-08-01

How has the interface between genetics and assisted reproduction technology (ART) evolved since 2005? The interface between ART and genetics has become more entwined as we increase our understanding about the genetics of infertility and we are able to perform more comprehensive genetic testing. In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and ART and published an extended background paper, recommendations and two Editorials. An interdisciplinary workshop was held, involving representatives of both professional societies and experts from the European Union Eurogentest2 Coordination Action Project. In March 2012, a group of experts from the European Society of Human Genetics, the European Society of Human Reproduction and Embryology and the EuroGentest2 Coordination Action Project met to discuss developments at the interface between clinical genetics and ART. As more genetic causes of reproductive failure are now recognized and an increasing number of patients undergo testing of their genome prior to conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and PGD may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from RCTs to substantiate that the technique is both effective and efficient. Whole genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving, but still remains very heterogeneous and often contradictory. The lack of legal harmonization and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe, and beyond. This continually evolving field requires communication between the clinical genetics and IVF teams and patients to ensure that they are fully informed and can make well-considered choices. Funding was received from ESHRE, ESHG and EuroGentest2 European Union Coordination Action project (FP7 - HEALTH-F4-2010-26146) to support attendance at this meeting. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients

PubMed Central

Windemuth, Andreas; de Leon, Jose; Goethe, John W.; Schwartz, Harold I.; Woolley, Stephen; Susce, Margaret; Kocherla, Mohan; Bogaard, Kali; Holford, Theodore R.; Seip, Richard L.; Ruaño, Gualberto

2016-01-01

The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI). Thirteen candidate genes from previous studies of the same phenotypes in non-psychiatric populations were tested for association. We confirmed 8 of the 13 candidate genes at the 95% confidence level. An increased genetic effect size was observed for triglycerides in the psychiatric population compared to that in the cardiovascular population. PMID:21851846

78 FR 15366 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... biomarkers of early effect (for pulmonary fibrosis, cardiovascular disease, and genetic damage) will be... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30Day-13-12RS] Agency Forms Undergoing Paperwork Reduction Act Review The Centers for Disease Control and Prevention...

Advancing Pharmacogenomics Education in the Core PharmD Curriculum through Student Personal Genomic Testing

PubMed Central

Adams, Solomon M.; Anderson, Kacey B.; Coons, James C.; Smith, Randall B.; Meyer, Susan M.; Parker, Lisa S.

2016-01-01

Objective. To develop, implement, and evaluate “Test2Learn” a program to enhance pharmacogenomics education through the use of personal genomic testing (PGT) and real genetic data. Design. One hundred twenty-two second-year doctor of pharmacy (PharmD) students in a required course were offered PGT as part of a larger program approach to teach pharmacogenomics within a robust ethical framework. The program added novel learning objectives, lecture materials, analysis tools, and exercises using individual-level and population-level genetic data. Outcomes were assessed with objective measures and pre/post survey instruments. Assessment. One hundred students (82%) underwent PGT. Knowledge significantly improved on multiple assessments. Genotyped students reported a greater increase in confidence in understanding test results by the end of the course. Similarly, undergoing PGT improved student’s self-perceived ability to empathize with patients compared to those not genotyped. Most students (71%) reported feeling PGT was an important part of the course, and 60% reported they had a better understanding of pharmacogenomics specifically because of the opportunity. Conclusion. Implementation of PGT in the core pharmacy curriculum was feasible, well-received, and enhanced student learning of pharmacogenomics. PMID:26941429

Characterization of the transcriptome, nucleotide sequence polymorphism, and natural selection in the desert adapted mouse Peromyscus eremicus.

PubMed

MacManes, Matthew D; Eisen, Michael B

2014-01-01

As a direct result of intense heat and aridity, deserts are thought to be among the most harsh of environments, particularly for their mammalian inhabitants. Given that osmoregulation can be challenging for these animals, with failure resulting in death, strong selection should be observed on genes related to the maintenance of water and solute balance. One such animal, Peromyscus eremicus, is native to the desert regions of the southwest United States and may live its entire life without oral fluid intake. As a first step toward understanding the genetics that underlie this phenotype, we present a characterization of the P. eremicus transcriptome. We assay four tissues (kidney, liver, brain, testes) from a single individual and supplement this with population level renal transcriptome sequencing from 15 additional animals. We identified a set of transcripts undergoing both purifying and balancing selection based on estimates of Tajima's D. In addition, we used the branch-site test to identify a transcript-Slc2a9, likely related to desert osmoregulation-undergoing enhanced selection in P. eremicus relative to a set of related non-desert rodents.

Drug & Gene Interaction Risk Analysis With & Without Genetic Testing Among Patients Undergoing MTM

ClinicalTrials.gov

2017-02-22

Cytochrome P450 CYP2D6 Enzyme Deficiency; Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Extensive Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Cytochrome P450 CYP2C9 Enzyme Deficiency; Cytochrome P450 CYP2C19 Enzyme Deficiency; Drug Metabolism, Poor, CYP2D6-RELATED; Drug Metabolism, Poor, CYP2C19-RELATED; CYP2D6 Polymorphism

Genetic diversity and population history of the red panda (Ailurus fulgens) as inferred from mitochondrial DNA sequence variations.

PubMed

Su, B; Fu, Y; Wang, Y; Jin, L; Chakraborty, R

2001-06-01

The red panda (Ailurus fulgens) is one of the flagship species in worldwide conservation and is of special interest in evolutionary studies due to its taxonomic uniqueness. We sequenced a 236-bp fragment of the mitochondrial D-loop region in a sample of 53 red pandas from two populations in southwestern China. Seventeen polymorphic sites were found, together with a total of 25 haplotypes, indicating a high level of genetic diversity in the red panda. However, no obvious genetic divergence was detected between the Sichuan and Yunnan populations. The consensus phylogenetic tree of the 25 haplotypes was starlike. The pairwise mismatch distribution fitted into a pattern of populations undergoing expansion. Furthermore, Fu's F(S) test of neutrality was significant for the total population (F(S) = -7.573), which also suggests a recent population expansion. Interestingly, the effective population size in the Sichuan population was both larger and more stable than that in the Yunnan population, implying a southward expansion from Sichuan to Yunnan.

Colorectal Liver Metastases: Does the Future of Precision Medicine Lie in Genetic Testing?

PubMed

Barbon, Carlotta; Margonis, Georgios Antonios; Andreatos, Nikolaos; Rezaee, Neda; Sasaki, Kazunari; Buettner, Stefan; Damaskos, Christos; Pawlik, Timothy M; He, Jin; Wolfgang, Christopher L; Weiss, Matthew J

2018-04-11

Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.

Early Diagnosis of Fibrodysplasia Ossificans Progressiva

PubMed Central

Kaplan, Frederick S.; Xu, Meiqi; Glaser, David L.; Collins, Felicity; Connor, Michael; Kitterman, Joseph; Sillence, David; Zackai, Elaine; Ravitsky, Vardit; Zasloff, Michael; Ganguly, Arupa; Shore, Eileen M.

2012-01-01

BACKGROUND Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodys-plasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification. METHODS We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation. RESULTS All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G>A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor. CONCLUSION Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory diagnostic genetic testing, and the avoidance of additional harmful diagnostic and treatment procedures. This is the first report of genetic confirmation of fibrodysplasia ossificans progressiva before the appearance of heterotopic ossification. Pediatricians should be aware of the early diagnostic features of fibrodysplasia ossificans progressiva, even before the appearance of heterotopic ossification. This awareness should prompt early genetic consultation and testing and the institution of assiduous precautions to prevent iatrogenic harm. PMID:18450872

Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

PubMed Central

Thapar, Anita; Harold, Gordon; Rice, Frances; Ge, XiaoJia; Boivin, Jacky; Hay, Dale; van den Bree, Marianne; Lewis, Allyson

2007-01-01

Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated. Conclusion A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects. PMID:17587444

Comprehensive embryo testing. Experts' opinions regarding future directions: an expert panel study on comprehensive embryo testing.

PubMed

Hens, Kristien; Dondorp, Wybo J; Geraedts, Joep P M; de Wert, Guido M

2013-05-01

What do scientists in the field of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) consider to be the future direction of comprehensive embryo testing? Although there are many biological and technical limitations, as well as uncertainties regarding the meaning of genetic variation, comprehensive embryo testing will impact the IVF/PGD practice and a timely ethical reflection is needed. Comprehensive testing using microarrays is currently being introduced in the context of PGD and PGS, and it is to be expected that whole-genome sequencing will also follow. Current ethical and empirical sociological research on embryo testing focuses on PGD as it is practiced now. However, empirical research and systematic reflection regarding the impact of comprehensive techniques for embryo testing is missing. In order to understand the potential of this technology and to be able to adequately foresee its implications, we held an expert panel with seven pioneers in PGD. We conducted an expert panel in October 2011 with seven PGD pioneers from Belgium, The Netherlands, Germany and the UK. Participants expected the use of comprehensive techniques in the context of PGD. However, the introduction of these techniques in embryo testing requires timely ethical reflection as it involves a shift from choosing an embryo without a particular genetic disease (i.e. PGD) or most likely to result in a successful pregnancy (i.e. PGS) to choosing the best embryo based on a much wider set of criteria. Such ethical reflection should take account of current technical and biological limitations and also of current uncertainties with regard to the meaning of genetic variance. However, ethicists should also not be afraid to look into the future. There was a general agreement that embryo testing will be increasingly preceded by comprehensive preconception screening, thus enabling smart combinations of genetic testing. The group was composed of seven participants from four Western Europe countries. As willingness to participate in this study may be connected with expectations regarding the pace and direction of future developments, selection bias cannot be excluded. The introduction of comprehensive screening techniques in embryo testing calls for further ethical reflection that is grounded in empirical work. Specifically, there is a need for studies querying the opinions of infertile couples undergoing IVF/PGS regarding the desirability of embryo screening beyond aneuploidy. This research was supported by the CSG, Centre for Society and Life Sciences (project number: 70.1.074). The authors declare no conflict of interest. N/A.

DECIDE: a Decision Support Tool to Facilitate Parents' Choices Regarding Genome-Wide Sequencing.

PubMed

Birch, Patricia; Adam, S; Bansback, N; Coe, R R; Hicklin, J; Lehman, A; Li, K C; Friedman, J M

2016-12-01

We describe the rationale, development, and usability testing for an integrated e-learning tool and decision aid for parents facing decisions about genome-wide sequencing (GWS) for their children with a suspected genetic condition. The online tool, DECIDE, is designed to provide decision-support and to promote high quality decisions about undergoing GWS with or without return of optional incidental finding results. DECIDE works by integrating educational material with decision aids. Users may tailor their learning by controlling both the amount of information and its format - text and diagrams and/or short videos. The decision aid guides users to weigh the importance of various relevant factors in their own lives and circumstances. After considering the pros and cons of GWS and return of incidental findings, DECIDE summarizes the user's responses and apparent preferred choices. In a usability study of 16 parents who had already chosen GWS after conventional genetic counselling, all participants found DECIDE to be helpful. Many would have been satisfied to use it alone to guide their GWS decisions, but most would prefer to have the option of consulting a health care professional as well to aid their decision. Further testing is necessary to establish the effectiveness of using DECIDE as an adjunct to or instead of conventional pre-test genetic counselling for clinical genome-wide sequencing.

Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

PubMed

Taylor, Natalie; Long, Janet C; Debono, Deborah; Williams, Rachel; Salisbury, Elizabeth; O'Neill, Sharron; Eykman, Elizabeth; Braithwaite, Jeffrey; Chin, Melvin

2016-03-12

Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high-likelihood Lynch syndrome patients pre-post intervention. Run charts will be used to continuously monitor change in referrals over time, based on scheduled monthly audits. This project is based on a tested and refined implementation strategy (TDFI approach). Enhancing the process of identifying and referring people at high-likelihood risk of Lynch syndrome for genetic counselling will improve outcomes for patients and their relatives, and potentially save public money.

Breast Cancer Risk Estimation and Personal Insurance: A Qualitative Study Presenting Perspectives from Canadian Patients and Decision Makers

PubMed Central

Dalpé, Gratien; Ngueng Feze, Ida; Salman, Shahad; Joly, Yann; Hagan, Julie; Lévesque, Emmanuelle; Dorval, Véronique; Blouin-Bougie, Jolyane; Amara, Nabil; Dorval, Michel; Simard, Jacques

2017-01-01

Genetic stratification approaches in personalized medicine may considerably improve our ability to predict breast cancer risk for women at higher risk of developing breast cancer. Notwithstanding these advantages, concerns have been raised about the use of the genetic information derived in these processes, outside of the research and medical health care settings, by third parties such as insurers. Indeed, insurance applicants are asked to consent to insurers accessing their medical information (implicitly including genetic) to verify or determine their insurability level, or eligibility to certain insurance products. This use of genetic information may result in the differential treatment of individuals based on their genetic information, which could lead to higher premium, exclusionary clauses or even the denial of coverage. This phenomenon has been commonly referred to as “Genetic Discrimination” (GD). In the Canadian context, where federal Bill S-201, An Act to prohibit and prevent genetic discrimination, has recently been enacted but may be subject to constitutional challenges, information about potential risks to insurability may raise issues in the clinical context. We conducted a survey with women in Quebec who have never been diagnosed with breast cancer to document their perspectives. We complemented the research with data from 14 semi-structured interviews with decision-makers in Quebec to discuss institutional issues raised by the use of genetic information by insurers. Our results provide findings on five main issues: (1) the reluctance to undergo genetic screening test due to insurability concerns, (2) insurers' interest in genetic information, (3) the duty to disclose genetic information to insurers, (4) the disclosure of potential impacts on insurability before genetic testing, and (5) the status of genetic information compared to other health data. Overall, both groups of participants (the women surveyed and the decision-makers interviewed) acknowledged having concerns about GD and reported a need for better communication tools discussing insurability risk. Our conclusions regarding concerns about GD and the need for better communication tools in the clinical setting may be transferable to the broader Canadian context. PMID:28983318

Breast Cancer Risk Estimation and Personal Insurance: A Qualitative Study Presenting Perspectives from Canadian Patients and Decision Makers.

PubMed

Dalpé, Gratien; Ngueng Feze, Ida; Salman, Shahad; Joly, Yann; Hagan, Julie; Lévesque, Emmanuelle; Dorval, Véronique; Blouin-Bougie, Jolyane; Amara, Nabil; Dorval, Michel; Simard, Jacques

2017-01-01

Genetic stratification approaches in personalized medicine may considerably improve our ability to predict breast cancer risk for women at higher risk of developing breast cancer. Notwithstanding these advantages, concerns have been raised about the use of the genetic information derived in these processes, outside of the research and medical health care settings, by third parties such as insurers. Indeed, insurance applicants are asked to consent to insurers accessing their medical information (implicitly including genetic) to verify or determine their insurability level, or eligibility to certain insurance products. This use of genetic information may result in the differential treatment of individuals based on their genetic information, which could lead to higher premium, exclusionary clauses or even the denial of coverage. This phenomenon has been commonly referred to as "Genetic Discrimination" (GD). In the Canadian context, where federal Bill S-201, An Act to prohibit and prevent genetic discrimination , has recently been enacted but may be subject to constitutional challenges, information about potential risks to insurability may raise issues in the clinical context. We conducted a survey with women in Quebec who have never been diagnosed with breast cancer to document their perspectives. We complemented the research with data from 14 semi-structured interviews with decision-makers in Quebec to discuss institutional issues raised by the use of genetic information by insurers. Our results provide findings on five main issues: (1) the reluctance to undergo genetic screening test due to insurability concerns, (2) insurers' interest in genetic information, (3) the duty to disclose genetic information to insurers, (4) the disclosure of potential impacts on insurability before genetic testing, and (5) the status of genetic information compared to other health data. Overall, both groups of participants (the women surveyed and the decision-makers interviewed) acknowledged having concerns about GD and reported a need for better communication tools discussing insurability risk. Our conclusions regarding concerns about GD and the need for better communication tools in the clinical setting may be transferable to the broader Canadian context.

Genetic factors contribute to bleeding after cardiac surgery.

PubMed

Welsby, I J; Podgoreanu, M V; Phillips-Bute, B; Mathew, J P; Smith, P K; Newman, M F; Schwinn, D A; Stafford-Smith, M

2005-06-01

Postoperative bleeding remains a common, serious problem for cardiac surgery patients, with striking inter-patient variability poorly explained by clinical, procedural, and biological markers. We tested the hypothesis that genetic polymorphisms of coagulation proteins and platelet glycoproteins are associated with bleeding after cardiac surgery. Seven hundred and eighty patients undergoing aortocoronary surgery with cardiopulmonary bypass were studied. Clinical covariates previously associated with bleeding were recorded and DNA isolated from preoperative blood. Matrix Assisted Laser Desorption/Ionization, Time-Of-Flight (MALDI-TOF) mass spectroscopy or polymerase chain reaction were used for genotype analysis. Multivariable linear regression modeling, including all genetic main effects and two-way gene-gene interactions, related clinical and genetic predictors to bleeding from the thorax and mediastinum. Nineteen candidate polymorphisms were assessed; seven [GPIaIIa-52C>T and 807C>T, GPIb alpha 524C>T, tissue factor-603A>G, prothrombin 20210G>A, tissue factor pathway inhibitor-399C>T, and angiotensin converting enzyme (ACE) deletion/insertion] demonstrate significant association with bleeding (P < 0.01). Adding genetic to clinical predictors results improves the model, doubling overall ability to predict bleeding (P < 0.01). We identified seven genetic polymorphisms associated with bleeding after cardiac surgery. Genetic factors appear primarily independent of, and explain at least as much variation in bleeding as clinical covariates; combining genetic and clinical factors double our ability to predict bleeding after cardiac surgery. Accounting for genotype may be necessary when stratifying risk of bleeding after cardiac surgery.

Phenotypic and Genetic Variations in Obligate Parthenogenetic Populations of Eriosoma lanigerum Hausmann (Hemiptera: Aphididae).

PubMed

Ruiz-Montoya, L; Zúñiga, G; Cisneros, R; Salinas-Moreno, Y; Peña-Martínez, R; Machkour-M'Rabet, S

2015-12-01

The study of phenotypic and genetic variation of obligate parthenogenetic organisms contributes to an understanding of evolution in the absence of genetic variation produced by sexual reproduction. Eriosoma lanigerum Hausmann undergoes obligate parthenogenesis in Mexico City, Mexico, due to the unavailability of the host plants required for sexual reproduction. We analysed the phenotypic and genetic variation of E. lanigerum in relation to the dry and wet season and plant phenology. Aphids were collected on two occasions per season on a secondary host plant, Pyracantha koidzumii, at five different sites in the southern area of Mexico City, Mexico. Thirteen morphological characteristics were measured from 147 to 276 individuals per site and per season. A multivariate analysis of variance was performed to test the effect of the season, site and their interaction on morphological traits. Morphological variation was summarised using a principal component analysis. Genetic variation was described using six enzymatic loci, four of which were polymorphic. Our study showed that the site and season has a significant effect on morphological trait variation. The largest aphids were recorded during cold temperatures with low relative humidity and when the plant was at the end of the fruiting period. The mean genetic diversity was low (mean H e =  .161), and populations were genetically structured by season and site. Morphological and genetic variations appear to be associated with environmental factors that directly affect aphid development and/or indirectly by host plant phenology.

TRACKING GENE FLOW FROM A GENETICALLY MODIFIED CREEPING BENTGRASS -- METHODS, MEASURES AND LESSONS LEARNED

EPA Science Inventory

Creeping bentgrass (CBG) expressing an engineered gene for resistance to glyphosate herbicide is one of the first genetically modified (GM) perennial crops to undergo regulatory review for commercial release by the US Department of Agriculture Animal Plant Health and Inspection S...

Associations between self-referral and health behavior responses to genetic risk information.

PubMed

Christensen, Kurt D; Roberts, J Scott; Zikmund-Fisher, Brian J; Kardia, Sharon Lr; McBride, Colleen M; Linnenbringer, Erin; Green, Robert C

2015-01-01

Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer's disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P < 0.01). They also dropped out of the study before genetic risk disclosure less frequently (26% versus 41%, P < 0.001). Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p < 0.001) and diets (21% vs 12%, p = 0.016) six weeks post-disclosure, whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities (15% vs 21%, p = 0.413) or diets (8% versus 16%, P = 0.190). Similarly, ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs (20% vs 5%, p < 0.001), but not ARPs (5% versus 9%, P = 0.365). Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. ClinicalTrials.gov NCT00089882 and NCT00462917.

Clinical Characteristics of Disaccharidase Deficiencies Among Children Undergoing Upper Endoscopy.

PubMed

Cohen, Stanley A; Oloyede, Hannah; Gold, Benjamin D; Mohammed, Aminu; Elser, Heather E

2018-06-01

The epidemiology and clinical significance of disaccharidase deficiencies have not been thoroughly characterized. Recent work suggests at least genetic sucrase-isomaltase deficiency is more prevalent than previously believed. Because lactase deficiency (LD) is well described, the present study focuses on the clinical characteristics of children with disaccharidase deficiencies determined by esophagogastroduodenoscopy. Endoscopic records were reviewed from patients undergoing esophagogastroduodenoscopies with biopsies assayed for disaccharidase activity performed by 13 pediatric gastroenterologists during 5 years (2010-2014). Presenting symptoms, clinical and histological diagnosis, treatment, disaccharidase results, and demographic variables were obtained from medical and endoscopic records of those with maltase and sucrase deficiency (SD). Among 963 patients undergoing intestinal disaccharidase testing, 73 (7.6%) had SD on biopsy (enzyme activity <25 μmol · min · g). Thirty-four (34/73; 47%) had normal duodenal histology and are the focus of this report. Four patients had SD without LD. Pan-disaccharidase deficiency was observed in 24 patients when maltase and palatinase assays were obtained (n = 646), and 11 had SD + LD when just those 2 enzymes were analyzed (n = 317). Those with SD without LD were younger 4.6 ± 6.1 versus 14.1 ± 3.6 years and uniformly presented with diarrhea. Patients with pan-disaccharidase deficiency or SD + LD primarily reported abdominal pain (33/35; 94%), diarrhea (16/35; 46%), nausea (14/35; 40%); and poor weight gain/weight loss (10/35; 29%); constipation, flatulence, and bloating were also noted. Maltase deficiency is less common (8/963; 0.8%), presenting with similar symptoms. Genetic sucrase-isomaltase deficiency often occurs together with lactase or pan-disaccharide deficiency. Disaccharidase deficiency should be considered a potential cause of abdominal pain and/or diarrhea in children and adolescents.

Diagnosis of primary ciliary dyskinesia: summary of the ERS Task Force report

PubMed Central

Lucas, Jane S.

2017-01-01

Key points Primary ciliary dyskinesia (PCD) is a genetically and clinically heterogeneous disease characterised by abnormal motile ciliary function. There is no “gold standard” diagnostic test for PCD. The European Respiratory Society (ERS) Task Force Guidelines for diagnosing PCD recommend that patients should be referred for diagnostic testing if they have several of the following features: persistent wet cough; situs anomalies; congenital cardiac defects; persistent rhinitis; chronic middle ear disease with or without hearing loss; or a history, in term infants, of neonatal upper and lower respiratory symptoms or neonatal intensive care admission. The ERS Task Force recommends that patients should be investigated in a specialist PCD centre with access to a range of complementary tests: nasal nitric oxide, high-speed video microscopy analysis and transmission electron microscopy. Additional tests including immunofluorescence labelling of ciliary proteins and genetic testing may also help determine the diagnosis. Educational aims This article is intended for primary and secondary care physicians interested in primary ciliary dyskinesia (PCD), i.e. those who identify patients for testing, and those involved in diagnosing and managing PCD patients. It aims: to inform readers about the new European Respiratory Society Task Force Guidelines for diagnosing patients with PCDto enable primary and secondary care physicians to: identify patients who need diagnostic testing; understand the diagnostic tests that their patients will undergo, the results of the tests and their limitations; and ensure that appropriate care is subsequently delivered. PMID:28894478

Designing specific chloroplast markers for black walnut from a set of universal primers

Treesearch

Erin Victory; Rodney L. Robichaud; Keith Woeste

2003-01-01

Chloroplasts are a valuable source of genetic information because their sequence is highly conserved, they undergo little or no recombination, and they are uniparentally inherited. Chloroplast polymorphisms are powerful genetic tools for identifying matrilineal family groups, studying gene flow from seed versus pollen movement, reconstructing phylogeographic...

How voluntary prenatal diagnosis and selective abortion increase the abnormal human gene pool.

PubMed

Boss, J A

1990-06-01

It is often assumed that prenatal diagnosis followed by the selective abortion of "defective" fetuses has a positive eugenic effect. Although mandatory selective abortion of "defective" fetuses and, more important, carriers would tend to reduce the number of deleterious genes in the gene pool, the present program of voluntary prenatal diagnosis and selective abortion actually increases the number of deleterious genes. This raises the issue of freedom of choice regarding selective abortion and societal pressure on parents to undergo prenatal testing and to abort their fetus should it have a genetic disorder or be a carrier of one.

American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.

PubMed

2003-06-15

As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that the scope of parental authority encompasses the right to decide for or against testing. In the absence of increased risk of a childhood malignancy, ASCO recommends delaying genetic testing until an individual is of sufficient age to make an informed decision regarding such tests. As in other areas of pediatric care, the clinical cancer genetics professional should be an advocate for the best interests of the child. Counseling About Medical Management After Testing: ASCO recommends that oncologists include in pre- and post-test counseling the discussion of possible risks and benefits of cancer early-detection and prevention modalities, some of which have presumed but unproven efficacy for individuals at increased hereditary risk of cancer. Regulation of Genetic Testing: ASCO recommends strengthening regulatory oversight of laboratories that provide clinical cancer predisposition tests. These quality assurance mechanisms should include oversight of the reagents used in genetic testing, interlaboratory comparisons of reference samples, standardization of laboratory genetic test reports, and proficiency testing. Protection From Insurance and Employment Discrimination: ASCO supports establishing a federal law to prohibit discrimination by health insurance providers and employers on the basis of an individual's inherited susceptibility to cancer. Protections against genetic discrimination should apply to those with group coverage, those with individual health insurance policies, and the uninsured. Coverage of Services: ASCO supports efforts to ensure that all individuals at significantly increased risk of hereditary cancer have access to appropriate genetic counseling, testing, screening, surveillance, and all related medical and surgical interventions, which should be covered without penalty by public and private third-party payers. Confidentiality and Communication of Familial Risk: ASCO recommends that providers make concerted efforts to protect the confidentiality of genetic information. However, they should remind patients of the importance of communicating test results to family members, as part of pretest counseling and informed consent discussions. ASCO believes that the cancer care provider's obligations (if any) to at-risk relatives are best fulfilled by communication of familial risk to the person undergoing testing, emphasizing the importance of sharing this information with family members so that they may also benefit. Educational Opportunities in Genetics: ASCO is committed to continuing to provide educational opportunities for physicians and other health care providers regarding the methods of cancer risk assessment, the clinical characteristics of hereditary cancer susceptibility syndromes, and the range of issues related to genetic testing, including pre- and post-test genetic counseling, and risk management, so that health professionals may responsibly integrate the care of persons at increased genetic risk of cancer into the practice of clinical and preventive oncology. Special Issues Relating to Genetic Research on Human Tissues:ASCO recommends that all researchers proposing to use or store human biologic specimens for genetic studies should consult either the responsible institutional review board (IRB) or a comparable body specifically constituted to assess human tissue research, to determine the requirements for protection specific to the study under consideration. This consultation should take place before the project is initiated. The determination of the need for informed consent or authorization in such studies should depend on whether the research involves tests for genetic markers of known clinical significance and whether research data will be linked to protected health information, as well as other considerations specific to the study proposed. Special attention should also be paid to 1) whether future research findings will be disclosed to the research participants, 2) whether future contact of participants is planned, 3) whether and how protected health information about the tissue donors will be stored, and what will happen to study specimens after the trial ends. In addition, ASCO affirms the right of people contributing tissue to a databank to rescind their permission, in accordance with federal privacy regulations.

Genetics Consultation Rates Following a Diagnosis of High-Grade Serous Ovarian Carcinoma in the Canadian Province of Ontario.

PubMed

McGee, Jacob; Panabaker, Karen; Leonard, Sean; Ainsworth, Peter; Elit, Laurie; Shariff, Salimah Z

2017-03-01

In 2001, the province of Ontario expanded cancer genetic testing eligibility to include all women with high-grade serous ovarian carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. The aim of this study was to determine the proportion of women who attended genetics counseling for consideration of BRCA1/2 gene analysis. We also sought to examine if regional differences in consultation rate exist across administrative health regions in the province of Ontario. We identified all women with a pathological diagnosis of HGSC in the province of Ontario between 1997 until 2011. Our primary outcome was the 2-year rate of genetics consultation following a diagnosis of HGSC. We compared consultation rates over time and geographical regions and applied multiple logistic regression to identify predictors of genetics consultation. Of the 5412 women with a diagnosis of HGSC over the study period, 6.6% were seen for genetics consultation within 2 years of diagnosis. Factors predictive of genetics consultation included history of breast cancer (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.87-6.78), era of diagnosis (2009-2011 vs 1997-2000; OR, 10.59; 95% CI, 5.02-22.33), and younger age at diagnosis (OR, 0.95; 95% CI, 0.94-0.97 for each additional year). No regional differences in consultation rate were seen. Despite an increasing rate across eras, a small proportion of women with HGSC undergo genetics consultation. Efforts are required to increase cancer genetics consultation in patients with HGSC in the province of Ontario.

Expanding the phenotype of alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome): description of an additional case and review of the literature.

PubMed

Schell-Apacik, Chayim; Hardt, Michael; Ertl-Wagner, Birgit; Klopocki, Eva; Möhrenschlager, Matthias; Heinrich, Uwe; von Voss, Hubertus

2008-09-01

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.

Genetic polymorphisms and the risk of stroke after cardiac surgery.

PubMed

Grocott, Hilary P; White, William D; Morris, Richard W; Podgoreanu, Mihai V; Mathew, Joseph P; Nielsen, Dahlia M; Schwinn, Debra A; Newman, Mark F

2005-09-01

Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery. Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies. A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3'UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (P=0.0020). We demonstrate that common genetic variants of CRP (3'UTR 1846C/T) and IL-6 (-174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post-cardiac surgery stroke.

"I Don't Want to Be an Ostrich": Managing Mothers' Uncertainty during BRCA1/2 Genetic Counseling.

PubMed

Fisher, Carla L; Roccotagliata, Thomas; Rising, Camella J; Kissane, David W; Glogowski, Emily A; Bylund, Carma L

2017-06-01

Families who face genetic disease risk must learn how to grapple with complicated uncertainties about their health and future on a long-term basis. Women who undergo BRCA 1/2 genetic testing describe uncertainty related to personal risk as well as their loved ones', particularly daughters', risk. The genetic counseling setting is a prime opportunity for practitioners to help mothers manage uncertainty in the moment but also once they leave a session. Uncertainty Management Theory (UMT) helps to illuminate the various types of uncertainty women encounter and the important role of communication in uncertainty management. Informed by UMT, we conducted a thematic analysis of 16 genetic counseling sessions between practitioners and mothers at risk for, or carriers of, a BRCA1/2 mutation. Five themes emerged that represent communication strategies used to manage uncertainty: 1) addresses myths, misunderstandings, or misconceptions; 2) introduces uncertainty related to science; 3) encourages information seeking or sharing about family medical history; 4) reaffirms or validates previous behavior or decisions; and 5) minimizes the probability of personal risk or family members' risk. Findings illustrate the critical role of genetic counseling for families in managing emotionally challenging risk-related uncertainty. The analysis may prove beneficial to not only genetic counseling practice but generations of families at high risk for cancer who must learn strategic approaches to managing a complex web of uncertainty that can challenge them for a lifetime.

Phylogeographic analyses and genetic structure illustrate the complex evolutionary history of Phragmites australis in Mexico.

PubMed

Colin, Ricardo; Eguiarte, Luis E

2016-05-01

Genetic data suggest that three lineages of Phragmites australis are found in North America: the Native North American lineage, the Gulf Coast lineage, and the Invasive lineage. In Mexico, P. australis is a common species, but nothing is known about the distribution or ecology of these lineages. We examined the phylogeography of P. australis to analyze the current geographic distribution of genetic variation, demographic history, and dispersal patterns to better understand its evolutionary history in Mexico. We sampled 427 individuals from 28 populations. We used two noncoding regions of chloroplast DNA to estimate the levels of genetic variation and identified the genetic groups across the species' geographical range in Mexico. We compared the genealogical relationships among haplotypes with those previously reported. A hypothesis of demographic expansion was also tested for the Mexican P. australis lineages. We found 13 new haplotypes native to Mexico that might be undergoing an active process of expansion and diversification. Genealogical analyses provided evidence that two independent lineages of P. australis are present in Mexico. The invasive lineage was not detected with our sampling. Our estimates of population expansions in Mexico ranged from 0.202 to 0.726 mya. Phragmites australis is a native species that has been in Mexico for thousands of years. Genetic data suggest that climatic changes during the Pleistocene played an important role in the demographic expansion of the populations that constitute the different genetic groups of P. australis in Mexico. © 2016 Botanical Society of America.

Preoperative risk assessment among women undergoing bilateral prophylactic mastectomy for cancer risk reduction.

PubMed

Rueth, Natasha M; McMahon, Melissa; Arrington, Amanda K; Swenson, Karen; Leach, Joseph; Tuttle, Todd M

2011-09-01

Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting. We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested. From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P < 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference. Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.

Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.

PubMed

Perez, E E; De Biasi, M

2015-05-01

Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high-throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal-associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test, or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behaviors, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time-consuming ethanol treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

BRCA Genetic Counseling Among At-Risk Latinas in New York City: New Beliefs Shape New Generation

PubMed Central

Edwards, Tiffany; Villagra, Cristina; Rodriguez, M. Carina; Thompson, Hayley S.; Jandorf, Lina; Valdimarsdottir, Heiddis B.

2015-01-01

Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas’ beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N=54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members’ cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately <55 years) reporting that they were more interested in educating themselves about counseling and other ways to prevent cancer. Younger women were also less likely to ascribe to traditionally Latino-centered cultural beliefs which could serve as barriers (e.g. machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this under-represented community. PMID:25120034

BRCA genetic counseling among at-risk Latinas in New York City: new beliefs shape new generation.

PubMed

Sussner, Katarina M; Edwards, Tiffany; Villagra, Cristina; Rodriguez, M Carina; Thompson, Hayley S; Jandorf, Lina; Valdimarsdottir, Heiddis B

2015-02-01

Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas' beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N = 54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members' cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately <55 years) reporting that they were more interested in educating themselves about counseling and other ways to prevent cancer. Younger women were also less likely to ascribe to traditionally Latino-centered cultural beliefs which could serve as barriers (e.g. machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this underrepresented community.

What made her give up her breasts: a qualitative study on decisional considerations for contralateral prophylactic mastectomy among breast cancer survivors undergoing BRCA1/2 genetic testing.

PubMed

Kwong, Ava; Chu, Annie T W

2012-01-01

This qualitative study retrospectively examined the experience and psychological impact of contralateral prophylactic mastectomy (CPM) among Southern Chinese females with unilateral breast cancer history who underwent BRCA1/2 genetic testing. Limited knowledge is available on this topic especially among Asians; therefore, the aim of this study was to acquire insight from Chinese females' subjective perspectives. A total of 12 semi-structured in-depth interviews, with 11 female BRCA1/BRCA 2 mutated gene carriers and 1 non-carrier with a history of one-sided breast cancer and genetic testing performed by the Hong Kong Hereditary Breast Cancer Family Registry, who subsequently underwent CPM, were assessed using thematic analysis and a Stage Conceptual Model. Breast cancer history, procedures conducted, cosmetic satisfaction, pain, body image and sexuality issues, and cancer risk perception were discussed. Retrieval of medical records using a prospective database was also performed. All participants opted for prophylaxis due to their reservations concerning the efficacy of surveillance and worries of recurrent breast cancer risk. Most participants were satisfied with the overall results and their decision. One-fourth expressed different extents of regrets. Psychological relief and decreased breast cancer risk were stated as major benefits. Spouses' reactions and support were crucial for post-surgery sexual satisfaction and long-term adjustment. Our findings indicate that thorough education on cancer risk and realistic expectations of surgery outcomes are crucial for positive adjustment after CPM. Appropriate genetic counseling and pre-and post-surgery psychological counseling were necessary. This study adds valuable contextual insights into the experiences of living with breast cancer fear and the importance of involving spouses when counseling these patients.

Using genetic and phenotypic comparisons to evaluate apparent segregation among Kokanee spawning groups

USGS Publications Warehouse

Whitlock, Steven L.; Campbell, Matthew R.; Quist, Michael C.; Dux, Andrew M.

2018-01-01

Genetic and phenotypic traits of spatially and temporally segregated kokanee Oncorhynchus nerka spawning groups in Lake Pend Oreille, Idaho, were compared to test for evidence of divergence on the basis of ecotype (stream spawners versus shoreline spawners) and spawn timing and to describe morphological, life history, and reproductive variation within and among groups. Early and late spawning runs were found to be reproductively isolated; however, there was no clear evidence of genetic differentiation between ecotypes. Spawning groups within the same ecotype differed in length, age distribution, mean length at age, fecundity, and egg size. Variation in reproductive attributes was due primarily to differences in length distributions. Larger‐bodied shore‐spawning kokanee were located in areas where egg survival is known to be enhanced by downwelling, suggesting that the distribution of shore‐spawning kokanee may be partly structured by competition for spawning habitats with groundwater influence. This study contributes to other research indicating that introduced kokanee populations are unlikely to undergo adaptive divergence if they have a history of population fluctuations and are supplemented regularly.

