Beyond Genetics in Mental Rotation Test Performance: The Power of Effort Attribution

ERIC Educational Resources Information Center

Moe, Angelica; Pazzaglia, Francesca

2010-01-01

This study compares the effects on Mental Rotation Test (MRT) performance of instructions that stress the importance of (a) personal effort, and (b) genetically driven ability. A total of 120 high-school students were assigned to three groups, and administered two sub-tests of the MRT. Between the first and second sub-tests, the groups received…

How Is Wilson Disease Inherited?

MedlinePlus

... ATP7B gene have been identified thus far. Testing Methods Available Linkage analysis (Haplotype analysis) Molecular genetic testing ... genetic counselor who can carefully discuss the best method of testing to perform and the benefits, limitations, ...

Genetic Testing for Hereditary Cancer Syndromes

MedlinePlus

... cancers A positive result on a prenatal genetic test for cancer risk may influence a decision about whether to continue a pregnancy. The results of pre-implantation testing (performed on embryos created by in ...

[Genetic predisposition to breast and ovarian cancer: importance of test results].

PubMed

Julian-Reynier, Claire

2011-01-01

Oncogenetic consultations and predictive BRCA1/2 testing are intertwined processes and the specific impact of these genetic tests if performed alone through direct-to-consumer offers remains unknown. Noteworthy, the expectations of patients vary with their own status, whether they are affected or not by breast cancer at the time genetic testing is performed. The prescription of genetic tests for BCRA mutations has doubled in France between 2003 and 2009. There is a consensus on the fact that genetic results disclosure led to a significant increase in the knowledge and understanding that the patients have of the genetic risk and also changed the medical follow-up of these patients. Evaluating the psychological burden of tests disclosure did not reveal any major distress in patients who are followed by high-quality multidisciplinary teams. Longitudinal cohorts studies have now evaluated the perception and behaviour of these patients, and observed sociodemographic as well as geographic and psychosocial differences both in the acceptation of prophylactic strategies such as surgery, and time to surgery. © 2011 médecine/sciences - Inserm / SRMS.

Against Genetic Tests for Athletic Talent: The Primacy of the Phenotype.

PubMed

Loland, Sigmund

2015-09-01

New insights into the genetics of sport performance lead to new areas of application. One area is the use of genetic tests to identify athletic talent. Athletic performances involve a high number of complex phenotypical traits. Based on the ACCE model (review of Analytic and Clinical validity, Clinical utility, and Ethical, legal and social implications), a critique is offered of the lack of validity and predictive power of genetic tests for talent. Based on the ideal of children's right to an open future, a moral argument is given against such tests on children and young athletes. A possible role of genetic tests in sport is proposed in terms of identifying predisposition for injury. In meeting ACCE requirements, such tests could improve individualised injury prevention and increase athlete health. More generally, limitations of science are discussed in the identification of talent and in the understanding of complex human performance phenotypes. An alternative approach to talent identification is proposed in terms of ethically sensitive, systematic and evidence-based holistic observation over time of relevant phenotypical traits by experienced observers. Talent identification in sport should be based on the primacy of the phenotype.

[Genetic diseases:recent scientific findings and health and ethical problems].

PubMed

Taruscio, D; D'Agnolo, G

1999-01-01

Genetic diseases are very numerous, even though rare as single conditions: therefore, overall they represent a significant portion of morbidity at population level. The improvement of molecular genetic techniques has brought a great increase in the diagnostic potential toward genetic diseases, concerning either symptomatic or pre-symptomatic individuals and healthy carriers. However, this has frequently unforeseen consequences, such as a discrepancy between diagnostic and therapeutic potentials. Moreover, the development of genetic tests has raised a number of questions regarding ethical, legal e social problems. The Italian guidelines for genetic tests (available on the Internet site of Istituto Superiore di Sanità: http:@www.iss.it) have been elaborated in 1998 to define general principles for performing and managing genetic tests as well as for programming and promoting genetic testing within the public health system. In accordance with recommendations by international bodies (WHO, EU), the Guidelines give emphasis to the appropriate use of both safe and efficacious tests, the performance in laboratories with high quality standards. A further crucial point is the relationship between the health system and individuals: authonomy of decision, psychological and social assistance, as well as adequate attention to ethical and privacy problems should be guaranteed.

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.

Ethics of genetic testing and research in sport: a position statement from the Australian Institute of Sport.

PubMed

Vlahovich, Nicole; Fricker, Peter A; Brown, Matthew A; Hughes, David

2017-01-01

As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

"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.

Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

PubMed

Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

2016-08-01

Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

[Genetic-statistical analysis of environmental and genetic influences on the outcome of the juvenile and breeding performance tests for behaviour traits in Hovawart dogs].

PubMed

Boenigk, Katharina; Hamann, Henning; Distl, Ottmar

2006-01-01

The objective of the present study was to evaluate the importance of genetic and environmental sources of variation for results of behaviour tests recorded at juvenile and breeding performance tests in the Hovawart dog. For these analyses behaviour test results of 1882 (juvenile evaluation), respectively 929 dogs (breeding performance test) born in 1995 to 2000 had been used. Variance component estimation was performed for the traits appearance, play instinct, hunting affinity, group of people, shoot, acoustical and optical influences and temperament using multivariate linear animal models and Residual Maximum Likelihood (REML). The models included test-year-season, sex, litter size, age and inbreeding coefficient of the animal as fixed effects. Additive genetic effects of the animal, permanent environmental effect of the litter and the effect of the kennel were considered as random factors. The sex of the dog was significant for appearance, play instinct, hunting affinity, acoustical and optical influences of juvenile evaluation and for the traits temperament, play instinct, hunting affinity, acoustical and one of the optical influences of breeding performance test. The age of the dog at test significantly influenced the traits play instinct, hunting affinity and acoustical influences of juvenile evaluation and optical influences and hunting affinity of breeding performance test. All traits with exception of hunting affinity and group of people were significantly affected by the test-year-season. The inbreeding coefficient was significant for appearance of juvenile evaluation and play affinity of breeding performance test. The effect litter size did not influence any of the traits significantly. The estimated heritabilities for the behaviour traits of juvenile and breeding performance test ranged from h2 = 0.01 to h2 = 0.13, respectively h2 = 0.01 to h2 = 0.14, with standard errors of up to 0.03. The additive genetic correlations between most of the traits were moderately to highly positive (r(g) = 0.20 to r(g) = 1.0, respectively r(g) = 0.29 to r(g) = 1.0). Negative additive genetic correlations were only found for a few traits of juvenile (r(g) = -0.02 to r(g) = -0.58) and breeding performance test (r(g) = -0.28 to r(g) = -0.83). Progress in breeding for the behaviour traits investigated here may only be meaningful when information from all relatives is used in an animal model instead of selection based on the phenotype of the single animal.

Genetic privacy in sports: clearing the hurdles.

PubMed

Callier, Shawneequa

2012-12-01

As genomic medicine continues to advance and inform clinical care, knowledge gained is likely to influence sports medicine and training practices. Susceptibility to injury, sudden cardiac failure, and other serious conditions may one day be tackled on a subclinical level through genetic testing programs. In addition, athletes may increasingly consider using genetic testing services to maximize their performance potential. This paper assesses the role of privacy and genetic discrimination laws that would apply to athletes who engage in genetic testing and the limits of these protections.

Test anxiety and a high-stakes standardized reading comprehension test: A behavioral genetics perspective.

PubMed

Wood, Sarah G; Hart, Sara A; Little, Callie W; Phillips, Beth M

2016-07-01

Past research suggests that reading comprehension test performance does not rely solely on targeted cognitive processes such as word reading, but also on other non-target aspects such as test anxiety. Using a genetically sensitive design, we sought to understand the genetic and environmental etiology of the association between test anxiety and reading comprehension as measured by a high-stakes test. Mirroring the behavioral literature of test anxiety, three different dimensions of test anxiety were examined in relation to reading comprehension, namely intrusive thoughts, autonomic reactions, and off-task behaviors. Participants included 426 sets of twins from the Florida Twin Project on Reading. The results indicated test anxiety was negatively associated with reading comprehension test performance, specifically through common shared environmental influences. The significant contribution of test anxiety to reading comprehension on a high-stakes test supports the notion that non-targeted factors may be interfering with accurately assessing students' reading abilities.

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.

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement

PubMed Central

Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

2015-01-01

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. PMID:26582191

[Study on tests of genetics experiments in universities].

PubMed

Jie, He; Hao, Zhang; Lili, Zhang

2015-03-01

Based on the present situation and the development of experiment tests in universities, we introduced a reform in tests of genetics experiments. According to the teaching goals and course contents of genetics experiment, the tests of genetics experiments contain four aspects on the performance of students: the adherence to the experimental procedures, the depth of participation in experiment, the quality of experiment report, and the mastery of experiment principles and skills, which account for 10 %, 20 %, 40 % and 30 % in the total scores, respectively. All four aspects were graded quantitatively. This evaluation system has been tested in our experiment teaching. The results suggest that it has an effect on the promotion of teaching in genetics experiments.

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

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.

Prospects and problems of direct-to-public genetic tests.

PubMed

Tracy, Erin E

2008-09-01

Direct-to-consumer advertising of genetic tests is prevalent, poorly regulated and fraught with potential negative public-health ramifications. While some genetic tests are available through means that safeguard patient understanding of the implications of having genetic tests performed, others are available to anyone who has a credit card, without any individualized counseling, assessment of whether such tests are indicated, or interpretation of test results. While the US FDA, the Centers for Medicare and Medicaid Services and the Federal Trade Commission all have a regulatory role, most experts agree that the industry is not adequately being reigned in to best protect the public it serves.

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.

Genetic and Environmental Influences on Language Ability in Older Adults: Findings from the Older Australian Twins Study.

PubMed

Lee, T; Thalamuthu, A; Henry, J D; Trollor, J N; Ames, D; Wright, M J; Sachdev, P S

2018-05-01

We used a sub-sample from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging.

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.

Organizational Benchmarks for Test Utilization Performance: An Example Based on Positivity Rates for Genetic Tests.

PubMed

Rudolf, Joseph; Jackson, Brian R; Wilson, Andrew R; Smock, Kristi J; Schmidt, Robert L

2017-04-01

Health care organizations are under increasing pressure to deliver value by improving test utilization management. Many factors, including organizational factors, could affect utilization performance. Past research has focused on the impact of specific interventions in single organizations. The impact of organizational factors is unknown. The objective of this study is to determine whether testing patterns are subject to organizational effects, ie, are utilization patterns for individual tests correlated within organizations. Comparative analysis of ordering patterns (positivity rates for three genetic tests) across 659 organizations. Hierarchical regression was used to assess the impact of organizational factors after controlling for test-level factors (mutation prevalence) and hospital bed size. Test positivity rates were correlated within organizations. Organizations have a statistically significant impact on the positivity rate of three genetic tests. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Implementation of personalized medicine in Central-Eastern Europe: pitfalls and potentials based on citizen's attitude.

PubMed

Balicza, Peter; Terebessy, Andras; Grosz, Zoltan; Varga, Noemi Agnes; Gal, Aniko; Fekete, Balint Andras; Molnar, Maria Judit

2018-03-01

Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants. A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic. Members of the general population were also recruited via public media. We used chi-square testing and binary logistic regression to examine factors influencing attitude. We identified a mixed attitude toward genetic testing. Access to physician consultation positively influenced attitude. A higher self-determined genetic familiarity score associated with higher perceived genetic influence score, which in turn associated with greater willingness to participate in genetic testing. Medical professionals constituted a skeptical group. We think that given the controversies and complexities of the next-generation sequencing field, the optimal clinical translation of NGS data should be performed in institutions which have the unique capability to provide interprofessional health education, transformative biomedical research, and crucial patient care. With optimization of the clinical translational process, improvement of genetic literacy may increase patient engagement and empowerment. The paper highlights that in countries with relatively low-genetic literacy, a special strategy is needed to enhance the implementation of personalized medicine.

Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models

PubMed Central

Wang, Yifan; Liu, Aiyi; Mills, James L.; Boehnke, Michael; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Xiong, Momiao; Wu, Colin O.; Fan, Ruzong

2015-01-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks’s Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. PMID:25809955

Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.

PubMed

Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong

2015-05-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.

Understanding the science-learning environment: A genetically sensitive approach.

PubMed

Haworth, Claire M A; Davis, Oliver S P; Hanscombe, Ken B; Kovas, Yulia; Dale, Philip S; Plomin, Robert

2013-02-01

Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000 pairs of 14-year-old twins from the UK Twins Early Development Study reported on their experiences of the science-learning environment and were assessed for their performance in science using a web-based test of scientific enquiry. Multivariate twin analyses were used to investigate the genetic and environmental links between environment and outcome. The most surprising result was that the science-learning environment was almost as heritable (43%) as performance on the science test (50%), and showed negligible shared environmental influence (3%). Genetic links explained most (56%) of the association between learning environment and science outcome, indicating gene-environment correlation.

Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan.

PubMed

Chen, Ying-Erh; Kao, Sung-Shuo; Chung, Ren-Hua

2016-01-01

Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC.

How Do Health Care Providers Diagnose Phenylketonuria (PKU)?

MedlinePlus

... born with PKU. To perform this test, a health care provider takes some cells, either through a needle inserted into the abdomen or a small tube inserted into the vagina. A genetic counselor who understands the risks and benefits of genetic testing can help explain the choices available for testing. ...

[Genetic information and future medicine].

PubMed

Sakurai, Akihiro

2012-11-01

Rapid technological advances in genetic analysis have revealed the genetic background of various diseases. Elucidation of the genes responsible for a disease enables better clinical management of the disease and helps to develop targeted drugs. Also, early diagnosis and management of at-risk family members can be made by identification of a genetic disease in the proband. On the other hand, genetic issues often cause psychological distress to the family. To perform genetic testing appropriately and to protect patients and family members from any harm, guidelines for genetic testing were released from the alliance of Japanese genetics-related academic societies in 2003. As genetic testing is becoming incorporated into clinical practice more broadly, the guideline was revised and released by the Japanese Society of Medical Sciences in 2011. All medical professionals in Japan are expected to follow this guideline.

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.

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys.

PubMed

Lyon, Elaine; Schrijver, Iris; Weck, Karen E; Ferreira-Gonzalez, Andrea; Richards, C Sue; Palomaki, Glenn E

2015-03-01

Molecular testing for cystic fibrosis mutations is widespread and routine in reproductive decision making and diagnosis. Our objective was to assess the level of performance of laboratories for this test. The College of American Pathologists administers external proficiency testing with multiple DNA samples distributed biannually. RESULTS are analyzed, reviewed, and graded by the joint College of American Pathologists/American College of Medical Genetics and Genomics Biochemical and Molecular Genetics Committee. Assessment is based on genotype and associated clinical interpretation. Overall, 357 clinical laboratories participated in the proficiency testing survey between 2003 and 2013 (322 in the United States and 35 international). In 2013, US participants reported performing nearly 120,000 tests monthly. Analytical sensitivity and specificity of US laboratories were 98.8% (95% confidence interval: 98.4-99.1%) and 99.6% (95% confidence interval: 99.4-99.7%), respectively. Analytical sensitivity improved between 2003 and 2008 (from 97.9 to 99.3%; P = 0.007) and remained steady thereafter. Clinical interpretation matched the intended response for 98.8, 86.0, and 91.0% of challenges with no, one, or two mutations, respectively. International laboratories performed similarly. Laboratory testing for cystic fibrosis in the United States has improved since 2003, and these data demonstrate a high level of quality. Neither the number of samples tested nor test methodology affected performance.

On the suitability of different representations of solid catalysts for combinatorial library design by genetic algorithms.

PubMed

Gobin, Oliver C; Schüth, Ferdi

2008-01-01

Genetic algorithms are widely used to solve and optimize combinatorial problems and are more often applied for library design in combinatorial chemistry. Because of their flexibility, however, their implementation can be challenging. In this study, the influence of the representation of solid catalysts on the performance of genetic algorithms was systematically investigated on the basis of a new, constrained, multiobjective, combinatorial test problem with properties common to problems in combinatorial materials science. Constraints were satisfied by penalty functions, repair algorithms, or special representations. The tests were performed using three state-of-the-art evolutionary multiobjective algorithms by performing 100 optimization runs for each algorithm and test case. Experimental data obtained during the optimization of a noble metal-free solid catalyst system active in the selective catalytic reduction of nitric oxide with propene was used to build up a predictive model to validate the results of the theoretical test problem. A significant influence of the representation on the optimization performance was observed. Binary encodings were found to be the preferred encoding in most of the cases, and depending on the experimental test unit, repair algorithms or penalty functions performed best.

Genetic and economic evaluation of Japanese Black (Wagyu) cattle breeding schemes.

PubMed

Kahi, A K; Hirooka, H

2005-09-01

Deterministic simulation was used to evaluate 10 breeding schemes for genetic gain and profitability and in the context of maximizing returns from investment in Japanese Black cattle breeding. A breeding objective that integrated the cow-calf and feedlot segments was considered. Ten breeding schemes that differed in the records available for use as selection criteria were defined. The schemes ranged from one that used carcass traits currently available to Japanese Black cattle breeders (Scheme 1) to one that also included linear measurements and male and female reproduction traits (Scheme 10). The latter scheme represented the highest level of performance recording. In all breeding schemes, sires were chosen from the proportion selected during the first selection stage (performance testing), modeling a two-stage selection process. The effect on genetic gain and profitability of varying test capacity and number of progeny per sire and of ultrasound scanning of live animals was examined for all breeding schemes. Breeding schemes that selected young bulls during performance testing based on additional individual traits and information on carcass traits from their relatives generated additional genetic gain and profitability. Increasing test capacity resulted in an increase in genetic gain in all schemes. Profitability was optimal in Scheme 2 (a scheme similar to Scheme 1, but selection of young bulls also was based on information on carcass traits from their relatives) to 10 when 900 to 1,000 places were available for performance testing. Similarly, as the number of progeny used in the selection of sires increased, genetic gain first increased sharply and then gradually in all schemes. Profit was optimal across all breeding schemes when sires were selected based on information from 150 to 200 progeny. Additional genetic gain and profitability were generated in each breeding scheme with ultrasound scanning of live animals for carcass traits. Ultrasound scanning of live animals was more important than the addition of any other traits in the selection criteria. These results may be used to provide guidance to Japanese Black cattle breeders.

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement.

PubMed

Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

2015-12-01

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[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.

Performance impact of mutation operators of a subpopulation-based genetic algorithm for multi-robot task allocation problems.

PubMed

Liu, Chun; Kroll, Andreas

2016-01-01

Multi-robot task allocation determines the task sequence and distribution for a group of robots in multi-robot systems, which is one of constrained combinatorial optimization problems and more complex in case of cooperative tasks because they introduce additional spatial and temporal constraints. To solve multi-robot task allocation problems with cooperative tasks efficiently, a subpopulation-based genetic algorithm, a crossover-free genetic algorithm employing mutation operators and elitism selection in each subpopulation, is developed in this paper. Moreover, the impact of mutation operators (swap, insertion, inversion, displacement, and their various combinations) is analyzed when solving several industrial plant inspection problems. The experimental results show that: (1) the proposed genetic algorithm can obtain better solutions than the tested binary tournament genetic algorithm with partially mapped crossover; (2) inversion mutation performs better than other tested mutation operators when solving problems without cooperative tasks, and the swap-inversion combination performs better than other tested mutation operators/combinations when solving problems with cooperative tasks. As it is difficult to produce all desired effects with a single mutation operator, using multiple mutation operators (including both inversion and swap) is suggested when solving similar combinatorial optimization problems.

Selection of performance-tested young bulls and indirect responses in commercial beef cattle herds on pasture and in feedlots.

PubMed

Raidan, Fernanda S S; Santos, Dalinne C C; Moraes, Mariana M; Araújo, Andresa E M; Ventura, Henrique T; Bergmann, José A G; Turra, Eduardo M; Toral, Fabio L B

2016-11-09

Central testing is used to select young bulls which are likely to contribute to increased net income of the commercial beef cattle herd. We present genetic parameters for growth and reproductive traits on performance-tested young bulls and commercial animals that are raised on pasture and in feedlots. Records on young bulls and heifers in performance tests or commercial herds were used. Genetic parameters for growth and reproductive traits were estimated. Correlated responses for commercial animals when selection was applied on performance-tested young bulls were computed. The 90% highest posterior density (HPD90) intervals for heritabilities of final weight (FW), average daily gain (ADG) and scrotal circumference (SC) ranged from 0.41 to 0.49, 0.23 to 0.30 and 0.47 to 0.57, respectively, for performance-tested young bulls on pasture, from 0.45 to 0.60, 0.20 to 0.32 and 0.56 to 0.70, respectively, for performance-tested young bulls in feedlots, from 0.29 to 0.33, 0.14 to 0.18 and 0.35 to 0.45, respectively, for commercial animals on pasture, and from 0.24 to 0.44, 0.13 to 0.24 and 0.35 to 0.57 respectively, for commercial animals in feedlots. The HPD90 intervals for genetic correlations of FW, ADG and SC in performance-tested young bulls on pasture (feedlots) with FW, ADG and SC in commercial animals on pasture (feedlots) ranged from 0.86 to 0.96 (0.83 to 0.94), 0.78 to 0.90 (0.40 to 0.79) and from 0.92 to 0.97 (0.50 to 0.83), respectively. Age at first calving was genetically related to ADG (HPD90 interval = -0.48 to -0.06) and SC (HPD90 interval = -0.41 to -0.05) for performance-tested young bulls on pasture, however it was not related to ADG (HPD90 interval = -0.29 to 0.10) and SC (HPD90 interval = -0.35 to 0.13) for performance-tested young bulls in feedlots. Heritabilities for growth and SC are higher for performance-tested young bulls than for commercial animals. Evaluating and selecting for increased growth and SC on performance-tested young bulls is efficient to improve growth, SC and age at first calving in commercial animals. Evaluating and selecting performance-tested young bulls is more efficient for young bulls on pasture than in feedlots.

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.

Detection of genetic variants affecting cattle behaviour and their impact on milk production: a genome-wide association study.

PubMed

Friedrich, Juliane; Brand, Bodo; Ponsuksili, Siriluck; Graunke, Katharina L; Langbein, Jan; Knaust, Jacqueline; Kühn, Christa; Schwerin, Manfred

2016-02-01

Behaviour traits of cattle have been reported to affect important production traits, such as meat quality and milk performance as well as reproduction and health. Genetic predisposition is, together with environmental stimuli, undoubtedly involved in the development of behaviour phenotypes. Underlying molecular mechanisms affecting behaviour in general and behaviour and productions traits in particular still have to be studied in detail. Therefore, we performed a genome-wide association study in an F2 Charolais × German Holstein cross-breed population to identify genetic variants that affect behaviour-related traits assessed in an open-field and novel-object test and analysed their putative impact on milk performance. Of 37,201 tested single nucleotide polymorphism (SNPs), four showed a genome-wide and 37 a chromosome-wide significant association with behaviour traits assessed in both tests. Nine of the SNPs that were associated with behaviour traits likewise showed a nominal significant association with milk performance traits. On chromosomes 14 and 29, six SNPs were identified to be associated with exploratory behaviour and inactivity during the novel-object test as well as with milk yield traits. Least squares means for behaviour and milk performance traits for these SNPs revealed that genotypes associated with higher inactivity and less exploratory behaviour promote higher milk yields. Whether these results are due to molecular mechanisms simultaneously affecting behaviour and milk performance or due to a behaviour predisposition, which causes indirect effects on milk performance by influencing individual reactivity, needs further investigation. © 2015 Stichting International Foundation for Animal Genetics.

Attitudes and anticipated reactions to genetic testing for cancer among patients in Mexico City.

PubMed

Romero-Hidalgo, Sandra; Urraca, Nora; Parra, Dionisio; Villa, Antonio R; Lisker, Rubén; Carnevale, Alessandra

2009-08-01

The aim of this study was to investigate the attitudes toward cancer predictive genetic testing in a group of non-high-risk women and men and to analyze the factors that may influence their intention to use these tests. We studied a sample of 859 outpatient women and men attending the four tertiary care hospitals of the ISSSTE (Institute of Social Security and Services for Government Employees) in Mexico City. Subjects between the ages of 30 and 74 years with no present or past history of cancer were asked to answer a questionnaire through face-to-face interview. Two different questionnaires were designed, one for women and the other for men, regarding genetic testing of a high-risk gene for breast and prostate cancer, respectively. Descriptive statistics and univariate comparisons were carried out using chi-square test, Wilcoxon's signed rank test, and Friedman test. Multivariate analysis was performed using logistic regression technique. Results showed that the majority of women attended clinics for regular check-ups and for performing screening tests to detect breast cancer, and men did not follow this pattern regarding prostate cancer. Women were more motivated to get genetic testing, more aware about its benefits, and more concerned about having cancer than men.

Correlations among Jamaican 12th-Graders' Five Variables and Performance in Genetics

ERIC Educational Resources Information Center

Bloomfield, Deen-Paul; Soyibo, Kola

2008-01-01

This study was aimed at finding out if the level of performance of selected Jamaican Grade 12 students on an achievement test on the concept of genetics was satisfactory; if there were statistically significant differences in their performance on the concept linked to their gender, self-esteem, cognitive abilities in biology, school-type and…

Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida.