Economic evaluation of using a genetic test to direct breast cancer chemoprevention in white women with a previous breast biopsy.

PubMed

Green, Linda E; Dinh, Tuan A; Hinds, David A; Walser, Bryan L; Allman, Richard

2014-04-01

Tamoxifen therapy reduces the risk of breast cancer but increases the risk of serious adverse events including endometrial cancer and thromboembolic events. The cost effectiveness of using a commercially available breast cancer risk assessment test (BREVAGen™) to inform the decision of which women should undergo chemoprevention by tamoxifen was modeled in a simulated population of women who had undergone biopsies but had no diagnosis of cancer. A continuous time, discrete event, mathematical model was used to simulate a population of white women aged 40-69 years, who were at elevated risk for breast cancer because of a history of benign breast biopsy. Women were assessed for clinical risk of breast cancer using the Gail model and for genetic risk using a panel of seven common single nucleotide polymorphisms. We evaluated the cost effectiveness of using genetic risk together with clinical risk, instead of clinical risk alone, to determine eligibility for 5 years of tamoxifen therapy. In addition to breast cancer, the simulation included health states of endometrial cancer, pulmonary embolism, deep-vein thrombosis, stroke, and cataract. Estimates of costs in 2012 US dollars were based on Medicare reimbursement rates reported in the literature and utilities for modeled health states were calculated as an average of utilities reported in the literature. A 50-year time horizon was used to observe lifetime effects including survival benefits. For those women at intermediate risk of developing breast cancer (1.2-1.66 % 5-year risk), the incremental cost-effectiveness ratio for the combined genetic and clinical risk assessment strategy over the clinical risk assessment-only strategy was US$47,000, US$44,000, and US$65,000 per quality-adjusted life-year gained, for women aged 40-49, 50-59, and 60-69 years, respectively (assuming a price of US$945 for genetic testing). Results were sensitive to assumptions about patient adherence, utility of life while taking tamoxifen, and cost of genetic testing. From the US payer's perspective, the combined genetic and clinical risk assessment strategy may be a moderately cost-effective alternative to using clinical risk alone to guide chemoprevention recommendations for women at intermediate risk of developing breast cancer.

Determination of genetic toxicity and potential carcinogenicity in vitro--challenges post the Seventh Amendment to the European Cosmetics Directive.

PubMed

Tweats, D J; Scott, A D; Westmoreland, C; Carmichael, P L

2007-01-01

Genetic toxicology and its role in the detection of carcinogens is currently undergoing a period of reappraisal. There is an increasing interest in developing alternatives to animal testing and the three R's of reduction, refinement and replacement are the basis for EU and national animal protection laws the Seventh Amendment to the EU Cosmetics Directive will ban the marketing of cosmetic/personal care products that contain ingredients that have been tested in animal models. Thus in vivo tests such as the bone marrow micronucleus test, which has a key role in current testing strategies for genotoxicity, will not be available for this class of products. The attrition rate for new, valuable and safe chemicals tested in an in vitro-only testing battery, using the in vitro tests currently established for genotoxicity screening, will greatly increase once this legislation is in place. In addition there has been an explosion of knowledge concerning the cellular and molecular events leading to carcinogenesis. This knowledge has not yet been fully factored into screening chemicals for properties that are not directly linked to mutation induction. Thus there is a pressing need for new, more accurate approaches to determine genotoxicity and carcinogenicity. However, a considerable challenge is presented for these new approaches to be universally accepted and new tests sufficiently validated by March 2009 when the animal testing and marketing bans associated with the Seventh Amendment are due to come into force. This commentary brings together ideas and approaches from several international workshops and meetings to consider these issues.

Embryonic aneuploidy does not differ among genetic ancestry according to continental origin as determined by ancestry informative markers.

PubMed

Franasiak, Jason M; Olcha, Meir; Shastri, Shefali; Molinaro, Thomas A; Congdon, Haley; Treff, Nathan R; Scott, Richard T

2016-10-01

Is embryonic aneuploidy, as determined by comprehensive chromosome screening (CCS), related to genetic ancestry, as determined by ancestry informative markers (AIMs)? In this study, when determining continental ancestry utilizing AIMs, genetic ancestry does not have an impact on embryonic aneuploidy. Aneuploidy is one of the best-characterized barriers to ART success and little information exists regarding ethnicity and whole chromosome aneuploidy in IVF. Classifying continental ancestry utilizing genetic profiles from a selected group of single nucleotide polymorphisms, termed AIMs, can determine ancestral origin with more accuracy than self-reported data. This is a retrospective cohort study of patients undergoing their first cycle of IVF with CCS at a single center from 2008 to 2014. There were 2328 patients identified whom had undergone IVF/CCS and AIM genotyping. All patients underwent IVF/ICSI and CCS after trophectoderm biopsy. Patients' serum was genotyped using 32 custom AIMs to identify continental origin. Admixture proportions were determined using Bayesian clustering algorithms. Patients were assigned to the population (European, African, East Asian or Central/South Asian) corresponding to their greatest admixture proportion. The mean number of embryos tested was 5.3 (range = 1-40) and the mode was 1. Patients' ethnic classifications revealed European (n = 1698), African (n = 103), East Asian (n = 206) or Central/South Asian (n = 321). When controlling for age and BMI, aneuploidy rate did not differ by genetic ancestry (P = 0.28). The study type (retrospective) and the ability to classify patients by continental rather than sub-continental origin as well as the predominantly European patient mix may impact generalizability. Post hoc power calculation revealed power to detect a 16.8% difference in embryonic aneuploidy between the two smallest sample size groups. These data do not support differences in embryonic aneuploidy among various genetic ancestry groups in patients undergoing IVF/CCS. We used a novel approach of determining continental origin using a validated panel of AIMs as opposed to patient self-reported ethnicities. It does not appear that specific recommendations for aneuploidy screening should be made based upon continental heritage. None. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A unified partial likelihood approach for X-chromosome association on time-to-event outcomes.

PubMed

Xu, Wei; Hao, Meiling

2018-02-01

The expression of X-chromosome undergoes three possible biological processes: X-chromosome inactivation (XCI), escape of the X-chromosome inactivation (XCI-E), and skewed X-chromosome inactivation (XCI-S). Although these expressions are included in various predesigned genetic variation chip platforms, the X-chromosome has generally been excluded from the majority of genome-wide association studies analyses; this is most likely due to the lack of a standardized method in handling X-chromosomal genotype data. To analyze the X-linked genetic association for time-to-event outcomes with the actual process unknown, we propose a unified approach of maximizing the partial likelihood over all of the potential biological processes. The proposed method can be used to infer the true biological process and derive unbiased estimates of the genetic association parameters. A partial likelihood ratio test statistic that has been proved asymptotically chi-square distributed can be used to assess the X-chromosome genetic association. Furthermore, if the X-chromosome expression pertains to the XCI-S process, we can infer the correct skewed direction and magnitude of inactivation, which can elucidate significant findings regarding the genetic mechanism. A population-level model and a more general subject-level model have been developed to model the XCI-S process. Finite sample performance of this novel method is examined via extensive simulation studies. An application is illustrated with implementation of the method on a cancer genetic study with survival outcome. © 2017 WILEY PERIODICALS, INC.

Exploring Indian women's reproductive decision-making regarding prenatal testing.

PubMed

Gupta, Jyotsna Agnihotri

2010-02-01

Pregnant women in large cities and small towns of India are increasingly undergoing prenatal testing (PNT) on the advice of medical practitioners to ensure foetal health and to prevent the birth of disabled children. In the last two decades, several studies have been conducted in India to determine the extent of proliferation of PNT for sex selection, the profile of women/couples who avail themselves of it and their attitudes towards it, but hardly any research exists which studies women's use of PNT for genetic purposes. Drawing on empirical research, this paper aims to identify factors and actors that influence women's decision-making regarding testing and whether to continue a pregnancy after PNT and how informed their choice is. The research shows that once placed in the role of autonomous and responsible decision-makers, women are making very pragmatic decisions, although the information they possess is highly inadequate and incomplete and their life circumstances too constraining.

Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions

PubMed Central

Essebier, Alexandra; Vera Wolf, Patricia; Cao, Minh Duc; Carroll, Bernard J.; Balasubramanian, Sureshkumar; Bodén, Mikael

2016-01-01

More than 30 human genetic diseases are linked to tri-nucleotide repeat expansions. There is no known mechanism that explains repeat expansions in full, but changes in the epigenetic state of the associated locus has been implicated in the disease pathology for a growing number of examples. A comprehensive comparative analysis of the genomic features associated with diverse repeat expansions has been lacking. Here, in an effort to decipher the propensity of repeats to undergo expansion and result in a disease state, we determine the genomic coordinates of tri-nucleotide repeat tracts at base pair resolution and computationally establish epigenetic profiles around them. Using three complementary statistical tests, we reveal that several epigenetic states are enriched around repeats that are associated with disease, even in cells that do not harbor expansion, relative to a carefully stratified background. Analysis of over one hundred cell types reveals that epigenetic states generally tend to vary widely between genic regions and cell types. However, there is qualified consistency in the epigenetic signatures of repeats associated with disease suggesting that changes to the chromatin and the DNA around an expanding repeat locus are likely to be similar. These epigenetic signatures may be exploited further to develop models that could explain the propensity of repeats to undergo expansions. PMID:27013954

Awareness of Pap testing and factors associated with intent to undergo Pap testing by level of sexual experience in unmarried university students in Korea: results from an online survey

PubMed Central

2014-01-01

Background Young and unmarried women have not been a target group for cervical cancer prevention in Korea. No previous studies have investigated the awareness of Pap testing, the intention to undergo Pap testing, or the factors associated with that intention, in this group of women. This information would be useful for an expansion in the focus of primary cervical cancer prevention. This study aimed to compare the awareness of Pap testing between groups of unmarried university students in Korea, and to investigate the factors associated with the intention to undergo Pap testing, by level of sexual experience. Methods A total of 475 unmarried university students who had never undergone a Pap test completed a web-based survey. Differences in awareness of the importance of the Pap test, confidence in Pap testing, intention to undergo the test, attitudes, subjective norms, perceived control, stigma, and shame by level of sexual experience were analysed using independent t-tests. Associations between measurement variables and intention to undergo Pap testing were analysed using correlation analysis. Variables yielding significant associations (p < 0.05) were included in a stepwise multiple regression model of intention to undergo Pap testing. Results Most participants perceived that the need for regular Pap testing was less important (score, 77.76) than other methods of cervical cancer prevention. They were not confident that is was an effective method of cervical cancer prevention for themselves (score, 59.56). There were differences in confidence in Pap testing and in the factors associated with intention to undergo Pap testing between sexually experienced and sexually inexperienced students. Regardless of level of sexual experience, the subjective norm was the most important predictor of intention to undergo Pap testing. Conclusions There was a low level of Pap screening awareness among the students. The factors associated with intention to undergo Pap testing differed by level of sexual experience. Social influence was an important factor that could be used to increase the intention to receive a Pap test in the university student population. Strategies to increase the intention to undergo Pap screening should be introduced and should be adapted to the level of sexual experience. PMID:25163938

A rationale for biopsying embryos reaching the morula stage on Day 6 in women undergoing preimplantation genetic testing for aneuploidy.

PubMed

Irani, M; Zaninovic, N; Canon, C; O'Neill, C; Gunnala, V; Zhan, Q; Palermo, G; Reichman, D; Rosenwaks, Z

2018-05-01

Is there a benefit to assessing ploidy in delayed embryos reaching the morula stage on Day 6 of development? Day-6 morulae should be considered for biopsy in women <40 years old undergoing preimplantation genetic testing for aneuploidy (PGT-A) because they are associated with acceptable, albeit reduced, euploidy and implantation rates (IRs). Embryo development and morphology have been shown to correlate with aneuploidy and pregnancy rates. During PGT-A cycles, embryos are biopsied if they reach the blastocyst stage by Day 5 or 6, whereas slow-developing embryos are typically deselected and discarded. Determining the viability of slow-developing embryos is particularly relevant for women undergoing PGT-A who have diminished ovarian reserve and a relatively low blastocyst yield. This is a retrospective cohort study that was performed at an academic medical center. Patients who underwent IVF with PGT-A were reviewed for inclusion. A total of 1615 cycles were reviewed. All cycles which involved a biopsy of a cavitating or compacted morula on Day 6 were included (n = 763). PGT-A was performed using array comparative genomic hybridization. The aneuploidy and implantation of morulae were compared to those of blastocysts originating from the same couples. The study included 763 cycles in which 1260 morulae and 3014 blastocysts were biopsied. Women were divided into four age groups (<35, 35-37, 38-39 and ≥40 years): the prevalence of aneuploidy was consistently lower among blastocysts (40.3, 50.8, 56 and 78.3%, respectively) than among compacted morulae (68.7, 75.5, 88.9 and 98.1%, respectively) and cavitating morulae (57, 66.4, 81 and 91.6%, respectively) throughout the different age groups (P < 0.001). Of note, the majority of compacted morulae (98.1%) and cavitating morulae (91.6%) were aneuploid in women aged ≥40 years. Compacted and cavitating morulae had significantly higher rates of complex aneuploidy, which involves ≥3 chromosomes, compared with blastocysts (P < 0.001). Furthermore, euploid morulae were associated with a significantly lower IR (28.2 versus 54.6%; P = 0.002) and live birth rate (23.1 versus 55.0%; P = 0.001) compared to euploid blastocysts. This study confirms that Day-6 morulae should not be discarded in young women undergoing PGT-A. However, a potential drawback of biopsying embryos at the morula stage is the inability to distinguish between inner cell mass and trophectoderm cell origin. The sample size of euploid morula transfer cycles in this study was limited. Thus, a larger cohort would be beneficial to validate the reassuring live birth and spontaneous abortion rates reported here. Furthermore, the reproducibility of our findings should be determined at different centers. Although Day-6 morulae are associated with higher aneuploidy rates and lower IRs compared to blastocysts, they still yielded successful pregnancies. Therefore, testing Day-6 morulae should be considered, especially for women <40 years old who are undergoing PGT-A with a small cohort of available blastocysts for biopsy. The authors have nothing to disclose. They received no specific funding for this work. N/A.

Long QT syndrome type 5-Lite: Defining the clinical phenotype associated with the potentially proarrhythmic p.Asp85Asn-KCNE1 common genetic variant.

PubMed

Lane, Conor; Giudicessi, John R; Ye, Dan; Tester, David J; Rohatgi, Ram K; Bos, J Martijn; Ackerman, Michael J

2018-04-03

Long QT syndrome (LQTS) genetic test reports commonly exclude potentially proarrhythmic common variants such as p.Asp85Asn-KCNE1. The purpose of this study was to determine whether a discernible phenotype is associated with p.Asp85Asn-KCNE1 and whether relatively common KCNE1 variants underlie transient QT prolongation pedigrees with negative commercial LQTS genetic tests. Retrospective review was used to compare demographics, symptomatology, and QT parameters of individuals with p.Asp85Asn-KCNE1 in the absence of other rare/ultra-rare variants in LQTS-susceptibility genes and those who underwent comprehensive LQTS genetic testing. Compared to the Genome Aggregation Database, p.Asp85Asn-KCNE1 was more prevalent in individuals undergoing LQTS genetic testing (33/1248 [2.6%] vs 1552/126,652 [1.2%]; P = .0001). In 19 of 33 patients (58%), only p.Asp85Asn-KCNE1 was observed. These patients were predominantly female (90% vs 62%; P = .02) and were less likely to experience syncope (0% vs 34%; P = .0007), receive β-blockers (53% vs 85%; P = .001), or require an implantable cardioverter-defibrillator (5.3% vs 33%; P = .01). However, they exhibited a similar degree of QT prolongation (QTc 460 ms vs 467 ms; P = NS). Whole exome sequencing of 2 commercially genotype-negative pedigrees revealed that p.Asp85Asn-KCNE1 and p.Arg36His-KCNE1 traced with a transient QT prolongation phenotype. Functional characterization of p.Arg36His-KCNE1 demonstrated loss of function, with a 47% reduction in peak I Ks current density in the heterozygous state. We provide further evidence that relatively common variants in KCNE1 may result in a mild QT phenotype designated as "LQT5-Lite" to distinguish such potentially proarrhythmic common variants (ie, functional risk alleles) from rare pathogenic variants that truly confer monogenic disease susceptibility, albeit with incomplete penetrance. Copyright © 2018. Published by Elsevier Inc.

Electrotransformation and clonal isolation of Rickettsia species

PubMed Central

Riley, Sean P; Macaluso, Kevin R; Martinez, Juan J

2015-01-01

Genetic manipulation of obligate intracellular bacteria of the genus Rickettsia is currently undergoing a rapid period of change. The development of viable genetic tools, including replicative plasmids, transposons, homologous recombination, fluorescent protein-encoding genes, and antibiotic selectable markers has provided the impetus for future research development. This unit is designed to coalesce the basic methods pertaining to creation of genetically modified Rickettsia. The unit describes a series of methods, from inserting exogenous DNA into Rickettsia to the final isolation of genetically modified bacterial clones. Researchers working towards genetic manipulation of Rickettsia or similar obligate intracellular bacteria will find these protocols to be a valuable reference. PMID:26528784

Disclosure of genetics research results after the death of the patient participant: a qualitative study of the impact on relatives.

PubMed

Ormondroyd, E; Moynihan, C; Watson, M; Foster, C; Davolls, S; Ardern-Jones, A; Eeles, R

2007-08-01

When a gene mutation is identified in a research study following the death of the study participant, it is not clear whether such information should be made available to relatives. We report here an evaluation of the impact on relatives of being informed of study results that detected pathogenic BRCA2 mutations in a male relative, now deceased, who had early onset (under the age of 55) prostate cancer. The breast and ovarian cancer risk was unknown to the living relatives. Qualitative analysis of interviews with thirteen relatives indicated that those who had a higher risk perception, resulting from an awareness of cancer family history or experiential knowledge of cancer in their family, tended to adjust more easily to the results. All participants believed that genetics research results of clinical significance should be fed back to relatives. Those who were fully aware of the BRCA2 results and implications for themselves felt they had benefited from the information, irrespective of whether or not they had elected for genetic testing, because of the consequent availability of surveillance programs. Initial anxiety upon learning about the BRCA2 result was alleviated by genetic counselling. Factors influencing those who have not engaged with the information included scepticism related to the relative who attempted to inform them, young age and fear of cancer. Those who had not sought genetic counselling did not attempt further dissemination, and some were not undergoing regular screening. Implications for informed consent in genetics research programs, and the requirement for genetic counselling when research results are disclosed, are discussed.

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development.

PubMed

Smith, E N; Ghia, E M; DeBoever, C M; Rassenti, L Z; Jepsen, K; Yoon, K-A; Matsui, H; Rozenzhak, S; Alakus, H; Shepard, P J; Dai, Y; Khosroheidari, M; Bina, M; Gunderson, K L; Messer, K; Muthuswamy, L; Hudson, T J; Harismendy, O; Barrett, C L; Jamieson, C H M; Carson, D A; Kipps, T J; Frazer, K A

2015-04-10

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.

A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification.

PubMed

Tognetto, Alessia; Michelazzo, Maria Benedetta; Calabró, Giovanna Elisa; Unim, Brigid; Di Marco, Marco; Ricciardi, Walter; Pastorino, Roberta; Boccia, Stefania

2017-01-01

Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3-5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS. We performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate. We identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%. This systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

Psychological outcomes and surgical decisions after genetic testing in women newly diagnosed with breast cancer with and without a family history.

PubMed

Meiser, Bettina; Quinn, Veronica F; Mitchell, Gillian; Tucker, Kathy; Watts, Kaaren J; Rahman, Belinda; Peate, Michelle; Saunders, Christobel; Geelhoed, Elizabeth; Gleeson, Margaret; Barlow-Stewart, Kristine; Field, Michael; Harris, Marion; Antill, Yoland C; Susman, Rachel; Bowen, Michael T; Mills, Llew; Kirk, Judy

2018-03-30

In patients with early breast cancer, personal and tumour characteristics other than family history are increasingly used to prompt genetic testing to guide women's cancer management (treatment-focused genetic testing, 'TFGT'). Women without a known strong family history of breast and/or ovarian may be more vulnerable to psychological sequelae arising from TFGT. We compared the impact of TFGT in women with (FH+) and without (FH-) a strong family history on psychological adjustment and surgical decisions. Women aged <50 years with high-risk features were offered TFGT before definitive breast cancer surgery and completed self-report questionnaires at four time points over 12 months. All 128 women opted for TFGT. TFGT identified 18 carriers of a disease-causing variant (50.0% FH+) and 110 non-carriers (59.1% FH+). There were no differences based on family history in bilateral mastectomy (BM) uptake, p = .190, or uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO), p = .093. FH- women had lower decreases in anxiety a year after diagnosis, p = .011, and regret regarding their decision whether to undergo BM, p = .022, or RRBSO, p = .016 than FH + women. FH- carriers reported significantly higher regret regarding their TFGT choice (p = .024) and test-related distress (p = .012) than FH + carriers, but this regret/distress could not be attributed to a concern regarding a possible worse prognosis. These findings indicate that FH- women may require additional counselling to facilitate informed decisions. Carriers without a family history may require additional follow-up counselling to facilitate psychological adjustment to their positive variant results, extra support in making surgical decisions, and counselling about how best to communicate results to family members.

Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

PubMed Central

2010-01-01

Background von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01). Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes. PMID:20064270

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

PubMed

Kerns, Sarah L; Dorling, Leila; Fachal, Laura; Bentzen, Søren; Pharoah, Paul D P; Barnes, Daniel R; Gómez-Caamaño, Antonio; Carballo, Ana M; Dearnaley, David P; Peleteiro, Paula; Gulliford, Sarah L; Hall, Emma; Michailidou, Kyriaki; Carracedo, Ángel; Sia, Michael; Stock, Richard; Stone, Nelson N; Sydes, Matthew R; Tyrer, Jonathan P; Ahmed, Shahana; Parliament, Matthew; Ostrer, Harry; Rosenstein, Barry S; Vega, Ana; Burnet, Neil G; Dunning, Alison M; Barnett, Gillian C; West, Catharine M L

2016-08-01

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling. Copyright © 2016 The Ohio State University Wexner Medical Center. Published by Elsevier B.V. All rights reserved.

Comparative landscape genetics of two frugivorous bats in a biological corridor undergoing agricultural intensification.

PubMed

Cleary, Katherine A; Waits, Lisette P; Finegan, Bryan

2017-09-01

Agricultural intensification in tropical landscapes poses a new threat to the ability of biological corridors to maintain functional connectivity for native species. We use a landscape genetics approach to evaluate impacts of expanding pineapple plantations on two widespread and abundant frugivorous bats in a biological corridor in Costa Rica. We hypothesize that the larger, more mobile Artibeus jamaicensis will be less impacted by pineapple than the smaller Carollia castanea. In 2012 and 2013, we sampled 735 bats in 26 remnant forest patches surrounded by different proportions of forest, pasture, crops and pineapple. We used 10 microsatellite loci for A. jamaicensis and 16 microsatellite loci for C. castanea to estimate genetic diversity and gene flow. Canonical correspondence analyses indicate that land cover type surrounding patches has no impact on genetic diversity of A. jamaicensis. However, for C. castanea, both percentage forest and pineapple surrounding patches explained a significant proportion of the variation in genetic diversity. Least-cost transect analyses (LCTA) and pairwise G″st suggest that for A. jamaicensis, pineapple is more permeable to gene flow than expected, while as expected, forest is the most permeable land cover for gene flow of C. castanea. For both species, LCTA indicate that development may play a role in inhibiting gene flow. The current study answers the call for landscape genetic research focused on tropical and agricultural landscapes, highlights the value of comparative landscape genetics in biological corridor design and management and is one of the few studies of biological corridors in any ecosystem to implement a genetic approach to test corridor efficacy. © 2017 John Wiley & Sons Ltd.

Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PubMed

Elmi, Maryam; Azin, Arash; Elnahas, Ahmad; McCready, David R; Cil, Tulin D

2018-05-14

Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

Histone H4 hyperacetylation and rapid turnover of its acetyl groups in transcriptionally inactive rooster testis spermatids.

PubMed Central

Oliva, R; Mezquita, C

1982-01-01

In order to study the relationship between acetylation of histones, chromatin structure and gene activity, the distribution and turnover of acetyl groups among nucleosomal core histones and the extent of histone H4 acetylation were examined in rooster testis cell nuclei at different stages of spermatogenesis. Histone H4 was the predominant acetylated histone in mature testes. Hyperacetylation of H4 and rapid turnover of its acetyl groups are not univocally correlated with transcriptional activity since they were detected in both genetically active testicular cells and genetically inactive elongated spermatids. During the transition from nucleohistone to nucleoprotamine in elongated spermatids the chromatin undergoes dramatic structural changes with exposition of binding sites on DNA (1). Hyperacetylation of H4 and rapid turnover of its acetyl groups could be correlated with the particular conformation of chromatin in elongated spermatids and might represent a necessary condition for binding of chromosomal proteins to DNA. Images PMID:7162988

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

PubMed Central

Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

2016-01-01

Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

The development of a cancer genetic-specific measure of coping: the GRACE.

PubMed

Phelps, C; Bennett, P; Jones, H; Hood, K; Brain, K; Murray, A

2010-08-01

Generic measures of coping fail to capture the process of undergoing specific health processes such as cancer genetic risk assessment. The Genetic Risk Assessment Coping Evaluation (GRACE) has been developed to provide greater specificity of measurement. Based upon previous research findings, the GRACE measures the degree of stress associated with 11 recognised sources of stress for individuals undergoing the early stages of cancer genetic risk assessment, and the use of up to eight coping strategies they may elicit. This paper reports preliminary data from the piloting of the GRACE within a randomised trial of a coping intervention. Of the 265 participants who completed and returned their baseline questionnaire (prior to being informed of their level of genetic risk), 257 completed the GRACE. The most highly endorsed sources of stress involved concerns relating to family members, endorsed by over 60% of respondents, and concerns about how the participants would cope if found to be at increased risk (59%). Participants made use of multiple coping strategies across different sources of stress. The most frequently reported coping strategies were emotion-focused, which may reflect the stage of the assessment process. The completion rates for the matrix and specificity of responses provided suggest that the GRACE may be an acceptable measurement tool. Further data collection and validation is ongoing. (c) 2009 John Wiley & Sons, Ltd.

46 CFR 178.320 - Intact stability requirements-non-sailing vessels.

Code of Federal Regulations, 2012 CFR

2012-10-01

... following vessels may undergo the simplified stability proof test detailed in § 178.330 of this part, in the... this part, a self-propelled pontoon vessel may undergo the pontoon simplified stability proof test... deck cargo, and is otherwise eligible to undergo the simplified stability proof test detailed in § 178...

46 CFR 178.320 - Intact stability requirements-non-sailing vessels.

Code of Federal Regulations, 2014 CFR

2014-10-01

... following vessels may undergo the simplified stability proof test detailed in § 178.330 of this part, in the... this part, a self-propelled pontoon vessel may undergo the pontoon simplified stability proof test... deck cargo, and is otherwise eligible to undergo the simplified stability proof test detailed in § 178...

46 CFR 178.320 - Intact stability requirements-non-sailing vessels.

Code of Federal Regulations, 2013 CFR

2013-10-01

... following vessels may undergo the simplified stability proof test detailed in § 178.330 of this part, in the... this part, a self-propelled pontoon vessel may undergo the pontoon simplified stability proof test... deck cargo, and is otherwise eligible to undergo the simplified stability proof test detailed in § 178...

Duplication and population dynamics shape historic patterns of selection and genetic variation at the major histocompatibility complex in rodents

PubMed Central

Winternitz, Jamie C; Wares, John P

2013-01-01

Genetic variation at the major histocompatibility complex (MHC) is vitally important for wildlife populations to respond to pathogen threats. As natural populations can fluctuate greatly in size, a key issue concerns how population cycles and bottlenecks that could reduce genetic diversity will influence MHC genes. Using 454 sequencing, we characterized genetic diversity at the DRB Class II locus in montane voles (Microtus montanus), a North American rodent that regularly undergoes high-amplitude fluctuations in population size. We tested for evidence of historic balancing selection, recombination, and gene duplication to identify mechanisms maintaining allelic diversity. Counter to our expectations, we found strong evidence of purifying selection acting on the DRB locus in montane voles. We speculate that the interplay between population fluctuations and gene duplication might be responsible for the weak evidence of historic balancing selection and strong evidence of purifying selection detected. To further explore this idea, we conducted a phylogenetically controlled comparative analysis across 16 rodent species with varying demographic histories and MHC duplication events (based on the maximum number of alleles detected per individual). On the basis of phylogenetic generalized linear model-averaging, we found evidence that the estimated number of duplicated loci was positively related to allelic diversity and, surprisingly, to the strength of purifying selection at the DRB locus. Our analyses also revealed that species that had undergone population bottlenecks had lower allelic richness than stable species. This study highlights the need to consider demographic history and genetic structure alongside patterns of natural selection to understand resulting patterns of genetic variation at the MHC. PMID:23789067

Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.

PubMed

Dai, Feng; Belfer, Inna; Schwartz, Carolyn E; Banco, Robert; Martha, Julia F; Tighioughart, Hocine; Tromanhauser, Scott G; Jenis, Louis G; Kim, David H

2010-11-01

Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies. To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD. Prospective genetic association study. Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis, spondylolisthesis, spondylolysis, or alternative diagnoses. Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP. Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable. Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with individuals homozygous for the less common "T" allele demonstrating the largest improvement in ODI. Haplotype analysis of four COMT SNPs, rs6269, rs4633, rs4818, and rs4680, also identified a common haplotype "ATCA" (haplotype frequency of 39.3% in the study population) associated with greater improvement in ODI (p=.046). The greatest mean improvement in ODI was observed in patients homozygous for the "ATCA"COMT haplotype. A nonsignificant trend was observed between SNP rs4633 and greater improvement in VAS score for LBP. This is the first study to report an association between surgical treatment success in DDD patients and genetic variation in the putative pain sensitivity gene COMT. These findings require replication in other DDD populations but suggest that genetic testing for pain-relevant genetic markers such as COMT may provide useful clinical information in terms of predicting outcome after surgery for patients diagnosed with DDD. Copyright © 2010 Elsevier Inc. All rights reserved.

Genetic therapy for the nervous system.

PubMed

Bowers, William J; Breakefield, Xandra O; Sena-Esteves, Miguel

2011-04-15

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state.

A Retrospective Exploration of the Impact of the 'Angelina Jolie Effect' on the Single State-Wide Familial Cancer Program in Perth, Western Australia.

PubMed

Freedman, Rebecca; Mountain, Helen; Karina, Dian; Schofield, Lyn

2017-02-01

Global media has the power to influence the ways the public engage with health services. On May 14th 2013, Angelina Jolie published an article in the New York Times magazine, outlining her decision to undergo BRCA mutation testing due to a family history of cancer; then proceed with a mastectomy. The article evoked significant interest from the media and the public. During the months that followed, the Familial Cancer Program (FCP) at Genetic Services of Western Australia (GSWA) experienced a significant increase in referrals and enquiries. Resources were overstretched and it became clear we needed to adjust work practices to manage the escalating numbers. New strategies were devised to cope with the influx of enquiries, albeit without the benefit of additional resources. We conducted an audit of referrals to the FCP made between January 2012 and December 2014. This included a comparison of the months prior to and following the New York Times article. The aim of the audit was to quantify the impact of the "Angelina Jolie effect" on referrals to the FCP. Whilst the increased awareness of the role of genetic services in risk assessment and testing for familial breast and ovarian cancer was considered positive, pre-referral risk assessment at the primary health level to evaluate the appropriateness of their patients for referral could have been helpful. Potentially, many inappropriate referrals to FCP may have been avoided with primary health evaluation thus lessening the burden on our service and preventing unnecessary worry in well women who possessed minimal family history or risk factors. It is important to understand the factors driving the uptake of risk reduction activities, particularly if engagement with a genetics service is considered part of that pathway. Continued education about cancer risk due to family history, individual features and awareness surrounding genetic testing criteria, costs and availability is required for both the public and health professionals.

The Warburg effect: molecular aspects and therapeutic possibilities.

PubMed

Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

2015-04-01

It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies.

Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research.

PubMed

Liu, Jianlin; Adhav, Ragini; Xu, Xiaoling

2017-01-01

Breast cancers display striking genetic and phenotypic diversities. To date, several hypotheses are raised to explain and understand the heterogeneity, including theories for cancer stem cell (CSC) and clonal evolution. According to the CSC theory, the most tumorigenic cells, while maintaining themselves through symmetric division, divide asymmetrically to generate non-CSCs with less tumorigenic and metastatic potential, although they can also dedifferentiate back to CSCs. Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. During tumorigenesis and evolution process, cancer cells undergo different degrees of genetic instability and consequently obtain varied genetic aberrations. Yet the heterogeneity in breast cancers is very complex, poorly understood and subjected to further investigation. In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast cancer therapies. In this review, we will summarize development of SCS technologies and recent advances of SCS in breast cancer.

Hereditary diffuse gastric cancer: implications of genetic testing for screening and prophylactic surgery.

PubMed

Cisco, Robin M; Ford, James M; Norton, Jeffrey A

2008-10-01

Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative. The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.

PERCHLORATE INDUCES HERMAPHRODITISM IN THREESPINE STICKLEBACKS

PubMed Central

Bernhardt, Richard R.; von Hippel, Frank A.; Cresko, William A.

2011-01-01

Recently, concern regarding perchlorate contamination has arisen in many contexts. Perchlorate has many military, commercial, and domestic applications, and it has been found in milk, drinking and irrigation water, and produce. Perchlorate is harmful at low levels, yet it remains unregulated in the United States while the U.S. Environmental Protection Agency attempts to establish acceptable exposure levels. The present study investigated potential reproductive effects on vertebrates using a model fish species, the threespine stickleback (Gasterosteus aculeatus). Sticklebacks were raised from syngamy through sexual maturity in untreated water and in three target concentrations of sodium perchlorate–treated water. Perchlorate was found to interfere with the expression of nuptial coloration, courtship behavior, and normal sexual development. Genetic testing revealed that some females were masculinized to the extent that they produced both sperm and eggs, and histological analysis showed that these individuals had intersexual gonads (ovotestes) containing both oocytes and cells undergoing spermatogenesis. In vitro fertilizations revealed that those gametes were capable of self- and cross-fertilization. However, crosses using sperm derived from genetic females died either during the blastula phase or near the onset of organogenesis. Sperm derived from genetic males produced viable fry when crossed with eggs derived from genetic females from all treatments. To our knowledge, the present study provides the first evidence that perchlorate produces androgenic effects and is capable of inducing functional hermaphroditism in a nonhermaphroditic vertebrate. PMID:16916028

Oncogene Discovery in Schwannomas

DTIC Science & Technology

2013-07-01

schwannomatosis .15-17 It is clear that schwannomas undergo many genetic events outside the NF2 gene that have the potential to be involved in tumor...2003). 15. Bacci, C. et al. Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation. Neurogenetics 11, 73-80 (2010...16. Buckley, P.G. et al. Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type

Genetics Home Reference: Crigler-Najjar syndrome

MedlinePlus

... from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form ... the body. The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers ...

What Is a Growth Disorder? (For Parents)

MedlinePlus

... hormone, which is essential for normal bone growth. Turner syndrome , one of the most common genetic growth disorders, ... chromosome. In addition to short stature, girls with Turner syndrome usually don't undergo normal sexual development because ...

Genetic therapy for the nervous system

PubMed Central

Bowers, William J.; Breakefield, Xandra O.; Sena-Esteves, Miguel

2011-01-01

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state. PMID:21429918

The efficacy of a standardized questionnaire in facilitating personalized communication about problems encountered in cancer genetic counseling: design of a randomized controlled trial

PubMed Central

2014-01-01

Background Individuals with a personal or family history of cancer, can opt for genetic counseling and DNA-testing. Approximately 25% of these individuals experience clinically relevant levels of psychosocial distress, depression and/or anxiety after counseling. These problems are frequently left undetected by genetic counselors. The aim of this study is to evaluate the efficacy of a cancer genetics-specific screening questionnaire for psychosocial problems, the ‘Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire’ together with the Distress Thermometer, in: (1) facilitating personalized counselor-counselee communication; (2) increasing counselors’ awareness of their counselees’ psychosocial problems; and (3) facilitating the management of psychosocial problems during and after genetic counseling. Methods This multicenter, randomized controlled trial will include 264 individuals undergoing cancer genetic counseling in two family cancer clinics in the Netherlands. Participants will be randomized to either: (1) an intervention group that completes the PAHC questionnaire, the results of which are made available to the genetic counselor prior to the counseling session; or (2) a control group that completes the PAHC questionnaire, but without feedback being given to the genetic counselor. The genetic counseling sessions will be audiotaped for content analysis. Additionally, study participants will be asked to complete questionnaires at baseline, three weeks after the initial counseling session, and four months after a telephone follow-up counseling session. The genetic counselors will be asked to complete questionnaires at the start of and at completion of the study, as well as a checklist directly after each counseling session. The questionnaires/checklists of the study include items on communication during genetic counseling, counselor awareness of their clients’ psychosocial problems, the (perceived) need for professional psychosocial support, cancer worries, general distress, specific psychosocial problems, satisfaction with care received, and experience using the PAHC questionnaire. Discussion This study will provide empirical evidence regarding the efficacy of a relatively brief psychosocial screening questionnaire in terms of facilitating personalized communication, increasing counselors’ awareness, and optimizing management of psychosocial problems in the cancer genetic counseling setting. Trial registration This study is registered at the Netherlands Trial Register (NTR3205) and ClinicalTrials.gov (NCT01562431). PMID:24428912

The efficacy of a standardized questionnaire in facilitating personalized communication about problems encountered in cancer genetic counseling: design of a randomized controlled trial.

PubMed

Eijzenga, Willem; Aaronson, Neil K; Kluijt, Irma; Sidharta, Grace N; Hahn, Daniela Ee; Ausems, Margreet Gem; Bleiker, Eveline Ma

2014-01-15

Individuals with a personal or family history of cancer, can opt for genetic counseling and DNA-testing. Approximately 25% of these individuals experience clinically relevant levels of psychosocial distress, depression and/or anxiety after counseling. These problems are frequently left undetected by genetic counselors. The aim of this study is to evaluate the efficacy of a cancer genetics-specific screening questionnaire for psychosocial problems, the 'Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire' together with the Distress Thermometer, in: (1) facilitating personalized counselor-counselee communication; (2) increasing counselors' awareness of their counselees' psychosocial problems; and (3) facilitating the management of psychosocial problems during and after genetic counseling. This multicenter, randomized controlled trial will include 264 individuals undergoing cancer genetic counseling in two family cancer clinics in the Netherlands. Participants will be randomized to either: (1) an intervention group that completes the PAHC questionnaire, the results of which are made available to the genetic counselor prior to the counseling session; or (2) a control group that completes the PAHC questionnaire, but without feedback being given to the genetic counselor. The genetic counseling sessions will be audiotaped for content analysis. Additionally, study participants will be asked to complete questionnaires at baseline, three weeks after the initial counseling session, and four months after a telephone follow-up counseling session. The genetic counselors will be asked to complete questionnaires at the start of and at completion of the study, as well as a checklist directly after each counseling session. The questionnaires/checklists of the study include items on communication during genetic counseling, counselor awareness of their clients' psychosocial problems, the (perceived) need for professional psychosocial support, cancer worries, general distress, specific psychosocial problems, satisfaction with care received, and experience using the PAHC questionnaire. This study will provide empirical evidence regarding the efficacy of a relatively brief psychosocial screening questionnaire in terms of facilitating personalized communication, increasing counselors' awareness, and optimizing management of psychosocial problems in the cancer genetic counseling setting. This study is registered at the Netherlands Trial Register (NTR3205) and ClinicalTrials.gov (NCT01562431).

Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper.

PubMed

Ginsburg, Elizabeth S; Baker, Valerie L; Racowsky, Catherine; Wantman, Ethan; Goldfarb, James; Stern, Judy E

2011-10-01

To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). Retrospective study. United States SART cohort data. Women undergoing a PGT cycle in which at least one embryo underwent biopsy. PGT. PGT use, indications, and delivery rates. Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Use of genetic programming, logistic regression, and artificial neural nets to predict readmission after coronary artery bypass surgery.

PubMed

Engoren, Milo; Habib, Robert H; Dooner, John J; Schwann, Thomas A

2013-08-01

As many as 14 % of patients undergoing coronary artery bypass surgery are readmitted within 30 days. Readmission is usually the result of morbidity and may lead to death. The purpose of this study is to develop and compare statistical and genetic programming models to predict readmission. Patients were divided into separate Construction and Validation populations. Using 88 variables, logistic regression, genetic programs, and artificial neural nets were used to develop predictive models. Models were first constructed and tested on the Construction populations, then validated on the Validation population. Areas under the receiver operator characteristic curves (AU ROC) were used to compare the models. Two hundred and two patients (7.6 %) in the 2,644 patient Construction group and 216 (8.0 %) of the 2,711 patient Validation group were re-admitted within 30 days of CABG surgery. Logistic regression predicted readmission with AU ROC = .675 ± .021 in the Construction group. Genetic programs significantly improved the accuracy, AU ROC = .767 ± .001, p < .001). Artificial neural nets were less accurate with AU ROC = 0.597 ± .001 in the Construction group. Predictive accuracy of all three techniques fell in the Validation group. However, the accuracy of genetic programming (AU ROC = .654 ± .001) was still trivially but statistically non-significantly better than that of the logistic regression (AU ROC = .644 ± .020, p = .61). Genetic programming and logistic regression provide alternative methods to predict readmission that are similarly accurate.

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

PubMed Central

2014-01-01

Background Recent advances in time-lapse monitoring in IVF treatment have provided new morphokinetic markers for embryonic competence. However, there is still very limited information about the relationship between morphokinetic parameters, chromosomal compositions and implantation potential. Accordingly, this study aimed at investigating the effects of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing on pregnancy and implantation outcomes for patients undergoing preimplantation genetic screening (PGS). Methods A total of 1163 metaphase II (MII) oocytes were retrieved from 138 PGS patients at a mean age of 36.6 ± 2.4 years. These sibling MII oocytes were then randomized into two groups after ICSI: 1) Group A, oocytes (n = 582) were cultured in the time-lapse system and 2) Group B, oocytes (n = 581) were cultured in the conventional incubator. For both groups, whole genomic amplification and array CGH testing were performed after trophectoderm biopsy on day 5. One to two euploid blastocysts within the most predictive morphokinetic parameters (Group A) or with the best morphological grade available (Group B) were selected for transfer to individual patients on day 6. Ongoing pregnancy and implantation rates were compared between the two groups. Results There were significant differences in clinical pregnancy rates between Group A and Group B (71.1% vs. 45.9%, respectively, p = 0.037). The observed implantation rate per embryo transfer significantly increased in Group A compared to Group B (66.2% vs. 42.4%, respectively, p = 0.011). Moreover, a significant increase in ongoing pregnancy rates was also observed in Group A compared to Group B (68.9% vs. 40.5%. respectively, p = 0.019). However, there was no significant difference in miscarriage rate between the time-lapse system and the conventional incubator (3.1% vs. 11.8%, respectively, p = 0.273). Conclusions This is the first prospective investigation using sibling oocytes to evaluate the efficiency of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for PGS patients. Our data clearly demonstrate that the combination of these two advanced technologies to select competent blastocysts for transfer results in improved implantation and ongoing pregnancy rates for PGS patients. PMID:24954518

Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PubMed

Hemmati, Philipp G; Vuong, Lam G; Terwey, Theis H; Jehn, Christian F; le Coutre, Philipp; Penack, Olaf; Na, Il-Kang; Dörken, Bernd; Arnold, Renate

2017-02-01

The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic and pharmacological intervention for treatment/prevention of hearing loss

PubMed Central

Cotanche, Douglas A.

2008-01-01

Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. Learning outcomes The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea. PMID:18455177

Genetic and pharmacological intervention for treatment/prevention of hearing loss.

PubMed

Cotanche, Douglas A

2008-01-01

Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea.

Site-specific genetic recombination: hops, flips, and flops.

PubMed

Sadowski, P D

1993-06-01

Genetic recombination plays a key role in the life of organisms as diverse as bacteriophages and humans. Contrary to our idea that chromosomes are stable structures, studies of recombination over the past few decades have shown that in fact DNA replicons are remarkably plastic, undergoing frequent recombination-induced rearrangements. This review summarizes our recent knowledge of the biochemistry of the two major classes of site-specific recombination: 1) transpositional recombination, and 2) conservative site-specific recombination.

Stable Nuclear Transformation System for the Coccolithophorid Alga Pleurochrysis carterae

PubMed Central

Endo, Hirotoshi; Yoshida, Megumi; Uji, Toshiki; Saga, Naotsune; Inoue, Koji; Nagasawa, Hiromichi

2016-01-01

Of the three dominant marine microalgal groups, dinoflagellates and diatoms can undergo genetic transformation; however, no transformation method has been established for haptophytes to date. Here, we report the first stable genetic transformation of a coccolithophore, Pleurochrysis carterae, by means of polyethylene glycol (PEG)-mediated transfer of a bacterial hygromycin B-resistance gene. Together with the novel transient green fluorescent protein (GFP) expression system, this approach should facilitate further molecular-based research in this phylum. PMID:26947136

Effect of enhanced information, values clarification, and removal of financial barriers on use of prenatal genetic testing: a randomized clinical trial.

PubMed

Kuppermann, Miriam; Pena, Sherri; Bishop, Judith T; Nakagawa, Sanae; Gregorich, Steven E; Sit, Anita; Vargas, Juan; Caughey, Aaron B; Sykes, Susan; Pierce, Lasha; Norton, Mary E

2014-09-24

Prenatal genetic testing guidelines recommend providing patients with detailed information to allow informed, preference-based screening and diagnostic testing decisions. The effect of implementing these guidelines is not well understood. To analyze the effect of a decision-support guide and elimination of financial barriers to testing on use of prenatal genetic testing and decision making among pregnant women of varying literacy and numeracy levels. Randomized trial conducted from 2010-2013 at prenatal clinics at 3 county hospitals, 1 community clinic, 1 academic center, and 3 medical centers of an integrated health care delivery system in the San Francisco Bay area. Participants were English- or Spanish-speaking women who had not yet undergone screening or diagnostic testing and remained pregnant at 11 weeks' gestation (n = 710). A computerized, interactive decision-support guide and access to prenatal testing with no out-of-pocket expense (n = 357) or usual care as per current guidelines (n = 353). The primary outcome was invasive diagnostic test use, obtained via medical record review. Secondary outcomes included testing strategy undergone, and knowledge about testing, risk comprehension, and decisional conflict and regret at 24 to 36 weeks' gestation. Women randomized to the intervention group, compared with those randomized to the control group, were less likely to have invasive diagnostic testing (5.9% vs 12.3%; odds ratio [OR], 0.45 [95% CI, 0.25-0.80]) and more likely to forgo testing altogether (25.6% vs 20.4%; OR, 3.30 [95% CI, 1.43-7.64], reference group screening followed by invasive testing). Women randomized to the intervention group also had higher knowledge scores (9.4 vs 8.6 on a 15-point scale; mean group difference, 0.82 [95% CI, 0.34-1.31]) and were more likely to correctly estimate the amniocentesis-related miscarriage risk (73.8% vs 59.0%; OR, 1.95 [95% CI, 1.39-2.75]) and their estimated age-adjusted chance of carrying a fetus with trisomy 21 (58.7% vs 46.1%; OR, 1.66 [95% CI, 1.22-2.28]). Significant differences did not emerge in decisional conflict or regret. Full implementation of prenatal testing guidelines using a computerized, interactive decision-support guide in the absence of financial barriers to testing resulted in less test use and more informed choices. If validated in additional populations, this approach may result in more informed and preference-based prenatal testing decision making and fewer women undergoing testing. clinicaltrials.gov Identifier: NCT00505596.

A role for molecular genetics in biological conservation.

PubMed Central

O'Brien, S J

1994-01-01

The recognition of recent accelerated depletion of species as a consequence of human industrial development has spawned a wide interest in identifying threats to endangered species. In addition to ecological and demographic perils, it has become clear that small populations that narrowly survive demographic contraction may undergo close inbreeding, genetic drift, and loss of overall genomic variation due to allelic loss or reduction to homozygosity. I review here the consequences of such genetic depletion revealed by applying molecular population genetic analysis to four endangered mammals: African cheetah, lion, Florida panther, and humpback whale. The accumulated genetic results, combined with physiological, ecological, and ethological data, provide a multifaceted perspective of the process of species diminution. An emerging role of population genetics, phylogenetics, and phylogeography as indicators of a population's natural history and its future prognosis provides valuable data of use in the development of conservation management plans for endangered species. PMID:7912434

Partnering in oncogenetic research--the INHERIT BRCAs experience: opportunities and challenges.

PubMed

Avard, Denise; Bridge, Peter; Bucci, Lucie M; Chiquette, Jocelyne; Dorval, Michel; Durocher, Francine; Easton, Doug; Godard, Béatrice; Goldgar, David; Knoppers, Bartha Maria; Laframboise, Rachel; Lespérance, Bernard; Plante, Marie; Tavtigian, Sean V; Vézina, Hélène; Wilson, Brenda; Simard, Jacques

2006-01-01

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented.

Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms.

PubMed

Kim, Yoon-Myung; Choi, In-Hee; Kim, Jun Suk; Kim, Ja Hye; Cho, Ja Hyang; Lee, Beom Hee; Kim, Gu-Hwan; Choi, Jin-Ho; Seo, Eul-Ju; Yoo, Han-Wook

2016-11-01

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3 , RAB , RABL2B , and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

Music therapy improves the mood of patients undergoing hematopoietic stem cells transplantation (controlled randomized study).

PubMed

Dóro, Carlos Antonio; Neto, José Zanis; Cunha, Rosemyriam; Dóro, Maribel Pelaez

2017-03-01

The allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic medical treatment for various neoplastic hematologic, congenital, genetic, or acquired disorders. In this procedure which combines high-dose chemotherapy and/or radiotherapy and has a high degree of cytotoxicity, the patient experiences solitary confinement, which causes psychological distress, pain, anxiety, mood disorders and can lead him/her to depression. Music therapy was applied with the purpose of decreasing this social confinement. This is a randomized controlled trial. Patients (n = 100) were selected randomly. Patients (n = 50) were selected for the Experimental Music Therapy Group (EMG) and n = 50 for the control group (CG) who received the standard treatment. The intervention of live music was applied using music therapy techniques. Assessment and quantification were made using the visual analog scale (VAS). The dependent variables were pain, anxiety, and mood of patients. The Mann-Whitney test (p < 0.05) applied was considered statistically significant when comparing the groups, improving mood significantly (EMG). Music therapy proved to be a strong ally in the treatment of patients undergoing allo-HSCT, providing bio-psychosocial welfare.

Polyploidy can drive rapid adaptation in yeast

NASA Astrophysics Data System (ADS)

Selmecki, Anna M.; Maruvka, Yosef E.; Richmond, Phillip A.; Guillet, Marie; Shoresh, Noam; Sorenson, Amber L.; de, Subhajyoti; Kishony, Roy; Michor, Franziska; Dowell, Robin; Pellman, David

2015-03-01

Polyploidy is observed across the tree of life, yet its influence on evolution remains incompletely understood. Polyploidy, usually whole-genome duplication, is proposed to alter the rate of evolutionary adaptation. This could occur through complex effects on the frequency or fitness of beneficial mutations. For example, in diverse cell types and organisms, immediately after a whole-genome duplication, newly formed polyploids missegregate chromosomes and undergo genetic instability. The instability following whole-genome duplications is thought to provide adaptive mutations in microorganisms and can promote tumorigenesis in mammalian cells. Polyploidy may also affect adaptation independently of beneficial mutations through ploidy-specific changes in cell physiology. Here we perform in vitro evolution experiments to test directly whether polyploidy can accelerate evolutionary adaptation. Compared with haploids and diploids, tetraploids undergo significantly faster adaptation. Mathematical modelling suggests that rapid adaptation of tetraploids is driven by higher rates of beneficial mutations with stronger fitness effects, which is supported by whole-genome sequencing and phenotypic analyses of evolved clones. Chromosome aneuploidy, concerted chromosome loss, and point mutations all provide large fitness gains. We identify several mutations whose beneficial effects are manifest specifically in the tetraploid strains. Together, these results provide direct quantitative evidence that in some environments polyploidy can accelerate evolutionary adaptation.

What Is Genetic Ancestry Testing?

MedlinePlus

... Testing What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, ... mixed with other groups. For more information about genetic ancestry testing: The University of Utah provides video ...

Direct-to-consumer genetic testing: an assessment of genetic counselors' knowledge and beliefs

PubMed Central

Hock, Kathryn T.; Christensen, Kurt D.; Yashar, Beverly M.; Roberts, J. Scott; Gollust, Sarah E.; Uhlmann, Wendy R.

2013-01-01

Purpose Direct-to-consumer genetic testing is a new means of obtaining genetic testing outside of a traditional clinical setting. This study assesses genetic counselors’ experience, knowledge, and beliefs regarding direct-to-consumer genetic testing for tests that would currently be offered in genetics clinics. Methods Members of the National Society of Genetic Counselors completed a web-administered survey in February 2008. Results Response rate was 36%; the final data analysis included 312 respondents. Eighty-three percent of respondents had two or fewer inquiries about direct-to-consumer genetic testing, and 14% had received requests for test interpretation or discussion. Respondents believed that genetic counselors have a professional obligation to be knowledgeable about direct-to-consumer genetic testing (55%) and interpret results (48%). Fifty-one percent of respondents thought genetic testing should be limited to a clinical setting; 56% agreed direct-to-consumer genetic testing is acceptable if genetic counseling is provided. More than 70% of respondents would definitely or possibly consider direct-to-consumer testing for patients who (1) have concerns about genetic discrimination, (2) want anonymous testing, or (3) have geographic constraints. Conclusions Results indicate that genetic counselors have limited patient experiences with direct-to-consumer genetic testing and are cautiously considering if and under what circumstances this approach should be used PMID:21233722

Impact of genetic counseling and Connexin-26 and Connexin-30 testing on deaf identity and comprehension of genetic test results in a sample of deaf adults: a prospective, longitudinal study.

PubMed

Palmer, Christina G S; Boudreault, Patrick; Baldwin, Erin E; Sinsheimer, Janet S

2014-01-01

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.

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

PubMed Central

Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

2015-01-01

Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). Conclusions VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

Knowledge of Genetics and Attitudes toward Genetic Testing among College Students in Saudi Arabia.

PubMed

Olwi, Duaa; Merdad, Leena; Ramadan, Eman

2016-01-01

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.

The Aerostructures Test Wing (ATW) experiment, which consisted of an 18-inch carbon fiber test wing with surface-mounted piezoelectric strain actuators, undergoing ground testing prior to flight on Dryden's F-15B Research Testbed aircraft

NASA Image and Video Library

2001-03-28

The Aerostructures Test Wing (ATW) experiment, which consisted of an 18-inch carbon fiber test wing with surface-mounted piezoelectric strain actuators, undergoing ground testing prior to flight on Dryden's F-15B Research Testbed aircraft

Public trust in genomic risk assessment for type 2 diabetes mellitus.

PubMed

Mills, Rachel; Barry, William; Haga, Susanne B

2014-06-01

Patient trust in personal medical information is critical to increasing adherence to physician recommendations and medications. One of the anticipated benefits of learning of one's genomic risk for common diseases is the increased adoption of screening, preventive care and lifestyle changes. However, the equivocal results thus far reported of the positive impact of knowledge of genomic risk on behavior change may be due to lack of patients' trust in the results. As part of a clinical study to compare two methods of communication of genomic risk results for Type 2 diabetes mellitus (T2DM), we assessed patients' trust and preferred methods of delivery of genomic risk information. A total of 300 participants recruited from the general public in Durham, NC were randomized to receive their genomic risk for T2DM in-person from a genetic counselor or online through the testing company's web-site. Participants completed a baseline survey and three follow-up surveys after receiving results. Overall, participants reported high levels of trust in the test results. Participants who received their results in-person from the genetic counselor were significantly more likely to trust their results than those who reviewed their results on-line (p = 0.005). There was not a statistically significant difference in levels of trust among participants with increased genetic risk, as compared to other those with decreased or same as population risk (p = 0.1154). In the event they undergo genomic risk testing again, 55 % of participants overall indicated they would prefer to receive their results online compared to 28 % that would prefer to receive future results in-person. Of those participants preferring to receive results online, 77 % indicated they would prefer to have the option to speak to someone if they had questions with the online results (compared to accessing results online without the option of professional consultation). This is the first study to assess satisfaction with genomic risk testing by the method of delivery of the test result. The higher rate of trust in results delivered in-person suggests that online access reports may not result in serious consideration of results and lack of adoption of recommended preventive recommendations.

Public Trust in Genomic Risk Assessment for Type 2 Diabetes Mellitus

PubMed Central

Mills, Rachel; Barry, William; Haga, Susanne B.

2014-01-01

Patient trust in personal medical information is critical to increasing adherence to physician recommendations and medications. One of the anticipated benefits of learning of one’s genomic risk for common diseases is the increased adoption of screening, preventive care and lifestyle changes. However, the equivocal results thus far reported of the positive impact of knowledge of genomic risk on behavior change may be due to lack of patients’ trust in the results. As part of a clinical study to compare two methods of communication of genomic risk results for Type 2 diabetes mellitus (T2DM), we assessed patients’ trust and preferred methods of delivery of genomic risk information. A total of 300 participants recruited from the general public in Durham, NC were randomized to receive their genomic risk for T2DM in-person from a genetic counselor or online through the testing company’s web-site. Participants completed a baseline survey and three follow-up surveys after receiving results. Overall, participants reported high levels of trust in the test results. Participants who received their results in-person from the genetic counselor were significantly more likely to trust their results than those who reviewed their results on-line (p=0.005). There was not a statistically significant difference in levels of trust among participants with increased genetic risk, as compared to other those with decreased or same as population risk (p = 0.1154). In the event they undergo genomic risk testing again, 55% of participants overall indicated they would prefer to receive their results online compared to 28% that would prefer to receive future results in-person. Of those participants preferring to receive results online, 77% indicated they would prefer to have the option to speak to someone if they had questions with the online results (compared to accessing results online without the option of professional consultation). This is the first study to assess satisfaction with genomic risk testing by the method of delivery of the test result. The higher rate of trust in results delivered in-person suggests that online access reports may not result in serious consideration of results and lack of adoption of recommended preventive recommendations. PMID:24292896

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

PubMed

Stafford-Smith, Mark; Podgoreanu, Mihai; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P; Hauser, Elizabeth H; Winn, Michelle P; Milano, Carmelo; Nielsen, Dahlia M; Smith, Mike; Morris, Richard; Newman, Mark F; Schwinn, Debra A

2005-03-01

Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Turtle groups or turtle soup: dispersal patterns of hawksbill turtles in the Caribbean.

PubMed

Blumenthal, J M; Abreu-Grobois, F A; Austin, T J; Broderick, A C; Bruford, M W; Coyne, M S; Ebanks-Petrie, G; Formia, A; Meylan, P A; Meylan, A B; Godley, B J

2009-12-01

Despite intense interest in conservation of marine turtles, spatial ecology during the oceanic juvenile phase remains relatively unknown. Here, we used mixed stock analysis and examination of oceanic drift to elucidate movements of hawksbill turtles (Eretmochelys imbricata) and address management implications within the Caribbean. Among samples collected from 92 neritic juvenile hawksbills in the Cayman Islands we detected 11 mtDNA control region haplotypes. To estimate contributions to the aggregation, we performed 'many-to-many' mixed stock analysis, incorporating published hawksbill genetic and population data. The Cayman Islands aggregation represents a diverse mixed stock: potentially contributing source rookeries spanned the Caribbean basin, delineating a scale of recruitment of 200-2500 km. As hawksbills undergo an extended phase of oceanic dispersal, ocean currents may drive patterns of genetic diversity observed on foraging aggregations. Therefore, using high-resolution Aviso ocean current data, we modelled movement of particles representing passively drifting oceanic juvenile hawksbills. Putative distribution patterns varied markedly by origin: particles from many rookeries were broadly distributed across the region, while others would appear to become entrained in local gyres. Overall, we detected a significant correlation between genetic profiles of foraging aggregations and patterns of particle distribution produced by a hatchling drift model (Mantel test, r = 0.77, P < 0.001; linear regression, r = 0.83, P < 0.001). Our results indicate that although there is a high degree of mixing across the Caribbean (a 'turtle soup'), current patterns play a substantial role in determining genetic structure of foraging aggregations (forming turtle groups). Thus, for marine turtles and other widely distributed marine species, integration of genetic and oceanographic data may enhance understanding of population connectivity and management requirements.

EHR based Genetic Testing Knowledge Base (iGTKB) Development

PubMed Central

2015-01-01

Background The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). Methods We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Results Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. Conclusions In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics. PMID:26606281

EHR based Genetic Testing Knowledge Base (iGTKB) Development.

PubMed

Zhu, Qian; Liu, Hongfang; Chute, Christopher G; Ferber, Matthew

2015-01-01

The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics.

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

Vygotsky's Sociocultural Theory in the Context of Globalization

ERIC Educational Resources Information Center

Marginson, Simon; Dang, Thi Kim Anh

2017-01-01

The article reviews the social-educational theorization of the early Soviet psychologist L. S. Vygotsky (1896-1934) in the light of the impact of communicative globalization in educational practice. Vygotsky proposed four "genetic domains" for investigating higher cognitive processes: the phylogenetic (humans undergoing natural…

Impact of Genetic Counseling and Connexin-26 and Connexin-30 Testing on Deaf Identity and Comprehension of Genetic Test Results in a Sample of Deaf Adults: A Prospective, Longitudinal Study

PubMed Central

Palmer, Christina G. S.; Boudreault, Patrick; Baldwin, Erin E.; Sinsheimer, Janet S.

2014-01-01

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

Drosophila melanogaster White Mutant w1118 Undergo Retinal Degeneration

PubMed Central

Ferreiro, María José; Pérez, Coralia; Marchesano, Mariana; Ruiz, Santiago; Caputi, Angel; Aguilera, Pedro; Barrio, Rosa; Cantera, Rafael

2018-01-01

Key scientific discoveries have resulted from genetic studies of Drosophila melanogaster, using a multitude of transgenic fly strains, the majority of which are constructed in a genetic background containing mutations in the white gene. Here we report that white mutant flies from w1118 strain undergo retinal degeneration. We observed also that w1118 mutants have progressive loss of climbing ability, shortened life span, as well as impaired resistance to various forms of stress. Retinal degeneration was abolished by transgenic expression of mini-white+ in the white null background w1118. We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance. Consequently, we suggest caution and attentiveness during the interpretation of old experiments employing white mutant flies and when planning new ones, especially within the research field of neurodegeneration and neuroprotection. We also encourage that the use of w1118 strain as a wild-type control should be avoided. PMID:29354028

Drosophila melanogaster White Mutant w 1118 Undergo Retinal Degeneration.

PubMed

Ferreiro, María José; Pérez, Coralia; Marchesano, Mariana; Ruiz, Santiago; Caputi, Angel; Aguilera, Pedro; Barrio, Rosa; Cantera, Rafael

2017-01-01

Key scientific discoveries have resulted from genetic studies of Drosophila melanogaster , using a multitude of transgenic fly strains, the majority of which are constructed in a genetic background containing mutations in the white gene. Here we report that white mutant flies from w 1118 strain undergo retinal degeneration. We observed also that w 1118 mutants have progressive loss of climbing ability, shortened life span, as well as impaired resistance to various forms of stress. Retinal degeneration was abolished by transgenic expression of mini-white + in the white null background w 1118 . We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance. Consequently, we suggest caution and attentiveness during the interpretation of old experiments employing white mutant flies and when planning new ones, especially within the research field of neurodegeneration and neuroprotection. We also encourage that the use of w 1118 strain as a wild-type control should be avoided.

Host and Toxoplasma gondii genetic and non-genetic factors influencing the development of ocular toxoplasmosis: A systematic review.

PubMed

Fernández, Carolina; Jaimes, Jesús; Ortiz, María Camila; Ramírez, Juan David

2016-10-01

Toxoplasmosis is a cosmopolitan infection caused by the apicomplexan parasite Toxoplasma gondii. This infectious disease is widely distributed across the world where cats play an important role in its spread. The symptomatology caused by this parasite is diverse but the ocular affectation emerges as the most important clinical phenotype. Therefore, we conducted a systematic review of the current knowledge of ocular toxoplasmosis from the genetic diversity of the pathogen towards the treatment available for this infection. This review represents an update to the scientific community regarding the genetic diversity of the parasite, the genetic factors of the host, the molecular pathogenesis and its association with disease, the available diagnostic tools and the available treatment of patients undergoing ocular toxoplamosis. This review will be an update for the scientific community in order to encourage researchers to deploy cutting-edge investigation across this field.

What Is Direct-to-Consumer Genetic Testing?

MedlinePlus

... consumer genetic testing? What is direct-to-consumer genetic testing? Most of the time, genetic testing is ... testing. For more information about direct-to-consumer genetic testing: Centers for Disease Control and Prevention (CDC) ...

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

Parents' Attitudes toward Clinical Genetic Testing for Autism Spectrum Disorder-Data from a Norwegian Sample.

PubMed

Johannessen, Jarle; Nærland, Terje; Hope, Sigrun; Torske, Tonje; Høyland, Anne Lise; Strohmaier, Jana; Heiberg, Arvid; Rietschel, Marcella; Djurovic, Srdjan; Andreassen, Ole A

2017-05-18

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.

A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

PubMed

Read, Timothy; Richmond, Phillip A; Dowell, Robin D

2016-01-01

Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.

Development of an Attitudes Measure for Prenatal Screening in Diverse Populations

ERIC Educational Resources Information Center

Posner, S. F.; Learman, L. A.; Gates, E. A.; Washington, A. E.; Kuppermann, M.

2004-01-01

Background: Prenatal screening for chromosomal abnormalities is routinely offered to all pregnant women who present for care by their 20th gestational week. Not all women, however, choose to undergo one of these tests, and choice of which test(s) to undergo also vary. The reasons for variation in screening test behavior have not been fully…

A missing ancestry - Genetic Testing | NIH MedlinePlus the Magazine

MedlinePlus

... Testing - From Genetics Home Reference: the benefits, costs, risks, and limitations of genetic testing Genetic Testing Registry -A publicly funded medical genetics information resource developed for physicians, other health care providers, and researchers MedlinePlus — Genetic Testing CLINSEQ®: ...

Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study

PubMed Central

2013-01-01

Background People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada. Methods Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada. Summary The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada. PMID:23356884

Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study.

PubMed

Anand, Sonia S; Vasudevan, Anil; Gupta, Milan; Morrison, Katherine; Kurpad, Anura; Teo, Koon K; Srinivasan, Krishnamachari

2013-01-28

People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada. Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada. The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada.

Dealing with the incidental finding of secondary variants by the example of SRNS patients undergoing targeted next-generation sequencing.

PubMed

Weber, Stefanie; Büscher, Anja K; Hagmann, Henning; Liebau, Max C; Heberle, Christian; Ludwig, Michael; Rath, Sabine; Alberer, Martin; Beissert, Antje; Zenker, Martin; Hoyer, Peter F; Konrad, Martin; Klein, Hanns-Georg; Hoefele, Julia

2016-01-01

Steroid-resistant nephrotic syndrome (SRNS) is a severe cause of progressive renal disease. Genetic forms of SRNS can present with autosomal recessive or autosomal dominant inheritance. Recent studies have identified mutations in multiple podocyte genes responsible for SRNS. Improved sequencing methods (next-generation sequencing, NGS) now promise rapid mutational testing of SRNS genes. In the present study, a simultaneous screening of ten SRNS genes in 37 SRNS patients was performed by NGS. In 38 % of the patients, causative mutations in one SRNS gene were found. In 22 % of the patients, in addition to these mutations, a secondary variant in a different gene was identified. This high incidence of accumulating sequence variants was unexpected but, although they might have modifier effects, the pathogenic potential of these additional sequence variants seems unclear so far. The example of molecular diagnostics by NGS in SRNS patients shows that these new sequencing technologies might provide further insight into molecular pathogenicity in genetic disorders but will also generate results, which will be difficult to interpret and complicate genetic counseling. Although NGS promises more frequent identification of disease-causing mutations, the identification of causative mutations, the interpretation of incidental findings and possible pitfalls might pose problems, which hopefully will decrease by further experience and elucidation of molecular interactions.

Myotonic Dystrophy Type 2 Found in Two of Sixty-Three Persons Diagnosed as Having Fibromyalgia

PubMed Central

Auvinen, Satu; Suominen, Tiina; Hannonen, Pekka; Bachinski, Linda L.; Krahe, Ralf; Udd, Bjarne

2008-01-01

Because of its high prevalence, fibromyalgia (FM) is a major general health issue. Myotonic dystrophy type 2 (DM2) is a recently described autosomal-dominant multisystem disorder. Besides variable proximal muscle weakness, myotonia, and precocious cataracts, muscle pain and stiffness are prominent presenting features of DM2. After noting that several of our mutation-positive DM2 patients had a previous diagnosis of FM, suggesting that DM2 may be misdiagnosed as FM, we invited 90 randomly selected patients diagnosed as having FM to undergo genetic testing for DM2. Of the 63 patients who agreed to participate, 2 (3.2%) tested positive for the DM2 mutation. Their cases are described herein. DM2 was not found in any of 200 asymptomatic controls. We therefore suggest that the presence of DM2 should be investigated in a large sample of subjects diagnosed as having FM, and clinicians should be aware of overlap in the clinical presentation of these 2 distinct disorders. PMID:18975316

Evolutionary Design of an X-Band Antenna for NASA's Space Technology 5 Mission

NASA Technical Reports Server (NTRS)

Lohn, Jason D.; Hornby, Gregory S.; Rodriguez-Arroyo, Adan; Linden, Derek S.; Kraus, William F.; Seufert, Stephen E.

2003-01-01

We present an evolved X-band antenna design and flight prototype currently on schedule to be deployed on NASA s Space Technology 5 spacecraft in 2004. The mission consists of three small satellites that wall take science measurements in Earth s magnetosphere. The antenna was evolved to meet a challenging set of mission requirements, most notably the combination of wide beamwidth for a circularly-polarized wave and wide bandwidth. Two genetic algorithms were used: one allowed branching an the antenna arms and the other did not. The highest performance antennas from both algorithms were fabricated and tested. A handdesigned antenna was produced by the contractor responsible for the design and build of the mission antennas. The hand-designed antenna is a quadrifilar helix, and we present performance data for comparison to the evolved antennas. As of this writing, one of our evolved antenna prototypes is undergoing flight qualification testing. If successful, the resulting antenna would represent the first evolved hardware in space, and the first deployed evolved antenna.

The Importance of Symptom Validity Testing in Adolescents and Young Adults Undergoing Assessments for Learning or Attention Difficulties

ERIC Educational Resources Information Center

Harrison, Allyson G.; Green, Paul; Flaro, Lloyd

2012-01-01

It is almost self-evident that test results will be unreliable and misleading if those undergoing assessments do not make a full effort on testing. Nevertheless, objective tests of effort have not typically been used with young adults to determine whether test results are valid or not. Because of the potential economic and/or recreational benefits…

A Diagnosis of Lynch Syndrome - Genetic Testing | NIH MedlinePlus the Magazine

MedlinePlus

... Testing - From Genetics Home Reference: the benefits, costs, risks, and limitations of genetic testing Genetic Testing Registry -A publicly funded medical genetics information resource developed for physicians, other health care providers, and researchers MedlinePlus — Genetic Testing CLINSEQ®: ...

Prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer.

PubMed

Kast, Karin; Dobberschütz, Catharina; Sadowski, Carolin Eva; Pistorius, Steffen; Wimberger, Pauline

2016-11-01

Lynch syndrome is known by healthcare providers mainly for patients with colorectal cancer. Awareness of other associated tumors, such as endometrial or ovarian cancer, is low. This study aimed to analyze the prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer. In addition, the willingness of patients and family members to undergo germline mutation testing was investigated. The medical records of all patients diagnosed with endometrial or ovarian cancer at the Department of Gynecology and Obsterics, University Hospital Dresden, between 1998 and 2012, were screened for a family history of HNPCC-associated cancer. Telephone interviews were used to screen, inform, and enroll patients in this genetic analysis study. Molecular analysis was performed by prescreening of tumor tissue, followed by germline mutation analysis. Two hundred and eighty-three patients were diagnosed with endometrial cancer, 291 with ovarian cancer, and 14 with both. A positive family history for tumors associated with Lynch syndrome was documented for 61 patients. Two pathogenic mutations in the genes MLH1 and MSH2 in nine genetic analyses had already been detected before. After genetic counseling, only 10 of 31 index patients (32.3 %) consented for mutation analysis. However, no additional pathogenic heterozygous mutations were found. In this retrospective cohort study in unselected patients with endometrial or ovarian cancer, only a small number of patients with suspected Lynch syndrome could be identified. Of those, acceptance of germline analyses was moderate, only. As a result, the rate of identified pathogenic germline mutations was lower than expected. Therefore, we are convinced that more information on cancer risks, options for predictive molecular testing and preventive procedures, needs to be provided to patients and gynecologists.

Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

PubMed Central

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC. PMID:20978318

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2011-08-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC. Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Genetic analysis of floating Enteromorpha prolifera in the Yellow Sea with AFLP marker

NASA Astrophysics Data System (ADS)

Liu, Cui; Zhang, Jing; Sun, Xiaoyu; Li, Jian; Zhang, Xi; Liu, Tao

2011-09-01

Extremely large accumulation of green algae Enteromorpha prolifera floated along China' coastal region of the Yellow Sea ever since the summer of 2008. Amplified Fragment Length Polymorphism (AFLP) analysis was applied to assess the genetic diversity and relationships among E. prolifera samples collected from 9 affected areas of the Yellow Sea. Two hundred reproducible fragments were generated with 8 AFLP primer combinations, of which 194 (97%) were polymorphic. The average Nei's genetic diversity, the coefficiency of genetic differentiation (Gst), and the average gene flow estimated from Gst in the 9 populations were 0.4018, 0.6404 and 0.2807 respectively. Cluster analysis based on the unweighed pair group method with arithmetic averages (UPGMA) showed that the genetic relationships within one population or among different populations were all related to their collecting locations and sampling time. Large genetic differentiation was detected among the populations. The E. prolifera originated from different areas and were undergoing a course of mixing.