PubMed

Vadaparampil, S T; Scherr, C L; Cragun, D; Malo, T L; Pal, T

2015-05-01

Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non-genetics professionals (NGPs) perform guideline-based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes scheduling a separate session for pre-test counseling lasting 11-30 min prior to testing, discussing familial implications of testing, benefits and limitations of risk management options, and discussing the potential psychological impact and insurance-related issues. Few constructed a three-generation pedigree, discussed alternative hereditary cancer syndromes, or the meaning of a variant result. This lack of adherence to guideline-based practice may result in direct harm to patients and their family members. NGPs who are unable to deliver guideline adherent cancer genetics services should focus on identification and referral of at-risk patients to in person or telephone services provided by genetics professionals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

PubMed

Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

2017-02-01

To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

Reader Reaction On the generalized Kruskal-Wallis test for genetic association studies incorporating group uncertainty

PubMed Central

Wu, Baolin; Guan, Weihua

2015-01-01

Summary Acar and Sun (2013, Biometrics, 69, 427-435) presented a generalized Kruskal-Wallis (GKW) test for genetic association studies that incorporated the genotype uncertainty and showed its robust and competitive performance compared to existing methods. We present another interesting way to derive the GKW test via a rank linear model. PMID:25351417

Reader reaction on the generalized Kruskal-Wallis test for genetic association studies incorporating group uncertainty.

PubMed

Wu, Baolin; Guan, Weihua

2015-06-01

Acar and Sun (2013, Biometrics 69, 427-435) presented a generalized Kruskal-Wallis (GKW) test for genetic association studies that incorporated the genotype uncertainty and showed its robust and competitive performance compared to existing methods. We present another interesting way to derive the GKW test via a rank linear model. © 2014, The International Biometric Society.

"If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

PubMed

Hillman, Sarah C; Skelton, John; Quinlan-Jones, Elizabeth; Wilson, Amie; Kilby, Mark D

2013-07-01

The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes. Five main themes were recognized; diagnosis, genetic testing, family and support, reflections of the treatment received and emotions. Our results showed that women recall being told about QFPCR for trisomy 13, 18, and 21 but often no further testing. Women expected the conventional karyotype and microarray result would be normal following a normal QFPCR result. There were frequent misconceptions by couples regarding aspects of counseling/testing. Communication of variants of unknown (clinical) significance (VOUS) presents a particularly difficult challenge. Good clear communication by health care professionals is paramount. When counseling women and their partners for fetal chromosomal testing it should be reinforced that although the most common, trisomy 13, 18, and 21 only account for some of the chromosomal changes resulting in abnormal scan findings. Couples should have literature to take home summarizing scan anomalies and reinforcing information about genetic testing. Copyright © 2013 Wiley Periodicals, Inc.

Impact of Genetics on the Clinical Management of Channelopathies

PubMed Central

Schwartz, Peter J.; Ackerman, Michael J.; George, Alfred L.; Wilde, Arthur A.M.

2013-01-01

There are few areas in cardiology where the impact of genetics and of genetic testing on clinical management has been as great as in cardiac channelopathies, arrhythmic disorders of genetic origin related to the ionic control of the cardiac action potential. Among the growing number of diseases identified as channelopathies, three are sufficiently prevalent to represent significant clinical and societal problems and to warrant adequate understanding by practicing cardiologists: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome. This review will focus selectively on the impact of genetic discoveries on clinical management of these three diseases. For each disorder, we will discuss to what extent genetic knowledge and clinical genetic test results modify the way cardiologists should approach and manage affected patients. We will also address the optimal use of genetic testing including its potential limitations and the potential medico-legal implications when such testing is not performed. We will highlight how important can be to understand the ways by which genotype can impact clinical manifestations, risk stratification, and responses to the therapy. We will also illustrate the close bridge between molecular biology and clinical medicine, and will emphasize that consideration of the genetic basis for these hereditable arrhythmia syndromes, as well as the proper use and interpretation of clinical genetic testing, should remain the standard-of-care. PMID:23684683

The MAX Statistic is Less Powerful for Genome Wide Association Studies Under Most Alternative Hypotheses.

PubMed

Shifflett, Benjamin; Huang, Rong; Edland, Steven D

2017-01-01

Genotypic association studies are prone to inflated type I error rates if multiple hypothesis testing is performed, e.g., sequentially testing for recessive, multiplicative, and dominant risk. Alternatives to multiple hypothesis testing include the model independent genotypic χ 2 test, the efficiency robust MAX statistic, which corrects for multiple comparisons but with some loss of power, or a single Armitage test for multiplicative trend, which has optimal power when the multiplicative model holds but with some loss of power when dominant or recessive models underlie the genetic association. We used Monte Carlo simulations to describe the relative performance of these three approaches under a range of scenarios. All three approaches maintained their nominal type I error rates. The genotypic χ 2 and MAX statistics were more powerful when testing a strictly recessive genetic effect or when testing a dominant effect when the allele frequency was high. The Armitage test for multiplicative trend was most powerful for the broad range of scenarios where heterozygote risk is intermediate between recessive and dominant risk. Moreover, all tests had limited power to detect recessive genetic risk unless the sample size was large, and conversely all tests were relatively well powered to detect dominant risk. Taken together, these results suggest the general utility of the multiplicative trend test when the underlying genetic model is unknown.

Polynomials to model the growth of young bulls in performance tests.

PubMed

Scalez, D C B; Fragomeni, B O; Passafaro, T L; Pereira, I G; Toral, F L B

2014-03-01

The use of polynomial functions to describe the average growth trajectory and covariance functions of Nellore and MA (21/32 Charolais+11/32 Nellore) young bulls in performance tests was studied. The average growth trajectories and additive genetic and permanent environmental covariance functions were fit with Legendre (linear through quintic) and quadratic B-spline (with two to four intervals) polynomials. In general, the Legendre and quadratic B-spline models that included more covariance parameters provided a better fit with the data. When comparing models with the same number of parameters, the quadratic B-spline provided a better fit than the Legendre polynomials. The quadratic B-spline with four intervals provided the best fit for the Nellore and MA groups. The fitting of random regression models with different types of polynomials (Legendre polynomials or B-spline) affected neither the genetic parameters estimates nor the ranking of the Nellore young bulls. However, fitting different type of polynomials affected the genetic parameters estimates and the ranking of the MA young bulls. Parsimonious Legendre or quadratic B-spline models could be used for genetic evaluation of body weight of Nellore young bulls in performance tests, whereas these parsimonious models were less efficient for animals of the MA genetic group owing to limited data at the extreme ages.

Exploring how symptoms of attention-deficit/hyperactivity disorder are related to reading and mathematics performance: general genes, general environments.

PubMed

Hart, Sara A; Petrill, Stephen A; Willcutt, Erik; Thompson, Lee A; Schatschneider, Christopher; Deater-Deckard, Kirby; Cutting, Laurie E

2010-11-01

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.

Learning Healthcare System for the Prescription of Genetic Testing in the Gynecological Cancer Risk.

PubMed

Suárez-Mejías, Cristina; Martínez-García, Alicia; Martínez-Maestre, María Ángeles; Silvan-Alfaro, José Manuel; Moreno Conde, Jesús; Parra-Calderón, Carlos Luis

2017-01-01

Clinical evidence demonstrates that BRCA 1 and BRCA2 mutations can develop a gynecological cancer but genetic testing has a high cost to the healthcare system. Besides, several studies in the literature indicate that performing these genetic tests to the population is not cost-efficient. Currently, our physicians do not have a system to provide them the support for prescribing genetic tests. A Decision Support System for prescribing these genetic tests in BRCA1 and BRCA2 and preventing gynecological cancer risks has been designed, developed and deployed in the Virgen del Rocío University Hospital (VRUH). The technological architecture integrates a set of open source tools like Mirth Connect, OpenClinica, OpenCDS, and tranSMART in addition to several interoperability standards. The system allows general practitioners and gynecologists to classify patients as low risk (they do not require a specific treatment) or high risk (they should be attended by the Genetic Council). On the other hand, by means of this system we are also able to standardize criteria among professionals to prescribe these genetic tests. Finally, this system will also contribute to improve the assistance for this kind of patients.

Genetic parameters for type classification of Nelore cattle on central performance tests at pasture in Brazil.

PubMed

Lima, Paulo Ricardo Martins; Paiva, Samuel Rezende; Cobuci, Jaime Araujo; Braccini Neto, José; Machado, Carlos Henrique Cavallari; McManus, Concepta

2013-10-01

The objective of this study was to characterize Nelore cattle on central performance tests in pasture, ranked by the visual classification method EPMURAS (structure, precocity, muscle, navel, breed, posture, and sexual characteristics), and to estimate genetic and phenotypic correlations between these parameters, including visual as well as production traits (initial and final weight on test, weight gain, and weight corrected for 550 days). The information used in the study was obtained on 21,032 Nelore bulls which were participants in the central performance test at pasture of the Brazilian Association for Zebu Breeders (ABCZ). Heritabilities obtained were from 0.19 to 0.50. Phenotypic correlations were positive from 0.70 to 0.97 between the weight traits, from 0.65 to 0.74 between visual characteristics, and from 0.29 to 0.47 between visual characteristics and weight traits. The genetic correlations were positive ranging from 0.80 to 0.98 between the characteristics of structure, precocity and musculature, from 0.13 to 0.64 between the growth characteristics, and from 0.41 to 0.97 between visual scores and weight gains. Heritability and genetic correlations indicate that the use of visual scores, along with the selection for growth characteristics, can bring positive results in selection of beef cattle for rearing on pasture.

Improving nurse practitioners' competence with genetics: Effectiveness of an online course.

PubMed

Whitt, Karen J; Macri, Charles; O'Brien, Travis J; Wright, Stephanie

2016-03-01

The purpose of this study was to assess the effectiveness of an online genetics course for improving nurse practitioners' knowledge, competence, and comfort with genetic principles and their application to clinical practice. A genetics knowledge test and survey were administered to 232 nurse practitioner students, between 2011 and 2013, before and after completing a 15-week online genetics course taught by a multidisciplinary team of instructors at a private east coast U.S. university. The 65-item survey allowed participants to rate competence regarding genetic principles, diseases, and terminology, as well as comfort performing various clinical tasks related to genetics. The 21-item knowledge test contained multiple choice questions regarding core competencies in genetics. Paired t-tests were used to compare mean pre- and postscores. Participants significantly increased postcourse knowledge (p < .001) and comfort with genetic core competencies and clinical skills related to genetics (p < .001). This study demonstrates the effectiveness of an online genetics course for increasing nurse practitioners' knowledge, competence, and confidence with genetics and identifies specific topics educators should consider when designing curricula for nurse practitioners. Findings from this study can improve genetics education for nurse practitioners, which will in turn improve patient health. ©2015 American Association of Nurse Practitioners.

Genetic deletion of HRP2 and HRP3 in Indian Plasmodium falciparum population and false negative malaria rapid diagnostic test.

PubMed

Kumar, Navin; Pande, Veena; Bhatt, R M; Shah, Naman K; Mishra, Neelima; Srivastava, Bina; Valecha, Neena; Anvikar, Anupkumar R

2013-01-01

Genetic polymorphisms in diagnostic antigens are important factors responsible for variable performance of rapid diagnostic tests. Additionally, the failure of antigen expression due to gene deletion may also contribute to variable performance. We report Indian Plasmodium falciparum field isolates lacking both Pfhrp2 and Pfhrp3 genes leading to false negative results of rapid diagnostic tests. The study highlights need to determine the prevalence of P. falciparum isolates lacking these genes in larger field populations in India. Copyright © 2012 Elsevier B.V. All rights reserved.

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition

PubMed Central

Hubbard, Leon; Tansey, Katherine E.; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D.; Moran, Jennifer L.; McCarroll, Steven A.; Linden, David E. J.; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.; Zammit, Stanley

2016-01-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophrenia en masse contribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n = 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n = 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P = .001) and lower full IQ (P = .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P = 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (r G = −.379, P = 6.62E-05) and full IQ (r G = −.202, P = 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. PMID:26678674

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.

PubMed

Hubbard, Leon; Tansey, Katherine E; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D; Moran, Jennifer L; McCarroll, Steven A; Linden, David E J; Owen, Michael J; O'Donovan, Michael C; Walters, James T R; Zammit, Stanley

2016-05-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

PubMed Central

Pfundt, Rolph; del Rosario, Marisol; Vissers, Lisenka E.L.M.; Kwint, Michael P.; Janssen, Irene M.; de Leeuw, Nicole; Yntema, Helger G.; Nelen, Marcel R.; Lugtenberg, Dorien; Kamsteeg, Erik-Jan; Wieskamp, Nienke; Stegmann, Alexander P.A.; Stevens, Servi J.C.; Rodenburg, Richard J.T.; Simons, Annet; Mensenkamp, Arjen R.; Rinne, Tuula; Gilissen, Christian; Scheffer, Hans; Veltman, Joris A.; Hehir-Kwa, Jayne Y.