New insight-guided approaches to detect, cure, prevent and eliminate malaria.

PubMed

Kumar, Sushil; Kumari, Renu; Pandey, Richa

2015-05-01

New challenges posed by the development of resistance against artemisinin-based combination therapies (ACTs) as well as previous first-line therapies, and the continuing absence of vaccine, have given impetus to research in all areas of malaria control. This review portrays the ongoing progress in several directions of malaria research. The variants of RTS,S and apical membrane antigen 1 (AMA1) are being developed and test adapted as multicomponent and multistage malaria control vaccines, while many other vaccine candidates and methodologies to produce antigens are under experimentation. To track and prevent the spread of artemisinin resistance from Southeast Asia to other parts of the world, rolling circle-enhanced enzyme activity detection (REEAD), a time- and cost-effective malaria diagnosis in field conditions, and a DNA marker associated with artemisinin resistance have become available. Novel mosquito repellents and mosquito trapping and killing techniques much more effective than the prevalent ones are undergoing field testing. Mosquito lines stably infected with their symbiotic wild-type or genetically engineered bacteria that kill sympatric malaria parasites are being constructed and field tested for stopping malaria transmission. A complementary approach being pursued is the addition of ivermectin-like drug molecules to ACTs to cure malaria and kill mosquitoes. Experiments are in progress to eradicate malaria mosquito by making it genetically male sterile. High-throughput screening procedures are being developed and used to discover molecules that possess long in vivo half life and are active against liver and blood stages for the fast cure of malaria symptoms caused by simple or relapsing and drug-sensitive and drug-resistant types of varied malaria parasites, can stop gametocytogenesis and sporogony and could be given in one dose. Target-based antimalarial drug designing has begun. Some of the putative next-generation antimalarials that possess in their scaffold structure several of the desired properties of malaria cure and control are exemplified by OZ439, NITD609, ELQ300 and tafenoquine that are already undergoing clinical trials, and decoquinate, usnic acid, torin-2, ferroquine, WEHI-916, MMV396749 and benzothiophene-type N-myristoyltransferase (NMT) inhibitors, which are candidates for future clinical usage. Among these, NITD609, ELQ300, decoquinate, usnic acid, torin-2 and NMT inhibitors not only cure simple malaria and are prophylactic against simple malaria, but they also cure relapsing malaria.

Biosynthesis of the Polycyclic Antimicrobial Peptides Lacticin 481, Haloduracin, and Cinnamycin

ERIC Educational Resources Information Center

Cooper, Lisa E.

2009-01-01

Lantibiotics are bacterial-derived polycyclic antimicrobial peptides. They are genetically encoded and ribosomally synthesized as precursor peptides containing a structural region that undergoes post-translational modification and a leader sequence that is not modified. Specific serine and threonine residues in the pre-lantibiotic structural…

Genetic Testing (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Genetic Testing KidsHealth / For Parents / Genetic Testing What's in ... blood, skin, bone, or other tissue is needed. Genetic Testing During Pregnancy For genetic testing before birth, ...

Improving Molecular Genetic Test Utilization through Order Restriction, Test Review, and Guidance.

PubMed

Riley, Jacquelyn D; Procop, Gary W; Kottke-Marchant, Kandice; Wyllie, Robert; Lacbawan, Felicitas L

2015-05-01

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.

Attitudes and Practices Among Internists Concerning Genetic Testing

PubMed Central

Chung, Wendy; Marder, Karen; Shanmugham, Anita; Chin, Lisa J.; Stark, Meredith; Leu, Cheng-Shiun; Appelbaum, Paul S.

2012-01-01

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 <2% have had patients report 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 (p<.001), and if physicians had a geneticist/genetic counselor to whom to refer patients (p<.002), had referred patients to a geneticist/genetic counselor in the past 6 months, had more comfort counseling patients about testing (p<.019), counseled patients about genetics, larger practices (p<.032), fewer African-American patients (p<.027), and patients who had reported genetic discrimination (p<.044). In a multiple logistic regression, ordering a genetic 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

Should patients with ocular genetic disorders have genetic testing?

PubMed

Zanolli, Mario T; Khetan, Vikas; Dotan, Gad; Pizzi, Laura; Levin, Alex V

2014-09-01

To discuss the risks, benefits and value of genetic testing for ocular genetic disease. Testing for ocular genetics diseases is becoming more available and successful gene therapy is being reported. Clinicians must prepare for this trend by considering diagnostic genetic testing for their patients. As advances continually occur in genetic testing for ocular genetic disorders, clinicians must develop an understanding of the potential risks and benefits for their patients.

The loss of a mother and dealing with genetic cancer risk: women who have undergone prophylactic removal of the ovaries.

PubMed

Mæland, Marie Kvamme; Eriksen, Elin Overaa; Synnes, Oddgeir

2014-10-01

The purpose of this article is to highlight some new findings from a qualitative study that have not been previously considered. The research was based on a qualitative phenomenological method. Data were collected by semi-structured individual interviews. A purposeful sample was recruited from West Norway of 14 women with a possible risk of developing breast and ovarian cancer. Data collection took place at least one year after prophylactic removal of the ovaries. Data from the study was analyzed according to the phenomenological method of Amedeo Giorgi. Two themes were revealed as essential factors of the interviewed women's experiences: "the loss of a mother" and "dealing with genetic cancer risk." For the most part, these two themes also appeared to be interrelated. When a mother died of ovarian cancer while her daughter was a child or a young woman, this often led to her daughter's strong desire to find an explanation for her mother's death, as well as to her efforts to undergo genetic testing and surgery to prevent cancer in her family in the future. The study indicates that women's experiences in families at risk of hereditary cancer are closely related to an understanding of their life stories, particularly their "loss of a mother," and how this influences how they deal with genetic cancer risk. Health care workers can thus help patients identify connections and establish coherence through the act of storytelling, by listening to their illness experiences as part of their life stories. Copyright © 2014 Elsevier Ltd. All rights reserved.

The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study.

PubMed

Han, Sang-Ah; Kim, Sung-Won; Kang, Eunyoung; Park, Sue K; Ahn, Sei-Hyun; Lee, Min Hyuk; Nam, Seok-Jin; Han, Wonshik; Bae, Young Tae; Kim, Hyun-Ah; Cho, Young Up; Chang, Myung Chul; Paik, Nam Sun; Hwang, Ki-Tae; Kim, Sei Joong; Noh, Dong-Young; Choi, Doo Ho; Noh, Woo-Chul; Kim, Lee Su; Kim, Ku Sang; Suh, Young Jin; Lee, Jeong Eon; Jung, Yongsik; Moon, Byung-In; Yang, Jung-Hyun; Son, Byung Ho; Yom, Cha Kyong; Kim, Sung Yong; Lee, Hyde; Jung, Sung Hoo

2013-03-01

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

Surrounded by work platforms, the full-scale Orion AFT crew module (center) is undergoing preparations for the first flight test of Orion's launch abort system.

NASA Image and Video Library

2008-05-20

Surrounded by work platforms, NASA's first full-scale Orion abort flight test (AFT) crew module (center) is undergoing preparations at the NASA Dryden Flight Research Center in California for the first flight test of Orion's launch abort system.

Antares alignment gimbal positioner linear bearing tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Day, R.D.; McKay, M.D.; Pierce, D.D.

1981-01-01

The data indicate that of the six configurations tested, the solid circular rails with either the wet or dry lubricant are superior to the other configurations. Therefore, these two will undergo additional tests. These tests will consist of (1) modifying the testing procedure to obtain a better estimation of the limits of precision; and (2) subjecting the bearings to moments more closely approximating the actual conditions they will undergo on the AGP.

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

PubMed Central

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

2016-01-01

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

A Prospective, Longitudinal Study of the Impact of GJB2/GJB6 Genetic Testing on the Beliefs and Attitudes of Parents of Deaf and Hard-of-Hearing Infants

PubMed Central

Palmer, Christina G.S.; Martinez, Ariadna; Fox, Michelle; Zhou, Jin; Shapiro, Nina; Sininger, Yvonne; Grody, Wayne W.; Schimmenti, Lisa A.

2010-01-01

There are limited data on the impact of incorporating genetic counseling and testing into the newborn hearing screening process. We report on results from a prospective, longitudinal study to determine the impact of genetic counseling and GJB2/GJB6 genetic testing on parental knowledge, attitudes, and beliefs about genetic testing. One hundred thirty culturally hearing parents of 93 deaf or hard-of-hearing children ages 0 – 3 years primarily identified through newborn hearing screening received pre- and post-test genetic counseling for GJB2 and GJB6. Parents completed questionnaires following pre-test counseling, and 1- and 6-months post-test result disclosure. Results indicate that following pre-test counseling all parents perceived benefits to genetic testing. While parents who received positive results continued to perceive benefits from testing, perceived benefit declined among parents who received inconclusive or negative results. Parents did not perceive genetic testing as harmful following pre-test counseling or receipt of test results. Parents who received positive test results performed better in understanding recurrence and causation of their child’s deafness and indicated greater interest in prenatal genetic testing than those who received inconclusive or negative test results. Parents felt that pediatricians and audiologists should inform parents of genetic testing availability; however, there was no consensus on timing of this discussion. Thus culturally hearing parents do not perceive genetic testing of their deaf or hard-of-hearing infants/toddlers as harmful; they feel that primary care providers should discuss genetic testing with them; and positive genetic test results with genetic counseling give rise to better understanding and perceived benefit than negative or inconclusive results. PMID:19449415

A prospective, longitudinal study of the impact of GJB2/GJB6 genetic testing on the beliefs and attitudes of parents of deaf and hard-of-hearing infants.

PubMed

Palmer, Christina G S; Martinez, Ariadna; Fox, Michelle; Zhou, Jin; Shapiro, Nina; Sininger, Yvonne; Grody, Wayne W; Schimmenti, Lisa A

2009-06-01

There are limited data on the impact of incorporating genetic counseling and testing into the newborn hearing screening process. We report on results from a prospective, longitudinal study to determine the impact of genetic counseling and GJB2/GJB6 genetic testing on parental knowledge, attitudes, and beliefs about genetic testing. One hundred thirty culturally hearing parents of 93 deaf or hard-of-hearing children ages 0-3 years primarily identified through newborn hearing screening received pre- and post-test genetic counseling for GJB2 and GJB6. Parents completed questionnaires following pre-test counseling, and 1- and 6-month post-test result disclosure. Results indicate that following pre-test counseling all parents perceived benefits to genetic testing. While parents who received positive results continued to perceive benefits from testing, perceived benefit declined among parents who received inconclusive or negative results. Parents did not perceive genetic testing as harmful following pre-test counseling or receipt of test results. Parents who received positive test results performed better in understanding recurrence and causation of their child's deafness and indicated greater interest in prenatal genetic testing than those who received inconclusive or negative test results. Parents felt that pediatricians and audiologists should inform parents of genetic testing availability; however, there was no consensus on timing of this discussion. Thus culturally hearing parents do not perceive genetic testing of their deaf or hard-of-hearing infants/toddlers as harmful; they feel that primary care providers should discuss genetic testing with them; and positive genetic test results with genetic counseling give rise to better understanding and perceived benefit than negative or inconclusive results. (c) 2009 Wiley-Liss, Inc.

Genetic Testing Integration Panels (GTIPs): A novel approach for considering integration of direct-to-consumer and other new genetic tests into patient care

PubMed Central

Uhlmann, Wendy R.; Sharp, Richard R.

2014-01-01

There has been a dramatic increase in the number of genetic tests available but few tests have practice guidelines. In addition, many tests have become available outside of genetics clinics through direct-to-consumer (DTC) companies and several offer tests not considered standard of care. To address several practical challenges associated with the rapid introduction of clinical and DTC genetic tests, we propose that genetic counselors and geneticists organize expert panels in their institutions to discuss the integration of new tests into patient care. We propose the establishment of Genetic Testing Integration Panels (GTIPs) to bring together local experts in medical genetics, genetic counseling, bioethics and law, health communication and clinical laboratory genetics. We describe key features of this approach and consider some of the potential advantages and limitations of using a GTIP to address the many clinical challenges raised by rapidly emerging clinical and DTC genetic tests. PMID:22246561

Blastocentesis: a source of DNA for preimplantation genetic testing. Results from a pilot study.

PubMed

Gianaroli, Luca; Magli, M Cristina; Pomante, Alessandra; Crivello, Anna M; Cafueri, Giulia; Valerio, Marzia; Ferraretti, Anna P

2014-12-01

To investigate the presence of DNA in blastocyst fluids (BFs) and to estimate whether the chromosomal status predicted by its analysis corresponds with the ploidy condition in trophectoderm (TE) cells, the whole embryo, and that predicted by polar bodies (PBs) or blastomeres. Prospective study. In vitro fertilization unit. Seventeen couples undergoing preimplantation genetic screening with the use of array comparative genomic hybridization on PBs (n = 12) or blastomeres (n = 5). BFs and TE cells were retrieved from 51 blastocysts for separate chromosomal analysis. Presence of DNA in BFs and assessment of the corresponding chromosome condition; correlation with the results in TE cells and those predicted by the analysis done at earlier stages. DNA was detected in 39 BFs (76.5%). In 38 of 39 cases (97.4%) the ploidy condition of BFs was confirmed in TE cells, and the rate of concordance per single chromosome was 96.6% (904/936). In relation to the whole embryo, the ploidy condition corresponded in all cases with a per-chromosome concordance of 98.1%. The testing of PBs and blastomeres had 93.3% and 100% prediction of BF ploidy condition with a concordance per chromosome of 93.5% and 94%, respectively. Blastocentesis could represent an alternative source of material for chromosomal testing, because the BF is highly predictive of the embryo ploidy condition and chromosome content. Our data confirm the relevance of the oocyte and of the early-cleavage embryo in determining the ploidy condition of the resulting blastocyst. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles

PubMed Central

Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

2016-01-01

The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and electrical signals may allow translating single-cell states into multicellular states which provide spatio-temporal information. The model results have clear implications for biological processes: (i) bioelectric signals can override slightly different genetic pre-patterns; (ii) ensembles of cells initially at the same potential can undergo an electrical regionalisation because of persistent genetic differences between adjacent spatial regions; and (iii) shifts in the normal cell electrical balance could trigger significant changes in the genetic regulation. PMID:27731412

The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles.

PubMed

Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

2016-10-12

The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and electrical signals may allow translating single-cell states into multicellular states which provide spatio-temporal information. The model results have clear implications for biological processes: (i) bioelectric signals can override slightly different genetic pre-patterns; (ii) ensembles of cells initially at the same potential can undergo an electrical regionalisation because of persistent genetic differences between adjacent spatial regions; and (iii) shifts in the normal cell electrical balance could trigger significant changes in the genetic regulation.

77 FR 24960 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30Day-12-0010... Description CDC has been monitoring the occurrence of serious birth defects and genetic diseases in Atlanta... early warning system for new teratogens. In 1997, the Birth Defects Risk Factor Surveillance (BDRFS...

Lamarck Will Not Lie Down.

ERIC Educational Resources Information Center

Lewin, Roger

1981-01-01

Describes recent research by Edward Steele appearing to support the Lamarckian theory of inheritance. Steele suggests that a mutant somatic cell favored by the environment will undergo clonal expansion. Altered genetic materials from these cells is then picked up by C-type viruses and inserted into the germ line genome. (CS)

The role of somatic recombination in natural populations of the root pathogen Armillaria mellea

USDA-ARS?s Scientific Manuscript database

Fungi have evolved various mechanisms of shuffling genetic material, which can occur in the absence of fruiting and meiosis. In the homobasidiomycete Armillaria (causal agent of Armillaria root disease), the predominant vegetative stage is diploid. Diploid and haploid mycelia can fuse and undergo ka...

Geographic variation in sexual attraction of Spodoptera frugiperda corn- and rice-strain males to pheromone lures

USDA-ARS?s Scientific Manuscript database

The corn- and rice-strains of Spodoptera frugiperda exhibit several genetic and behavioral differences and appear to be undergoing ecological speciation in sympatry. Previous studies reported conflicting results when investigating male attraction to pheromone lures in different regions, but this cou...

Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-09-08

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

Genetic counseling and the ethical issues around direct to consumer genetic testing.

PubMed

Hawkins, Alice K; Ho, Anita

2012-06-01

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.

NASA Dryden's F-15B aircraft with the Gulfstream Quiet Spike sonic boom mitigator attached undergoes ground vibration testing in preparation for test flights

NASA Image and Video Library

2006-05-01

NASA Dryden's F-15B testbed aircraft with the Gulfstream Quiet Spike sonic boom mitigator attached undergoes ground vibration testing in preparation for test flights. The project seeks to verify the structural integrity of the multi-segmented, articulating spike attachment designed to reduce and control a sonic boom.

How Is Genetic Testing Done?

MedlinePlus

... does it take to get the results? Will health insurance cover the costs of genetic testing? What are the benefits of genetic testing? What are the risks and limitations of genetic testing? What is genetic ...

Am I My Family's Keeper? Disclosure Dilemmas in Next-Generation Sequencing.

PubMed

Wouters, Roel H P; Bijlsma, Rhodé M; Ausems, Margreet G E M; van Delden, Johannes J M; Voest, Emile E; Bredenoord, Annelien L

2016-12-01

Ever since genetic testing is possible for specific mutations, ethical debate has sparked on the question of whether professionals have a duty to warn not only patients but also their relatives that might be at risk for hereditary diseases. As next-generation sequencing (NGS) swiftly finds its way into clinical practice, the question who is responsible for conveying unsolicited findings to family members becomes increasingly urgent. Traditionally, there is a strong emphasis on the duties of the professional in this debate. But what is the role of the patient and her family? In this article, we discuss the question of whose duty it is to convey relevant genetic risk information concerning hereditary diseases that can be cured or prevented to the relatives of patients undergoing NGS. We argue in favor of a shared responsibility for professionals and patients and present a strategy that reconciles these roles: a moral accountability nudge. Incorporated into informed consent and counseling services such as letters and online tools, this nudge aims to create awareness on specific patient responsibilities. Commitment of all parties is needed to ensure adequate dissemination of results in the NGS era. © 2016 WILEY PERIODICALS, INC.

Effects of aging on the male reproductive system.

PubMed

Gunes, Sezgin; Hekim, Gulgez Neslihan Taskurt; Arslan, Mehmet Alper; Asci, Ramazan

2016-04-01

The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

Reassortment process after co-infection of pigs with avian H1N1 and swine H3N2 influenza viruses.

PubMed

Urbaniak, Kinga; Markowska-Daniel, Iwona; Kowalczyk, Andrzej; Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Frącek, Barbara; Pejsak, Zygmunt

2017-07-08

The influenza A virus is highly variable, which, to some degree, is caused by the reassortment of viral genetic material. This process plays a major role in the generation of novel influenza virus strains that can emerge in a new host population. Due to the susceptibility of pigs to infections with avian, swine and human influenza viruses, they are considered intermediate hosts for the adaptation of the avian influenza virus to humans. In order to test the reassortment process in pigs, they were co-infected with H3N2 A/swine/Gent/172/2008 (Gent/08) and H1N1 A/duck/Italy/1447/2005 (Italy/05) and co-housed with a group of naïve piglets. The Gent/08 strains dominated over Italy/05, but reassortment occurred. The reassortant strains of the H1N1 subtype (12.5%) with one gene (NP or M) of swine-origin were identified in the nasal discharge of the contact-exposed piglets. These results demonstrate that despite their low efficiency, genotypically and phenotypically different influenza A viruses can undergo genetic exchange during co-infection of pigs.

Genetic Testing and Parkinson Disease: Assessment of Patient Knowledge, Attitudes, and Interest

PubMed Central

Wood, Elisabeth McCarty; Xie, Sharon X.; Siderowf, Andrew; Van Deerlin, Vivianna M.

2012-01-01

The most common genetic contributor to late-onset Parkinson disease (PD) is the LRRK2 gene. In order to effectively integrate LRRK2 genetic testing into clinical practice, a strategy tailored to the PD population must be developed. We assessed 168 individuals with PD for baseline knowledge of genetics, perceived risk, and interest and opinions regarding genetic counseling and testing. Most participants felt that they were familiar with general genetics terms but overall knowledge levels were low, with an average score of 55%. The majority of participants thought it was likely they inherited a PD gene (72%), believed genetic testing for PD would be useful (86%), and were interested in genetic testing (59%) and genetic counseling (56%). However, only a few participants had heard of any genetic tests for PD (29%) or LRRK2 (10%). There appears to be a significant level of interest in genetics and genetic testing within the PD population, but a considerable deficit in genetics knowledge and an over-estimation of risk. Genetic education and counseling tools to address these needs were developed to provide patients with the ability to make informed and knowledgeable genetic testing decisions. PMID:21476119

What Do the Results of Genetic Tests Mean?

MedlinePlus

... does it take to get the results? Will health insurance cover the costs of genetic testing? What are the benefits of genetic testing? What are the risks and limitations of genetic testing? What is genetic ...

Genetic testing: medico-legal issues.

PubMed

Bird, Sara

2014-07-01

The availability and frequency of genetic testing is increasing. Genetic testing poses some unique ethical and legal issues for medical practitioners because of the potential to identify genetic variants that carry implications for the risk of disease in the future for the patient and their relatives. The regulatory framework within which genetic testing is provided in Australia is also changing. This article examines some medico-legal issues associated with genetic testing that general practitioners (GPs) are likely encounter in their practices. There is inevitable involvement of the GP in the long term care of a patient (and possibly their family) following genetic testing, regardless of whether or not the GP has ordered the testing. Cases are presented to illustrate some of the medico-legal issues that may arise from direct-to-consumer genetic testing, information disclosure to genetic relatives and requests for parentage testing.

THE MURINE LOCAL LYMPH NODE ASSAY: AN ALTERNATIVE TEST METHOD FOR THE EVALUATION OF THE POTENTIAL FOR CHEMICALS TO ELICIT ALLERGIC CONTACT DERMATITIS

EPA Science Inventory

ABSTRACT
The process that a new toxicology test method must undergo to attain acceptance and regulatory implementation may seem daunting. As the first test method to undergo Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) review, the local...

Adults' perceptions of genetic counseling and genetic testing.

PubMed

Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley

2015-02-01

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.

Incidence of Fanconi anemia in children with congenital thumb anomalies referred for diepoxybutane testing.

PubMed

Webb, Michelle L; Rosen, Heather; Taghinia, Amir; McCarty, Erika R; Cerrato, Felecia; Upton, Joseph; Labow, Brian I

2011-06-01

Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive. We queried our database for patients who presented with congenital thumb anomalies and who underwent diepoxybutane (DEB) testing for FA between 1999 and 2008 at Children's Hospital Boston and the Dana-Farber Cancer Institute. During this time period, 543 congenital thumb anomaly patients (235 with thumb hypoplasia) presented to our institution. A total of 81 patients with thumb abnormalities underwent DEB testing. Six patients (7% of those tested; 1% of the total; 3% of thumb hypoplasia patients) had a positive DEB test consistent with the diagnosis of FA; all had other non-upper-extremity anomalies associated with FA. Of 6 FA patients, 5 had bilateral involvement; all had some degree of thumb hypoplasia (3 also had radial dysplasia). Mean age at testing was 2.6 years (SD 4.3). Most of the patients tested had multiple physical anomalies (n = 66). The anomaly distribution was: thumb hypoplasia and radial dysplasia (n = 29), thumb hypoplasia (n = 26), radial polydactyly (n = 12), radial polydactyly and radial dysplasia (n = 1), and proximally placed thumb and radial dysplasia (n = 1). Twelve patients had other thumb anomalies. Although the incidence of FA in patients with thumb anomalies may be low, patients with thumb hypoplasia and other physical findings associated with FA, specifically café au lait spots and short stature, appear to have an increased risk of FA. Because hand surgeons see these patients early in life, they have the opportunity to refer these patients for FA testing to initiate early education, family genetic counseling, and treatment if warranted. Prognostic IV. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.

PubMed

Tavares, Isabel; Oliveira, João Paulo; Pinho, Ana; Moreira, Luciana; Rocha, Liliana; Santos, Josefina; Pinheiro, Joaquim; Costa, Paulo Pinho; Lobato, Luísa

2017-08-01

Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. Case series. 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. Kidney disease, kidney disease progression, and survival. The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. Retrospective data collection for patients with amyloidosis previously diagnosed. AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

PubMed

Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L

2012-07-01

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 <1% reported having used DTC genetic 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.

Ethnic differences in parental perceptions of genetic testing for deaf infants.

PubMed

Palmer, Christina G S; Martinez, Ariadna; Fox, Michelle; Sininger, Yvonne; Grody, Wayne W; Schimmenti, Lisa A

2008-02-01

As genetic testing becomes an integral part of the evaluation of deaf infants and children, it is important to understand parental views on genetic testing. The purpose of this study is to examine parental reasons for, and beliefs about, genetic testing for deafness in early-identified infants, and to determine if they differ as a function of ethnicity. We present baseline data collected from 56 Caucasian, 59 Hispanic, and 24 Asian parents of deaf children participating in a longitudinal, prospective study on genetic testing for connexin-related deafness. The overall finding is that reasons for, and beliefs about, genetic testing for deafness varied as a function of ethnicity. Virtually all parents sought genetic testing to understand why their child is deaf. However, Asian and/or Hispanic parents were more likely than Caucasian parents to view family planning, helping with their child's medical care, and helping the family as other important reasons for testing, and were more likely than Caucasian parents to perceive genetic testing to be useful for these purposes. Asian and Hispanic parents were more likely than Caucasian parents to perceive genetic testing in harmful terms. Genetic testing fulfills a cognitive need for parents to understand why their child is deaf, yet differences in responses suggest that Asian and Hispanic parents may seek testing for other purposes. Understanding different perspectives on genetic testing for deafness will enhance genetic counselors' cultural competence and facilitate the pre-test genetic counseling session.

Genetic Literacy and Patient Perceptions of IBD Testing Utility and Disease Control: A Randomized Vignette Study of Genetic Testing

PubMed Central

Hooker, Gillian W.; Peay, Holly; Erby, Lori; Bayless, Theodore; Biesecker, Barbara B.; Roter, Debra L.

2014-01-01

Background Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests. PMID:24691112

What Are the Risks and Limitations of Genetic Testing?

MedlinePlus

... does it take to get the results? Will health insurance cover the costs of genetic testing? What are the benefits of genetic testing? What are the risks and limitations of genetic testing? What is genetic ...

[A survey of willingness about genetic counseling and tests in patients of epithelial ovarian cancer].

PubMed

Li, L; Qiu, L; Wu, M

2017-11-21

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.

The still uncertain identity of the channel-forming unit(s) of the mitochondrial permeability transition pore.

PubMed

Baines, Christopher P; Gutiérrez-Aguilar, Manuel

2018-07-01

Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against- putative channel-forming components of the MPT pore. We conclude that the structure of the MPT pore still remains largely undefined and suggest that future studies should follow established technical considerations to unambiguously consolidate the channel forming constituent(s) of the MPT pore. Copyright © 2018 Elsevier Ltd. All rights reserved.

AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

PubMed

Tollenaere, C; Duplantier, J-M; Rahalison, L; Ranjalahy, M; Brouat, C

2011-03-01

The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

Emergence of a New Pathogenic Ehrlichia Species, Wisconsin and Minnesota, 2009

PubMed Central

Pritt, Bobbi S.; Sloan, Lynne M.; Johnson, Diep K. Hoang; Munderloh, Ulrike G.; Paskewitz, Susan M.; McElroy, Kristina M.; McFadden, Jevon D.; Binnicker, Matthew J.; Neitzel, David F.; Liu, Gongping; Nicholson, William L.; Nelson, Curtis M.; Franson, Joni J.; Martin, Scott A.; Cunningham, Scott A.; Steward, Christopher R.; Bogumill, Kay; Bjorgaard, Mary E.; Davis, Jeffrey P.; McQuiston, Jennifer H.; Warshauer, David M.; Wilhelm, Mark P.; Patel, Robin; Trivedi, Vipul A.; Eremeeva, Marina E.

2012-01-01

Background Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause. Methods We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis. Results On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species. All patients had fever, malaise, headache, and lymphopenia; three had thrombocytopenia; and two had elevated liver-enzyme levels. All recovered after receiving doxycycline treatment. At least 17 of 697 Ixodes scapularis ticks collected in Minnesota or Wisconsin were positive for the same ehrlichia species on polymerase-chain-reaction testing. Genetic analyses revealed that this new ehrlichia species is closely related to E. muris. Conclusions We report a new ehrlichia species in Minnesota and Wisconsin and provide supportive clinical, epidemiologic, culture, DNA-sequence, and vector data. Physicians need to be aware of this newly discovered close relative of E. muris to ensure appropriate testing, treatment, and regional surveillance. (Funded by the National Institutes of Health and the Centers for Disease Control and Prevention.) PMID:21812671

"RCL-Pooling Assay": A Simplified Method for the Detection of Replication-Competent Lentiviruses in Vector Batches Using Sequential Pooling.

PubMed

Corre, Guillaume; Dessainte, Michel; Marteau, Jean-Brice; Dalle, Bruno; Fenard, David; Galy, Anne

2016-02-01

Nonreplicative recombinant HIV-1-derived lentiviral vectors (LV) are increasingly used in gene therapy of various genetic diseases, infectious diseases, and cancer. Before they are used in humans, preparations of LV must undergo extensive quality control testing. In particular, testing of LV must demonstrate the absence of replication-competent lentiviruses (RCL) with suitable methods, on representative fractions of vector batches. Current methods based on cell culture are challenging because high titers of vector batches translate into high volumes of cell culture to be tested in RCL assays. As vector batch size and titers are continuously increasing because of the improvement of production and purification methods, it became necessary for us to modify the current RCL assay based on the detection of p24 in cultures of indicator cells. Here, we propose a practical optimization of this method using a pairwise pooling strategy enabling easier testing of higher vector inoculum volumes. These modifications significantly decrease material handling and operator time, leading to a cost-effective method, while maintaining optimal sensibility of the RCL testing. This optimized "RCL-pooling assay" ameliorates the feasibility of the quality control of large-scale batches of clinical-grade LV while maintaining the same sensitivity.

Pulmonary arterial hypertension: Specialists’ knowledge, practices, and attitudes of genetic counseling and genetic testing in the USA

PubMed Central

Jacher, Joseph E.; Martin, Lisa J.; Chung, Wendy K.; Loyd, James E.; Nichols, William C.

2017-01-01

Pulmonary arterial hypertension (PAH) is characterized by obstruction of pre-capillary pulmonary arteries, which leads to sustained elevation of pulmonary arterial pressure. Identifying those at risk through early interventions, such as genetic testing, may mitigate disease course. Current practice guidelines recommend genetic counseling and offering genetic testing to individuals with heritable PAH, idiopathic PAH, and their family members. However, it is unclear if PAH specialists follow these recommendations. Thus, our research objective was to determine PAH specialists’ knowledge, utilization, and perceptions about genetic counseling and genetic testing. A survey was designed and distributed to PAH specialists who primarily work in the USA to assess their knowledge, practices, and attitudes about the genetics of PAH. Participants’ responses were analyzed using parametric and non-parametric statistics and groups were compared using the Wilcoxon rank sum test. PAH specialists had low perceived and actual knowledge of the genetics of PAH, with 13.2% perceiving themselves as knowledgeable and 27% actually being knowledgeable. Although these specialists had positive or ambivalent attitudes about genetic testing and genetic counseling, they had poor utilization of these genetic services, with almost 80% of participants never or rarely ordering genetic testing or referring their patients with PAH for genetic counseling. Physicians were more knowledgeable, but had lower perceptions of the value of genetic testing and genetic counseling compared to non-physicians (P < 0.05). The results suggest that increased education and awareness is needed about the genetics of PAH as well as the benefits of genetic testing and genetic counseling for individuals who treat patients with PAH. PMID:28597770

Microsatellite Analysis of Museum Specimens Reveals Historical Differences in Genetic Diversity between Declining and More Stable Bombus Species.

PubMed

Maebe, Kevin; Meeus, Ivan; Ganne, Maarten; De Meulemeester, Thibaut; Biesmeijer, Koos; Smagghe, Guy

2015-01-01

Worldwide most pollinators, e.g. bumblebees, are undergoing global declines. Loss of genetic diversity can play an essential role in these observed declines. In this paper, we investigated the level of genetic diversity of seven declining Bombus species and four more stable species with the use of microsatellite loci. Hereto we genotyped a unique collection of museum specimens. Specimens were collected between 1918 and 1926, in 6 provinces of the Netherlands which allowed us to make interspecific comparisons of genetic diversity. For the stable species B. pascuorum, we also selected populations from two additional time periods: 1949-1955 and 1975-1990. The genetic diversity and population structure in B. pascuorum remained constant over the three time periods. However, populations of declining bumblebee species showed a significantly lower genetic diversity than co-occurring stable species before their major declines. This historical difference indicates that the repeatedly observed reduced genetic diversity in recent populations of declining bumblebee species is not caused solely by the decline itself. The historically low genetic diversity in the declined species may be due to the fact that these species were already rare, making them more vulnerable to the major drivers of bumblebee decline.

How Can Consumers Be Sure a Genetic Test Is Valid and Useful?

MedlinePlus

... does it take to get the results? Will health insurance cover the costs of genetic testing? What are the benefits of genetic testing? What are the risks and limitations of genetic testing? What is genetic ...

Assessing Genetic Literacy Awareness and Knowledge Gaps in the US Population: Results from the Health Information National Trends Survey.

PubMed

Krakow, Melinda; Ratcliff, Chelsea L; Hesse, Bradford W; Greenberg-Worisek, Alexandra J

2018-05-31

Public understanding of the role of genetics in disease risk is key to appropriate disease prevention and detection. This study assessed the current extent of awareness and use of genetic testing in the US population. Additionally, the study identified characteristics of subgroups more likely to be at risk for low genetic literacy. The study used data from the National Cancer Institute's 2017 Health Information National Trends Survey, including measures of genetic testing awareness, genetic testing applications and genetic testing usage. Multivariable logistic regression models estimated associations between sociodemographics, genetic testing awareness, and genetic testing use. Fifty-seven percent of respondents were aware of genetic tests. Testing awareness differed by age, household income, and race/ethnicity. Most participants had heard of using tests to determine personal disease risk (82.58%) or inherited disease risk in children (81.41%), but less were familiar with determining treatment (38.29%) or drug efficacy (40.76%). Among those with genetic testing awareness, actual testing uptake was low. A large portion of the general public lacks genetic testing awareness and may benefit from educational campaigns. As precision medicine expands, increasing public awareness about genetic testing applications for disease prevention and treatment will be important to support population health. This is a work of the US Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Patients with Amyotrophic Lateral Sclerosis Have High Interest in and Limited Access to Genetic Testing.

PubMed

Wagner, Karin N; Nagaraja, Haikady; Allain, Dawn C; Quick, Adam; Kolb, Stephen; Roggenbuck, Jennifer

2017-06-01

Although genetic testing for amyotrophic lateral sclerosis (ALS) is widely available, it is unknown what proportion of patients with ALS have access to genetic counseling and testing, and patient attitudes towards ALS genetic testing have not been studied. We conducted a national survey of ALS patients enrolled in the Agency for Toxic Substances and Disease Registry, which consisted of multiple choice questions and two 12 item Likert scale series assessing respondents' experience with and attitude toward genetic testing. The survey had an 8 % response rate, with 449 completed responses. Genetic testing was offered to 33.4 % and completed by 67.1 % of those offered. A minority of respondents (12.5 %) saw a genetic counselor, and were much more likely to be offered genetic testing (p = 0.0001). Respondents with a family history of ALS (8.4 %) were more likely to be offered testing (p = 0.0001) and complete testing (p = 0.05). Respondents with a family history of ALS were more likely to report a favorable attitude towards genetic testing (p = 0.0003), as were respondents who saw a genetic counselor (p = 0.02). The majority of respondents (82.7 %) felt that genetic testing should be offered to all patients with ALS. Our results indicate that ALS patients may have limited access to genetic testing, but perceive benefit from this service. Development of practice guidelines for genetic testing in ALS, to include the routine offer of genetic counseling, may result in broader and more consistent access to these services.

Introducing genetic testing for cardiovascular disease in primary care: a qualitative study.

PubMed

Middlemass, Jo B; Yazdani, Momina F; Kai, Joe; Standen, Penelope J; Qureshi, Nadeem

2014-05-01

While primary care systematically offers conventional cardiovascular risk assessment, genetic tests for coronary heart disease (CHD) are increasingly commercially available to patients. It is unclear how individuals may respond to these new sources of risk information. To explore how patients who have had a recent conventional cardiovascular risk assessment, perceive additional information from genetic testing for CHD. Qualitative interview study in 12 practices in Nottinghamshire from both urban and rural settings. Interviews were conducted with 29 adults, who consented to genetic testing after having had a conventional cardiovascular risk assessment. Individuals' principal motivation for genetic testing was their family history of CHD and a desire to convey the results to their children. After testing, however, there was limited recall of genetic test results and scepticism about the value of informing their children. Participants dealt with conflicting findings from the genetic test, family history, and conventional assessment by either focusing on genetic risk or environmental lifestyle factors. In some participants, genetic test results appeared to reinforce healthy behaviour but others were falsely reassured, despite having an 'above-average' conventional cardiovascular risk score. Although genetic testing was acceptable, participants were unclear how to interpret genetic risk results. To facilitate healthy behaviour, health professionals should explore patients' understanding of genetic test results in light of their family history and conventional risk assessment.

Genetics educational needs in China: physicians' experience and knowledge of genetic testing.

PubMed

Li, Jing; Xu, Tengda; Yashar, Beverly M

2015-09-01

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 < 0.05). Sixty-six percent of physicians indicated a desire for specialized genetic services, and 84% reported a desire for additional genetics 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.

Perception of Genetic Testing for Deafness and Factors Associated with Interest in Genetic Testing Among Deaf People in a Selected Population in Sub-Saharan Africa.

PubMed

Adedokun, Babatunde O; Yusuf, Bidemi O; Lasisi, J Taye; Jinadu, A A; Sunmonu, M T; Ashanke, A F; Lasisi, O Akeem

2015-12-01

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.

Direct-to-consumer sales of genetic services on the Internet.

PubMed

Gollust, Sarah E; Wilfond, Benjamin S; Hull, Sara Chandros

2003-01-01

PURPOSE The increasing use of the Internet to obtain genetics information and to order medical services without a prescription, combined with a rise in direct-to-consumer marketing for genetic testing, suggests the potential for the Internet to be used to sell genetic services. METHODS A systematic World Wide Web search was conducted in May 2002 to assess the availability of genetic services sold directly to consumers on the Internet. RESULTS Out of 105 sites that offered genetic services directly, most offered non-health-related services, including parentage confirmation testing (83%), identity testing (56%), and DNA banking (24%); however, health-related genetic tests were offered through 14 sites (13%). The health-related genetic tests available ranged from standard tests, such as hemochromatosis and cystic fibrosis, to more unconventional tests related to nutrition, behavior, and aging. Of these 14 sites, 5 described risks associated with the genetic services and 6 described the availability of counseling. CONCLUSIONS The availability of direct sales of health-related genetic tests creates the potential for inadequate pretest decision making, misunderstanding test results, and access to tests of questionable clinical value.

Direct-to-consumer sales of genetic services on the Internet

PubMed Central

Gollust, Sarah E.; Wilfond, Benjamin S.; Hull, Sara Chandros

2016-01-01

Purpose The increasing use of the Internet to obtain genetics information and to order medical services without a prescription, combined with a rise in direct-to-consumer marketing for genetic testing, suggests the potential for the Internet to be used to sell genetic services. Methods A systematic World Wide Web search was conducted in May 2002 to assess the availability of genetic services sold directly to consumers on the Internet. Results Out of 105 sites that offered genetic services directly, most offered non–health-related services, including parentage confirmation testing (83%), identity testing (56%), and DNA banking (24%); however, health-related genetic tests were offered through 14 sites (13%). The health-related genetic tests available ranged from standard tests, such as hemochromatosis and cystic fibrosis, to more unconventional tests related to nutrition, behavior, and aging. Of these 14 sites, 5 described risks associated with the genetic services and 6 described the availability of counseling. Conclusions The availability of direct sales of health-related genetic tests creates the potential for inadequate pretest decision making, misunderstanding test results, and access to tests of questionable clinical value. PMID:12865763

Statement of the ESHG on direct-to-consumer genetic testing for health-related purposes

PubMed Central

2010-01-01

Many private companies offer direct-to-consumer (DTC) genetic testing services. Some tests may detect severe and highly penetrant monogenic disorders, while other tests are for genetic variants found associated with increased susceptibility for common and complex diseases in large-scale population studies. Through its Public and Professional Policy committee followed by member and expert consultation, the European Society of Human Genetics has developed the following policy on advertising and provision of predictive genetic tests by such DTC companies: (1) clinical utility of a genetic test shall be an essential criterion for deciding to offer this test to a person or a group of persons; (2) laboratories providing genetic tests should comply with accepted quality standards, including those regarding laboratory personnel qualifications; (3) information about the purpose and appropriateness of testing should be given before the test is done; (4) genetic counselling appropriate to the type of test and disease should be offered; and for some tests psychosocial evaluation and follow-up should be available; (5) privacy and confidentiality of sensitive genetic information should be secured and the data safely guarded; (6) special measures should be taken to avoid inappropriate testing of minors and other legally incapacitated persons; (7) all claims regarding genetic tests should be transparent; advertisement should be unbiased and marketing of genetic tests should be fair; (8) in biomedical research, health care and marketing, respect should be given to relevant ethical principles, as well as international treaties and recommendations regarding genetic testing; and (9) nationally approved guidelines considering all the above-mentioned aspects should be made and followed. PMID:20736974

Factors Associated With Anthropometric Indicators of Nutritional Status in Children With Chronic Kidney Disease Undergoing Peritoneal Dialysis, Hemodialysis, and After Kidney Transplant.

PubMed

García De Alba Verduzco, Julieta; Hurtado López, Erika Fabiola; Pontón Vázquez, Consuelo; de la Torre Serrano, Adriana; Romero Velarde, Enrique; Vásquez Garibay, Edgar Manuel

2018-05-11

The objective of the study was to demonstrate that there are differences in the factors associated with anthropometric indicators of nutritional status, with particular emphasis on arm indicators, in children with end-stage kidney disease undergoing peritoneal dialysis (PD), hemodialysis (HD), and after kidney transplant (KT). An analytical cross-sectional study of consecutive cases included 130 children and adolescents with end-stage kidney disease undergoing substitutive treatment: 49 patients who underwent KT, 33 undergoing PD, and 47 undergoing HD. Socioeconomic data were obtained from all the 3 groups; anthropometric indicators of nutritional status were calculated. Student's t-test and analysis of variance were used for parametric variables. Chi-square test, Mann-Whitney U test, Kruskal-Wallis test, and odds ratio (OR) were used for nonparametric variables. The number of parents living as couples was higher for patients who underwent KT (OR = 3.5 [95% confidence interval {CI} 1.34-9.0]) and undergoing PD (OR = 3.0 [95% CI 1.06-8.8]) than those undergoing HD. The number of mothers who worked outside the home was higher for patients who underwent KT and undergoing PD than the mothers of patients undergoing HD (OR = 13.7 [95% CI: 4.56-41.05]; OR = 15.4 [CI 95% 4.8-49], respectively). Family income was higher for patients who underwent KT and undergoing PD (P = .019, P = .093, respectively). More than 40% of patients in all the 3 groups had growth impairment. Body mass index, mid-upper arm circumference, tricipital and subscapular skinfolds, total arm area, and arm fat area were affected in HD and PD groups (9 to 40%), while of the patients who underwent KT, 36.7% were overweight or obese. More than 50% of patients who underwent KT and undergoing HD and PD had involvement in the arm muscular area. Socioeconomic conditions are more influential for children in the HD program. The nutritional status of children after KT improves; however, not all anthropometric indicators are fully recovered. Children after KT are up to 9 times more likely to be overweight or obese. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Populus homeobox gene ARBORKNOX2 regulates cell differentiation during secondary growth

Treesearch

Juan Du; Shawn D. Mansfield; Andrew T. Groover

2009-01-01

The stem cells of the vascular cambium divide to produce daughter cells, which in turn divide before undergoing differentiation during the radial growth of woody stems. The genetic regulation of these developmental events is poorly understood, however. We report here the cloning and functional characterization of a Populus class-I KNOX...

Genetic control of phyllotaxy phase shift in juvenile vines in a rootstock hybrid population

USDA-ARS?s Scientific Manuscript database

Grapevine seedlings initially display spiral phyllotaxy of true leaves, then undergo a shift to alternate phyllotaxy with the production of the first lateral meristems (typically tendrils). The node at which the shift from spiral to alternate phyllotaxy occurs varies from about the 4th to about the...

Association of ITPA Genotype with Event-Free Survival and Relapse Rates in Children with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy

PubMed Central

Smid, Alenka; Karas-Kuzelicki, Natasa; Milek, Miha; Jazbec, Janez; Mlinaric-Rascan, Irena

2014-01-01

Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL. PMID:25303517

Therapeutic cloning and reproductive liberty.

PubMed

Sparrow, Robert

2009-04-01

Concern for "reproductive liberty" suggests that decisions about embryos should normally be made by the persons who would be the genetic parents of the child that would be brought into existence if the embryo were brought to term. Therapeutic cloning would involve creating and destroying an embryo, which, if brought to term, would be the offspring of the genetic parents of the person undergoing therapy. I argue that central arguments in debates about parenthood and genetics therefore suggest that therapeutic cloning would be prima facie unethical unless it occurred with the consent of the parents of the person being cloned. Alternatively, if therapeutic cloning is thought to be legitimate, this undermines the case for some uses of reproductive cloning by implying that the genetic relation it establishes between clones and DNA donors does not carry the same moral weight as it does in cases of normal reproduction.

Geographic patterns of genetic variation and conservation consequences in three South American rodents.

PubMed

Miranda, Gustavo B; Andrades-Miranda, Jaqueline; Oliveira, Luiz F B; Langguth, Alfredo; Mattevi, Margarete S

2007-12-01

In this study, the geographic patterns of genetic variation of three rodent species belonging to the tribe Oryzomyini were investigated using the mitochondrial cytochrome b and nuclear IRBP genes in biomes that are undergoing degradation processes to a greater or lesser degree. The samples are from 25 collecting localities distributed throughout the Amazon, Cerrado, Atlantic Forest, and Pampa biomes. The results show that the three species have a population and geographic structure, besides being in demographic equilibrium. The phylogenetic analyses performed on Euryoryzomys russatus and Hylaeamys megacephalus showed these specimens grouped in three distinct clades forming geographic gradients (North-South direction in H. megacephalus). Intraspecific genetic divergence was higher in H. megacephalus (4.53%), followed by E. russatus (1.79%), and lowest in Sooretamys angouya (0.88%). The results obtained indicate that, necessarily, the management strategies to preserve genetic diversity should be different for each species, since each of them presented specific population parameters.

Genetic diversity analysis of Zingiber Officinale Roscoe by RAPD collected from subcontinent of India.

PubMed

Ashraf, Kamran; Ahmad, Altaf; Chaudhary, Anis; Mujeeb, Mohd; Ahmad, Sayeed; Amir, Mohd; Mallick, N

2014-04-01

The present investigation was undertaken for the assessment of 12 accessions of Zingiber officinale Rosc. collected from subcontinent of India by RAPD markers. DNA was isolated using CTAB method. Thirteen out of twenty primers screened were informative and produced 275 amplification products, among which 261 products (94.90%) were found to be polymorphic. The percentage polymorphism of all 12 accessions ranged from 88.23% to 100%. Most of the RAPD markers studied showed different levels of genetic polymorphism. The data of 275 RAPD bands were used to generate Jaccard's similarity coefficients and to construct a dendrogram by means of UPGMA. Results showed that ginger undergoes genetic variation due to a wide range of ecological conditions. This investigation was an understanding of genetic variation within the accessions. It will also provide an important input into determining resourceful management strategies and help to breeders for ginger improvement program.

Genetic diversity analysis of Zingiber Officinale Roscoe by RAPD collected from subcontinent of India

PubMed Central

Ashraf, Kamran; Ahmad, Altaf; Chaudhary, Anis; Mujeeb, Mohd.; Ahmad, Sayeed; Amir, Mohd.; Mallick, N.

2013-01-01

The present investigation was undertaken for the assessment of 12 accessions of Zingiber officinale Rosc. collected from subcontinent of India by RAPD markers. DNA was isolated using CTAB method. Thirteen out of twenty primers screened were informative and produced 275 amplification products, among which 261 products (94.90%) were found to be polymorphic. The percentage polymorphism of all 12 accessions ranged from 88.23% to 100%. Most of the RAPD markers studied showed different levels of genetic polymorphism. The data of 275 RAPD bands were used to generate Jaccard’s similarity coefficients and to construct a dendrogram by means of UPGMA. Results showed that ginger undergoes genetic variation due to a wide range of ecological conditions. This investigation was an understanding of genetic variation within the accessions. It will also provide an important input into determining resourceful management strategies and help to breeders for ginger improvement program. PMID:24600309

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

PubMed

Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

2018-02-01

Purpose 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, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

[Evaluation of psychological fear in children undergoing head-up tilt test].

PubMed

Chu, Wei-Hong; Wu, Li-Jia; Wang, Cheng; Lin, Ping; Li, Fang; Zhu, Li-Ping; Ran, Jing; Zou, Run-Mei; Liu, De-Yu

2014-03-01

To investigate the effects of different tilt angles of head-up tilt test (HUTT) and different responses to HUTT on the psychological fear in children undergoing the test. HUTT was performed on children with unexplained syncope or pre-syncope (107 cases: 52 males and 55 females), aged 5.5-17.8 years (mean 12.0±2.8 years). All subjects were randomly assigned to undergo HUTT at an angle of 60°, 70° or 80°; the negative cases underwent sublingual nitroglycerin-provocation HUTT at the same tilt angle. The Wong-Baker Faces Pain Rating Scale was used for self-assessment of psychological fear in subjects during HUTT at the end point of the test. The positive rate, hemodynamic changes and distribution of response types showed no significant differences between children at tilt angles of 60°, 70° and 80° (P>0.05). The greater the tilt angle, the higher the degree of psychological fear in children undergoing the test, but there were no significant differences between them (P>0.05). The degree of psychological fear in children who showed a positive response to HUTT (n=76) was significantly higher than that in children who showed a negative response (n=31) (P<0.01). HUTT can cause psychological fear in children undergoing the test, and the degree of psychological fear increases in children tested at tilt angles from 60° to 80°, but the differences have no statistical significance. A positive response to HUTT can significantly increase the psychological fear in children.

An audit of clinical service examining the uptake of genetic testing by at-risk family members.

PubMed

Forrest, Laura; Delatycki, Martin; Curnow, Lisette; Gen Couns, M; Skene, Loane; Aitken, Maryanne

2012-01-01

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.

Introducing genetic testing for cardiovascular disease in primary care: a qualitative study

PubMed Central

Middlemass, Jo B; Yazdani, Momina F; Kai, Joe; Standen, Penelope J; Qureshi, Nadeem

2014-01-01

Background While primary care systematically offers conventional cardiovascular risk assessment, genetic tests for coronary heart disease (CHD) are increasingly commercially available to patients. It is unclear how individuals may respond to these new sources of risk information. Aim To explore how patients who have had a recent conventional cardiovascular risk assessment, perceive additional information from genetic testing for CHD. Design and setting Qualitative interview study in 12 practices in Nottinghamshire from both urban and rural settings. Method Interviews were conducted with 29 adults, who consented to genetic testing after having had a conventional cardiovascular risk assessment. Results Individuals’ principal motivation for genetic testing was their family history of CHD and a desire to convey the results to their children. After testing, however, there was limited recall of genetic test results and scepticism about the value of informing their children. Participants dealt with conflicting findings from the genetic test, family history, and conventional assessment by either focusing on genetic risk or environmental lifestyle factors. In some participants, genetic test results appeared to reinforce healthy behaviour but others were falsely reassured, despite having an ‘above-average’ conventional cardiovascular risk score. Conclusion Although genetic testing was acceptable, participants were unclear how to interpret genetic risk results. To facilitate healthy behaviour, health professionals should explore patients’ understanding of genetic test results in light of their family history and conventional risk assessment. PMID:24771842

A longitudinal pre-pregnancy to post-delivery comparison of genetic and gestational surrogate and intended mothers: confidence and genealogy.

PubMed

Van Den Akker, Olga B A

2005-12-01

For women opting to use surrogacy to overcome subfertility, a choice can be made to have a genetically related or unrelated baby. Similarly, women opting to become surrogate mothers also have to choose to gestate and relinquish a genetically related or unrelated baby. This study explored the cognitions behind the initial choices made and determined the strength of those cognitions six months post-delivery of the surrogate baby. Surrogate and Intended mothers (N=81) undergoing Artificial Insemination (AI, genetic) or Embryo Transfer (ET, gestational) were studied separately (four groups) at the start of their surrogate arrangement and those with a positive outcome (n=34) were re-interviewed at six months post-relinquishment. There were significant differences between surrogate and intended mothers in their confidence about the arrangement. Beliefs about the importance of a genetic link were predictors of ET arrangements. Responses were consistent over a one and a half-year study period. The ethical and clinical implications of the results are discussed in relation to appropriate self-selection and confidence with the surrogate process and the importance of genetic offspring.

Hopes and Expectations Regarding Genetic Testing for Schizophrenia Among Young Adults at Clinical High-Risk for Psychosis.

PubMed

Friesen, Phoebe; Lawrence, Ryan E; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa

2016-11-01

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.

Acceptance of Genetic Testing in a General Population: Age, Education and Gender Differences.

ERIC Educational Resources Information Center

Aro, A. R.; Hakonen, A.; Hietala, M.; Lonnqvist, J.; Niemela, P.; Peltonen, L; Aula, P.

1997-01-01

Effects of age, education, and gender on acceptance of genetic testing were studied. Finnish participants responded to a questionnaire presenting reasons for and against genetic testing (N=1,967). Intentions to take genetic tests, worries, and experience of genetic test or hereditary disease were also assessed. Results are presented and discussed.…

[Difficulties of genetic counselling in rare, mainly neurogenetic disorders].

PubMed

Horváth, Emese; Nagy, Nikoletta; Széll, Márta

2014-08-03

In recent decades methods used for the investigation of the genetic background of rare diseases showed a great improvement. The aim of the authors was to demonstrate difficulties of genetic counselling and investigations in case of five rare, mainly neurogenetic diseases. During pre-test genetic counselling, the disease suspected from the clinical symptoms and the available genetic tests were considered. During post-test genetic counselling, the results of the genetic tests were discussed. In three of the five cases genetic tests identified the disease-causing genetic abnormalities, while in two cases the causative abnormalities were not identified. Despite a great improvement of the available genetic methods, the causative genetic abnormalities cannot be identified in some cases. The genetic counsellor has a key role in the assessment and interpretation of the results and in helping the family planning.

Perceptions of genetic testing and genomic medicine among drug users.

PubMed

Perlman, David C; Gelpí-Acosta, Camila; Friedman, Samuel R; Jordan, Ashly E; Hagan, Holly

2015-01-01

Genetic testing will soon enter care for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and for addiction. There is a paucity of data on how to disseminate genetic testing into healthcare for marginalized populations. We explored drug users' perceptions of genetic testing. Six focus groups were conducted with 34 drug users recruited from syringe exchange programmes and an HIV clinic between May and June 2012. Individual interviews were conducted with participants reporting previous genetic testing. All participants expressed acceptance of genetic testing to improve care, but most had concerns regarding confidentiality and implications for law enforcement. Most expressed more comfort with genetic testing based on individual considerations rather than testing based on race/ethnicity. Participants expressed comfort with genetic testing in medical care rather than drug treatment settings and when specifically asked permission, with peer support, and given a clear rationale. Although participants understood the potential value of genetic testing, concerns regarding breaches in confidentiality and discrimination may reduce testing willingness. Safeguards against these risks, peer support, and testing in medical settings based on individual factors and with clear rationales provided may be critical in efforts to promote acceptance of genetic testing among drug users. Copyright © 2014 Elsevier B.V. All rights reserved.

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

PubMed

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

A weighted U statistic for association analyses considering genetic heterogeneity.

PubMed

Wei, Changshuai; Elston, Robert C; Lu, Qing

2016-07-20

Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene.

PubMed

Volpi, Ludovica; Roversi, Gaia; Colombo, Elisa Adele; Leijsten, Nico; Concolino, Daniela; Calabria, Andrea; Mencarelli, Maria Antonietta; Fimiani, Michele; Macciardi, Fabio; Pfundt, Rolph; Schoenmakers, Eric F P M; Larizza, Lidia

2010-01-01

Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]), a rare autosomal-recessive genodermatosis characterised by poikiloderma, pachyonychia, and chronic neutropenia. The siblings were initially diagnosed as affected with Rothmund-Thomson syndrome (RTS [MIM #268400]), with which PN shows phenotypic overlap. Linkage analysis on all living subjects of the family identified a large 16q region inherited identically by descent (IBD) in all affected family members. Deep sequencing of this 3.4 Mb region previously enriched with array capture revealed a homozygous c.504-2 A>C mismatch in all affected siblings. The mutation destroys the invariant AG acceptor site of intron 4 of the evolutionarily conserved C16orf57 gene. Two distinct deleterious mutations (c.502A>G and c.666_676+1del12) identified in an unrelated PN patient confirmed that the C16orf57 gene is responsible for PN. The function of the predicted C16orf57 gene is unknown, but its product has been shown to be interconnected to RECQL4 protein via SMAD4 proteins. The unravelled clinical and genetic identity of PN allows patients to undergo genetic testing and follow-up. 2010 The American Society of Human Genetics. Published by Elsevier Inc.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.

PubMed

Mikstacki, Adam; Skrzypczak-Zielinska, Marzena; Zakerska-Banaszak, Oliwia; Tamowicz, Barbara; Skibinska, Maria; Molinska-Glura, Marta; Szalata, Marlena; Slomski, Ryszard

2016-05-14

The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane. The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia. GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

[Survey on the attitude toward genetic testing of neurologists certified by the Japanese Society of Neurology].

PubMed

Yoshida, Kunihiro; Ohata, Takako; Muto, Kaori; Tsuchiya, Atsushi; Sawada, Jinichi; Hazama, Takanori; Ikeda, Shu-Ichi; Toda, Tatsushi

2013-01-01

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.

Genetic Testing for Cardiomyopathies in Clinical Practice.

PubMed

Ingles, Jodie; Bagnall, Richard D; Semsarian, Christopher

2018-04-01

Cardiac genetic testing for inherited cardiomyopathies has become a routine aspect of care. Advances in genetic testing technologies have made testing more comprehensive and affordable. With this increase come greater understanding of the genetic basis of these diseases, but also shines a light on the challenges. Ability to ascertain whether a rare variant is causative of disease is problematic. A genetic diagnosis in a family can offer an invaluable tool for cascade genetic testing of at-risk relatives and avenues for reproductive testing options. A careful approach to cardiac genetic testing that recognizes where there is potential for harm ensures the best possible outcomes for families. Copyright © 2017 Elsevier Inc. All rights reserved.

Parental attitudes toward genetic testing for prelingual deafness in China.

PubMed

Fu, Siqing; Dong, Jiashu; Wang, Chunfang; Chen, Guanming

2010-10-01

Recent advances in molecular biology of hearing and deafness have made genetic testing an option for deaf individuals and their families. In China, DNA microarray and other genetic testing method has been applied to rapid genetic diagnosis of non-syndromic hearing loss. However, there is no information about the interests in such testing in China. The purpose of this study is to document the attitudes of parents with normal hearing who have one or more deaf children toward diagnostic, carrier, and prenatal genetic testing for deafness. A structured, self-completion questionnaire was given to delegates at a conference held at Hubei Rehabilitation Research Center for Deaf Children, Wuhan, China on March 3, 2010. Of 366 surveys distributed, 290 were completed and returned. Ninety-four percent of the respondents had a positive attitude toward genetic testing. Seventy-two percent stated that they were interested in genetic testing of deaf child. Of the individuals who were interested in such testing, 69% would consider having prenatal genetic testing for deafness. The present study provided evidence of a predominantly positive attitude toward genetics. Appropriate genetic counseling can help parents to understand the risk, benefits, and limitations of genetic testing for prelingual deafness. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Researcher responsibilities and genetic counseling for pure-bred dog populations.

PubMed

Bell, Jerold S

2011-08-01

Breeders of dogs have ethical responsibilities regarding the testing and management of genetic disease. Molecular genetics researchers have their own responsibilities, highlighted in this article. Laboratories offering commercial genetic testing should have proper sample identification and quality control, official test result certificates, clear explanations of test results and reasonably priced testing fees. Providing test results to a publicly-accessible genetic health registry allows breeders and the public to search for health-tested parents to reduce the risk of producing or purchasing affected offspring. Counseling on the testing and elimination of defective genes must consider the effects of genetic selection on the population. Recommendations to breed quality carriers to normal-testing dogs and replacing them with quality normal-testing offspring will help to preserve breeding lines and breed genetic diversity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetics Home Reference: Pompe disease

MedlinePlus

... Genetic Testing (2 links) Genetic Testing Registry: Glycogen storage disease type II, infantile Genetic Testing Registry: Glycogen storage disease, type II Other Diagnosis and Management Resources ( ...

Abnormally fertilized oocytes can result in healthy live births: improved genetic technologies for preimplantation genetic testing can be used to rescue viable embryos in in vitro fertilization cycles.

PubMed

Capalbo, Antonio; Treff, Nathan; Cimadomo, Danilo; Tao, Xin; Ferrero, Susanna; Vaiarelli, Alberto; Colamaria, Silvia; Maggiulli, Roberta; Orlando, Giovanna; Scarica, Catello; Scott, Richard; Ubaldi, Filippo Maria; Rienzi, Laura

2017-12-01

To test whether abnormally fertilized oocyte (AFO)-derived blastocysts are diploid and can be rescued for clinical use. Longitudinal-cohort study from January 2015 to September 2016 involving IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A). Ploidy assessment was incorporated whenever a blastocyst from a monopronuclear (1PN) or tripronuclear zygote (2PN + 1 smaller PN; 2.1 PN) was obtained. Private IVF clinics and genetics laboratories. A total of 556 women undergoing 719 PGT-A cycles. Conventional chromosome analysis was performed on trophectoderm biopsies by quantitative polymerase chain reaction. For AFO-derived blastocysts, ploidy assessment was performed on the same biopsy with the use of allele ratios for hetorozygous SNPs analyzed by means of next-generation sequencing (1:1 = diploid; 2:1 = triploid; loss of heterozygosity = haploid). Balanced-diploid 1PN- and 2.1PN-derived blastocysts were transferred in the absence of normally fertilized transferable embryos. Ploidy constitution and clinical value of AFO-derived blastocysts in IVF PGT-A cycles. Of the 5,026 metaphase II oocytes injected, 5.2% and 0.7% showed 1PN and 2.1PN, respectively. AFOs showed compromised embryo development (P<.01). Twenty-seven AFO-derived blastocysts were analyzed for ploidy constitution. The 1PN-derived blastocysts were mostly diploid (n = 9/13; 69.2%), a few were haploid (n = 3/13; 23.1%), and one was triploid (n = 1/13; 7.7%). The 2.1PN-derived blastocysts were also mostly diploid (n = 12/14; 85.7%), and the remainder were triploid. Twenty-six PGT-A cycles resulted in one or more AFO-derived blastocysts (n = 26/719; 3.6%). Overall, eight additional balanced-diploid transferable embryos were obtained from AFOs. In three cycles, the only balanced-diploid blastocyst produced was from an AFO (n = 3/719; 0.4%). Three AFO-derived live births were achieved: one from a 1PN zygote and two from 2.1PN zygotes. Enhanced PGT-A technologies incorporating reliable ploidy assessment provide an effective tool to rescue AFO-derived blastocysts for clinical use. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Nutrigenomics and ethics interface: direct-to-consumer services and commercial aspects.

PubMed

Ries, Nola M; Castle, David

2008-12-01

A growing variety and number of genetic tests are advertised and sold directly to consumers (DTC) via the Internet, including nutrigenomic tests and associated products and services. Consumers have more access to genetic information about themselves, but access does not entail certainty about the implications of test results. Potential personal and public health harms and benefits are associated with DTC access to genetic testing services. Early policy responses to direct-to-consumer (DTC) genetic testing often involved calls for bans, and some jurisdictions prohibited DTC genetic tests. Recent policy responses by oversight bodies acknowledge expansion in the range of DTC tests available and suggest that a "one-size-fits-all" regulatory approach is not appropriate for all genetic tests. This review discusses ethical and regulatory aspects of DTC genetic testing, focusing particularly on nutrigenomic tests. We identify policy options for regulating DTC genetic tests, including full or partial prohibitions, enforcement of existing truth-in-advertising laws, and more comprehensive information disclosure about genetic tests. We advocate the latter option as an important means to improve transparency about current evidence on the strengths and limits of gene-disease associations and allow consumers to make informed purchasing decisions in the DTC marketplace.

ACOG Technology Assessment No. 11: Genetics and molecular diagnostic testing.

PubMed

2014-02-01

Human genetics and molecular testing are playing an increasingly important role in medicine, including obstetric and gynecologic practice. As the genetic basis for reproductive disorders, common diseases, and cancer is elucidated with improved molecular technology, genetic testing opportunities are expanding and influencing treatment options and prevention strategies. It is essential that obstetrician-gynecologists be aware of advances in the understanding of genetic disease and the fundamental principles of genetic screening and molecular testing as genetics becomes a more integral part of routine medical practice. This document reviews the basics of genetic transmission and genetic technologies in current use.

"Genetic exceptionalism" in medicine: clarifying the differences between genetic and nongenetic tests.

PubMed

Green, Michael J; Botkin, Jeffrey R

2003-04-01

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.

Patient Education and Informed Consent for Preimplantation Genetic Diagnosis: Health Literacy for Genetics and Assisted Reproductive Technology

PubMed Central

McGowan, Michelle L.; Burant, Chris; Moran, Rocio; Farrell, Ruth

2013-01-01

Introduction Innovative applications of genetic testing have emerged within the field of assisted reproductive technology through preimplantation genetic diagnosis (PGD). As in all forms of genetic testing, adequate genetic counseling and informed consent are critical. Despite the growing recognition of the role of informed consent in genetic testing, there is little data available about how this process occurs in the setting of PGD. Methods A cross sectional study of IVF clinics offering PGD in the U.S. was conducted to assess patient education and informed consent practices. Descriptive data were collected with a self-administered survey instrument. Results More than half of the clinics offering PGD required genetic counseling prior to PGD (56%). Genetic counseling was typically performed by certified genetic counselors (84 %). Less than half (37%) of the clinics required a separate informed consent process for genetic testing of embryonic cells. At a majority of those clinics requiring a separate informed consent for genetic testing (54%), informed consent for PGD and genetic testing took place as a single event before beginning IVF procedures. Conclusions The results suggest that patient education and informed consent practices for PGD have yet to be standardized. These findings warrant the establishment of professional guidelines for patient education and informed consent specific to embryonic genetic testing. PMID:19652605

US system of oversight for genetic testing: a report from the Secretary's Advisory Committee on Genetics, Health and Society.

PubMed

Ferreira-Gonzalez, Andrea; Teutsch, Steven; Williams, Marc S; Au, Sylvia M; Fitzgerald, Kevin T; Miller, Paul Steven; Fomous, Cathy

2008-09-01

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.

Pre- and post-testing counseling considerations for the provision of expanded carrier screening: exploration of European geneticists' views.

PubMed

Janssens, Sandra; Chokoshvili, Davit; Vears, Danya F; De Paepe, Anne; Borry, Pascal

2017-08-01

Carrier screening is generally performed with the aim of identifying healthy couples at risk of having a child affected with a monogenic disorder to provide them with reproductive options. Expanded carrier screening (ECS), which provides the opportunity for multiple conditions to be screened in one test, offers a more cost-effective and comprehensive option than screening for single disorders. However, implementation of ECS at a population level would have implications for genetic counseling practice. We conducted semi-structured interviews with sixteen European clinical and molecular geneticists with expertise in carrier screening to explore their views on the implementation of ECS in the clinical setting. Using inductive content analysis, we identified content categories relevant to the pre- and post-test settings. Participants believed ECS would ideally be targeted at couples before pregnancy. There was some disagreement regarding the acceptability of performing ECS in individuals, with several participants actively opposing individual-based screening. In addition, participants discussed the importance of ensuring informed and voluntary participation in ECS, recommending measures to minimize external pressure on prospective parents to undergo testing. A need for adequate counseling to foster informed, autonomous reproductive decision-making and provide support for couples found to be at risk was emphasized. Practical challenges in optimizing pre-test education and post-test counseling should not be underestimated and they should be carefully addressed before implementing ECS in the clinical setting.

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States

PubMed Central

2011-01-01

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers. PMID:22204616

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States.

PubMed

Myers, Melanie F

2011-12-28

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers.

Health-related direct-to-consumer genetic testing: a review of companies' policies with regard to genetic testing in minors.

PubMed

Borry, Pascal; Howard, Heidi C; Sénécal, Karine; Avard, Denise

2010-03-01

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.

Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey.

PubMed

Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R

2009-06-09

To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. Cross sectional, self reported survey. Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (P<0.001). Genetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.

Characterizing biased cancer-related cognitive processing: relationships with BRCA1/2 genetic mutation status, personal cancer history, age, and prophylactic surgery.

PubMed

Carpenter, Kristen M; Eisenberg, Stacy; Weltfreid, Sharone; Low, Carissa A; Beran, Tammy; Stanton, Annette L

2014-09-01

This study evaluated associations of cancer-related cognitive processing with BRCA1/2 mutation carrier status, personal cancer history, age, and election of prophylactic surgery in women at high risk for breast cancer. In a 2 (BRCA1/2 mutation carrier status) × 2 (personal cancer history) matched-control design, with age as an additional predictor, participants (N = 115) completed a computerized cancer Stroop task. Dependent variables were response latency to cancer-related stimuli (reaction time [RT]) and cancer-related cognitive interference (cancer RT minus neutral RT). RT and interference were tested as predictors of prophylactic surgery in the subsequent four years. RT for cancer-related words was significantly slower than other word groups, indicating biased processing specific to cancer-related stimuli. Participants with a cancer history evidenced longer RT to cancer-related words than those without a history; moreover, a significant Cancer History × Age interaction indicated that, among participants with a cancer history, the typical advantage associated with younger age on Stroop tasks was absent. BRCA mutation carriers demonstrated more cancer-related cognitive interference than noncarriers. Again, the typical Stroop age advantage was absent among carriers. Exploratory analyses indicated that BRCA+ status and greater cognitive interference predicted greater likelihood of undergoing prophylactic surgery. Post hoc tests suggest that cancer-related distress does not account for these relationships. In the genetic testing context, younger women with a personal cancer history or who are BRCA1/2 mutation carriers might be particularly vulnerable to biases in cancer-related cognitive processing. Biased processing was associated marginally with greater likelihood of prophylactic surgery. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The role of religious and existential well-being in families with Lynch syndrome: prevention, family communication, and psychosocial adjustment.

PubMed

Morris, Bronwyn A; Hadley, Donald W; Koehly, Laura M

2013-08-01

This study explored the role of religious (RWB) and existential well-being (EWB) on psychosocial factors, support network characteristics, and screening practices in families with Lynch syndrome, also referred to as hereditary nonpolyposis colon cancer (HNPCC). Participants were individuals with Lynch syndrome associated cancers and their first-degree relatives at risk of inheriting an identified deleterious mutation. Analyses considered both family RWB and EWB norms and individual deviations from that norm. Analyses controlled for age, gender, cancer diagnosis, number of respondents, and network size. Higher family RWB was associated with increased depressive symptoms (p < .05) and avoidant cognitions (p < .05). Higher family EWB was related to decreased depression symptoms (p < .001). Higher family EWB was associated with fecal occult blood testing (p < .01), and family communication about genetic counselling and testing (p < .01). Analyses pointed to individual effects of EWB above and beyond family-level effects. Individuals with lower EWB than their family had lower perceived risk for colorectal cancer (p < .05), communicated disease risk information to less family members (p < .05), and were less likely to undergo recent colonoscopies (p < .05). Participants with lower EWB than their family also had higher cancer worry (p < .01) and increased depressive symptoms (p < .001). Findings indicate the importance of assessing individuals within the context of their family network and being aware of family characteristics which may impact individual adjustment to disease risk. Interventions considering family-level factors may provide efficient pathways to improving psychosocial factors, screening practices, communication about disease risk and genetic testing, and cancer prevention.

Integrating surgery and genetic testing for the modern surgeon.

PubMed

Caso, Raul; Beamer, Matthew; Lofthus, Alexander D; Sosin, Michael

2017-10-01

The field of cancer genetics is rapidly evolving and several genetic mutations have been identified in hereditary cancer syndromes. These mutations can be diagnosed via routine genetic testing allowing prompt intervention. This is especially true for certain variants of colorectal, breast, and thyroid cancers where genetic testing may guide surgical therapy. Ultimately, surgical intervention may drastically diminish disease manifestation or progression in individuals deemed as high-risk based on their genetic makeup. Understanding the concepts of gene-based testing and integrating into current surgical practice is crucial. This review addresses common genetic syndromes, tests, and interventions salient to the current surgeon.

Factors influencing behavioral intention to undergo Papanicolaou testing in early adulthood: Comparison of Japanese and Korean women.

PubMed

Kang, Kyung-Ah; Kim, Shin-Jeong; Kaneko, Noriyo

2017-12-01

In this study, we identified the factors influencing behavioral intention to undergo Papanicolaou testing among Japanese and Korean women in early adulthood. Their behavioral intentions were compared in this cross-sectional descriptive study. In total, 887 women (Japanese = 498, Korean = 389) aged 20-39 years participated in this study. Using a self-report questionnaire, knowledge, attitudes, subjective norm, perceived behavioral control, and behavioral intention were surveyed. There were significant differences between Japanese and Korean women's scores on all main variables. For Japanese women, all the variables moderately correlated with behavioral intention. In comparison, for Korean women, all independent variables, except for knowledge, moderately correlated with behavioral intention. Through a multiple regression analysis, age, undergoing Papanicolaou testing, attitudes, subjective norm, and perceived behavioral control were identified as significant predictors of behavioral intention among Japanese women. Among Korean women, job status, undergoing a Papanicolaou test, attitudes, subjective norm, and perceived behavioral control were demonstrated as significant predictors of behavioral intention. Health professionals should consider these factors to encourage Papanicolaou testing in women in early adulthood. © 2017 John Wiley & Sons Australia, Ltd.

Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records.

PubMed

Darcy, Diana C; Lewis, Eleanor T; Ormond, Kelly E; Clark, David J; Trafton, Jodie A

2011-11-02

Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results. As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use. This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications.

Appreciating Uncertainty and Personal Preference in Genetic Testing.

PubMed

Kadlac, Adam

2015-01-01

Genetic testing seems to hold out hope for the cure of a number of debilitating conditions. At the same time, many people fear the information that genetic testing can make available. In this commentary, I argue that as of now, the nature of the information revealed in such tests should lead to cautious views about the value of genetic testing. Moreover, I suggest that our overall views about such testing should account for the fact that individuals place different sorts of value on the possession of their own genetic information. As a result, we should largely defer to personal preference in thinking about the propriety of genetic testing.

Surrounded by work platforms, the full-scale Orion AFT crew module (center) is undergoing preparations for the first flight test of Orion's launch abort system.

NASA Image and Video Library

2008-05-20

Surrounded by work platforms, NASA's first full-scale Orion abort flight test (AFT) crew module (center) is undergoing preparations at the NASA Dryden Flight Research Center in California for the first flight test of Orion's launch abort system. To the left is a space shuttle orbiter purge vehicle sharing the hangar.

[Practical guidelines for genetic testing in cardiovascular diseases].

PubMed

Reinhard, W; Trenkwalder, T; Schunkert, H

2017-08-01

In the last decade, genetic testing for cardiovascular disorders has become more and more relevant. Progress in molecular genetics has led to new opportunities for diagnostics, improved risk prediction and could lead to novel therapeutic approaches. Genetic diagnostic testing is relevant for both confirming a diagnosis as well as deciding on therapeutic consequences, if applicable. Furthermore, predictive testing in family members for specific cardiovascular diseases is now a standard procedure in holistic patient management. The process of genetic testing as well as documentation requirements and discussion of test results with patients are subject to legal regulations. These regulations might be confusing for clinical practitioners/cardiologists. The aim of this article is to provide a clinical framework for genetic testing. First, we explain the legal and ethical background. Second, we illustrate the process of genetic testing step by step and present updates on remuneration. Finally, we discuss the significance of genetic testing and specific disease indications in cardiology.

Quality assurance and quality improvement in U.S. clinical molecular genetic laboratories.

PubMed

Chen, Bin; Richards, C Sue; Wilson, Jean Amos; Lyon, Elaine

2011-04-01

A robust quality-assurance program is essential for laboratories that perform molecular genetic testing to maintain high-quality testing and be able to address challenges associated with performance or delivery of testing services as the use of molecular genetic tests continues to expand in clinical and public health practice. This unit discusses quality-assurance and quality-improvement considerations that are critical for molecular genetic testing performed for heritable diseases and conditions. Specific discussion is provided on applying regulatory standards and best practices in establishing/verifying test performance, ensuring quality of the total testing process, monitoring and maintaining personnel competency, and continuing quality improvement. The unit provides a practical reference for laboratory professionals to use in recognizing and addressing essential quality-assurance issues in human molecular genetic testing. It should also provide useful information for genetics researchers, trainees, and fellows in human genetics training programs, as well as others who are interested in quality assurance and quality improvement for molecular genetic testing. 2011 by John Wiley & Sons, Inc.

Unisexual and Heterosexual Meiotic Reproduction Generate Aneuploidy and Phenotypic Diversity De Novo in the Yeast Cryptococcus neoformans

PubMed Central

Li, Wenjun; Floyd-Averette, Anna; Mieczkowski, Piotr; Dietrich, Fred S.; Heitman, Joseph

2013-01-01

Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistance and enables rapid adaptive evolution. We report here that sexual reproduction generates phenotypic and genotypic diversity in the human pathogenic yeast Cryptococcus neoformans, which is globally distributed and commonly infects individuals with compromised immunity, such as HIV/AIDS patients, causing life-threatening meningoencephalitis. C. neoformans has a defined a-α opposite sexual cycle; however, >99% of isolates are of the α mating type. Interestingly, α cells can undergo α-α unisexual reproduction, even involving genotypically identical cells. A central question is: Why would cells mate with themselves given that sex is costly and typically serves to admix preexisting genetic diversity from genetically divergent parents? In this study, we demonstrate that α-α unisexual reproduction frequently generates phenotypic diversity, and the majority of these variant progeny are aneuploid. Aneuploidy is responsible for the observed phenotypic changes, as chromosome loss restoring euploidy results in a wild-type phenotype. Other genetic changes, including diploidization, chromosome length polymorphisms, SNPs, and indels, were also generated. Phenotypic/genotypic changes were not observed following asexual mitotic reproduction. Aneuploidy was also detected in progeny from a-α opposite-sex congenic mating; thus, both homothallic and heterothallic sexual reproduction can generate phenotypic diversity de novo. Our study suggests that the ability to undergo unisexual reproduction may be an evolutionary strategy for eukaryotic microbial pathogens, enabling de novo genotypic and phenotypic plasticity and facilitating rapid adaptation to novel environments. PMID:24058295

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

PubMed

Buseh, A; Kelber, S; Millon-Underwood, S; Stevens, P; Townsend, L

2014-01-01

Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

Genetic demixing and evolution in linear stepping stone models

NASA Astrophysics Data System (ADS)

Korolev, K. S.; Avlund, Mikkel; Hallatschek, Oskar; Nelson, David R.

2010-04-01

Results for mutation, selection, genetic drift, and migration in a one-dimensional continuous population are reviewed and extended. The population is described by a continuous limit of the stepping stone model, which leads to the stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms describing mutations. Although the stepping stone model was first proposed for population genetics, it is closely related to “voter models” of interest in nonequilibrium statistical mechanics. The stepping stone model can also be regarded as an approximation to the dynamics of a thin layer of actively growing pioneers at the frontier of a colony of micro-organisms undergoing a range expansion on a Petri dish. The population tends to segregate into monoallelic domains. This segregation slows down genetic drift and selection because these two evolutionary forces can only act at the boundaries between the domains; the effects of mutation, however, are not significantly affected by the segregation. Although fixation in the neutral well-mixed (or “zero-dimensional”) model occurs exponentially in time, it occurs only algebraically fast in the one-dimensional model. An unusual sublinear increase is also found in the variance of the spatially averaged allele frequency with time. If selection is weak, selective sweeps occur exponentially fast in both well-mixed and one-dimensional populations, but the time constants are different. The relatively unexplored problem of evolutionary dynamics at the edge of an expanding circular colony is studied as well. Also reviewed are how the observed patterns of genetic diversity can be used for statistical inference and the differences are highlighted between the well-mixed and one-dimensional models. Although the focus is on two alleles or variants, q -allele Potts-like models of gene segregation are considered as well. Most of the analytical results are checked with simulations and could be tested against recent spatial experiments on range expansions of inoculations of Escherichia coli and Saccharomyces cerevisiae.

Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest: Elucidation of the Triadin Knockout Syndrome.

PubMed

Altmann, Helene M; Tester, David J; Will, Melissa L; Middha, Sumit; Evans, Jared M; Eckloff, Bruce W; Ackerman, Michael J

2015-06-09

Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive. We performed whole-exome sequencing child-parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13 TRDN-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of TRDN revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V1 through V4, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%; P=0.0009). We identified TRDN as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac TRDN genetic testing. © 2015 American Heart Association, Inc.

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

PubMed

Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases.Key words: preimplantation genetic diagnosis; monogenic eye diseases; in vitro fertilization.

Inference in the age of big data: Future perspectives on neuroscience.

PubMed

Bzdok, Danilo; Yeo, B T Thomas

2017-07-15

Neuroscience is undergoing faster changes than ever before. Over 100 years our field qualitatively described and invasively manipulated single or few organisms to gain anatomical, physiological, and pharmacological insights. In the last 10 years neuroscience spawned quantitative datasets of unprecedented breadth (e.g., microanatomy, synaptic connections, and optogenetic brain-behavior assays) and size (e.g., cognition, brain imaging, and genetics). While growing data availability and information granularity have been amply discussed, we direct attention to a less explored question: How will the unprecedented data richness shape data analysis practices? Statistical reasoning is becoming more important to distill neurobiological knowledge from healthy and pathological brain measurements. We argue that large-scale data analysis will use more statistical models that are non-parametric, generative, and mixing frequentist and Bayesian aspects, while supplementing classical hypothesis testing with out-of-sample predictions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Microsatellite Analysis of Museum Specimens Reveals Historical Differences in Genetic Diversity between Declining and More Stable Bombus Species

PubMed Central

Maebe, Kevin; Meeus, Ivan; Ganne, Maarten; De Meulemeester, Thibaut; Biesmeijer, Koos; Smagghe, Guy

2015-01-01

Worldwide most pollinators, e.g. bumblebees, are undergoing global declines. Loss of genetic diversity can play an essential role in these observed declines. In this paper, we investigated the level of genetic diversity of seven declining Bombus species and four more stable species with the use of microsatellite loci. Hereto we genotyped a unique collection of museum specimens. Specimens were collected between 1918 and 1926, in 6 provinces of the Netherlands which allowed us to make interspecific comparisons of genetic diversity. For the stable species B. pascuorum, we also selected populations from two additional time periods: 1949–1955 and 1975–1990. The genetic diversity and population structure in B. pascuorum remained constant over the three time periods. However, populations of declining bumblebee species showed a significantly lower genetic diversity than co-occurring stable species before their major declines. This historical difference indicates that the repeatedly observed reduced genetic diversity in recent populations of declining bumblebee species is not caused solely by the decline itself. The historically low genetic diversity in the declined species may be due to the fact that these species were already rare, making them more vulnerable to the major drivers of bumblebee decline. PMID:26061732

[Issues on business of genetic testing in near future].

PubMed

Takada, Fumio

2009-06-01

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.

Population genetic testing for cancer susceptibility: founder mutations to genomes.

PubMed

Foulkes, William D; Knoppers, Bartha Maria; Turnbull, Clare

2016-01-01

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.

Genetics of hereditary neurological disorders in children.

PubMed

Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

Hereditary arrhythmias and cardiomyopathies: decision-making about genetic testing.

PubMed

Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M

2018-01-01

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.

Perceptions of genetic discrimination among people at risk for Huntington’s disease: a cross sectional survey

PubMed Central

Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L

2009-01-01

Objective To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington’s disease who had undergone genetic testing or remained untested. Design Cross sectional, self reported survey. Setting Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. Participants 233 genetically tested and untested asymptomatic people at risk for Huntington’s disease (response rate 80%): 167 underwent testing (83 had the Huntington’s disease mutation, 84 did not) and 66 chose not to be tested. Main outcome measures Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Results Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington’s disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington’s disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (P<0.001). Conclusions Genetic discrimination was commonly reported by people at risk for Huntington’s disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination. PMID:19509425

Regulation of Genetic Tests

MedlinePlus

... Informed Consent for Genomics Research Intellectual Property Online Bioethics Resources Privacy in Genomics Regulation of Genetic Tests ... Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of Genetic Tests ...

Direct-to-consumer genetic testing in Slovenia: availability, ethical dilemmas and legislation.

PubMed

Vrecar, Irena; Peterlin, Borut; Teran, Natasa; Lovrecic, Luca

2015-01-01

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.

Genetic testing in inherited polyposis syndromes - how and why?

PubMed

Lee, G H; Payne, S J; Melville, A; Clark, S K

2014-08-01

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.

Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

ERIC Educational Resources Information Center

Rabino, Isaac

2003-01-01

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)

Willingness to undergo HIV testing in the Kintampo districts of Ghana.

PubMed

Abokyi, L V; Zandoh, C; Mahama, E; Sulemana, A; Adda, R; Amenga-Etego, S; Baiden, F; Owusu-Agyei, S

2014-03-01

HIV testing is currently a major prevention intervention and remains an entry point to early treatment, care and support. Uptake is however low and alternative approaches are currently being adopted. An HIV module was incorporated into the routine survey of the Kintampo Health and Demographic Surveillance System (KHDSS) to assess the willingness of adults living in the Kintampo North and South districts to undergo HIV testing. The study was a descriptive cross-sectional household survey. Univariate and multivariate analysis were used to identify predictors of the willingness to undergo HIV testing. Respondents were community members aged 15 to 49 years and selected from randomly generated household listings from the KHDSS. A total of 11,604 respondents were interviewed, 10,982 (94.6%) of respondents had good general knowledge on HIV/AIDS. Among those with knowledge about HIV/AIDS, 10,819 (98.5%) indicated their willingness to get tested for HIV. Rural residents were more willing to undergo HIV testing than urban dwellers Odds ratio=1.42 (95% Confidence interval: 1.03, 1.96; P-value=0.031). Respondents with primary education were more likely to go for testing relative to those without any education OR=2.02 (95% CI: 0.87, 4.70; P-value=0.046). Expressed willingness to test for HIV is high in this population. Exploring community and population-based interventions to HIV testing and counseling could increase uptake of HIV testing services and should be considered. The underlying motivations need to be explored in order to translate willingness into actual testing.

Deaf Adults' Reasons for Genetic Testing Depend on Cultural Affiliation: Results from a Prospective, Longitudinal Genetic Counseling and Testing Study

ERIC Educational Resources Information Center

Boudreault, Patrick; Baldwin, Erin E.; Fox, Michelle; Dutton, Loriel; Tullis, LeeElle; Linden, Joyce; Kobayashi, Yoko; Zhou, Jin; Sinsheimer, Janet S.; Sininger, Yvonne; Grody, Wayne W.; Palmer, Christina G. S.

2010-01-01

This article examines the relationship between cultural affiliation and deaf adults' motivations for genetic testing for deafness in the first prospective, longitudinal study to examine the impact of genetic counseling and genetic testing on deaf adults and the deaf community. Participants (n = 256), classified as affiliating with hearing, Deaf,…

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease.

PubMed

Morren, Mattijn; Rijken, Mieke; Baanders, Arianne N; Bensing, Jozien

2007-02-01

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, patients were asked about their preferred source of genetic information. Questionnaires were mailed to participants of a nationwide representative sample of patients with chronic diseases in the Netherlands (n = 1916). The response rate was 82% (n = 1496). Perceived genetic knowledge was low, particularly among older and lower educated patients. Attitudes towards genetics were rather positive, especially among younger and higher educated patients. Some concerns were also documented, mainly about the consequences of genetic testing for employment and taking insurance. Patients who perceived to have little knowledge found it difficult to formulate an opinion about genetic testing. Higher levels of genetic knowledge were associated with a more favourable attitude towards genetics. Chronic patients prefer to receive genetic information from their GP. Chronic patients are ill prepared when they require genetic knowledge to make decisions regarding the treatment of their disease. This seems to result from a knowledge deficiency rather than from disagreement with the genetic developments. When chronic patients are in need of information about genetics or genetic testing, their general practitioner should provide this.

Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise.

PubMed

Giudicessi, John R; Ackerman, Michael J

2013-01-01

In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

Pathways from Autism Spectrum Disorder (ASD) Diagnosis to Genetic Testing

PubMed Central

Barton, Krysta S.; Tabor, Holly K.; Starks, Helene; Garrison, Nanibaa’ A.; Laurino, Mercy; Burke, Wylie

2017-01-01

Purpose This study examines challenges faced by families and health providers related to genetic testing for autism spectrum disorder (ASD). Methods This qualitative study of 14 parents and 15 health providers identified an unstandardized three-step process for families who pursue ASD genetic testing. Results Step 1 is the clinical diagnosis of ASD, confirmed by providers practicing alone or in a team. Step 2 is the offer of genetic testing to find an etiology. For those offered testing, step 3 involves the parents’ decision whether to pursue testing. Despite professional guidelines and recommendations, interviews describe considerable variability in approaches to genetic testing for ASD, a lack of consensus among providers, and questions about clinical utility. Many families in our study were unaware of the option for genetic testing; testing decisions by parents appear to be influenced by both provider recommendations and insurance coverage. Conclusion Consideration of genetic testing for ASD should take into account different views about the clinical utility of testing and variability in insurance coverage. Ideally, policy makers from the range of clinical specialties involved in ASD care should revisit policies to clarify the purpose of genetic testing for ASD and promote consensus about its appropriate use. PMID:29048417

Incorporating gene-environment interaction in testing for association with rare genetic variants.

PubMed

Chen, Han; Meigs, James B; Dupuis, Josée

2014-01-01

The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants. In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions. We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study. Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient.

Genetic Testing: What It Means for Your Health and Your Family's Health

MedlinePlus

... cost of the genetic testing and whether your health insurance will cover the cost. The availability of genetics professionals who can talk with you about all of the benefits and possible risks of genetic testing. A federal law called the Genetic Information Nondiscrimination ...

[Ethical guidelines on genetic testing and gene therapy].

PubMed

Fukushima, Yoshimitsu

2005-03-01

According to the recent and rapid advances in molecular genetics research, genetic testing and gene therapy have a potential of giving unexpected influence to the human beings. To prevent and to solve various ethical, legal and social implementations (ELSI) of genetic testing and gene therapy, several guidelines have been established. In Japan, all researchers and all clinicians have to know and keep the following three guidelines on genetic testing and a guideline on gene therapy: 1) "Guidelines for Researches on Human Genome and Gene (2001)" by the three Ministries (Education, Health and Economy), 2) "Guidelines for Genetic Testing (2001)" by the Genetic--medicine--related 10 societies, 3) "Ethical Principles on Entrusted Genetic Testing (2001)" by the Japan Registered Clinical Laboratories Association, and 4) "Guidelines for Clinical Research on Gene Therapy (2002)" by the two Ministries (Health and Education).

Understanding the impact of genetic testing for inherited retinal dystrophy

PubMed Central

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

2013-01-01

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. PMID:23403902

Understanding the impact of genetic testing for inherited retinal dystrophy.

PubMed

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

2013-11-01

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.

Genetic Testing between Private and Public Interests: Some Legal and Ethical Reflections

PubMed Central

Sándor, Judit

2018-01-01

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. PMID:29445722

Genetic Testing between Private and Public Interests: Some Legal and Ethical Reflections.

PubMed

Sándor, Judit

2018-01-01

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.

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper.

PubMed

Randall, Leslie M; Pothuri, Bhavana; Swisher, Elizabeth M; Diaz, John P; Buchanan, Adam; Witkop, Catherine T; Bethan Powell, C; Smith, Ellen Blair; Robson, Mark E; Boyd, Jeff; Coleman, Robert L; Lu, Karen

2017-08-01

To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care. Copyright © 2017. Published by Elsevier Inc.

Direct to consumer genetic testing-law and policy concerns in Ireland.

PubMed

de Paor, Aisling

2017-11-25

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.

Pharmacogenomic Testing

MedlinePlus

... Financial Planning Who Should I Tell? Genetic Testing & Counseling Compensation for Genetic Testing Whole Genome Sequencing Screening vs. Testing What Is Genetic Counseling? Participating in Research Disease Research Patient Privacy Clinical ...

Predictive Testing

MedlinePlus

... Financial Planning Who Should I Tell? Genetic Testing & Counseling Compensation for Genetic Testing Whole Genome Sequencing Screening vs. Testing What Is Genetic Counseling? Participating in Research Disease Research Patient Privacy Clinical ...

Limitations of direct-to-consumer advertising for clinical genetic testing.

PubMed

Gollust, Sarah E; Hull, Sara Chandros; Wilfond, Benjamin S

2002-10-09

Although direct-to-consumer (DTC) advertisements for pharmaceuticals have been appearing in the mass media for 20 years, DTC advertisements for genetic testing have only recently appeared. Advertisements for genetic testing can provide both consumers and physicians with information about test availability in an expanding market. However, 3 factors limit the value and appropriateness of advertisements: complex information, a complicated social context surrounding genetics, and a lack of consensus about the clinical utility of some tests. Consideration of several advertisements suggests that they overstate the value of genetic testing for consumers' clinical care. Furthermore, advertisements may provide misinformation about genetics, exaggerate consumers' risks, endorse a deterministic relationship between genes and disease, and reinforce associations between diseases and ethnic groups. Advertising motivated by factors other than evidence of the clinical value of genetic tests can manipulate consumers' behavior by exploiting their fears and worries. At this time, DTC advertisements are inappropriate, given the public's limited sophistication regarding genetics and the lack of comprehensive premarket review of tests or oversight of advertisement content. Existing Federal Trade Commission and Food and Drug Administration regulations for other types of health-related advertising should be applied to advertisements for genetic tests.

Ethical principles and pitfalls of genetic testing for dementia.

PubMed

Hedera, P

2001-01-01

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.

Direct-to-consumer genetic testing: where and how does genetic counseling fit?

PubMed

Middleton, Anna; Mendes, Álvaro; Benjamin, Caroline M; Howard, Heidi Carmen

2017-05-01

Direct-to-consumer genetic testing for disease ranges from well-validated diagnostic and predictive tests to 'research' results conferring increased risks. While being targeted at public curious about their health, they are also marketed for use in reproductive decision-making or management of disease. By virtue of being 'direct-to-consumer' much of this testing bypasses traditional healthcare systems. We argue that direct-to-consumer genetic testing companies should make genetic counseling available, pre- as well as post-test. While we do not advocate that mandatory genetic counseling should gate-keep access to direct-to-consumer genetic testing, if the testing process has the potential to cause psychological distress, then companies have a responsibility to provide support and should not rely on traditional healthcare systems to pick up the pieces. A video abstract is available for this article via this link .

Clinical germline diagnostic exome sequencing for hereditary cancer: Findings within novel candidate genes are prevalent.

PubMed

Powis, Zöe; Espenschied, Carin R; LaDuca, Holly; Hagman, Kelly D; Paudyal, Tripti; Li, Shuwei; Inaba, Hiroto; Mauer, Ann; Nathanson, Katherine L; Knost, James; Chao, Elizabeth C; Tang, Sha

2018-08-01

Clinical diagnostic exome sequencing (DES) has been effective in diagnosing individuals with suspected genetic conditions; nevertheless little has been described regarding its clinical utility in individuals with a personal and family history of cancer. This study aimed to assess diagnostic yield and clinical characteristics of pediatric and adult patients undergoing germline DES for hereditary cancer. We retrospectively reviewed 2171 patients referred for DES; cases with a personal and/or family history of cancer were further studied. Of 39 cancer patients, relevant alterations were found in eight individuals (21%), including one (3%) positive pathogenic alteration within a characterized gene, two (5%) uncertain findings in characterized genes, and five (13%) alterations in novel candidate genes. Two of the 5 pediatric patients, undergoing testing, (40%) had findings in novel candidate genes, with the remainder being negative. We include brief case studies to illustrate the variety of challenging issues related to these patients. Our observations demonstrate utility of family-based exome sequencing in patients for suspected hereditary cancer, including familial co-segregation analysis, and comprehensive medical review. DES may be particularly useful when traditional approaches do not result in a diagnosis or in families with unique phenotypes. This work also highlights the importance and complexity of analysis of uncharacterized genes in exome sequencing for hereditary cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Pediatric cataract: challenges and future directions

PubMed Central

Medsinge, Anagha; Nischal, Ken K

2015-01-01

Cataract is a significant cause of visual disability in the pediatric population worldwide and can significantly impact the neurobiological development of a child. Early diagnosis and prompt surgical intervention is critical to prevent irreversible amblyopia. Thorough ocular evaluation, including the onset, duration, and morphology of a cataract, is essential to determine the timing for surgical intervention. Detailed assessment of the general health of the child, preferably in conjunction with a pediatrician, is helpful to rule out any associated systemic condition. Although pediatric cataracts have a diverse etiology, with the majority being idiopathic, genetic counseling and molecular testing should be undertaken with the help of a genetic counselor and/or geneticist in cases of hereditary cataracts. Advancement in surgical techniques and methods of optical rehabilitation has substantially improved the functional and anatomic outcomes of pediatric cataract surgeries in recent years. However, the phenomenon of refractive growth and the process of emmetropization have continued to puzzle pediatric ophthalmologists and highlight the need for future prospective studies. Posterior capsule opacification and secondary glaucoma are still the major postoperative complications necessitating long-term surveillance in children undergoing cataract surgery early in life. Successful management of pediatric cataracts depends on individualized care and experienced teamwork. We reviewed the etiology, preoperative evaluation including biometry, choice of intraocular lens, surgical techniques, and recent developments in the field of childhood cataract. PMID:25609909

Ecological factors rather than temporal factors dominate the evolution of vesicular stomatitis virus.

PubMed

Rodríguez, L L; Fitch, W M; Nichol, S T

1996-11-12

Vesicular stomatitis New Jersey virus (VSV-NJ) is a rhabdovirus that causes economically important disease in cattle and other domestic animals in endemic areas from southeastern United States to northern South America. Its negatively stranded RNA genome is capable of undergoing rapid evolution, which allows phylogenetic analysis and molecular epidemiology studies to be performed. Previous epidemiological studies in Costa Rica showed the existence of at least two distinct ecological zones of high VSV-NJ activity, one located in the highlands (premontane tropical moist forest) and the other in the lowlands (tropical dry forest). We wanted to test the hypothesis that the viruses circulating in these ecological zones were genetically distinct. For this purpose, we sequenced the hypervariable region of the phosphoprotein gene for 50 VSV-NJ isolates from these areas. Phylogenetic analysis showed that viruses from each ecological zone had distinct genotypes. These genotypes were maintained in each area for periods of up to 8 years. This evolutionary pattern of VSV-NJ suggests an adaptation to ecological factors that could exert selective pressure on the virus. As previous data indicated an absence of virus adaptation to factors related to the bovine host (including immunological pressure), it appears that VSV genetic divergence represents positive selection to adapt to specific vectors and/or reservoirs at each ecological zone.

Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk.

PubMed

Ishikawa, Toshihisa; Aw, Wanping; Kaneko, Kiyoko

2013-11-04

In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

Aneuploidy as a mechanism for stress-induced liver adaptation

PubMed Central

Duncan, Andrew W.; Hanlon Newell, Amy E.; Bi, Weimin; Finegold, Milton J.; Olson, Susan B.; Beaudet, Arthur L.; Grompe, Markus

2012-01-01

Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question of whether this unusual somatic genetic variation evolved as an adaptive mechanism in response to hepatic injury. According to this model, hepatotoxic insults select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in the homogentisic acid dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16–specific aneuploidy was approximately 50%. This result indicates that selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans remains under investigation. PMID:22863619

Primary care providers' cancer genetic testing-related knowledge, attitudes, and communication behaviors: A systematic review and research agenda.

PubMed

Hamilton, Jada G; Abdiwahab, Ekland; Edwards, Heather M; Fang, Min-Lin; Jdayani, Andrew; Breslau, Erica S

2017-03-01

Primary care providers (PCPs) can play a critical role in helping patients receive the preventive health benefits of cancer genetic risk information. Thus, the objective of this systematic review was to identify studies of US PCPs' knowledge, attitudes, and communication-related behaviors regarding genetic tests that could inform risk-stratification approaches for breast, colorectal, and prostate cancer screening in order to describe current findings and research gaps. We conducted a systematic search of six electronic databases to identify peer-reviewed empirical articles relating to US PCPs and genetic testing for breast, colorectal, or prostate cancer published in English from 2008 to 2016. We reviewed these data and used narrative synthesis methods to integrate findings into a descriptive summary and identify research needs. We identified 27 relevant articles. Most focused on genetic testing for breast cancer (23/27) and colorectal cancer risk (12/27); only one study examined testing for prostate cancer risk. Most articles addressed descriptive research questions (24/27). Many studies (24/27) documented PCPs' knowledge, often concluding that providers' knowledge was incomplete. Studies commonly (11/27) examined PCPs' attitudes. Across studies, PCPs expressed some concerns about ethical, legal, and social implications of testing. Attitudes about the utility of clinical genetic testing, including for targeted cancer screening, were generally favorable; PCPs were more skeptical of direct-to-consumer testing. Relatively fewer studies (9/27) examined PCPs' communication practices regarding cancer genetic testing. This review indicates a need for investigators to move beyond descriptive research questions related to PCPs' knowledge and attitudes about cancer genetic testing. Research is needed to address important gaps regarding the development, testing, and implementation of innovative interventions and educational programs that can improve PCPs' genetic testing knowledge, assuage concerns about the appropriateness of cancer genetic testing, and promote open and effective patient-provider communication about genetic risk and genetic testing.

Obtaining genetic testing in pediatric epilepsy.

PubMed

Ream, Margie A; Patel, Anup D

2015-10-01

The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Antibiotic-Free Selection in Biotherapeutics: Now and Forever

PubMed Central

Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

2015-01-01

The continuously improving sophistication of molecular engineering techniques gives access to novel classes of bio-therapeutics and new challenges for their production in full respect of the strengthening regulations. Among these biologic agents are DNA based vaccines or gene therapy products and to a lesser extent genetically engineered live vaccines or delivery vehicles. The use of antibiotic-based selection, frequently associated with genetic manipulation of microorganism is currently undergoing a profound metamorphosis with the implementation and diversification of alternative selection means. This short review will present examples of alternatives to antibiotic selection and their context of application to highlight their ineluctable invasion of the bio-therapeutic world. PMID:25854922

Engineering Genetically Encoded FRET Sensors

PubMed Central

Lindenburg, Laurens; Merkx, Maarten

2014-01-01

Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

Recent advances in the molecular genetics of epilepsy.

PubMed

Hildebrand, Michael S; Dahl, Hans-Henrik M; Damiano, John Anthony; Smith, Richard J H; Scheffer, Ingrid E; Berkovic, Samuel F

2013-05-01

Recent advances in molecular genetics have translated into the increasing utilisation of genetic testing in the routine clinical practice of neurologists. There has been a steady, incremental increase in understanding the genetic variation associated with epilepsies. Genetic testing in the epilepsies is not yet widely practiced, but the advent of new screening technologies promises to exponentially expand both knowledge and clinical utility. To maximise the value of this new genetic insight we need to rapidly extrapolate genetic findings to inform patients of their diagnosis, prognosis, recurrence risk and the clinical management options available for their specific genetic condition. Comprehensive, highly specific and sensitive genetic test results improve the management of patients by neurologists and clinical geneticists. Here we discuss the latest developments in clinical genetic testing for epilepsy and describe new molecular genetics platforms that will transform both genetic screening and novel gene discovery.

What Is Diagnostic Testing?

MedlinePlus

... Financial Planning Who Should I Tell? Genetic Testing & Counseling Compensation for Genetic Testing Whole Genome Sequencing Screening vs. Testing What Is Genetic Counseling? Participating in Research Disease Research Patient Privacy Clinical ...

[Analysis of 14 individuals who requested predictive genetic testing for hereditary neuromuscular diseases].

PubMed

Yoshida, Kunihiro; Tamai, Mariko; Kubota, Takeo; Kawame, Hiroshi; Amano, Naoji; Ikeda, Shu-ichi; Fukushima, Yoshimitsu

2002-02-01

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 receiving an increased-risk or a decreased-risk result. Sufficient time should be taken to build a good relationship between the individual and his/her family and the medical staff during pre-test counseling sessions. This will help the individuals feel satisfied with their own decisions for the future, whether they receive genetic testing or not.

Adaptation to an extraordinary environment by evolution of phenotypic plasticity and genetic assimilation.

PubMed

Lande, Russell

2009-07-01

Adaptation to a sudden extreme change in environment, beyond the usual range of background environmental fluctuations, is analysed using a quantitative genetic model of phenotypic plasticity. Generations are discrete, with time lag tau between a critical period for environmental influence on individual development and natural selection on adult phenotypes. The optimum phenotype, and genotypic norms of reaction, are linear functions of the environment. Reaction norm elevation and slope (plasticity) vary among genotypes. Initially, in the average background environment, the character is canalized with minimum genetic and phenotypic variance, and no correlation between reaction norm elevation and slope. The optimal plasticity is proportional to the predictability of environmental fluctuations over time lag tau. During the first generation in the new environment the mean fitness suddenly drops and the mean phenotype jumps towards the new optimum phenotype by plasticity. Subsequent adaptation occurs in two phases. Rapid evolution of increased plasticity allows the mean phenotype to closely approach the new optimum. The new phenotype then undergoes slow genetic assimilation, with reduction in plasticity compensated by genetic evolution of reaction norm elevation in the original environment.

Consumers' views of direct-to-consumer genetic information.

PubMed

McBride, Colleen M; Wade, Christopher H; Kaphingst, Kimberly A

2010-01-01

In this report, we describe the evolution and types of genetic information provided directly to consumers, discuss potential advantages and disadvantages of these products, and review research evaluating consumer responses to direct-to-consumer (DTC) genetic testing. The available evidence to date has focused on predictive tests and does not suggest that individuals, health care providers, or health care systems have been harmed by a DTC provision of genetic information. An understanding of consumer responses to susceptibility tests has lagged behind. The Multiplex Initiative is presented as a case study of research to understand consumers' responses to DTC susceptibility tests. Three priority areas are recommended for accelerated research activities to inform public policy regarding DTC genetic information: (a) exploring consumer's long-term responses to DTC genetic testing on a comprehensive set of outcomes, (b) evaluating optimal services to support decision making about genetic testing, and (c) evaluating best practices in promoting genetic competencies among health providers.

Comparison of neurocognitive results after coronary artery bypass grafting and thoracic aortic surgery using retrograde cerebral perfusion.

PubMed

Miyairi, Takeshi; Takamoto, Shinichi; Kotsuka, Yutaka; Takeuchi, Atsuko; Yamanaka, Katsuo; Sato, Hajime

2005-07-01

Retrograde cerebral perfusion (RCP) is used as an adjunctive method to hypothermic circulatory arrest to enhance cerebral protection in patients undergoing thoracic aortic surgery. It remains unclear whether RCP provides improved neurological and neuropsychological outcome. Forty-six patients undergoing thoracic aortic surgery using RCP, and 28 undergoing coronary artery bypass grafting (CABG; n = 28) with CPB, were enrolled in the study. Patients receiving RCP were subdivided into two groups, those with less than 60 min of RCP (S-RCP; n = 27) and with 60 min or more (L-RCP; n = 19). The patients' neurocognitive state was assessed by the revised Wechsler Adult Intelligence Scale a few days before operation, at 2-3 weeks and 4-6 months after operation. There were no stroke, seizure, and hospital mortality in either group. Significant decline between baseline and early scores were seen in three subtests (digit span, arithmetic, and picture completion) for S-RCP and four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP. Significant decline between baseline and late scores were seen in one subtest (arithmetic) for S-RCP, four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP, and one (object assembly) for CABG. The mean change of scores for one late test (digit symbol) was significantly lower in S-RCP than in CABG. The mean change of scores for three early tests (digit span, vocabulary, and picture arrangement) and four late tests (information, digit span, picture completion, and picture arrangement) were significantly lower in L-RCP than in CABG. Stepwise logistic regression analysis disclosed that, after considering the other variables, significant difference in test score changes were observed between CABG and L-RCP for two early tests (picture completion and digit symbol) as well as for three late tests (digit span, similarities, and picture completion). None of test score changes showed significant difference between CABG and S-RCP. The neurocognitive outcome in patients undergoing RCP less than 60 min were comparable with patients undergoing CABG without circulatory arrest. Prolonged RCP of 60 min or more in patients undergoing surgery of the thoracic aorta was associated with postoperative neurocognitive impairment.

Neuroscience research on the addictions: a prospectus for future ethical and policy analysis.

PubMed

Hall, Wayne; Carter, Lucy; Morley, Katherine I

2004-09-01

The increasing evidence that many addictive phenomena have a genetic and neurobiological basis promises improvements in societal responses to addiction that raise important ethical and social policy issues. One of the major potential benefits of such research is improved treatment of drug addiction, but in order to do the research required to realize this promise, it will be necessary to address ethical doubts raised about the capacity of addicted persons to give free and informed consent to participate in studies that involve the administration of drugs of dependence. Neuroscience research on addiction promises to transform the long running debate between moral and medical models of addiction by providing a detailed causal explanation of addiction in terms of brain processes. We must avoid causal models of addiction being misinterpreted as supporting simple-minded social policies, e.g., that we identify the minority of the community that is genetically and biologically vulnerable to addiction and hence can neglect social policy options for reducing addiction, including drug control policies. Causal accounts of addiction supplied by neuroscience and genetic research may also be seen to warrant the use of pharmacotherapies and drug vaccines under legal coercion. Neuroscientists also need to anticipate the ethical issues that may arise if the knowledge that they produce delivers interventions that enhance human cognitive and other capacities. Advances in neuroimaging that enable us to identify "addicts" or predict future risk of addiction will raise concerns about invasion of privacy, third-party use of neuroimaging data, the powers of courts to coerce defendants to undergo such tests, and consumer protection against the overinterpretation of test results. Given the strong public and media interest in the results of their research, neuroscientists and geneticists have a moral obligation, and a professional interest, to minimize popular misunderstandings of their work in the media that may rebound to its detriment. Copyright 2004 Elsevier Ltd.