2017-01-01

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10–20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test. Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting. Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to –5.8% per disorder). Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics. Genet Med advance online publication 27 October 2016 PMID:28574513

What factors may influence psychological well being at three months and one year post BRCA genetic result disclosure?

PubMed

Bosch, Nina; Junyent, Núria; Gadea, Neus; Brunet, Joan; Ramon y Cajal, Teresa; Torres, Asunción; Graña, Begoña; Velasco, Angela; Darder, Esther; Mensa, Irene; Balmaña, Judith

2012-12-01

Genetic testing for breast cancer predisposition has been available in the clinical practice for more than a decade. How the result of genetic testing affects the psychological well-being of the individuals is an under-researched area in many populations. Follow-up analysis of psychological well-being via HADS scale was performed in 364 individuals at 3 months and 1 year after the disclosure of BRCA1/2 genetic result. We analyzed potential predictors for pathological anxiety and variables associated to the variation of HADS scores over time. At pre-test only 16% and 4% of individuals presented symptoms of anxiety and depression, respectively. Having a prior diagnosis of cancer and presenting a pathological HADS-A score at the baseline were associated with clinically significant anxiety scores at one year, but the genetic test result was not. Thus, BRCA genetic testing does not influence short and long term anxiety and depression levels among those identified as mutation carriers. It is our task to demystify the allegedly negative impact of BRCA testing on psychological well being to increase the uptake of genetic testing and benefit those who are at high risk of developing breast, ovarian and prostate cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

The nature of creativity: The roles of genetic factors, personality traits, cognitive abilities, and environmental sources.

PubMed

Kandler, Christian; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M; Borkenau, Peter; Penke, Lars

2016-08-01

This multitrait multimethod twin study examined the structure and sources of individual differences in creativity. According to different theoretical and metrological perspectives, as well as suggestions based on previous research, we expected 2 aspects of individual differences, which can be described as perceived creativity and creative test performance. We hypothesized that perceived creativity, reflecting typical creative thinking and behavior, should be linked to specific personality traits, whereas test creativity, reflecting maximum task-related creative performance, should show specific associations with cognitive abilities. Moreover, we tested whether genetic variance in intelligence and personality traits account for the genetic component of creativity. Multiple-rater and multimethod data (self- and peer reports, observer ratings, and test scores) from 2 German twin studies-the Bielefeld Longitudinal Study of Adult Twins and the German Observational Study of Adult Twins-were analyzed. Confirmatory factor analyses yielded the expected 2 correlated aspects of creativity. Perceived creativity showed links to openness to experience and extraversion, whereas tested figural creativity was associated with intelligence and also with openness. Multivariate behavioral genetic analyses indicated that the heritability of tested figural creativity could be accounted for by the genetic component of intelligence and openness, whereas a substantial genetic component in perceived creativity could not be explained. A primary source of individual differences in creativity was due to environmental influences, even after controlling for random error and method variance. The findings are discussed in terms of the multifaceted nature and construct validity of creativity as an individual characteristic. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Developing genetic privacy legislation: the South Carolina experience.

PubMed

Edwards, J G; Young, S R; Brooks, K A; Aiken, J H; Patterson, E D; Pritchett, S T

1998-01-01

The availability of presymptomatic and predisposition genetic testing has spawned the need for legislation prohibiting health insurance discrimination on the basis of genetic information. The federal effort, the Health Insurance Portability and Accountability Act (HIPAA) of 1996, falls short by protecting only those who access insurance through group plans. A committee of University of South Carolina professionals convened in 1996 to develop legislation in support of genetic privacy for the state of South Carolina. The legislation prevents health insurance companies from denying coverage or setting insurance rates on the basis of genetic information. It also protects the privacy of genetic information and prohibits performance of genetic tests without specific informed consent. In preparing the bill, genetic privacy laws from other states were reviewed, and a modified version of the Virginia law adopted. The South Carolina Committee for the Protection of Genetic Privacy version went a step further by including enforcement language and excluding Virginia's sunset clause. The definition of genetic information encompassed genetic test results, and importantly, includes family history of genetic disease. Our experience in navigating through the state legislature and working through opposition from the health insurance lobby is detailed herein.

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy.

PubMed

Shaw, Kaitlyn; Amstutz, Ursula; Kim, Richard B; Lesko, Lawrence J; Turgeon, Jacques; Michaud, Veronique; Hwang, Soomi; Ito, Shinya; Ross, Colin; Carleton, Bruce C

2015-08-01

To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. Testing of VKORC1 (-1639G>A), CYP2C9*2, and CYP2C9*3 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C9*5, *6, *8, or *11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Higher criticism approach to detect rare variants using whole genome sequencing data

PubMed Central

2014-01-01

Because of low statistical power of single-variant tests for whole genome sequencing (WGS) data, the association test for variant groups is a key approach for genetic mapping. To address the features of sparse and weak genetic effects to be detected, the higher criticism (HC) approach has been proposed and theoretically has proven optimal for detecting sparse and weak genetic effects. Here we develop a strategy to apply the HC approach to WGS data that contains rare variants as the majority. By using Genetic Analysis Workshop 18 "dose" genetic data with simulated phenotypes, we assess the performance of HC under a variety of strategies for grouping variants and collapsing rare variants. The HC approach is compared with the minimal p-value method and the sequence kernel association test. The results show that the HC approach is preferred for detecting weak genetic effects. PMID:25519367

Genetic testing and sports medicine ethics.

PubMed

McNamee, Michael John; Müller, Arno; van Hilvoorde, Ivo; Holm, Søren

2009-01-01

Sports medicine ethics is neither a well established branch of sports medicine nor of medical ethics. It is therefore important to raise to more general awareness some of the significant ethical implications of sports medicine practices. The field of genetics in sports is likewise in its infancy and raises significant ethical concerns. It is not yet clear how genetics will alter our understanding of human potential and performance in sports. While a number of professional medical bodies accept genetic interventions of a therapeutic nature, we argue that the use of genetic technologies to predict sports potential may well breach both the European bioethics convention and North American anti-discrimination legislation, which are designed to support important ethical ideals and the ongoing commitment of the physician to the welfare of their patient. We highlight further ethical problems associated with confidentiality and consent that may arise in genetic testing as opposed to more conventional methods of testing in sports medicine. We conclude that genetic testing in sport that is not strictly limited to the protection of the athlete against harm, should be viewed in a very sceptical light by sports medicine professionals.

Genetic mutations of young patients admitted to an emergency department for syncope during sport practice.

PubMed

Gómez Alcaraz, Jorge; Bustamante, José; Corral, Ervigio; Casado Florez, Maria Isabel; Vivas, David; Cañadas-Godoy, Victoria; González Del Castillo, Juan; González Armengol, Juan Jorge; López-Farré, Antonio; Martín Sánchez, Francisco Javier

2018-04-25

To study the frequency of genetic mutations related to genetic heart disease among young patients admitted for syncope during sport practice. A case series study that included patients≤45 years admitted for syncope during sport practice during 2010-2011. We collected demographic and clinical variables, genetic tests mutations and final clinical diagnosis. A genetic test was performed in 46 (76.7%) of 60 patients evaluated. The genetic test was positive in 12 (26%; 95% CI 15.6-40.3) patients; 10 (21.7%) had PKP2 mutation related to arrhythmogenic right ventricular dysplasia mutation, one (2.2%) KCNQ1 mutation and one (2.2%) SCN5A mutation related to channelopathies. The genetic test was positive in 11 (35.5%) cases of undetermined syncope and one (50%) case of cardiac syncope, being negative in all cases with neuromediated syncopes (P=.037). Gene mutations are common in young patients suffering from syncope during sports, especially in those with cardiac or undetermined aetiology. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

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.

Prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli families.

PubMed

Rosenmann, Ada; Bejarano-Achache, Idit; Eli, Dalia; Maftsir, Genia; Mizrahi-Meissonnier, Liliana; Blumenfeld, Anat

2009-10-01

To present our accumulated data on prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli albino families. Albinism consists of variable phenotypes, but only families with predicted severely handicapped albino offspring, who declared their wish to terminate a pregnancy of such a fetus, are eligible for prenatal testing. Prenatal testing is not offered otherwise. Following detailed genetic investigation and counseling, molecular prenatal testing was performed using the combination of mutation screening, direct sequencing, and haplotype analysis. A total of 55 prenatal tests were performed in 37 families; in 26 families the propositus was the child, and in 11, a parent or a close relative. In 32 families tyrosinase (TYR) mutations were diagnosed. In 5 families a P gene mutation was detected. Twelve albino fetuses were diagnosed. Following further genetic counseling, all couples elected to terminate the pregnancy. Three additional pregnancies were terminated for other reasons. Families with increased risk for an albino child with severe visual handicap, seek premarital and prenatal genetic counseling and testing, for the prevention of affected offspring. Our combined methods of molecular genetic testing enable a nationwide approach for prevention of albinism. The same paradigm can be applied to other populations affected with albinism.

Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

PubMed

Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

2015-04-02

Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

Improving the value of costly genetic reference laboratory testing with active utilization management.

PubMed

Dickerson, Jane A; Cole, Bonnie; Conta, Jessie H; Wellner, Monica; Wallace, Stephanie E; Jack, Rhona M; Rutledge, Joe; Astion, Michael L

2014-01-01

Tests that are performed outside of the ordering institution, send-out tests, represent an area of risk to patients because of complexity associated with sending tests out. Risks related to send-out tests include increased number of handoffs, ordering the wrong or unnecessary test, specimen delays, data entry errors, preventable delays in reporting and acknowledging results, and excess financial liability. Many of the most expensive and most misunderstood tests are send-out genetic tests. To design and develop an active utilization management program to reduce the risk to patients and improve value of genetic send-out tests. Send-out test requests that met defined criteria were reviewed by a rotating team of doctoral-level consultants and a genetic counselor in a pediatric tertiary care center. Two hundred fifty-one cases were reviewed during an 8-month period. After review, nearly one-quarter of genetic test requests were modified in the downward direction, saving a total of 2% of the entire send-out bill and 19% of the test requests under management. Ultimately, these savings were passed on to patients. Implementing an active utilization strategy for expensive send-out tests can be achieved with minimal technical resources and results in improved value of testing to patients.

Automated Test Assembly for Cognitive Diagnosis Models Using a Genetic Algorithm

ERIC Educational Resources Information Center

Finkelman, Matthew; Kim, Wonsuk; Roussos, Louis A.

2009-01-01

Much recent psychometric literature has focused on cognitive diagnosis models (CDMs), a promising class of instruments used to measure the strengths and weaknesses of examinees. This article introduces a genetic algorithm to perform automated test assembly alongside CDMs. The algorithm is flexible in that it can be applied whether the goal is to…

Genetic Testing for Hereditary Breast Cancer: The Decision to Decline.

PubMed

White, V Brook; Walsh, Kendall K; Foss, Kimberly Showers; Amacker-North, Lisa; Lenarcic, Stacy; McNeely, Lindsay; White, Richard L

2018-01-01

Genetic testing is important for comprehensive cancer care. Commercial analysis of the BRCA1/2 genes has been available since 1996, and testing for hereditary breast and ovarian cancer syndrome is well established. The National Comprehensive Cancer Network (NCCN) guidelines identify individuals for whom BRCA1/2 analysis is appropriate and define management recommendations for mutation carriers. Despite recommendations, not all who meet NCCN criteria undergo genetic testing. We assess the frequency that individuals meeting NCCN criteria decline BRCA1/2 analysis, as well as factors that affect the decision-making process. A retrospective chart review was performed from September 2013 through August 2014 of individuals who received genetic counseling at the Levine Cancer Institute. A total of 1082 individuals identified through the retrospective chart review met NCCN criteria for BRCA1/2 analysis. Of these, 267 (24.7%) did not pursue genetic testing. Of the Nontested cohort, 59 (22.1%) were disinterested in testing and 108 (40.4%) were advised to gather additional genetic or medical information about their relatives before testing. The remaining 100 (37.5%) individuals were insured and desired to undergo genetic testing but were prohibited by the expense. Eighty five of these 100 patients were responsible for the total cost of the test, whereas the remaining 15 faced a prohibitive copay expense. Financial concerns are a major deterrent to the pursuit of BRCA1/2 analysis among those who meet NCNN criteria, especially in patients diagnosed with breast or ovarian cancer. These findings highlight the need to address financial concerns for genetic testing in this high-risk population.

The effectiveness of argumentation in tutorial dialogues with an Intelligent Tutoring System for genetic risk of breast cancer.

PubMed

Cedillos-Whynott, Elizabeth M; Wolfe, Christopher R; Widmer, Colin L; Brust-Renck, Priscila G; Weil, Audrey; Reyna, Valerie F

2016-09-01

BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings.

The effectiveness of argumentation in tutorial dialogues with an Intelligent Tutoring System for genetic risk of breast cancer

PubMed Central

Cedillos-Whynott, Elizabeth M.; Wolfe, Christopher R.; Widmer, Colin L.; Brust-Renck, Priscila G.; Weil, Audrey; Reyna, Valerie F.