Genetic effects on mating success and partner choice in a social mammal

PubMed Central

Tung, Jenny; Charpentier, Marie JE; Mukherjee, Sayan; Altmann, Jeanne; Alberts, Susan C

2012-01-01

Mating behavior has profound consequences for two phenomena – individual reproductive success and the maintenance of species boundaries – that contribute to evolutionary processes. Studies of mating behavior in relation to individual reproductive success are common in many species, but studies of mating behavior in relation to genetic variation and species boundaries are less commonly conducted in socially complex species. Here, we leveraged extensive observations of a wild yellow baboon (Papio cynocephalus) population that has experienced recent gene flow from a close sister taxon, the anubis baboon (Papio anubis), to examine how admixture-related genetic background affects mating behavior. We identified novel effects of genetic background on mating patterns, including an advantage accruing to anubis-like males and assortative mating among both yellow-like and anubis-like pairs. These genetic effects acted alongside social dominance rank, inbreeding avoidance, and age to produce highly nonrandom mating patterns. Our results suggest that this population may be undergoing admixture-related evolutionary change, driven in part by nonrandom mating. However, the strength of the genetic effects is mediated by behavioral plasticity and social interactions, emphasizing the strong influence of social context on mating behavior in socially complex species. PMID:22673655

Genetic Testing in Clinical Settings.

PubMed

Franceschini, Nora; Frick, Amber; Kopp, Jeffrey B

2018-04-11

Genetic testing is used for screening, diagnosis, and prognosis of diseases consistent with a genetic cause and to guide drug therapy to improve drug efficacy and avoid adverse effects (pharmacogenomics). This In Practice review aims to inform about DNA-related genetic test availability, interpretation, and recommended clinical actions based on results using evidence from clinical guidelines, when available. We discuss challenges that limit the widespread use of genetic information in the clinical care setting, including a small number of actionable genetic variants with strong evidence of clinical validity and utility, and the need for improving the health literacy of health care providers and the public, including for direct-to-consumer tests. Ethical, legal, and social issues and incidental findings also need to be addressed. Because our understanding of genetic factors associated with disease and drug response is rapidly increasing and new genetic tests are being developed that could be adopted by clinicians in the short term, we also provide extensive resources for information and education on genetic testing. Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.

Implementation and utilization of genetic testing in personalized medicine

PubMed Central

Abul-Husn, Noura S; Owusu Obeng, Aniwaa; Sanderson, Saskia C; Gottesman, Omri; Scott, Stuart A

2014-01-01

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 acceptance is pharmacogenetic testing, which interrogates sequence variants implicated in interindividual drug response variability. Although clinical pharmacogenetic testing has not previously been widely adopted, advances in rapid turnaround time genetic testing technology and the recent implementation of preemptive genotyping programs at selected medical centers suggest that personalized medicine through pharmacogenetics is now a reality. This review aims to summarize the current state of implementing genetic testing for personalized medicine, with an emphasis on clinical pharmacogenetic testing. PMID:25206309

Cancer genetics education in a low- to middle-income country: evaluation of an interactive workshop for clinicians in Kenya.

PubMed

Hill, Jessica A; Lee, Su Yeon; Njambi, Lucy; Corson, Timothy W; Dimaras, Helen

2015-01-01

Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills. The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire. Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions. A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.

Knowledge and Attitudes Regarding Non-Invasive Prenatal Testing (NIPT) and Preferences for Risk Information among High School Students in Sweden.

PubMed

Georgsson, Susanne; Sahlin, Ellika; Iwarsson, Moa; Nordenskjöld, Magnus; Gustavsson, Peter; Iwarsson, Erik

2017-06-01

Non-invasive prenatal testing (NIPT) was recently introduced for prenatal testing of genetic disorders. Cell-free fetal DNA is present in maternal blood during pregnancy and enables detection of fetal chromosome aberrations in a maternal blood sample. The public perspective to this new, simple method has not been illuminated. The views of young people (i.e. future parents) are important to develop suitable counseling strategies regarding prenatal testing. The aim was to explore Swedish high school students' attitudes, knowledge and preferences regarding NIPT. A questionnaire was completed by 305 students recruited from one high school in Stockholm, November and December 2014. Most students (80 %) considered prenatal testing as good. The majority (65 %) was positive or very positive towards NIPT and 62 % stated that they potentially would like to undergo the test if they or their partner was pregnant. The vast majority (94 %) requested further information about NIPT. Most students (61 %) preferred verbal information, whereas 20 % preferred information via the Internet. The majority of the high school students was positive towards prenatal testing and most was positive towards NIPT. Further, information was requested by the vast majority before making a decision about NIPT. Most of the students preferred verbal information and to a lesser extent information via the Internet. The attitudes, knowledge and preferences for risk information concerning NIPT in young adults are important, in order to increase knowledge on how to educate and inform future parents.

Genetic testing when there is a mix of compulsory and voluntary health insurance.

PubMed

Hoel, Michael; Iversen, Tor

2002-03-01

When the insurer has access to information about test status, genetic insurance can handle the negative effects of genetic testing on insurance coverage and income distribution. Hence, efficient testing is promoted. When information about prevention and test status is private, two types of social inefficiencies may occur; genetic testing may not be done when it is socially efficient and genetic testing may be done although it is socially inefficient. The first type of inefficiency is shown to be likely for consumers with compulsory insurance only, while the second type of inefficiency is more likely for those who have supplemented the compulsory insurance with substantial voluntary insurance. This second type of inefficiency is more important the less effective prevention is. It is therefore a puzzle that many countries have imposed strict regulation on the genetic information insurers have access to. A reason may be that genetic insurance is not yet a political issue, and the advantage of shared genetic information is therefore not transparent.

Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses

PubMed Central

Betjemann, Rebecca S.; Keenan, Janice M.; Olson, Richard K.; DeFries, John C.

2010-01-01

Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences. PMID:21804757

Are the kids really all right? Direct-to-consumer genetic testing in children: are company policies clashing with professional norms?

PubMed

Howard, Heidi Carmen; Avard, Denise; Borry, Pascal

2011-11-01

The genetic testing of minors within the direct-to-consumer (DTC) genetic testing (GT) context has been given relatively little attention. The issue of testing healthy children for diseases that would only develop in adulthood raises many important ethical, legal and social issues. As genetic testing is now available outside of the traditional health care system, often without even the intermediate of a health care professional, we surveyed 37 DTC GT companies regarding their policies for testing in children. Although the response rate is relatively low (35%, 13/37), our findings reveal that a clear majority of companies do perform genetic testing in minors. As such, companies testing for adult onset diseases are acting in contradiction of established professional guidelines, which state, among others, that, for predictive genetic testing, the availability of therapeutic or preventive measures is necessary for testing to be performed in asymptomatic minors. The community of stakeholders in children's health care and genetic testing should, therefore, decide which standards need to be upheld by DTC GT companies and ensure that these are met.

Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

PubMed Central

Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

2014-01-01

Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao; Kabekkodu, Shama Prasada

Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluatemore » the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by gene–gene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles.« less

Development of a Streamlined Work Flow for Handling Patients' Genetic Testing Insurance Authorizations.

PubMed

Uhlmann, Wendy R; Schwalm, Katie; Raymond, Victoria M

2017-08-01

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.

Estimating heritability of disease resistance and factors that contribute to long-term survival in butternut (Juglans cinerea L.)

Treesearch

Nicholas R. LaBonte; Michael E. Ostry; Amy Ross-Davis; Keith E. Woeste

2015-01-01

For most wild species affected by exotic pests or pathogens, the relative importance of heritable genetic differences in determining apparent variation in disease resistance is unknown. This is true in particular for butternut, a North American hardwood affected by butternut canker disease and undergoing demographic contraction. Little is known about site effects on...

Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge.

PubMed

Parish, Masoud; Farzin, Haleh

2018-01-01

Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications.

Ethical issues in neurogenetics.

PubMed

Uhlmann, Wendy R; Roberts, J Scott

2018-01-01

Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for the patient's relatives and can raise ethical issues. Predictive genetic testing offers asymptomatic relatives the opportunity to determine their risk status for a neurogenetic condition, and professional guidelines emphasize patients' autonomy and informed, voluntary decision making. Beneficence and nonmaleficence both need to be considered when making decisions about disclosure and nondisclosure of genetic information and test results. There can be disclosure concerns and challenges in determining whose autonomy to prioritize when a patient makes a genetic testing decision that can reveal the genetic status of a relative (e.g., testing an adult child when the at-risk parent has not been tested). Ethical issues are prominent when genetic testing for neurogenetic conditions is requested prenatally, on minors, adoptees, adult children at 25% risk, and for individuals with psychiatric issues or cognitive impairment. Neurogenetic conditions can result in cognitive decline which can affect decisional capacity and lead to ethical challenges with decision making, informed consent, and determining the patient's ability to comprehend test results. The ethical implications of genetic testing and emerging issues, including direct-to-consumer genetic testing, disclosure of secondary findings from genomic sequencing, and use of apolipoprotein E testing in clinical and research settings, are also discussed. Resources for information about genetic testing practice guidelines, insurance laws, and directories of genetics clinics are included. Copyright © 2018 Elsevier B.V. All rights reserved.

Ethical Issues in Neurogenetics

PubMed Central

Uhlmann, Wendy R.; Roberts, J. Scott

2018-01-01

Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for their relatives and can raise ethical issues. Predictive genetic testing offers asymptomatic relatives the opportunity to determine their risk status for a neurogenetic condition, and professional guidelines emphasize patients’ autonomy and informed, voluntary decision-making. Beneficence and non-maleficence both need to be considered when making decisions about disclosure and nondisclosure of genetic information and test results. There can be disclosure concerns and issues of determining whose autonomy to prioritize when a patient makes a genetic testing decision that can reveal the genetic status of a relative (e.g. testing an adult child when the at-risk parent has not been tested). Ethical issues are prominent when genetic testing for neurogenetic conditions is requested prenatally, on minors, adoptees, adult children at 25% risk, and for individuals with psychiatric issues or cognitive impairment. Neurogenetic conditions can result in cognitive decline which can affect decisional capacity and lead to ethical challenges with decision-making, informed consent and determining the patient’s ability to comprehend test results. The ethical implications of genetic testing and emerging issues, including direct-to-consumer genetic testing, disclosure of secondary findings from genomic sequencing, and use of APOE testing in clinical and research settings, are also discussed. Resources for information about genetic testing practice guidelines, insurance laws and directories of genetics clinics are included. PMID:29325614

Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis.

PubMed

Anadón, C; Guil, S; Simó-Riudalbas, L; Moutinho, C; Setien, F; Martínez-Cardús, A; Moran, S; Villanueva, A; Calaf, M; Vidal, A; Lazo, P A; Zondervan, I; Savola, S; Kohno, T; Yokota, J; Ribas de Pouplana, L; Esteller, M

2016-08-18

The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.

Cancer and intercellular cooperation

PubMed Central

Dieli, Anna Maria

2017-01-01

The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing. However, the gene-centric version of Darwinian evolution, which is often adopted in cancer research, runs into empirical problems: proto-tumoural and tumoural features in precancerous cells that would undergo ‘natural selection’ have proved hard to demonstrate; cells are radically context-dependent, and some stages of cancer are poorly related to genetic change. Recent perspectives propose that breakdown of intercellular cooperation could depend on ‘fields’ and other higher-level phenomena, and could be even mutations independent. Indeed, the field would be the context, allowing (or preventing) genetic mutations to undergo an intra-organism process analogous to natural selection. The complexities surrounding somatic evolution call for integration between multiple incomplete frameworks for interpreting intercellular cooperation and its pathologies. PMID:29134064

Finance issue brief: genetic testing.

PubMed

Herstek, J

1999-06-25

States have enacted genetic testing laws to address the contentious privacy, consent, research, discrimination, insurance and employment issues surrounding genetic information. These genetic testing laws attempt to strike a balance between the concerns of the consumer, research, insurance and business communities.

Utilization of Genetic Testing Prior to Subspecialist Referral for Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Vickrey, Barbara G.; Walton-Wetzel, Jenny; Lieber, Eli

2013-01-01

Objective: To evaluate the utilization of laboratory testing in the diagnosis of cerebellar ataxia, including the completeness of initial standard testing for acquired causes, the early use of genetic testing, and associated clinical and nonclinical factors, among a cohort referred for subspecialty consultation. Methods: Data were abstracted from records of 95 consecutive ataxia patients referred to one neurogenetics subspecialist from 2006–2010 and linked to publicly available data on characteristics of referral clinicians. Multivariable logistic and linear regression models were used to analyze unique associations of clinical and nonclinical factors with laboratory investigation of acquired causes and with early genetic testing prior to referral. Results: At referral, 27 of 95 patients lacked evidence of any of 14 laboratory studies suggested for initial work-up of an acquired cause for ataxia (average number of tests=4.5). In contrast, 92% of patients had undergone brain magnetic resonance imaging prior to referral. Overall, 41.1% (n=39) had genetic testing prior to referral; there was no association between family history of ataxia and obtaining genetic testing prior to referral (p=0.39). The level of early genetic testing was 31.6%, primarily due to genetic testing despite an incomplete laboratory evaluation for acquired causes and no family history. A positive family history was consistently associated with less extensive laboratory testing (p=0.004), and referral by a neurologist was associated with higher levels of early genetic testing. Conclusions: Among consecutive referrals to a single center, a substantial proportion of sporadic cases had genetic testing without evidence of a work-up for acquired causes. Better strategies to guide decision making and subspecialty referrals in rare neurologic disorders are needed, given the cost and consequences of genetic testing. PMID:23725007

Psychosocial and Clinical Factors Associated with Family Communication of Cancer Genetic Test Results Among Women Diagnosed with Breast Cancer at a Young Age

PubMed Central

Elrick, Ashley; Ashida, Sato; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara B.; Goodman, Melody S.; Kaphingst, Kimberly A.

2016-01-01

Genetic test results have medical implications beyond the patient that extend to biological family members. We examined psychosocial and clinical factors associated with communication of genetic test results within families. Women (N=1080) diagnosed with breast cancer at age 40 or younger completed an online survey; 920 women that reported prior cancer genetic testing were included in analysis. We examined the proportion of immediate family members to whom they communicated genetic test results, and built multivariable regression models to examine clinical and psychosocial variables associated with the proportion score. Participants were most likely to communicate test results to their mother (83%) and least likely to their son (45%). Participants who carried a BRCA mutation (OR=1.34; 95% CI = 1.06, 1.70), had higher interest in genomic information (OR=1.55; 95% CI = 1.26, 1.91) and lower genetic worry (OR=0.91; 95% CI = 0.86, 0.96) communicated genetic test results to a greater proportion of their immediate family members. Participants with a BRCA1/2 mutation shared their genetic test results with more male family members (OR=1.72; 95% CI = 1.02, 2.89). Our findings suggest that patients with high worry about genetic risks, low interest in genomic information, or receive a negative genetic test result will likely need additional support to encourage family communication. PMID:27422778

Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

PubMed Central

Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.

2010-01-01

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

Direct-to-consumer genetic testing for addiction susceptibility: a premature commercialisation of doubtful validity and value.

PubMed

Mathews, Rebecca; Hall, Wayne; Carter, Adrian

2012-12-01

Genetic research on addiction liability and pharmacogenetic research on treatments for addiction have identified some genetic variants associated with disease risk and treatment. Genetic testing for addiction liability and treatment response has not been used widely in clinical practice because most of the genes identified only modestly predict addiction risk or treatment response. However, many of these genetic tests have been commercialized prematurely and are available direct to the consumer (DTC). The easy availability of DTC tests for addiction liability and lack of regulation over their use raises a number of ethical concerns. Of paramount concern is the limited predictive power and clinical utility of these tests. Many DTC testing companies do not provide the consumer with the necessary genetic counselling to assist them in interpreting and acting on their test results. They may also engage in misleading marketing to entice consumers to purchase their products. Consumers' genetic information may be vulnerable to misuse by third parties, as there are limited standards to protect the privacy of the genetic information. Non-consensual testing and inappropriate testing of minors may also occur. The United States Food and Drug Administration plans to regulate DTC genetic tests. Based on the ethical concerns we discuss below, we believe there is a strong case for regulation of DTC genetic tests for addiction liability and treatment response. We argue that until this occurs, these tests have more potential to cause harm than to contribute to improved prevention and treatment of addiction. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

[Current status of the predictive genetic testing for hereditary neurological diseases in Shinshu University Hospital].

PubMed

Tanaka, Keiko; Sekijima, Yoshiki; Yoshida, Kunihiro; Mizuuchi, Asako; Yamashita, Hiromi; Tamai, Mariko; Ikeda, Shu-ichi; Fukushima, Yoshimitsu

2013-01-01

The current status of predictive genetic testing for late-onset hereditary neurological diseases in Japan is largely unknown. In this study, we analyzed data from 73 clients who visited the Division of Clinical and Molecular Genetics, Shinshu University Hospital, for the purpose of predictive genetic testing. The clients consisted of individuals with family histories of familial amyloid polyneuropathy (FAP; n=30), Huntington's disease (HD; n=16), spinocerebellar degeneration (SCD; n=14), myotonic dystrophy type 1 (DM1; n=9), familial amyotrophic lateral sclerosis type 1 (ALS1; n=3), and Alzheimer's disease (AD; n=1). Forty-nine of the 73 (67.1%) clients were in their twenties or thirties. Twenty-seven of the 73 (37.0%) clients visited a medical institution within 3 months after becoming aware of predictive genetic testing. The most common reason for requesting predictive genetic testing was a need for certainty or to reduce uncertainty and anxiety. The decision-making about marriage and having a child was also a main reason in clients in the twenties and thirties. The numbers of clients who actually underwent predictive genetic testing was 22 of 30 (73.3%) in FAP, 3 of 16 (18.8%) in HD, 6 of 10 (60.0%) in SCD, 7 of 9 (77.8%) in DM1, and 0 of 3 (0%) in ALS1 (responsible gene of the disease was unknown in 4 SCD patients and an AD patient). The percentage of test usage was lower in untreatable diseases such as HD and SCD than that in FAP, suggesting that many clients changed their way of thinking on the significance of testing through multiple genetic counseling sessions. In addition, it was obvious that existence of disease-modifying therapy promoted usage of predictive genetic testing in FAP. Improvement of genetic counseling system to manage predictive genetic testing is necessary, as consultation concerning predictive genetic testing is the main motivation to visit genetic counseling clinic in many at-risk clients.

Direct-to-Consumer Genetic Tests

MedlinePlus

... sell their tests online and through multi-level marketing networks. The Federal Trade Commission (FTC) wants you to know the facts about the DTC marketing of genetic tests. Genes and Genetic Tests Interpreting ...

Disparities in genetic testing: thinking outside the BRCA box.

PubMed

Hall, Michael J; Olopade, Olufunmilayo I

2006-05-10

The impact of predictive genetic testing on cancer care can be measured by the increased demand for and utilization of genetic services as well as in the progress made in reducing cancer risks in known mutation carriers. Nonetheless, differential access to and utilization of genetic counseling and cancer predisposition testing among underserved racial and ethnic minorities compared with the white population has led to growing health care disparities in clinical cancer genetics that are only beginning to be addressed. Furthermore, deficiencies in the utility of genetic testing in underserved populations as a result of limited testing experience and in the effectiveness of risk-reducing interventions compound access and knowledge-base disparities. The recent literature on racial/ethnic health care disparities is briefly reviewed, and is followed by a discussion of the current limitations of risk assessment and genetic testing outside of white populations. The importance of expanded testing in underserved populations is emphasized.

Psychological opportunities and hazards in predictive genetic testing for cancer risk.

PubMed

Codori, A M

1997-03-01

Although the availability of genetic tests seems like an unequivocally favorable turn of events, they are, in fact, not without controversy. At the center of the controversy is a question regarding the risks and benefits of genetic testing. Many geneticists, ethicists, psychologists, and persons at risk for cancer are concerned about the potentially adverse psychological effects of genetic testing on tested persons and their families. In addition, the screening and interventions that are useful in the general population remain to be shown effective in those with high genetic cancer risk. Consequently, there have been calls for caution in moving genetic testing out of research laboratories and into commercial laboratories until their impact and the effectiveness of cancer prevention strategies can be studied. This article examines the arguments and data for and against this caution, citing examples related to hereditary nonpolyposis colon cancer and drawing upon literature on testing for other genetic diseases.

A randomized controlled trial of a brief self-help coping intervention designed to reduce distress when awaiting genetic risk information.

PubMed

Bennett, Paul; Phelps, Ceri; Brain, Kate; Hood, Kerenza; Gray, Jonathon

2007-07-01

The aim of this study was to evaluate the effectiveness of a distraction-based coping leaflet in reducing distress in women undergoing genetic risk assessment for breast/ovarian cancer. One hundred sixty-two women participated in a randomized controlled trial, receiving either the intervention or standard information. Data were collected through a postal questionnaire at entry into a genetic risk assessment programme and 1 month later. Analysis of covariance revealed a nonsignificant reduction in distress in all women, and a significant reduction of distress among those with high baseline stress, who received the intervention. No gains were found among the control group. Measures of emotional response while thinking about cancer genetic assessment suggested these benefits were achieved in the absence of any rebound emotional response. The intervention offers a low-cost effective coping intervention, which could be integrated into existing services with minimal disruption and may also be appropriate for other periods of waiting and uncertainty.

Genetic recombination of tick-borne flaviviruses among wild-type strains.

PubMed

Norberg, Peter; Roth, Anette; Bergström, Tomas

2013-06-05

Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses. Copyright © 2013 Elsevier Inc. All rights reserved.

A population-based survey in Australia of men's and women's perceptions of genetic risk and predictive genetic testing and implications for primary care.

PubMed

Taylor, S

2011-01-01

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.

Direct-to-consumer genetic testing: good, bad or benign?

PubMed

Caulfield, T; Ries, N M; Ray, P N; Shuman, C; Wilson, B

2010-02-01

A wide variety of genetic tests are now being marketed and sold in direct-to-consumer (DTC) commercial transactions. However, risk information revealed through many DTC testing services, especially those based on emerging genome wide-association studies, has limited predictive value for consumers. Some commentators contend that tests are being marketed prematurely, while others support rapid translation of genetic research findings to the marketplace. The potential harms and benefits of DTC access to genetic testing are not yet well understood, but some large-scale studies have recently been launched to examine how consumers understand and use genetic risk information. Greater consumer access to genetic tests creates a need for continuing education for health care professionals so they can respond to patients' inquiries about the benefits, risks and limitations of DTC services. Governmental bodies in many jurisdictions are considering options for regulating practices of DTC genetic testing companies, particularly to govern quality of commercial genetic tests and ensure fair and truthful advertising. Intersectoral initiatives involving government regulators, professional bodies and industry are important to facilitate development of standards to govern this rapidly developing area of personalized genomic commerce.

A Knowledge Base for Teaching Biology Situated in the Context of Genetic Testing

NASA Astrophysics Data System (ADS)

van der Zande, Paul; Waarlo, Arend Jan; Brekelmans, Mieke; Akkerman, Sanne F.; Vermunt, Jan D.

2011-10-01

Recent developments in the field of genomics will impact the daily practice of biology teachers who teach genetics in secondary education. This study reports on the first results of a research project aimed at enhancing biology teacher knowledge for teaching genetics 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 such a situated learning approach. What content knowledge do biology teachers need for teaching genetics in the personal health context of genetic testing? This study describes the required content knowledge by exploring the educational practice and clinical genetic practices. Nine experienced teachers and 12 respondents representing the clinical genetic practices (clients, medical professionals, and medical ethicists) were interviewed about the biological concepts and ethical, legal, and social aspects (ELSA) of testing they considered relevant to empowering students as future health care clients. The ELSA suggested by the respondents were complemented by suggestions found in the literature on genetic counselling. The findings revealed that the required teacher knowledge consists of multiple layers that are embedded in specific genetic test situations: on the one hand, the knowledge of concepts represented by the curricular framework and some additional concepts (e.g. multifactorial and polygenic disorder) and, on the other hand, more knowledge of ELSA and generic characteristics of genetic test practice (uncertainty, complexity, probability, and morality). Suggestions regarding how to translate these characteristics, concepts, and ELSA into context-based genetics education are discussed.

Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint statement.

PubMed

Vlahovich, Nicole; Hughes, David C; Griffiths, Lyn R; Wang, Guan; Pitsiladis, Yannis P; Pigozzi, Fabio; Bachl, Nobert; Eynon, Nir

2017-11-14

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.

Method for detecting pollutants. [through chemical reactions and heat treatment

NASA Technical Reports Server (NTRS)

Rogowski, R. S.; Richards, R. R.; Conway, E. J. (Inventor)

1976-01-01

A method is described for detecting and measuring trace amounts of pollutants of the group consisting of ozone, nitrogen dioxide, and carbon monoxide in a gaseous environment. A sample organic solid material that will undergo a chemical reaction with the test pollutant is exposed to the test environment and thereafter, when heated in the temperature range of 100-200 C., undergoes chemiluminescence that is measured and recorded as a function of concentration of the test pollutant. The chemiluminescence of the solid organic material is specific to the pollutant being tested.

Validation of the breast evaluation questionnaire for breast hypertrophy and breast reduction.

PubMed

Lewin, Richard; Elander, Anna; Lundberg, Jonas; Hansson, Emma; Thorarinsson, Andri; Claudelin, Malin; Bladh, Helena; Lidén, Mattias

2018-06-13

There is a lack of published, validated questionnaires for evaluating psychosocial morbidity in patients with breast hypertrophy undergoing breast reduction surgery. To validate the breast evaluation questionnaire (BEQ), originally developed for the assessment of breast augmentation patients, for the assessment of psychosocial morbidity in patients with breast hypertrophy undergoing breast reduction surgery. Validation study Subjects: Women with macromastia Methods: The validation of the BEQ, adapted to breast reduction, was performed in several steps. Content validity, reliability, construct validity and responsiveness were assessed. The original version was adjusted according to the results for content validity and resulted in item reduction and a modified BEQ (mBEQ) that was then assessed for reliability, construct validity and responsiveness. Internal and external validation was performed for the modified BEQ. Convergent validity was tested against Breast-Q (reduction) and discriminate validity was tested against the SF-36. Known-groups validation revealed significant differences between the normal population and patients undergoing breast reduction surgery. The BEQ showed good reliability by test-re-test analysis and high responsiveness. The modified BEQ may be reliable, valid and responsive instrument for assessing women who undergo breast reduction.

Genetics Home Reference: Paget disease of bone

MedlinePlus

... genetic cause of classic Paget disease of bone , accounting for 10 to 50 percent of cases that ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (6 links) Genetic Testing Registry: ...

The clinical application of genetic testing in type 2 diabetes: a patient and physician survey.

PubMed

Grant, R W; Hivert, M; Pandiscio, J C; Florez, J C; Nathan, D M; Meigs, J B

2009-11-01

Advances in type 2 diabetes genetics have raised hopes that genetic testing will improve disease prediction, prevention and treatment. Little is known about current physician and patient views regarding type 2 diabetes genetic testing. We hypothesised that physician and patient views would differ regarding the impact of genetic testing on motivation and adherence. We surveyed a nationally representative sample of US primary care physicians and endocrinologists (n = 304), a random sample of non-diabetic primary care patients (n = 152) and patients enrolled in a diabetes pharmacogenetics study (n = 89). Physicians and patients favoured genetic testing for diabetes risk prediction (79% of physicians vs 80% of non-diabetic patients would be somewhat/very likely to order/request testing, p = 0.7). More patients than physicians (71% vs 23%, p < 0.01) indicated that a 'high risk' result would be very likely to improve motivation to adopt preventive lifestyle changes. Patients favoured genetic testing to guide therapy (78% of patients vs 48% of physicians very likely to request/recommend testing, p < 0.01) and reported that genetic testing would make them 'much more motivated' to adhere to medications (72% vs 18% of physicians, p < 0.01). Many physicians (39%) would be somewhat/very likely to order genetic testing before published evidence of clinical efficacy. Despite the paucity of current data, physicians and patients reported high expectations that genetic testing would improve patient motivation to adopt key behaviours for the prevention or control of type 2 diabetes. This suggests the testable hypothesis that 'genetic' risk information might have greater value to motivate behaviour change compared with standard risk information.

Genetic tests obtainable through pharmacies: the good, the bad, and the ugly.

PubMed

Patrinos, George P; Baker, Darrol J; Al-Mulla, Fahd; Vasiliou, Vasilis; Cooper, David N

2013-07-08

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 training about the genetic tests that they offer for sale.

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

A nationwide genetic testing survey in Italy, year 2007.

PubMed

Dallapiccola, Bruno; Torrente, Isabella; Agolini, Emanuele; Morena, Arnaldo; Mingarelli, Rita

2010-02-01

The aim of this study was to collect the practices of cytogenetic and molecular genetic testing and genetic counseling activities in Italy in the year 2007 and provide guidance to the national and regional health systems to improve the organization of genetic services. A web-based survey was carried out to assess the total number and the type of analyses, the number and type of genetic counseling sessions, and the personnel attending these activities. The quality management system of the responding structures, in terms of certification and accreditation standards, was also investigated. The appropriateness of requests for genetic testing was evaluated for six disorders. Data were collected from 278 responding centers, half of which were located in the northern regions of the country. Twenty-eight percent of the total were certified according to quality standards. A total of 217 molecular genetic and 171 cytogenetic laboratories, and 102 clinical genetic services were surveyed. About 560,000 genetic tests, including 311,069 cytogenetic and 248,691 molecular genetic analyses of 556 genes, were recorded. The fetal karyotype was examined on either trophoblast or amniocytes in about one of every 4.4 pregnancies. Only 11.5% of cytogenetic analyses and 13.5% of molecular tests were accompanied by genetic counseling. Concerning the appropriateness of a request for genetic testing, a low congruity was found between the clinical diagnosis and the laboratory results. This study highlights the need for reorganizing the genetic structure network in Italy, which at present is oversized, improving the quality management systems, expanding the availability of testing for rare disease genes, and improving access to pretest and posttest genetic counseling.

Ethical and clinical practice considerations for genetic counselors related to direct-to-consumer marketing of genetic tests.

PubMed

Wade, Christopher H; Wilfond, Benjamin S

2006-11-15

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.

Valuations of genetic test information for treatable conditions: the case of colorectal cancer screening.

PubMed

Kilambi, Vikram; Johnson, F Reed; González, Juan Marcos; Mohamed, Ateesha F

2014-12-01

The value of the information that genetic testing services provide can be questioned for insurance-based health systems. The results of genetic tests oftentimes may not lead to well-defined clinical interventions; however, Lynch syndrome, a genetic mutation for which carriers are at an increased risk for colorectal cancer, can be identified through genetic testing, and meaningful health interventions are available via increased colonoscopic surveillance. Valuations of test information for such conditions ought to account for the full impact of interventions and contingent outcomes. To conduct a discrete-choice experiment to elicit individuals' preferences for genetic test information. A Web-enabled discrete-choice experiment survey was administered to a representative sample of US residents aged 50 years and older. In addition to specifying expenditures on colonoscopies, respondents were asked to make a series of nine selections between two hypothetical genetic tests or a no-test option under the premise that a relative had Lynch syndrome. The hypothetical genetic tests were defined by the probability of developing colorectal cancer, the probability of a false-negative test result, privacy of the result, and out-of-pocket cost. A model specification identifying necessary interactions was derived from assumptions of risk behavior and the decision context and was estimated using random-parameters logit. A total of 650 respondents were contacted, and 385 completed the survey. The monetary equivalent of test information was approximately $1800. Expenditures on colonoscopies to reduce mortality risks affected valuations. Respondents with lower income or who reported being employed significantly valued genetic tests more. Genetic testing may confer benefits through the impact of subsequent interventions on private individuals. Copyright © 2014. Published by Elsevier Inc.

To Test or Not to Test? The Role of Attitudes, Knowledge, and Religious Involvement among U.s. Adults on Intent-to-Obtain Adult Genetic Testing

ERIC Educational Resources Information Center

Botoseneanu, Anda; Alexander, Jeffrey A.; Banaszak-Holl, Jane

2011-01-01

Genetic testing can advance cancer prevention if current screening behaviors improve. Increased prevalence of high-risk genotypes within specific religious groups, use of religious venues for recruiting to genetic screening, and ethical-religious considerations argue for exploring the role of religiosity in forming genetic testing decisions. This…

Environmental Test Screening Procedure

NASA Technical Reports Server (NTRS)

Zeidler, Janet

2000-01-01

This procedure describes the methods to be used for environmental stress screening (ESS) of the Lightning Mapper Sensor (LMS) lens assembly. Unless otherwise specified, the procedures shall be completed in the order listed, prior to performance of the Acceptance Test Procedure (ATP). The first unit, S/N 001, will be subjected to the Qualification Vibration Levels, while the remainder will be tested at the Operational Level. Prior to ESS, all units will undergo Pre-ESS Functional Testing that includes measuring the on-axis and plus or minus 0.95 full field Modulation Transfer Function and Back Focal Length. Next, all units will undergo ESS testing, and then Acceptance testing per PR 460.

State of play in direct-to-consumer genetic testing for lifestyle-related diseases: market, marketing content, user experiences and regulation.

PubMed

Saukko, Paula

2013-02-01

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.

Use of Contemporary Genetics in Cardiovascular Diagnosis

PubMed Central

George, Alfred L.

2015-01-01

An explosion of knowledge regarding the genetic and genomic basis for rare and common diseases has provided a framework for revolutionizing the practice of medicine. Achieving the reality of a genomic medicine era requires that basic discoveries are effectively translated into clinical practice through implementation of genetic and genomic testing. Clinical genetic tests have become routine for many inherited disorders and can be regarded as the standard-of-care in many circumstances including disorders affecting the cardiovascular system. New, high-throughput methods for determining the DNA sequence of all coding exons or complete genomes are being adopted for clinical use to expand the speed and breadth of genetic testing. Along with these extraordinary advances have emerged new challenges to practicing physicians for understanding when and how to use genetic testing along with how to appropriately interpret test results. This review will acquaint readers with general principles of genetic testing including newer technologies, test interpretation and pitfalls. The focus will be on testing genes responsible for monogenic disorders and on other emerging applications such as pharmacogenomic profiling. The discussion will be extended to the new paradigm of direct-to-consumer genetic testing and the value of assessing genomic risk for common diseases. PMID:25421045

Legislation on direct-to-consumer genetic testing in seven European countries.

PubMed

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

2012-07-01

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.

Legislation on direct-to-consumer genetic testing in seven European countries

PubMed Central

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

2012-01-01

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. PMID:22274578

[Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease].

PubMed

Mantilla, Carolina; Toro, Mónica; Sepúlveda, María Elsy; Insuasty, Margarita; Di Filippo, Diana; López, Juan Álvaro; Baquero, Carolina; Navas, María Cristina; Arias, Andrés Augusto

2018-05-01

Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

PubMed Central

Chisholm, Andrew D.; Hutter, Harald; Jin, Yishi; Wadsworth, William G.

2016-01-01

The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regeneration-specific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. PMID:28114100

Technique-associated outcomes in horses following large colon resection.

PubMed

Pezzanite, Lynn M; Hackett, Eileen S

2017-11-01

To compare survival and complications in horses undergoing large colon resection with either sutured end-to-end or stapled functional end-to-end anastomoses. Retrospective cohort study. Twenty-six client-owned horses with gastrointestinal disease. Retrospective data were retrieved from the medical records of 26 horses undergoing colectomy, including 14 horses with sutured end-to-end and 12 horses with stapled functional end-to-end anastomoses, between 2003 and 2016. Records were evaluated for signalment, medical and surgical treatments, and survival to hospital discharge. Long-term follow-up was obtained through owner contact. Continuous variables were compared with Mann-Whitney tests. Fisher's exact testing was used to compare survival to hospital discharge. Survival time was compared by constructing Kaplan-Meier survival curves and performing log-rank curve comparison testing. Mean age of horses undergoing colectomy was 13 years. Reason for colectomy was prophylaxis (12) or salvage (14). Mean surgical time was 169 minutes. Mean hospitalization time was 9 days, which did not differ with anastomosis type (P = .62). Nine of 12 horses undergoing stapled functional end-to-end anastomosis and 12 of 14 horses undergoing sutured end-to-end anastomosis survived to hospital discharge (P = .63). Survival time did not differ with anastomosis technique (P = .35). Short- and long-term survival outcomes are not different between sutured end-to-end or stapled functional end-to-end anastomoses in horses undergoing colectomy. © 2017 The American College of Veterinary Surgeons.

The Impact of Gene-Environment Dependence and Misclassification in Genetic Association Studies Incorporating Gene-Environment Interactions

PubMed Central

Lindström, Sara; Yen, Yu-Chun; Spiegelman, Donna; Kraft, Peter

2009-01-01

The possibility of gene-environment interaction can be exploited to identify genetic variants associated with disease using a joint test of genetic main effect and gene-environment interaction. We consider how exposure misclassification and dependence between the true exposure E and the tested genetic variant G affect this joint test in absolute terms and relative to three other tests: the marginal test (G), the standard test for multiplicative gene-environment interaction (GE), and the case-only test for interaction (GE-CO). All tests can have inflated Type I error rate when E and G are correlated in the underlying population. For the GE and G-GE tests this inflation is only noticeable when the gene-environment dependence is unusually strong; the inflation can be large for the GE-CO test even for modest correlation. The joint G-GE test has greater power than the GE test generally, and greater power than the G test when there is no genetic main effect and the measurement error is small to moderate. The joint G-GE test is an attractive test for assessing genetic association when there is limited knowledge about casual mechanisms a priori, even in the presence of misclassification in environmental exposure measurement and correlation between exposure and genetic variants. PMID:19521099

[Quality of genetic services--analysis of medical genetic expert opinions solicited by private health insurance companies].

PubMed

Nippert, Reinhardt Peter; Schmidtke, Jörg

2012-01-01

Service quality for patients with genetic conditions can be assessed through the analysis of clinical genetic data sets, as was the case in this study. It represents a secondary analysis of a compilation of a single genetic expert's medical opinions covering the years 2000 to 2009, solicited by private health insurance companies with the intention of probing into medical necessity and adequacy of genetic testing ordered by physicians. Genetic testing has become an increasingly important part of clinical diagnostic services. Controlling these services does not only reduce costs but also saves patients from unwarranted over-utilisation. Therefore, the reasons given by doctors when ordering genetic tests are part of the quality of service delivery. The study revealed that more than 30% of the molecular genetic tests ordered lack sound medical reasoning and 30% of the cases studied show violation or neglect of guidelines and recommendations for diagnostic procedures with respect to genetic testing. In essence, the findings indicate a need for human genetic information among physicians. Their professional organisations are called upon to design and offer CME/CPD programmes in medical genetics to maintain and continually improve the quality of medical genetic care for patients with genetic conditions. Copyright © 2012. Published by Elsevier GmbH.

Genetic Tests for Ability?: Talent Identification and the Value of an Open Future

ERIC Educational Resources Information Center

Miah, Andy; Rich, Emma

2006-01-01

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…

Effects of a decision support intervention on decisional conflict associated with microsatellite instability testing.

PubMed

Hall, Michael J; Manne, Sharon L; Winkel, Gary; Chung, Daniel S; Weinberg, David S; Meropol, Neal J

2011-02-01

Decision support to facilitate informed consent is increasingly important for complicated medical tests. Here, we test a theoretical model of factors influencing decisional conflict in a study examining the effects of a decision support aid that was designed to assist patients at high risk for hereditary nonpolyposis colorectal cancer (CRC) deciding whether to pursue the microsatellite instability (MSI) test. Participants were 239 CRC patients at high familial risk for a genetic mutation who completed surveys before and after exposure to the intervention. Half of the sample was assigned to the CD-ROM aid and half received a brief description of the test. Structural equation modeling was employed to examine associations among the intervention, knowledge, pros and cons to having MSI testing, self-efficacy, preparedness, and decisional conflict. The goodness of fit for the model was acceptable [FIML, full information maximum likelihood, χ(2) (df = 280) = 392.24; P = 0.00]. As expected, the paths to decisional conflict were significant for postintervention pros of MSI testing (t = -2.43; P < 0.05), cons of MSI testing (t = 2.78; P < 0.05), and preparedness (t = -7.27; P < 0.01). The intervention impacted decisional conflict by increasing knowledge about the MSI test and knowledge exerted its effects on decisional conflict by increasing preparedness to make a decision about the test and by increases in perceived benefits of having the test. Increasing knowledge, preparedness, and perceived benefits of undergoing the MSI test facilitate informed decision making for this test. Understanding mechanisms underlying health decisions is critical for improving decisional support. Individuals with Lynch syndrome have an elevated lifetime risk of CRC. Risk of Lynch syndrome may be assessed with a tumor-based screening test (MSI testing or immunohistochemical tissue staining). ©2011 AACR.

Use of Genetic Testing for Primary Immunodeficiency Patients.

PubMed

Heimall, Jennifer R; Hagin, David; Hajjar, Joud; Henrickson, Sarah E; Hernandez-Trujillo, Hillary S; Tan, Yuval; Kobrynski, Lisa; Paris, Kenneth; Torgerson, Troy R; Verbsky, James W; Wasserman, Richard L; Hsieh, Elena W Y; Blessing, Jack J; Chou, Janet S; Lawrence, Monica G; Marsh, Rebecca A; Rosenzweig, Sergio D; Orange, Jordan S; Abraham, Roshini S

2018-04-01

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS's recommendations for the use of genetic testing in light of these issues.

Access to genetic testing and genetic counseling in vulnerable populations: the d/Deaf and hard of hearing population.

PubMed

Cooke-Hubley, Sandra; Maddalena, Victor

2011-09-01

Genetic testing holds great potential for preventing morbidities and mortalities for a number of diseases through early detection and effective intervention. As the number of genetic tests expand, so will public demand for these services. Therefore, it is essential to evaluate access to genetic testing and genetic services to ensure that all Canadians, including vulnerable groups, have equitable access to all forms of health care, in keeping with the mandate of the Canadian Health Act. The purpose of this paper is to examine the literature to determine if and how the Deaf community, as a vulnerable group, is at an increased risk of inequitable access to genetic services in Canada and to discuss how those who are deaf and hard of hearing are subject to the same risks. First, we define vulnerability and describe why the Deaf community, as a social group, can be considered a vulnerable group, followed by a description of the benefits of genetic testing. Second, we describe the barriers to accessing genetic testing, and how the d/Deaf and hard of hearing population experience additional barriers. Third, we examine the difficulties incorporating genetic testing into medical practice, and how this creates additional barriers to those already at risk. Finally, we discuss the steps necessary to promote equitable access to genetic testing among the d/Deaf and hard of hearing populations within Canada, and provide recommendations for further research in this topic area. Lastly, we comment on how barriers to genetic testing vary among the d/Deaf and hard of hearing is dependent upon the type of health care system available (whether public or private).

General practitioner attitudes to direct-to-consumer genetic testing in New Zealand.

PubMed

Ram, Sanyogita; Russell, Bruce; Gubb, Mary; Taylor, Rebekah; Butler, Cassandra; Khan, Imran; Shelling, Andrew

2012-10-26

The aim of the study was to explore the attitudes of general practitioners (GPs) towards direct to consumer (DTC) genetic testing and elicit their perceptions of the risks and benefits associated with DTC genetic testing. A postal questionnaire was mailed to a national random sample of 300 registered GPs from a list provided by the New Zealand Medical Council. Non-responders were followed up with an abridged survey questionnaire. Responses were received from 38% of the GPs contacted. This consisted of 113 responses from the full questionnaire. The proportion of respondents who had heard about DTC genetic testing was 47.8%. Respondents considered convenience to be the greatest benefit for the individual requesting DTC genetic testing. Misunderstanding of results and inadequate provision of information were perceived to be the greatest risks associated. Lack of knowledge, experience and time were all considered barriers to GPs providing genetic counselling, and a genetic specialist was highlighted as the most appropriate to provide this. Respondents thought advertising of DTC genetic testing should be regulated in a similar manner to DTC advertising of prescription medicines. Clinical validity of tests and counselling were thought to be the most important aspects to be regulated. As public access to DTC genetic testing increases, the role of GPs knowledge and training to reflect this growth will become increasingly more important. The 'Patient-Doctor-Counsellor Model of Delivery of Genetic Services' may be more appropriate for the provision of this service than the current model of direct access by patients. The involvement of health professionals in the DTC genetic testing process will aid patients in making informed health decisions, and ensure increased benefit from recent advances in genetic information.

Public Awareness of Direct-to-Consumer Genetic Tests: Findings from the 2013 U.S. Health Information National Trends Survey.

PubMed

Agurs-Collins, Tanya; Ferrer, Rebecca; Ottenbacher, Allison; Waters, Erika A; O'Connell, Mary E; Hamilton, Jada G

2015-12-01

Although the availability of direct-to-consumer (DTC) genetic testing has increased in recent years, the general public's awareness of this testing is not well understood. This study examined levels of public awareness of DTC genetic testing, sources of information about testing, and psychosocial factors associated with awareness of testing in the USA. Data were obtained from the nationally representative 2013 U.S. Health Information National Trends Survey. Guided by a social-cognitive conceptual framework, univariable and multivariable logistic regressions were conducted to identify factors associated with awareness of DTC genetic tests. Of 3185 participants, 35.6% were aware of DTC genetic tests, with the majority learning about these tests through radio, television, and the Internet. In the final adjusted model, participants with annual incomes of $99,999 or less had lower odds of being aware of DTC genetic testing (ORs ranging from 0.46-0.61) than did those participants with incomes of $100,000 or more. The odds of awareness of DTC genetic tests were significantly higher for those who actively seek cancer information (OR=1.91, 95% CI=1.36-2.69), use the Internet (OR=1.81, 95% CI=1.05-3.13), and have high numeracy skills (OR=1.67, 95% CI=1.17-2.38). It will be critical for healthcare researchers and practitioners to understand predictors and consequences of the public's awareness of DTC genetic tests, as well as how such awareness may translate into DTC genetic testing uptake, health behavior change, and ultimately disease prevention.

Genetics of Movement Disorders and the Practicing Clinician; Who and What to Test for?

PubMed

Di Fonzo, Alessio; Monfrini, Edoardo; Erro, Roberto

2018-05-23

This review aims to provide the basic knowledge on the genetics of hypokinetic and hyperkinetic movement disorders to guide clinicians in the decision of "who and what to test for?" In recent years, the identification of various genetic causes of hypokinetic and hyperkinetic movement disorders has had a great impact on a better definition of different clinical syndromes. Indeed, the advent of next-generation sequencing (NGS) techniques has provided an impressive step forward in the easy identification of genetic forms. However, this increased availability of genetic testing has challenges, including the ethical issue of genetic testing in unaffected family members, "commercially" available home testing kits and the increasing number and relevance of "variants of unknown significance." The emergent role of genetic factors has important implications on clinical practice and counseling. As a consequence, it is fundamental that practicing neurologists have a proper knowledge of the genetic background of the diseases and perform an accurate selection of who has to be tested and for which gene mutations.

BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.

PubMed

Hall, Michael J; Reid, Julia E; Burbidge, Lynn A; Pruss, Dmitry; Deffenbaugh, Amie M; Frye, Cynthia; Wenstrup, Richard J; Ward, Brian E; Scholl, Thomas A; Noll, Walter W

2009-05-15

In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high-risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease-associated) mutations in non-white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing. In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing. From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non-European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1-1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1-1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non-European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%-->5.9%), and women of African ancestry experienced the largest decline (58%). Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women.

The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru

PubMed Central

Robinson, Colin L; Baumann, Lauren M; Gilman, Robert H; Romero, Karina; Combe, Juan Manuel; Cabrera, Lilia; Hansel, Nadia N; Barnes, Kathleen; Gonzalvez, Guillermo; Wise, Robert A; Breysse, Patrick N

2012-01-01

Objectives According to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation. Design A cross-sectional study. Participants Using census data of 13–15-year-old adolescents from two communities in Peru, the authors invited a random sample of participants in Lima (n=725) and all adolescents in Tumbes (n=716) to participate in our study. Primary and secondary outcome measures The authors asked participants to complete a questionnaire on asthma symptoms, environmental exposures and socio-demographics and to undergo spirometry before and after bronchodilator, skin allergy testing and exhaled nitric oxide testing. The authors obtained blood samples for haematocrit, total IgE levels, vitamin D levels and DNA in all participants and measured indoor particulate matter concentrations for 48 h in a random subset of 70–100 households at each site. Results Of 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of enrolled) completed all physical tests. 1283 (89%) performed spirometry according to standard guidelines, of which 86% of prebronchodilator tests and 92% of postbronchodilator tests were acceptable and reproducible. 92% of allergy skin tests had an adequate negative control. The authors collected blood from 1146 participants (79%) and saliva samples from 148 participants (9%). Overall amounts of DNA obtained from blood or saliva were 25.8 μg, with a 260/280 ratio of 1.86. Conclusions This study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study. PMID:22357570

Psychosocial and Clinical Factors Associated with Family Communication of Cancer Genetic Test Results among Women Diagnosed with Breast Cancer at a Young Age.

PubMed

Elrick, Ashley; Ashida, Sato; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara B; Goodman, Melody S; Kaphingst, Kimberly A

2017-02-01

Genetic test results have medical implications beyond the patient that extend to biological family members. We examined psychosocial and clinical factors associated with communication of genetic test results within families. Women (N = 1080) diagnosed with breast cancer at age 40 or younger completed an online survey; 920 women that reported prior cancer genetic testing were included in analysis. We examined the proportion of immediate family members to whom they communicated genetic test results, and built multivariable regression models to examine clinical and psychosocial variables associated with the proportion score. Participants were most likely to communicate test results to their mother (83 %) and least likely to their son (45 %). Participants who carried a BRCA mutation (OR = 1.34; 95 % CI = 1.06, 1.70), had higher interest in genomic information (OR = 1.55; 95 % CI = 1.26, 1.91) and lower genetic worry (OR = 0.91; 95 % CI = 0.86, 0.96) communicated genetic test results to a greater proportion of their immediate family members. Participants with a BRCA1/2 mutation shared their genetic test results with more male family members (OR = 1.72; 95 % CI = 1.02, 2.89). Our findings suggest that patients with high worry about genetic risks, low interest in genomic information, or receive a negative genetic test result will likely need additional support to encourage family communication.

Critical overview of applications of genetic testing in sport talent identification.

PubMed

Roth, Stephen M

2012-12-01

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).

Genetic testing in asymptomatic minors Background considerations towards ESHG Recommendations

PubMed Central

Borry, Pascal; Evers-Kiebooms, Gerry; Cornel, Martina C; Clarke, Angus; Dierickx, Kris

2009-01-01

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 background document in preparation of the development of the policy recommendations of the Public and Professional Committee of the European Society of Human Genetics. This background paper first discusses some general considerations with regard to the provision of genetic tests to minors. It discusses the concept of best interests, participation of minors in health-care decisions, parents' responsibilities to share genetic information, the role of clinical genetics and the health-care system in communication within the family. Second, it discusses, respectively, the presymptomatic and predictive genetic testing for adult-onset disorders, childhood-onset disorders and carrier testing. PMID:19277061

Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

PubMed

McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

2014-09-01

Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations.

Anticipating the Ethical Challenges of Psychiatric Genetic Testing.

PubMed

Appelbaum, Paul S; Benston, Shawna

2017-07-01

Genetic testing for mental illness is likely to become increasingly prevalent as the science behind it is refined. This article identifies anticipated ethical challenges for patients, psychiatrists, and genetic counselors and makes recommendations for addressing them. Many of the ethical challenges of psychiatric genetic testing are likely to stem from failures to comprehend the nature and implications of test results. Recent studies have identified gaps in the knowledge base of psychiatrists and genetic counselors, which limit their abilities to provide patients with appropriate education. A small number of studies have demonstrated the value of counseling in empowering patients to deal with relevant genetic information. Psychiatrists and other health professionals must be able to assist patients and families in making informed decisions about genetic testing and interpreting test results. Filling their knowledge gaps on these issues will be a critical step towards meeting these responsibilities.

Individual and family characteristics associated with BRCA1/2 genetic testing in high-risk families.

PubMed

Katapodi, Maria C; Northouse, Laurel L; Milliron, Kara J; Liu, Guipeng; Merajver, Sofia D

2013-06-01

Little is known about family members' interrelated decisions to seek genetic testing for breast cancer susceptibility. The specific aims of this cross-sectional, descriptive, cohort study were (i) to examine whether individual and family characteristics have a direct effect on women's decisions to use genetic testing for hereditary susceptibility to breast cancer and (ii) to explore whether family characteristics moderate the relationships between individual characteristics and the decision to use genetic testing. Participants were women (>18 years old) who (i) received genetic testing for hereditary breast cancer and who agreed to invite one of their female relatives into the study and (ii) female relatives who had NOT obtained genetic testing and were identified by pedigree analysis as having >10% chances of hereditary susceptibility to breast cancer. The final sample consisted of 168 English-speaking, family dyads who completed self-administered, mailed surveys with validated instruments. Multivariate conditional logistic regression analyses showed that the proposed model explained 62% of the variance in genetic testing. The factors most significantly associated with genetic testing were having a personal history of cancer; perceiving genetic testing to have more benefits than barriers; having greater family hardiness; and perceiving fewer negative consequences associated with a breast cancer diagnosis. No significant interaction effects were observed. Findings suggest that both individual and family characteristics are associated with the decision to obtain genetic testing for hereditary breast cancer; hence, there is a need for interventions that foster a supportive family environment for patients and their high-risk relatives. Copyright © 2012 John Wiley & Sons, Ltd.

The cost of genetic testing for ocular disease: who pays?

PubMed

Capasso, Jenina E

2014-09-01

To facilitate ophthalmologists' understanding on the cost of genetic testing in ocular disease, the complexities of insurance coverage and its impact on the availability of testing. Many insurance carriers address coverage for genetic testing in written clinical policies. They provide criteria for medically necessary testing. These policies mostly cover testing for individuals who are symptomatic and in whom testing will have a direct impact on medical treatment. In cases in which no treatments are currently available, other than research trials, patients may have difficulty in getting insurance coverage for genetic testing. Genetic testing for inherited eye diseases can be costly but has many benefits to patient care, including confirmation of a diagnosis, insight into prognostic information, and identification of associated health risks, inheritance patterns, and possible current and future treatments. As gene therapy advances progress, the availability for treatment in ocular diseases, coverage for genetic testing by third-party payers could increase on the basis of current clinical policies.

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c.

PubMed

Rudland, Victoria L; Hinchcliffe, Marcus; Pinner, Jason; Cole, Stuart; Mercorella, Belinda; Molyneaux, Lynda; Constantino, Maria; Yue, Dennis K; Ross, Glynis P; Wong, Jencia

2016-01-01

Glucokinase monogenic diabetes (GCK-maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5-1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Clinical applications of preimplantation genetic testing.

PubMed

Brezina, Paul R; Kutteh, William H

2015-02-19

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.

Feline Genetics: Clinical Applications and Genetic Testing

PubMed Central

Lyons, Leslie A.

2010-01-01

DNA testing for domestic cat diseases and appearance traits is a rapidly growing asset for veterinary medicine. Approximately thirty-three genes contain fifty 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 using 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. PMID:21147473

Feline genetics: clinical applications and genetic testing.

PubMed

Lyons, Leslie A

2010-11-01

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.

A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

PubMed

Yotsumoto, Junko; Sekizawa, Akihiko; Suzumori, Nobuhiro; Yamada, Takahiro; Samura, Osamu; Nishiyama, Miyuki; Miura, Kiyonori; Sawai, Hideaki; Murotsuki, Jun; Kitagawa, Michihiro; Kamei, Yoshimasa; Masuzaki, Hideaki; Hirahara, Fumiki; Endo, Toshiaki; Fukushima, Akimune; Namba, Akira; Osada, Hisao; Kasai, Yasuyo; Watanabe, Atsushi; Katagiri, Yukiko; Takeshita, Naoki; Ogawa, Masaki; Okai, Takashi; Izumi, Shunichiro; Hamanoue, Haruka; Inuzuka, Mayuko; Haino, Kazufumi; Hamajima, Naoki; Nishizawa, Haruki; Okamoto, Yoko; Nakamura, Hiroaki; Kanegawa, Takeshi; Yoshimatsu, Jun; Tairaku, Shinya; Naruse, Katsuhiko; Masuyama, Hisashi; Hyodo, Maki; Kaji, Takashi; Maeda, Kazuhisa; Matsubara, Keiichi; Ogawa, Masanobu; Yoshizato, Toshiyuki; Ohba, Takashi; Kawano, Yukie; Sago, Haruhiko

2016-12-01

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

PubMed Central

2013-01-01

Background Colorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening. Methods/Design A total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC. Discussion This study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC. Trial registration ClinicalTrials.gov Identifier: NCT01651624. PMID:23497601

What Is Carrier Screening?

MedlinePlus

... Financial Planning Who Should I Tell? Genetic Testing & Counseling Compensation for Genetic Testing Whole Genome Sequencing Screening vs. Testing What Is Genetic Counseling? Participating in Research Disease Research Patient Privacy Clinical ...

Genetic Testing in a Drama and Discussion Workshop: Exploring Knowledge Construction

ERIC Educational Resources Information Center

Dawson, Emily; Hill, Anne; Barlow, John; Weitkamp, Emma

2009-01-01

In this pilot project, drama was used to situate genetic testing in a social and cultural context--that of the family. The drama was used to stimulate discussion about social issues relating to genetic testing, such as who has the right to know the results of the test and whether participants would want to know their "genetic future". A…

High-Risk Palliative Care Patients' Knowledge and Attitudes about Hereditary Cancer Testing and DNA Banking.

PubMed

Quillin, John M; Emidio, Oluwabunmi; Ma, Brittany; Bailey, Lauryn; Smith, Thomas J; Kang, In Guk; Yu, Brandon J; Owodunni, Oluwafemi Patrick; Abusamaan, Mohammed; Razzak, Rab; Bodurtha, Joann N

2017-12-04

Even at the end of life, testing cancer patients for inherited susceptibility may provide life-saving information to their relatives. Prior research suggests palliative care inpatients have suboptimal understanding of genetic importance, and testing may be underutilized in this clinical setting. These conclusions are based on limited research. This study aimed to estimate genetic testing prevalence among high-risk palliative care patients in a National Cancer Institute-designated comprehensive cancer center. We also aimed to understand these patients' understanding of, and attitudes toward, hereditary cancer testing and DNA banking. Palliative care in-patients with cancer completed structured interviews, and their medical records were reviewed. Among patients at high risk for hereditary cancer, we assessed history of genetic testing/DNA banking; and related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said they/their relatives had genetic testing or they had been referred for a genetics consultation. Of the remaining 10 patients, seven (70%) said they would "probably" or "definitely" get tested. Patients who had not had testing were least concerned about the impact of future testing on their family relationships; two (20%) said they were "extremely concerned" about privacy related to genetic testing. Of patients without prior testing, five (50%) said they had heard or read "a fair amount" about genetic testing. No high-risk patients had banked DNA. Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively little" about DNA banking. Written materials and clinician discussion were most preferred ways to learn about genetic testing and DNA banking. Overall, this study demonstrates underutilization of genetics services at the end of life continues to be problematic, despite high patient interest.

You're a What? Genetic Counselor

ERIC Educational Resources Information Center

Mullins, John

2011-01-01

When it first emerged about 50 years ago, genetic counseling focused primarily on prenatal testing to detect genetic conditions. But counseling services have evolved to keep pace with a greater knowledge of genetics and wider application of genetic diagnostic testing. Today, there are several types of genetic counselors, and their expertise covers…

Genetic Counseling

MedlinePlus

... Testing Evaluating Genomic Tests Epidemiology Pathogen Genomics Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

Genetics and Personal Insurance: the Perspectives of Canadian Cancer Genetic Counselors.

PubMed

Lane, Michelle; Ngueng Feze, Ida; Joly, Yann

2015-12-01

Genetic discrimination in the context of genetic testing has been identified as a concern for symptomatic and asymptomatic individuals for more than three decades. Genetic counselors are often the health care professionals who discuss risks and benefits of genetic testing with patients, thereby making them most appropriate to address patient concerns about genetics and personal insurance (i.e., life, life as related to mortgage or group insurance, disability, critical illness and travel). A pilot study was conducted to ascertain the current practices of Canadian cancer genetic counselors in regard to their discussions with patients about genetic testing and access to personal insurance. Among the 36 counselors surveyed, 100 % reported discussing the issue of genetic testing and personal insurance with their patients. Several factors influenced the content, depth and length of these discussions including age, cancer status, family members, and patients' current and future insurance needs. Counselors reported discussing with patients the possible impact of genetic test results on access to personal insurance, possible access and use of patient genetic information by insurance companies, and whom patients should contact if they have additional questions. The most commonly reported inquiries from patients included questions about the possible impact of genetic testing on their ability to obtain insurance, and the insurability of family members. While 28 % of counselors reported having been contacted by an insurer requesting access to patient information, only one counselor was aware of or could recall the outcome of such a request. This pilot study revealed that issues concerning genetics and personal insurance are commonly discussed in Canadian cancer genetic counseling sessions. Counselors furthermore expressed a need for additional educational resources on the topic of genetics and personal insurance for themselves and their patients.

'Battling my biology': psychological effects of genetic testing for risk of weight gain.

PubMed

Meisel, S F; Wardle, J

2014-04-01

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.

Institute of forest tree breeding: Improvement and gene conservation of iconic tree species in the 21st Century

Treesearch

C. Dana Nelson; Jennifer L. Koch

2017-01-01

Our nation’s forests and forest trees are undergoing unprecedented stress from invasive pathogens and pests, climate change, land fragmentation, and urbanization. Some of these stresses are acute, either regionally or locally, and are having significant negative impacts on regional and local economies and ecosystems. Managing and improving the genetic resources of...

[Leber hereditary optic neuropathy].

PubMed

Mazunin, I O; Volodko, N V

2018-01-01

Leber hereditary optic neuropathy is characterized by bilateral, painless loss of vision in children and young adults (generally up to 25 years old). Since its first description in 1871, the understanding of its etiology and pathogenesis has improved considerably. The article considers Leber neuropathy from the points of view of ophthalmology, neurology and molecular genetics, and presents data on experimental treatment methods, one of which is undergoing clinical trial.

Confronting Science: The Dilemma of Genetic Testing.

ERIC Educational Resources Information Center

Zallen, Doris T.

1997-01-01

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)

"Would you test your children without their consent?" and other sticky dilemmas in the field of cancer genetic testing.

PubMed

Brierley, Karina L; Bonadies, Danielle C; Moyer, Anne; Matloff, Ellen T

2014-09-01

Cancer genetic testing is surrounded by myriad ethical, legal, and psychosocial implications which are being revisited as testing expands into an everyday practice and into more complicated areas like whole exome and direct-to-consumer testing. We chose to survey cancer genetic counselors and physicians from a wide range of non-genetics specialties to determine what they would do if faced with the complex decisions associated with cancer genetic testing, how their views compare, and how they align with current guidelines and data. Genetic counselors were significantly more likely than non-genetics physicians to bill their insurance for testing (94.9 vs. 86.8 %; p = 0.001) and purchase life insurance before testing (86.6 vs. 68.6 %; p = 0.000) and were less likely to use an alias (3.2 vs. 13.2 %; p = 0.000) or order testing on their own DNA (15.3 vs. 24.2 %; p = 0.004). They were also less likely to test their minor children (0.9 vs. 33.1 %; p = 0.000) or test their children without their knowledge and consent/assent (1.4 vs.11.5 %; p = 0.000). The results of our study indicate that there is wide variation regarding what clinicians predict they would do in the areas of ethical, legal and psychosocial issues in cancer genetic testing. Cancer genetic counselors' choices are more aligned with professional guidelines, likely due to their experience in the field and awareness of current guidelines. These data are a starting point for a broader discussion of who should offer cancer genetic counseling and testing to patients, particularly as the complexity of the available testing options and associated issues increase with whole exome sequencing.

Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

PubMed

Christian, Susan; Atallah, Joseph; Clegg, Robin; Giuffre, Michael; Huculak, Cathleen; Dzwiniel, Tara; Parboosingh, Jillian; Taylor, Sherryl; Somerville, Martin

2018-02-01

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

Learning Cue Phrase Patterns from Radiology Reports Using a Genetic Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patton, Robert M; Beckerman, Barbara G; Potok, Thomas E

2009-01-01

Various computer-assisted technologies have been developed to assist radiologists in detecting cancer; however, the algorithms still lack high degrees of sensitivity and specificity, and must undergo machine learning against a training set with known pathologies in order to further refine the algorithms with higher validity of truth. This work describes an approach to learning cue phrase patterns in radiology reports that utilizes a genetic algorithm (GA) as the learning method. The approach described here successfully learned cue phrase patterns for two distinct classes of radiology reports. These patterns can then be used as a basis for automatically categorizing, clustering, ormore » retrieving relevant data for the user.« less

Valuing the benefits of genetic testing for retinitis pigmentosa: a pilot application of the contingent valuation method.

PubMed

Eden, Martin; Payne, Katherine; Combs, Ryan M; Hall, Georgina; McAllister, Marion; Black, Graeme C M

2013-08-01

Technological advances present an opportunity for more people with, or at risk of, developing retinitis pigmentosa (RP) to be offered genetic testing. Valuation of these tests using current evaluative frameworks is problematic since benefits may be derived from diagnostic information rather than improvements in health. This pilot study aimed to explore if contingent valuation method (CVM) can be used to value the benefits of genetic testing for RP. CVM was used to elicit willingness-to-pay (WTP) values for (1) genetic counselling and (2) genetic counselling with genetic testing. Telephone and face-to-face interviews with a purposive sample of individuals with (n=25), and without (n=27), prior experience of RP were used to explore the feasibility and validity of CVM in this context. Faced with a hypothetical scenario, the majority of participants stated that they would seek genetic counselling and testing in the context of RP. Between participant groups, respondents offered similar justifications for stated WTP values. Overall stated WTP was higher for genetic counselling plus testing (median=£524.00) compared with counselling alone (median=£224.50). Between-group differences in stated WTP were statistically significant; participants with prior knowledge of the condition were willing to pay more for genetic ophthalmology services. Participants were able to attach a monetary value to the perceived potential benefit that genetic testing offered regardless of prior experience of the condition. This exploratory work represents an important step towards evaluating these services using formal cost-benefit analysis.

Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study.

PubMed

Erim, Yesim; Scheel, Jennifer; Breidenstein, Anja; Metz, Claudia Hd; Lohmann, Dietmar; Friederich, Hans-Christoph; Tagay, Sefik

2016-07-07

Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking. The aim of the current study is therefore to investigate the psychosocial impact (psychological distress and quality of life) of prognostic genetic testing in patients with uveal melanoma. This study is a non-randomized controlled prospective clinical observational trial. Subjects are patients with uveal melanoma, in whom genetic testing is possible. Patients who consent to genetic testing are allocated to the intervention group and patients who refuse genetic testing form the observational group. Both groups receive cancer therapy and psycho-oncological intervention when needed. The psychosocial impact of prognostic testing is investigated with the following variables: resilience, social support, fear of tumor progression, depression, general distress, cancer-specific and general health-related quality of life, attitude towards genetic testing, estimation of the perceived risk of metastasis, utilization and satisfaction with psycho-oncological crisis intervention, and sociodemographic data. Data are assessed preoperatively (at initial admission in the clinic) and postoperatively (at discharge from hospital after surgery, 6-12 weeks, 6 and 12 months after initial admission). Genetic test results are communicated 6-12 weeks after initial admission to the clinic. We created optimal conditions for investigation of the psychosocial impact of prognostic genetic testing. This study will provide information on the course of disease and psychosocial outcomes after prognostic genetic testing. We expect that empirical data from our study will give a scientific basis for medico-ethical considerations.

Genetic counseling in monogenic diabetes GCK MODY.

PubMed

Skała-Zamorowska, Eliza; Deja, Grażyna; Borowiec, Maciej; Fendler, Wojciech; Małachowska, Beata; Kamińska, Halla; Młynarski, Wojciech; Jarosz-Chobot, Przemysława

2016-01-01

Genetic testing in families with monogenic GCK MODY has predictive, diagnostic, and preventive utility. Predictive tests relate to people who have no features of the disorder themselves at the time of testing. Diagnostic tests relate to family members who have been previously diagnosed with diabetes mellitus or glucose metabolism disturbances. The preventive value of genetic testing for families is to raise awareness of the circumstances leading to glucose metabolism disorders. The detection of mutation carriers among family members of patients with GCK MODY and the determination of the clinical significance of the genetic test result. The study group included 27 families of adolescent patients with GCK MODY (39 (75%) of parents and 19 (73.08%) of siblings) monitored in the Department of Pediatrics, Endocrinology and Diabetes and in the Diabetes Clinic of John Paul II Upper Silesian Child Health Centre in Katowice in the years 2007-2012. Subjects underwent a blood sample drawing for genetic and biochemical testing. Through the genetic diagnostics we diagnosed GCK MODY in 14 (63.64%) mothers, 6 (35.29%) fathers and in 7 (36,84%) siblings. Genetic testing has contributed to the detection of 7 (26.92%) asymptomatic carriers of GCK gene mutation among parents and 3 (15,79%) asymptomatic carriers among siblings declaring no carbohydrate metabolism disturbances (before genetic testing there were no indications suggesting carbohydrate metabolism disturbances; OGTT were performed after positive genetic testing). Each case of mutation detection, which is the cause of monogenic diabetes in a patient, justifies the genetic testing in other members of his/her family. Awareness of the genetic status may allow sick family member to confirm the diagnosis, while asymptomatic mutation carriers could benefit from an early clinical observation. Consequently, in each case it gives an opportunity to take diagnostic and therapeutic measures in accordance with the current state of knowledge. © Polish Society for Pediatric Endocrinology and Diabetology.

Genetic testing in cardiovascular diseases.

PubMed

Arndt, Anne-Karin; MacRae, Calum A

2014-05-01

The review is designed to outline the major developments in genetic testing in the cardiovascular arena in the past year or so. This is an exciting time in genetic testing as whole exome and whole genome approaches finally reach the clinic. These new approaches offer insight into disease causation in families in which this might previously have been inaccessible, and also bring a wide range of interpretative challenges. Among the most significant recent findings has been the extent of physiologic rare coding variation in the human genome. New disease genes have been identified through whole exome studies in neonatal arrhythmia, congenital heart disease and coronary artery disease that were simply inaccessible with other techniques. This has not only shed light on the challenges of genetic testing at this scale, but has also sharply defined the limits of prior gene-panel focused testing. As novel therapies targeting specific genetic subsets of disease become available, genetic testing will become a part of routine clinical care. The pace of change in sequencing technologies has begun to transform clinical medicine, and cardiovascular disease is no exception. The complexity of such studies emphasizes the importance of real-time communication between the genetics laboratory and genetically informed clinicians. New efforts in data and knowledge management will be central to the continued advancement of genetic testing.

Perceptions and understanding of genetics and genetic eye disease and attitudes to genetic testing and gene therapy in a primary eye care setting.

PubMed

Ganne, Pratyusha; Garrioch, Robert; Votruba, Marcela

2015-03-01

Genetic eye pathology represents a significant percentage of the causes of blindness in industrialized countries. This study explores the level of understanding and perceptions of genetics and inherited eye diseases and the attitudes to genetic testing and gene therapy. The study was conducted in two parts. Participant groups included were: undergraduate students of optometry, primary eye care professionals and members of the general public. A preliminary study aimed to understand perceptions and to explore the level of knowledge about genetics in general, eye genetics and gene therapy. A second survey was designed to explore attitudes to genetic testing and gene therapy. The majority of participants (82%) perceived genetics as an important science. However, none of them showed a high level of understanding of genetics and inherited eye diseases. Undergraduate students and primary eye care professionals were better informed about inherited eye diseases than the general public (p = 0.001). The majority (80%) across all three groups had a positive attitude to genetic testing and gene therapy. There was a lack of knowledge about the genetic services available among all groups of participants. This calls for serious thinking about the level of dissemination of information about genetics and inherited eye diseases. It shows a broadly supportive attitude to genomic medicine among the public. Improving public awareness and education in inherited eye diseases can improve the utility of genetic testing and therapy.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Experience, knowledge, and opinions about childhood genetic testing in Batten disease.

PubMed

Adams, Heather R; Rose, Katherine; Augustine, Erika F; Kwon, Jennifer M; deBlieck, Elisabeth A; Marshall, Frederick J; Vierhile, Amy; Mink, Jonathan W; Nance, Martha A

2014-02-01

Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents' perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease - a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children. Copyright © 2013 Elsevier Inc. All rights reserved.

Ethics, policy, and educational issues in genetic testing.

PubMed

Williams, Janet K; Skirton, Heather; Masny, Agnes

2006-01-01

Analyze ethics, public policy, and education issues that arise in the United States (US) and the United Kingdom (UK) when genomic information acquired as a result of genetic testing is introduced into healthcare services. Priorities in the Ethical, Legal, and Social Issues Research Program include privacy, integration of genetic services into clinical health care, and educational preparation of the nursing workforce. These constructs are used to examine health policies in the US and UK, and professional interactions of individuals and families with healthcare providers. Individual, family, and societal goals may conflict with current healthcare practices and policies when genetic testing is done. Current health policies do not fully address these concerns. Unresolved issues include protection of privacy of individuals while considering genetic information needs of family members, determination of appropriate monitoring of genetic tests, addressing genetic healthcare discrepancies, and assuring appropriate nursing workforce preparation. Introduction of genetic testing into health care requires that providers are knowledgeable regarding ethical, policy, and practice issues in order to minimize risk for harm, protect the rights of individuals and families, and consider societal context in the management of genetic test results. Understanding of these issues is a component of genetic nursing competency that must be addressed at all levels of nursing education.

Bio science: genetic genealogy testing and the pursuit of African ancestry.

PubMed

Nelson, Alondra

2008-10-01

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.

Parental narratives about genetic testing for hearing loss: a one year follow up study.

PubMed

Kaimal, Girija; Steinberg, Annie G; Ennis, Sara; Harasink, Sue Moyer; Ewing, Rachel; Li, Yuelin

2007-12-01

Few studies examine whether and how parental attitudes towards genetic testing change over time. In this study we interviewed parents of 14 children with newly identified hearing loss at two time points: after referral to genetics and 1 year later. Qualitative analyses of parental narratives indicate that parental attitudes did not change significantly over this time. Parents who perceived genetic testing to be useful continued to value it after testing, while parents who did not perceive it as being useful for their child's future held the same view a year later. The only parents who changed their views regarding the usefulness of genetic testing for hearing loss were those who reported that their children underwent significant changes in their hearing loss or were faced with other life threatening conditions. Parents were also often unaware of the role of the genetic counselor and how genetic counseling could help address many of their lingering questions and concerns. These emergent themes indicate the need for geneticists and genetic counselors to be aware of and sensitized to the questions and attitudes that bring parents to a genetic evaluation, as well as the reasons why parents may not follow up with genetic testing for hearing loss when recommended.

Genetic privacy.

PubMed

Sankar, Pamela

2003-01-01

During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.

Genetics Home Reference: myasthenia gravis

MedlinePlus

... ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (2 links) Genetic Testing Registry: ...