2017-01-01

BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings. PMID:26511370

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

McEwen, J.E.; McCarty, K.; Reilly, P.R.

Rapid advances in the ability to test persons presymptomatically for genetic diseases have generated increasing concern that genetic information will be abused by insurance companies. Reasoning that the insurance companies may have the strongest interest in using genetic data and that the medical directors of those companies with responsibility for rating applicants would be a good source of information on the use of such data, the authors conducted a large survey of medical directors of North American life insurance companies. They received responses from 27 medical directors. The results suggest that (1) few insurers perform genetic tests on applicants, butmore » most are interested in accessing genetic test information about applicants that already exists; (2) the degree of insurers' interest in using genetic test results may depend on the face amount of the policy applied for and on the specificity and sensitivity of the test; (3) many companies employ underwriting guidelines with respect to certain genetic conditions but may not always have specific actuarial data in house to support their rating decisions; (4) a considerable degree of subjectivity is involved in most insurers' rating decisions; and (5) some of the medical directors who responded to the survey are not fully informed about certain basic principles of medical genetics. 8 refs., 7 tabs.« less

The use of genetic information in the insurance sector--a German perspective.

PubMed

Armbrüster, Christian; Obal, Monika

2013-01-01

The following paper offers an introduction to the legal framework concerning the use of genetic information in the insurance sector in Germany. The main contents and the controversial issues of the key regulation are examined. The aim of this rule being to secure human dignity by respecting the right to informational self-determination regarding genetic data, including the individual's right not to know about their genetic characteristics, there are a number of open issues which are being addressed. For instance, the influence of the prohibition to ask for genetic testing and to use the results of any such testing by the insurer is examined. This examination leads to some explicit results, such as the assumption that in addition to the ban on the use of genetic testing no questions about family medical history are admissible. The authors embark on the definition of genetic testing and the question to what extent the results of diagnostic genetic testing may still be made use of in the context of the insured person's obligation to display pre-existing conditions and diseases when the contract is concluded. In this respect distinctions between diagnostic and predictive genetic testing as well as between disease and disposition are drawn. Furthermore, the exceptions from the prohibition to use results of genetic testing are examined, and the scope of the prohibition of acceptance of results of genetic testing even if performed at the instigation of the insured is explored. Finally the consequences, encompassing criminal liability and private law ramifications, of the violation of the prohibition are presented. In this context, a narrow understanding of the aggravated criminal offence of using results of genetic testing with the intent to personal enrichment or in return for payments is developed. Finally the effects on the validity of the insurance contract and the question whether the insurer may be forced to conclude a contract are examined.

Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations.

PubMed

D'Andrea, Elvira; Marzuillo, Carolina; De Vito, Corrado; Di Marco, Marco; Pitini, Erica; Vacchio, Maria Rosaria; Villari, Paolo

2016-12-01

There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness. We performed a systematic review of full economic evaluations of health-care programs involving BRCA testing. Nine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) population-based genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i.e., testing individuals without cancer but with FH suggestive of BRCA mutation; (iii) familial mutation (FM)-based genetic screening, i.e., testing individuals without cancer but with known familial BRCA mutation; and (iv) cancer-based genetic screening, i.e., testing individuals with BRCA-related cancers. Currently BRCA1/2 population-based screening represents good value for the money among Ashkenazi Jews only. FH-based screening is potentially very cost-effective, although further studies that include costs of identifying high-risk women are needed. There is no evidence of cost-effectiveness for BRCA screening of all newly diagnosed cases of breast/ovarian cancers followed by cascade testing of relatives, but programs that include tools for identifying affected women at higher risk for inherited forms are promising. Cost-effectiveness is highly sensitive to the cost of BRCA1/2 testing.Genet Med 18 12, 1171-1180.

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

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.

Exploring How Symptoms of Attention-Deficit/Hyperactivity Disorder Are Related to Reading and Mathematics Performance: General Genes, General Environments

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Willcutt, Erik; Thompson, Lee A.; Schatschneider, Christopher; Deater-Deckard, Kirby; Cutting, Laurie E.

2013-01-01

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance. PMID:20966487

Genetic and economic benefits of selection based on performance recording and genotyping in lower tiers of multi-tiered sheep breeding schemes.

PubMed

Santos, Bruno F S; van der Werf, Julius H J; Gibson, John P; Byrne, Timothy J; Amer, Peter R

2017-01-17

Performance recording and genotyping in the multiplier tier of multi-tiered sheep breeding schemes could potentially reduce the difference in the average genetic merit between nucleus and commercial flocks, and create additional economic benefits for the breeding structure. The genetic change in a multiple-trait breeding objective was predicted for various selection strategies that included performance recording, parentage testing and genomic selection. A deterministic simulation model was used to predict selection differentials and the flow of genetic superiority through the different tiers. Cumulative discounted economic benefits were calculated based on trait gains achieved in each of the tiers and considering the extra revenue and associated costs of applying recording, genotyping and selection practices in the multiplier tier of the breeding scheme. Performance recording combined with genomic or parentage information in the multiplier tier reduced the genetic lag between the nucleus and commercial flock by 2 to 3 years. The overall economic benefits of improved performance in the commercial tier offset the costs of recording the multiplier. However, it took more than 18 years before the cumulative net present value of benefits offset the costs at current test prices. Strategies in which recorded multiplier ewes were selected as replacements for the nucleus flock did modestly increase profitability when compared to a closed nucleus structure. Applying genomic selection is the most beneficial strategy if testing costs can be reduced or by genotyping only a proportion of the selection candidates. When the cost of genotyping was reduced, scenarios that combine performance recording with genomic selection were more profitable and reached breakeven point about 10 years earlier. Economic benefits can be generated in multiplier flocks by implementing performance recording in conjunction with either DNA pedigree recording or genomic technology. These recording practices reduce the long genetic lag between the nucleus and commercial flocks in multi-tiered breeding programs. Under current genotyping costs, the time to breakeven was found to be generally very long, although this varied between strategies. Strategies using either genomic selection or DNA pedigree verification were found to be economically viable provided the price paid for the tests is lower than current prices, in the long-term.

Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing.

PubMed

Sun, Young; Kang, Eunyoung; Baek, Hyunnam; Jung, Jaehag; Hwang, Euijun; Koo, Jauk; Kim, Eun-Kyu; Kim, Sung-Won

2015-06-01

The aim of our study was to determine the rate of participation in genetic testing, to determine the reasons for non-participation and to identify the factors affecting participation in BRCA genetic testing for high-risk patients. This study was performed through a retrospective review of 804 individuals who underwent genetic counseling for BRCA1/2 gene mutations at Seoul National University Bundang Hospital between July 2003 and September 2012. In total, 728 (90.5%) individuals underwent BRCA1/2 mutation screening after the initial genetic counseling; 88.2% of 647 probands and 100% of 157 family members were screened. In multivariate analysis, family history of breast cancer and younger age were independent variables affecting participation in genetic testing. Of the 132 people who initially declined genetic testing, 58 (43.9%) postponed the decision, 30 (22.7%) needed time to discuss the issue with family members, 22 (16.7%) did not want to know if they had a BRCA1/2 mutation, and 22 (16.7%) declined the test because of financial problems. When analyzing refusal of testing according to the time period before and after the implementation of national health insurance coverage for BRCA1/2 genetic testing, the critical reason given for refusal was different. After insurance coverage, refusal for financial reason was decreased from 61.1 to 9.6%. A family history of breast cancer and a younger age were important factors associated with participation in genetic testing. National health insurance decreased the proportion of individuals who did not participate in testing owing to a financial reason. In genetic counseling, we have to understand these issues and consider several factors that may influence an individual's decision to be tested. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A report template for molecular genetic tests designed to improve communication between the clinician and laboratory.

PubMed

Scheuner, Maren T; Hilborne, Lee; Brown, Julie; Lubin, Ira M

2012-07-01

Errors are most likely to occur during the pre- and postanalytic phases of the genetic testing process, which can contribute to underuse, overuse, and misuse of genetic tests. To mitigate these errors, we created a template for molecular genetic test reports that utilizes the combined features of synoptic reporting and narrative interpretation. A variation of the Delphi consensus process with an expert panel was used to create a draft report template, which was further informed by focus group discussions with primary care physicians. There was agreement that molecular genetic test reports should present information in groupings that flow in a logical manner, and most participants preferred the following order of presentation: patient and physician information, test performed, test results and interpretation, guidance on next steps, and supplemental information. We define data elements for the report as "required," "optional," "possible," and "not necessary"; provide recommendations regarding the grouping of these data elements; and describe the ideal design of the report template, including the preferred order of the report sections, formatting of data, and length of the report. With input from key stakeholders and building upon prior work, we created a template for molecular genetic test reports designed to improve clinical decision making at the point of care. The template design should lead to more effective communication between the laboratory and ordering clinician. Studies are needed to assess the usefulness and effectiveness of molecular genetic test reports generated using this template.

Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies

PubMed Central

Liu, Zhonghua; Lin, Xihong

2017-01-01

Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391

Multiple phenotype association tests using summary statistics in genome-wide association studies.

PubMed

Liu, Zhonghua; Lin, Xihong

2018-03-01

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.

Assessing the readiness of precision medicine interoperabilty: An exploratory study of the National Institutes of Health genetic testing registry.

PubMed

Ronquillo, Jay G; Weng, Chunhua; Lester, William T

2017-11-17

  Precision medicine involves three major innovations currently taking place in healthcare:  electronic health records, genomics, and big data.  A major challenge for healthcare providers, however, is understanding the readiness for practical application of initiatives like precision medicine.   To better understand the current state and challenges of precision medicine interoperability using a national genetic testing registry as a starting point, placed in the context of established interoperability formats.   We performed an exploratory analysis of the National Institutes of Health Genetic Testing Registry.  Relevant standards included Health Level Seven International Version 3 Implementation Guide for Family History, the Human Genome Organization Gene Nomenclature Committee (HGNC) database, and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT).  We analyzed the distribution of genetic testing laboratories, genetic test characteristics, and standardized genome/clinical code mappings, stratified by laboratory setting. There were a total of 25472 genetic tests from 240 laboratories testing for approximately 3632 distinct genes.  Most tests focused on diagnosis, mutation confirmation, and/or risk assessment of germline mutations that could be passed to offspring.  Genes were successfully mapped to all HGNC identifiers, but less than half of tests mapped to SNOMED CT codes, highlighting significant gaps when linking genetic tests to standardized clinical codes that explain the medical motivations behind test ordering.  Conclusion:  While precision medicine could potentially transform healthcare, successful practical and clinical application will first require the comprehensive and responsible adoption of interoperable standards, terminologies, and formats across all aspects of the precision medicine pipeline.

Illness representations, knowledge and motivation to perform presymptomatic testing for late-onset genetic diseases.

PubMed

Leite, Ângela; Dinis, Maria Alzira P; Sequeiros, Jorge; Paúl, Constança

2017-02-01

This study addresses the relation between illness representations, knowledge and motivation to perform the presymptomatic testing (PST) of subjects at-risk for Familial Amyloydotic Polyneuropathy (FAP), Huntington's disease (HD) and Machado-Joseph disease (MJD), compared with subjects at-risk for Hereditary Hemochromatosis (HH). The sample comprised a clinical group of 213 subjects at genetic risk for FAP, HD and MJD, and a comparison group of 31 subjects at genetic risk for HH, that answered three open-ended questions relating illness representations, knowledge about the disease, and motivation to perform PST. People at-risk for FAP, HD and MJD use more metaphors, make more references to the family, are more concerned with the future and feel more out of curiosity and to learn, than for HH. These subjects at-risk correspond to the profile of somatic individual or personhood, wherein the unsubjectivation of the disease can function as a coping mechanism.

Gene Level Meta-Analysis of Quantitative Traits by Functional Linear Models.

PubMed

Fan, Ruzong; Wang, Yifan; Boehnke, Michael; Chen, Wei; Li, Yun; Ren, Haobo; Lobach, Iryna; Xiong, Momiao

2015-08-01

Meta-analysis of genetic data must account for differences among studies including study designs, markers genotyped, and covariates. The effects of genetic variants may differ from population to population, i.e., heterogeneity. Thus, meta-analysis of combining data of multiple studies is difficult. Novel statistical methods for meta-analysis are needed. In this article, functional linear models are developed for meta-analyses that connect genetic data to quantitative traits, adjusting for covariates. The models can be used to analyze rare variants, common variants, or a combination of the two. Both likelihood-ratio test (LRT) and F-distributed statistics are introduced to test association between quantitative traits and multiple variants in one genetic region. Extensive simulations are performed to evaluate empirical type I error rates and power performance of the proposed tests. The proposed LRT and F-distributed statistics control the type I error very well and have higher power than the existing methods of the meta-analysis sequence kernel association test (MetaSKAT). We analyze four blood lipid levels in data from a meta-analysis of eight European studies. The proposed methods detect more significant associations than MetaSKAT and the P-values of the proposed LRT and F-distributed statistics are usually much smaller than those of MetaSKAT. The functional linear models and related test statistics can be useful in whole-genome and whole-exome association studies. Copyright © 2015 by the Genetics Society of America.

Test- and behavior-specific genetic factors affect WKY hypoactivity in tests of emotionality.

PubMed

Baum, Amber E; Solberg, Leah C; Churchill, Gary A; Ahmadiyeh, Nasim; Takahashi, Joseph S; Redei, Eva E

2006-05-15

Inbred Wistar-Kyoto rats consistently display hypoactivity in tests of emotional behavior. We used them to test the hypothesis that the genetic factors underlying the behavioral decision-making process will vary in different environmental contexts. The contexts used were the open-field test (OFT), a novel environment with no explicit threats present, and the defensive-burying test (DB), a habituated environment into which a threat has been introduced. Rearing, a voluntary behavior was measured in both tests, and our study was the first to look for genetic loci affecting grooming, a relatively automatic, stress-responsive stereotyped behavior. Quantitative trait locus analysis was performed on a population of 486 F2 animals bred from reciprocal inter-crosses. The genetic architectures of DB and OFT rearing, and of DB and OFT grooming, were compared. There were no common loci affecting grooming behavior in both tests. These different contexts produced the stereotyped behavior via different pathways, and genetic factors seem to influence the decision-making pathways and not the expression of the behavior. Three loci were found that affected rearing behavior in both tests. However, in both contexts, other loci had greater effects on the behavior. Our results imply that environmental context's effects on decision-making vary depending on the category of behavior.

Genetic Evaluation of Short Stature

PubMed Central

Rosenfeld, Ron G.

2014-01-01

Context: Genetics plays a major role in determining an individual's height. Although there are many monogenic disorders that lead to perturbations in growth and result in short stature, there is still no consensus as to the role that genetic diagnostics should play in the evaluation of a child with short stature. Evidence Acquisition: A search of PubMed was performed, focusing on the genetic diagnosis of short stature as well as on specific diagnostic subgroups included in this article. Consensus guidelines were reviewed. Evidence Synthesis: There are a multitude of rare genetic causes of severe short stature. There is no high-quality evidence to define the optimal approach to the genetic evaluation of short stature. We review genetic etiologies of a number of diagnostic subgroups and propose an algorithm for genetic testing based on these subgroups. Conclusion: Advances in genomic technologies are revolutionizing the diagnostic approach to short stature. Endocrinologists must become facile with the use of genetic testing in order to identify the various monogenic disorders that present with short stature. PMID:24915122

Genetic relationships between feed efficiency in growing males and beef cow performance.

PubMed

Crowley, J J; Evans, R D; Mc Hugh, N; Kenny, D A; McGee, M; Crews, D H; Berry, D P

2011-11-01

Most studies on feed efficiency in beef cattle have focused on performance in young animals despite the contribution of the cow herd to overall profitability of beef production systems. The objective of this study was to quantify, using a large data set, the genetic covariances between feed efficiency in growing animals measured in a performance-test station, and beef cow performance including fertility, survival, calving traits, BW, maternal weaning weight, cow price, and cull cow carcass characteristics in commercial herds. Feed efficiency data were available on 2,605 purebred bulls from 1 test station. Records on cow performance were available on up to 94,936 crossbred beef cows. Genetic covariances were estimated using animal and animal-dam linear mixed models. Results showed that selection for feed efficiency, defined as feed conversion ratio (FCR) or residual BW gain (RG), improved maternal weaning weight as evidenced by the respective genetic correlations of -0.61 and 0.57. Despite residual feed intake (RFI) being phenotypically independent of BW, a negative genetic correlation existed between RFI and cow BW (-0.23; although the SE of 0.31 was large). None of the feed efficiency traits were correlated with fertility, calving difficulty, or perinatal mortality. However, genetic correlations estimated between age at first calving and FCR (-0.55 ± 0.14), Kleiber ratio (0.33 ± 0.15), RFI (-0.29 ± 0.14), residual BW gain (0.36 ± 0.15), and relative growth rate (0.37 ± 0.15) all suggest that selection for improved efficiency may delay the age at first calving, and we speculate, using information from other studies, that this may be due to a delay in the onset of puberty. Results from this study, based on the estimated genetic correlations, suggest that selection for improved feed efficiency will have no deleterious effect on cow performance traits with the exception of delaying the age at first calving.

Frequency of five disease-causing genetic mutations in a large mixed-breed dog population (2011–2012)

PubMed Central

Zierath, Sharon; Hughes, Angela M.; Fretwell, Neale; Dibley, Mark

2017-01-01

Background A large and growing number of inherited genetic disease mutations are now known in the dog. Frequencies of these mutations are typically examined within the breed of discovery, possibly in related breeds, but nearly always in purebred dogs. No report to date has examined the frequencies of specific genetic disease mutations in a large population of mixed-breed dogs. Further, veterinarians and dog owners typically dismiss inherited/genetic diseases as possibilities for health problems in mixed-breed dogs, assuming hybrid vigor will guarantee that single-gene disease mutations are not a cause for concern. Therefore, the objective of this study was to screen a large mixed-breed canine population for the presence of mutant alleles associated with five autosomal recessive disorders: hyperuricosuria and hyperuricemia (HUU), cystinuria (CYST), factor VII deficiency (FVIID), myotonia congenita (MYC) and phosphofructokinase deficiency (PKFD). Genetic testing was performed in conjunction with breed determination via the commercially-available Wisdom PanelTM test. Results From a population of nearly 35,000 dogs, homozygous mutant dogs were identified for HUU (n = 57) and FVIID (n = 65). Homozygotes for HUU and FVIID were identified even among dogs with highly mixed breed ancestry. Carriers were identified for all disorders except MYC. HUU and FVIID were of high enough frequency to merit consideration in any mixed-breed dog, while CYST, MYC, and PKFD are vanishingly rare. Conclusions The assumption that mixed-breed dogs do not suffer from single-gene genetic disorders is shown here to be false. Within the diseases examined, HUU and FVIID should remain on any practitioner’s rule-out list, when clinically appropriate, for all mixed-breed dogs, and judicious genetic testing should be performed for diagnosis or screening. Future testing of large mixed-breed dog populations that include additional known canine genetic mutations will refine our knowledge of which genetic diseases can strike mixed-breed dogs. PMID:29166669

Frequency of five disease-causing genetic mutations in a large mixed-breed dog population (2011-2012).

PubMed

Zierath, Sharon; Hughes, Angela M; Fretwell, Neale; Dibley, Mark; Ekenstedt, Kari J

2017-01-01

A large and growing number of inherited genetic disease mutations are now known in the dog. Frequencies of these mutations are typically examined within the breed of discovery, possibly in related breeds, but nearly always in purebred dogs. No report to date has examined the frequencies of specific genetic disease mutations in a large population of mixed-breed dogs. Further, veterinarians and dog owners typically dismiss inherited/genetic diseases as possibilities for health problems in mixed-breed dogs, assuming hybrid vigor will guarantee that single-gene disease mutations are not a cause for concern. Therefore, the objective of this study was to screen a large mixed-breed canine population for the presence of mutant alleles associated with five autosomal recessive disorders: hyperuricosuria and hyperuricemia (HUU), cystinuria (CYST), factor VII deficiency (FVIID), myotonia congenita (MYC) and phosphofructokinase deficiency (PKFD). Genetic testing was performed in conjunction with breed determination via the commercially-available Wisdom PanelTM test. From a population of nearly 35,000 dogs, homozygous mutant dogs were identified for HUU (n = 57) and FVIID (n = 65). Homozygotes for HUU and FVIID were identified even among dogs with highly mixed breed ancestry. Carriers were identified for all disorders except MYC. HUU and FVIID were of high enough frequency to merit consideration in any mixed-breed dog, while CYST, MYC, and PKFD are vanishingly rare. The assumption that mixed-breed dogs do not suffer from single-gene genetic disorders is shown here to be false. Within the diseases examined, HUU and FVIID should remain on any practitioner's rule-out list, when clinically appropriate, for all mixed-breed dogs, and judicious genetic testing should be performed for diagnosis or screening. Future testing of large mixed-breed dog populations that include additional known canine genetic mutations will refine our knowledge of which genetic diseases can strike mixed-breed dogs.

Current Landscape and New Paradigms of Proficiency Testing and External Quality Assessment for Molecular Genetics

PubMed Central

Kalman, Lisa V.; Lubin, Ira M.; Barker, Shannon; du Sart, Desiree; Elles, Rob; Grody, Wayne W.; Pazzagli, Mario; Richards, Sue; Schrijver, Iris; Zehnbauer, Barbara

2015-01-01

Context Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests which quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests. Objective To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies. Data Sources The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers. Conclusions PT/EQA schemes are available for common genetic disorders tested in many clinical laboratories, but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of a large number of tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in the testing process. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed. PMID:23808472

An observational study of the impact of genetic testing for pain perception in the clinical management of chronic non-cancer pain.

PubMed

Sharma, Maneesh; Kantorovich, Svetlana; Lee, Chee; Anand, Natasha; Blanchard, John; Fung, Eric T; Meshkin, Brian; Brenton, Ashley; Richeimer, Steven

2017-06-01

Pain levels are a key metric in clinical care. However, the assessment of pain is limited to basic questionnaires and physician interpretation, which yield subjective data. Genetic markers of pain sensitivity, such as single nucleotide polymorphisms in the catechol-O-methyltransferase gene, have been shown to be associated with pain perception and have been used to provide objective information about a patient's pain. The goal of this study was to determine if physician treatment adjustments based on genetic tests of pain perception resulted in improved outcomes for patients. A prospective, longitudinal study was conducted with 134 chronic non-cancer pain patients genotyped for pain perception-related catechol-O-methyltransferase haplotypes. Physicians were provided with patients' results and asked to document 1) their assessment of benefit of the genetic test; 2) treatment changes made based on the genetic test; and 3) patient clinical responses to changes implemented. Based on genetic testing results, physicians adjusted treatment plans for 40% of patients. When medication changes were made based on genetic testing results, 72% of patients showed improvement in clinical status. When non-pharmacological actions were performed, 69% of physicians felt their patients' clinical status improved. Moreover, physicians believed the genetic test results were consistent with patient pain levels in 85% of cases. These results demonstrate that providing personalized medicine with genetic information related to pain perception affected physician clinical decision-making for a substantial proportion of patients in this study, and that the availability and utilization of this information was a contributing factor in clinical improvement. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Advantages and disadvantages of direct-to-consumer genetic tests].

PubMed

Christiansen, Camilla Worm; Gerdes, Anne-Marie Axø

2017-03-13

Direct-to-consumer genetic tests are sold over the internet to consumers all over the world - including Denmark. No regulation of these tests has been introduced neither in Denmark nor in Europe, even though they have been on the market since 2007. Such tests have several advantages, but indeed also a long list of potential disadvantages, which are most often ignored, and among these is insufficient training of general practitioners in performing the necessary counselling but also the risk of increased expenses to unnecessary follow-up consultations.

Model-Based Linkage Analysis of a Quantitative Trait.

PubMed

Song, Yeunjoo E; Song, Sunah; Schnell, Audrey H

2017-01-01

Linkage Analysis is a family-based method of analysis to examine whether any typed genetic markers cosegregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single-marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model-based linkage analysis the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it also includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single-marker analysis, and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait.

Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study.

PubMed

Ream, Margie A; Mikati, Mohamad A

2014-08-01

The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing. Copyright © 2014. Published by Elsevier Inc.

An International Genetic Survey of Breed-Specific Diseases in Working Dogs from the United States, Israel, and Poland.

PubMed

Shaffer, Lisa G; Ramirez, Christina J; Phelps, Patricia; Aviram, Maya; Walczak, Marta; Bar-Gal, Gila Kahila; Ballif, Blake C

2017-01-01

Genetic diseases occur in breeds used for law enforcement. As important team members, dogs are expected to operate at peak performance for several years and are significant investments for both the initial purchase and extensive, specialized training. Previous studies have not focused on causes for retirement or euthanasia as genetic (inherited) versus acquired (environmental). We performed direct mutational analysis for breed-specific conditions on samples from 304 dogs including 267 law enforcement (122 US, 87 Israeli, and 58 Polish) and 37 search and rescue dogs. Genetic testing identified 29% (n = 89) of the dogs tested to be carriers of a genetic mutation and 6% (n = 19) to be at risk for a debilitating inherited condition that may eventually impair the dog's ability to work. At-risk dogs included Labrador Retrievers (n = 4) with exercise-induced collapse, Bloodhounds (n = 2) with degenerative myelopathy (DM), and German Shepherd dogs with DM (n = 12) or leukocyte adhesion deficiency, type III (n = 1). A substantial number of working dogs were shown to be at risk for genetic conditions that may shorten the dog's career. The loss of dogs, due to early retirement or euthanasia, as a result of preventable genetic conditions has an emotional cost to handlers and financial cost to service organizations that can be avoided with genetic screening prior to breeding, buying, or training. © 2018 S. Karger AG, Basel.

Committee Opinion No. 693: Counseling About Genetic Testing and Communication of Genetic Test Results.

PubMed

2017-04-01

Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.

Committee Opinion No. 693 Summary: Counseling About Genetic Testing and Communication of Genetic Test Results.

PubMed

2017-04-01

Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.

The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies

PubMed Central

Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong

2017-01-01

It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online. PMID:28736464

Health-Care Referrals from Direct-to-Consumer Genetic Testing

PubMed Central

Giovanni, Monica A.; Fickie, Matthew R.; Lehmann, Lisa S.; Green, Robert C.; Meckley, Lisa M.; Veenstra, David

2010-01-01

Background: Direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. Aim: To query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. Methods: Invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. Results: The invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT. Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be “clinically useful.” BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. Conclusions: This clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system. PMID:20979566

Health-care referrals from direct-to-consumer genetic testing.

PubMed

Giovanni, Monica A; Fickie, Matthew R; Lehmann, Lisa S; Green, Robert C; Meckley, Lisa M; Veenstra, David; Murray, Michael F

2010-12-01

direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. to query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. the invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT. Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be "clinically useful." BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. this clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

PubMed Central

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-01-01

Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. PMID:27208206

Merits and pitfalls of genetic testing in a hypertrophic cardiomyopathy clinic.

PubMed

Arad, Michael; Monserrat, Lorenzo; Haron-Khun, Shiraz; Seidman, Jonathan G; Seidman, Christine E; Arbustini, Eloisa; Glikson, Michael; Freimark, Dov

2014-11-01

Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM. To analyze the impact of genetic diagnosis on the clinical management of HCM. Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation. Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation. Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.

A twin study of spatial and non-spatial delayed response performance in middle age.

PubMed

Kremen, William S; Mai, Tuan; Panizzon, Matthew S; Franz, Carol E; Blankfeld, Howard M; Xian, Hong; Eisen, Seth A; Tsuang, Ming T; Lyons, Michael J

2011-06-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. Copyright © 2011 Elsevier Inc. All rights reserved.

A Twin Study of Spatial and Non-Spatial Delayed Response Performance in Middle Age

PubMed Central

Kremen, William S.; Mai, Tuan; Panizzon, Matthew S.; Franz, Carol E.; Blankfeld, Howard M.; Xian, Hong; Eisen, Seth A.; Tsuang, Ming T.; Lyons, Michael J.

2011-01-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h2=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (rg=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high “failure” rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. PMID:21477911

Bend it like Beckham! The Ethics of Genetically Testing Children for Athletic Potential

PubMed Central

Camporesi, Silvia

2016-01-01

The recent boom of direct-to-consumer (DTC) genetic tests, aimed at measuring children’s athletic potential, is the latest wave in the ‘pre-professionalization’ of children that has characterized, especially but not exclusively, the USA in the last 15 years or so. In this paper, I analyse the use of DTC genetic tests, sometimes coupled with more traditional methods of ‘talent scouting’, to assess a child’s predisposition to athletic performance. I first discuss the scientific evidence at the basis of these tests, and the parental decision in terms of education, and of investing in the children’s future, taken on the basis of the results of the tests. I then discuss how these parental practices impact on the children’s right to an open future, and on their developing sense of autonomy. I also consider the meaning and role of sports in childhood, and conclude that the use of DTC genetic tests to measure children’s athletic potential should be seen as a ‘wake up’ call for other problematic parental attitudes aimed at scouting and developing children’s talent. PMID:27996058

A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis.

PubMed

Lee, Hwa Jeen; Park, Seungman; Kang, Hyoung Jin; Jun, Jong Kwan; Lee, Jung Ae; Lee, Dong Soon; Park, Sung Sup; Seong, Moon-Woo

2012-09-01

Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.

Revealing barriers and facilitators to use a new genetic test: comparison of three user involvement methods.

PubMed

Rhebergen, Martijn D F; Visser, Maaike J; Verberk, Maarten M; Lenderink, Annet F; van Dijk, Frank J H; Kezic, Sanja; Hulshof, Carel T J

2012-10-01

We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well.

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing

PubMed Central

Susswein, Lisa R.; Marshall, Megan L.; Nusbaum, Rachel; Vogel Postula, Kristen J.; Weissman, Scott M.; Yackowski, Lauren; Vaccari, Erica M.; Bissonnette, Jeffrey; Booker, Jessica K.; Cremona, M. Laura; Gibellini, Federica; Murphy, Patricia D.; Pineda-Alvarez, Daniel E.; Pollevick, Guido D.; Xu, Zhixiong; Richard, Gabi; Bale, Sherri; Klein, Rachel T.; Hruska, Kathleen S.; Chung, Wendy K.

2016-01-01

Purpose: Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance. Genet Med 18 8, 823–832. Methods: Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history. Genet Med 18 8, 823–832. Results: Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2. Genet Med 18 8, 823–832. Conclusion: The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes. Genet Med 18 8, 823–832. PMID:26681312

Genome-based prediction of test cross performance in two subsequent breeding cycles.

PubMed

Hofheinz, Nina; Borchardt, Dietrich; Weissleder, Knuth; Frisch, Matthias

2012-12-01

Genome-based prediction of genetic values is expected to overcome shortcomings that limit the application of QTL mapping and marker-assisted selection in plant breeding. Our goal was to study the genome-based prediction of test cross performance with genetic effects that were estimated using genotypes from the preceding breeding cycle. In particular, our objectives were to employ a ridge regression approach that approximates best linear unbiased prediction of genetic effects, compare cross validation with validation using genetic material of the subsequent breeding cycle, and investigate the prospects of genome-based prediction in sugar beet breeding. We focused on the traits sugar content and standard molasses loss (ML) and used a set of 310 sugar beet lines to estimate genetic effects at 384 SNP markers. In cross validation, correlations >0.8 between observed and predicted test cross performance were observed for both traits. However, in validation with 56 lines from the next breeding cycle, a correlation of 0.8 could only be observed for sugar content, for standard ML the correlation reduced to 0.4. We found that ridge regression based on preliminary estimates of the heritability provided a very good approximation of best linear unbiased prediction and was not accompanied with a loss in prediction accuracy. We conclude that prediction accuracy assessed with cross validation within one cycle of a breeding program can not be used as an indicator for the accuracy of predicting lines of the next cycle. Prediction of lines of the next cycle seems promising for traits with high heritabilities.

Growth Hormone Deficiency in Adults

MedlinePlus

... tests that help detect GHD are performed after fasting overnight. These tests involve giving patients a substance ... Genetic Diseases Pituitary Disorders Thyroid Disorders Transgender Health Obesity and Weight Management Women's Health International Resource Center ...

Evaluation of Residual Static Corrections by Hybrid Genetic Algorithm Steepest Ascent Autostatics Inversion.Application southern Algerian fields

NASA Astrophysics Data System (ADS)

Eladj, Said; bansir, fateh; ouadfeul, sid Ali

2016-04-01

The application of genetic algorithm starts with an initial population of chromosomes representing a "model space". Chromosome chains are preferentially Reproduced based on Their fitness Compared to the total population. However, a good chromosome has a Greater opportunity to Produce offspring Compared To other chromosomes in the population. The advantage of the combination HGA / SAA is the use of a global search approach on a large population of local maxima to Improve Significantly the performance of the method. To define the parameters of the Hybrid Genetic Algorithm Steepest Ascent Auto Statics (HGA / SAA) job, we Evaluated by testing in the first stage of "Steepest Ascent," the optimal parameters related to the data used. 1- The number of iterations "Number of hill climbing iteration" is equal to 40 iterations. This parameter defines the participation of the algorithm "SA", in this hybrid approach. 2- The minimum eigenvalue for SA '= 0.8. This is linked to the quality of data and S / N ratio. To find an implementation performance of hybrid genetic algorithms in the inversion for estimating of the residual static corrections, tests Were Performed to determine the number of generation of HGA / SAA. Using the values of residual static corrections already calculated by the Approaches "SAA and CSAA" learning has Proved very effective in the building of the cross-correlation table. To determine the optimal number of generation, we Conducted a series of tests ranging from [10 to 200] generations. The application on real seismic data in southern Algeria allowed us to judge the performance and capacity of the inversion with this hybrid method "HGA / SAA". This experience Clarified the influence of the corrections quality estimated from "SAA / CSAA" and the optimum number of generation hybrid genetic algorithm "HGA" required to have a satisfactory performance. Twenty (20) generations Were enough to Improve continuity and resolution of seismic horizons. This Will allow us to achieve a more accurate structural interpretation Key words: Hybrid Genetic Algorithm, number of generations, model space, local maxima, Number of hill climbing iteration, Minimum eigenvalue, cross-correlation table

Genomics in rugby union: A review and future prospects.

PubMed

Heffernan, Shane M; Kilduff, Liam P; Day, Stephen H; Pitsiladis, Yannis P; Williams, Alun G

2015-01-01

This article introduces some aspects of sports genomics in a rugby union context, considers the rugby-specific genetic data in the published literature and outlines the next research steps required if the potential applications of genetic technology in rugby union, also identified here, are to become possible. A substantial proportion of the inter-individual variation for many traits related to rugby performance, including strength, short-term muscle power, VO2 max, injury susceptibility and the likelihood of being an elite athlete is inherited and can be investigated using molecular genetic techniques. In sports genomics, significant efforts have been made in recent years to develop large DNA biobanks of elite athletes for detailed exploration of the heritable bases of those traits. However, little effort has been devoted to the study of rugby athletes, and most of the little research that has focused on rugby was conducted with small cohorts of non-elite players. With steadily growing knowledge of the molecular mechanisms underpinning complex performance traits and the aetiology of injury, investigating sports genomics in the context of rugby is now a viable proposition and a worthwhile endeavour. The RugbyGene project we describe briefly in this article is a multi-institutional research collaboration in rugby union that will perform molecular genetic analyses of varying complexity. Genetic tests could become useful tools for rugby practitioners in the future and provide complementary and additional information to that provided by the non-genetic tests currently used.

Where Lab Tests Are Performed

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Accessed June 2011. Genetics and Public Policy Center. Survey of Direct-to-Consumer Testing Statutes and Regulations. ...

Analytical criteria for performance characteristics of IgE binding methods for evaluating safety of biotech food products.

PubMed

Holzhauser, Thomas; Ree, Ronald van; Poulsen, Lars K; Bannon, Gary A

2008-10-01

There is detailed guidance on how to perform bioinformatic analyses and enzymatic degradation studies for genetically modified crops under consideration for approval by regulatory agencies; however, there is no consensus in the scientific community on the details of how to perform IgE serum studies. IgE serum studies are an important safety component to acceptance of genetically modified crops when the introduced protein is novel, the introduced protein is similar to known allergens, or the crop is allergenic. In this manuscript, we describe the characteristics of the reagents, validation of assay performance, and data analysis necessary to optimize the information obtained from serum testing of novel proteins and genetically modified (GM) crops and to make results more accurate and comparable between different investigations.

Performance of Loblolly Pine Seed Sources in Argentina

Treesearch

Timothy La Farge; Floyd E. Bridgwater; Mirta N. Baez

1999-01-01

Four test series of loblolly pine (Pinus taeda L.) were evaluated to determine the performance in northeastern Argentina of seed sources from three breeding populations in the southeastern United States. Three half-sib progeny tests of seed sources from Florida and Louisiana demonstrated strong genetic gains for height, dbh, and volume growth....

Utility of Genetic Testing in Elite Volleyball Players with Aortic Root Dilation.

PubMed

Herrick, Nicole; Davis, Christopher; Vargas, Lisa; Dietz, Hal; Grossfeld, Paul

2017-07-01

Basketball and volleyball attract individuals with a characteristic biophysical profile, mimicking features of Marfan syndrome. Consequently, identification of these abnormalities can be lifesaving. To determine how physical examination, echocardiography, and genetic screening can identify elite volleyball players with a previously undiagnosed aortopathy. We have performed cardiac screening on 90 US Volleyball National Team members and identified four individuals with dilated sinuses of Valsalva. This case series reports on three individuals who underwent a comprehensive genetics evaluation, including gene sequencing. Cardiac screening combined with genetic testing can identify previously undiagnosed tall athletes with an aortopathy, in the absence of noncardiac findings of a connective tissue disorder. Subject 1 had a revised Ghent systems (RGS) score of 2 and a normal aortopathy gene panel. Subject 2 had a RGS score of 1 and genetic testing revealed a de novo disease causing mutation in the gene encoding fibrillin-1 (FBN1). Subject 3 had an RGS score of 4.0 and had a normal aortopathy gene panel. Despite variable clinical features of Marfan syndrome, dilated sinuses of Valsalva were found in 4.9% of the athletes. A disease-causing mutation in the FBN1 gene was identified in subject 2, who had the lowest RGS but the largest aortic root measurement. Subjects 1 and 3, with the highest RGS, had a normal aortopathy gene panel. Our findings provide further evidence suggesting that a cardiac evaluation, including a screening echocardiogram, should be performed on all elite tall adult athletes independent of other physical findings. Genetic testing should be considered for athletes with dilated sinuses of Valsalva (male, >4.2 cm; female, >3.4 cm), regardless of other extracardiac findings.

Conventional and genetic talent identification in sports: will recent developments trace talent?

PubMed

Breitbach, Sarah; Tug, Suzan; Simon, Perikles

2014-11-01

The purpose of talent identification (TI) is the earliest possible selection of auspicious athletes with the goal of systematically maximizing their potential. The literature proposes excellent reviews on various facets of talent research on different scientific issues such as sports sciences or genetics. However, the approaches of conventional and genetic testing have only been discussed separately by and for the respective groups of interest. In this article, we combine the discoveries of these disciplines into a single review to provide a comprehensive overview and elucidate the prevailing limitations. Fundamental problems in TI reside in the difficulties of defining the construct ‘talent’ or groups of different performance levels that represent the target variable of testing. Conventional and genetic testing reveal a number of methodological and technical limitations, and parallels are summarised in terms of the test designs, the point in time of testing, psychological skills or traits and unknown interactions between different variables. In conclusion, many deficiencies in the current talent research have gained attention. Alternative solutions include the talent development approach, while genetic testing is re-emphasised as a tool for risk stratification in sport participation. Future research needs to clearly define the group of interest and comprehensively implement all methodological improvement suggestions.

DNA: The Strand that Connects Us All

ScienceCinema

Kaplan, Matt [Univ. of Arizona, Tucson, AZ (United States). Genetics Core Facility

2018-04-26

Learn how the methods and discoveries of human population genetics are applied for personal genealogical reconstruction and anthropological testing. Dr. Kaplan starts with a short general review of human genetics and the biology behind this form of DNA testing. He looks at how DNA testing is performed and how samples are processed in the University of Arizona laboratory. He also examines examples of personal genealogical results from Family Tree DNA and personal anthropological results from the Genographic Project. Finally, he describes the newest project in the UA laboratory, the DNA Shoah Project.

Mathematical Ability of 10-Year-Old Boys and Girls: Genetic and Environmental Etiology of Typical and Low Performance

PubMed Central

Kovas, Yulia; Haworth, Claire M. A.; Petrill, Stephen A.; Plomin, Robert

2009-01-01

The genetic and environmental etiologies of 3 aspects of low mathematical performance (math disability) and the full range of variability (math ability) were compared for boys and girls in a sample of 5,348 children age 10 years (members of 2,674 pairs of same-sex and opposite-sex twins) from the United Kingdom (UK). The measures, which we developed for Web-based testing, included problems from 3 domains of mathematics taught as part of the UK National Curriculum. Using quantitative genetic model-fitting analyses, similar results were found for math disabilities and abilities for all 3 measures: Moderate genetic influence and environmental influence were mainly due to nonshared environmental factors that were unique to the individual, with little influence from shared environment. No sex differences were found in the etiologies of math abilities and disabilities. We conclude that low mathematical performance is the quantitative extreme of the same genetic and environmental factors responsible for variation throughout the distribution. PMID:18064980

An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.

PubMed

Jalaly, Niloofar Y; Moran, Robert A; Fargahi, Farshid; Khashab, Mouen A; Kamal, Ayesha; Lennon, Anne Marie; Walsh, Christi; Makary, Martin A; Whitcomb, David C; Yadav, Dhiraj; Cebotaru, Liudmila; Singh, Vikesh K

2017-08-01

We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis. Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)<35 years of age; and (4) family history of pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants. Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis. Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

Clinically relevant lessons from Family HealthLink: a cancer and coronary heart disease familial risk assessment tool.

PubMed

Sweet, Kevin; Sturm, Amy C; Rettig, Amy; McElroy, Joseph; Agnese, Doreen

2015-06-01

A descriptive retrospective study was performed using two separate user cohorts to determine the effectiveness of Family HealthLink as a clinical triage tool. Cohort 1 consisted of 2,502 users who accessed the public website. Cohort 2 consisted of 194 new patients in a Comprehensive Breast Center setting. For patient users, we assessed documentation of family history and genetics referral. For all users seen in a genetics clinic, the Family HealthLink assessment was compared with that performed by genetic counselors and genetic testing outcomes. For general public users, the percentage meeting high-risk criteria were: for cancer only, 22.2%; for coronary heart disease only, 24.3%; and for both diseases, 10.4%. These risk stratification percentages were similar for the patient users. For the patient users, there often was documentation of family history of certain cancer types by oncology professionals, but age of onset and coronary heart disease family history were less complete. Of 142 with high-risk assignments seen in a genetics clinic, 130 (91.5%) of these assignments were corroborated. Forty-two underwent genetic testing and 17 (40.5%) had new molecular diagnoses established. A significant percentage of individuals are at high familial risk and may require more intensive screening and referral. Interactive family history triage tools can aid this process.Genet Med 17 6, 493-500.

Legal implications of genetics and crime research.

PubMed

Denno, D W

1996-01-01

Two controversial topics dominate discussions of the legal implications of genetics and crime research; (1) the viability and politics of such research, which has sparked fervent debate in the USA; and (2) the current status of new or atypical criminal law defences, which would include a genetic-defect defence to criminal behaviour. This chapter begins by examining the scientifically discredited XYY chromosome syndrome defence, the major genetic-defect defence that defendants have attempted, albeit unsuccessfully. It then focuses on attorneys' efforts to test for evidence of genetic abnormality in the recent and highly publicized case involving convicted murderer Stephen Mobley, whose family history reveals four generations of violent, aggressive and behaviourally disordered men and women. Mobley is currently appealing his death sentence before the Georgia Supreme Court on the basis that the trial court denied his request both to have genetic testing performed and to have such testing allowed as evidence into court. This chapter concludes by emphasizing that the question is not whether genetic evidence will ever be admitted into court, but when and under what kinds of circumstances. No doubt, genetic evidence, and comparable kinds of biological evidence, will have a major impact on juries when such evidence is more fully accepted by the legal and scientific communities.

Genetic testing of aetiology of intellectual disability in a dedicated physical healthcare outpatient clinic for adults with intellectual disability.

PubMed

Wallace, R A

2016-02-01

No guidelines exist for assessment of aetiology of intellectual disability in adults with intellectual disability by adult physicians, although robust guidelines exist for paediatric populations. It was speculated that the paediatric guidelines would also be suitable for adults. In rural/regional setting with limited clinical genetics, to perform a quality assurance evaluation on genetics assessment of aetiology of developmental disability in adults attending a dedicated healthcare clinic for adults with intellectual disability, compared results with paediatric standards, speculates if these seem appropriate for adults and speculates on a role for clinical genetics services. Retrospective chart audit of eligible patients looking at genetic clinical assessment, tests selected (molecular karyotype, G banding, metabolics), and yields of positive results. The results were compared with the recommended paediatric guidelines. Of 117 eligible adult patients, ideal genetic history was incomplete for 40% of patients without Down syndrome because of physician cause and lack of information. The number of abnormal genetic results increased from 46% to 66%, mainly from the molecular karyotype, though not all may have been clinically relevant. The improved yield from this test was similar to that in paediatric studies. Use of G banding and metabolic testing could be refined. Improvement can be made in clinical genetic assessment, but results generally support use of molecular karyotyping as first tier testing of cause of unknown intellectual disability in adults, as in the case for paediatric populations. The study highlights a necessary complementary role for clinical geneticists to interpret abnormal results. © 2016 Royal Australasian College of Physicians.

Genetic testing and counseling of a recipient after bone marrow transplant from a sibling harboring a germline BRCA1 pathogenic mutation.

PubMed

Škerl, Petra; Krajc, Mateja; Blatnik, Ana; Novaković, Srdjan

2017-07-01

Allogenic bone marrow transplant recipients represent a unique challenge, when they are referred for genetic testing and counseling. When performing genetic testing, it is extremely important to ensure that the detected DNA mutations originate from the patients own DNA, and therefore the most appropriate and reliable biological sample for DNA isolation must be obtained. The aim of the present study was to present the germline testing and counseling approach utilized in a rare case of a chimeric woman who received an allogenic bone marrow transplant from a sibling with a germline BRCA1 pathogenic mutation. According to our results, hairs with follicles are a reliable and ready source of DNA in a patient whose blood is of allogenic bone marrow transplant donor origin. Compared with a fibroblast culture, which is more difficult to obtain, the hair follicles are much more accessible and hair sampling is less invasive for the patient. Genetic testing based on the other sources of DNA, such as buccal swabs, is questionable due to the known risk of donor DNA contamination.

Heritability of Boldness and Hypoxia Avoidance in European Seabass, Dicentrarchus labrax.

PubMed

Ferrari, Sébastien; Horri, Khaled; Allal, François; Vergnet, Alain; Benhaim, David; Vandeputte, Marc; Chatain, Béatrice; Bégout, Marie-Laure

2016-01-01

To understand the genetic basis of coping style in European seabass, fish from a full factorial mating (10 females x 50 males) were reared in common garden and individually tagged. Individuals coping style was characterized through behavior tests at four different ages, categorizing fish into proactive or reactive: a hypoxia avoidance test (at 255 days post hatching, dph) and 3 risk-taking tests (at 276, 286 and 304 dph). We observed significant heritability of the coping style, higher for the average of risk-taking scores (h2 = 0.45 ± 0.14) than for the hypoxia avoidance test (h2 = 0.19 ± 0.10). The genetic correlations between the three risk-taking scores were very high (rA = 0.96-0.99) showing that although their repeatability was moderately high (rP = 0.64-0.72), successive risk-taking tests evaluated the same genetic variation. A mild genetic correlation between the results of the hypoxia avoidance test and the average of risk-taking scores (0.45 ± 0.27) suggested that hypoxia avoidance and risk-taking tests do not address exactly the same behavioral and physiological responses. Genetic correlations between weight and risk taking traits showed negative values whatever the test used in our population i.e. reactive individual weights were larger. The results of this quantitative genetic analysis suggest a potential for the development of selection programs based on coping styles that could increase seabass welfare without altering growth performances. Overall, it also contributes to a better understanding of the origin and the significance of individual behavioral differences.

Familial Hypercholesterolemia: A Systematic Review of Guidelines on Genetic Testing and Patient Management.

PubMed

Migliara, Giuseppe; Baccolini, Valentina; Rosso, Annalisa; D'Andrea, Elvira; Massimi, Azzurra; Villari, Paolo; De Vito, Corrado

2017-01-01

Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways. We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument. Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy. Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members via cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention.

Behavioural changes, sharing behaviour and psychological responses after receiving direct-to-consumer genetic test results: a systematic review and meta-analysis.

PubMed

Stewart, Kelly F J; Wesselius, Anke; Schreurs, Maartje A C; Schols, Annemie M W J; Zeegers, Maurice P

2018-01-01

It has been hypothesised that direct-to-consumer genetic tests (DTC-GTs) could stimulate health behaviour change. However, genetic testing may also lead to anxiety and distress or unnecessarily burden the health care system. The aim is to review and meta-analyse the effects of DTC-GT on (1) behaviour change, (2) psychological response and (3) medical consumption. A systematic literature search was performed in three databases, using "direct-to-consumer genetic testing" as a key search term. Random effects meta-analyses were performed when at least two comparable outcomes were available. After selection, 19 articles were included involving 11 unique studies. Seven studies involved actual consumers who paid the retail price, whereas four included participants who received free genetic testing as part of a research trial (non-actual consumers). In meta-analysis, 23% had a positive lifestyle change. More specifically, improved dietary and exercise practices were both reported by 12%, whereas 19% quit smoking. Seven percent of participants had subsequent preventive checks. Thirty-three percent shared their results with any health care professional and 50% with family and/or friends. Sub-analyses show that behaviour change was more prevalent among non-actual consumers, whereas sharing was more prevalent among actual consumers. Results on psychological responses showed that anxiety, distress and worry were low or absent and that the effect faded with time. DTC-GT has potential to be effective as a health intervention, but the right audience needs to be addressed with tailored follow-up. Research is needed to identify consumers who do and do not change behaviour or experience adverse psychological responses.

Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

PubMed

Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David

2018-05-15

Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

On the Optimization of Aerospace Plane Ascent Trajectory

NASA Astrophysics Data System (ADS)

Al-Garni, Ahmed; Kassem, Ayman Hamdy

A hybrid heuristic optimization technique based on genetic algorithms and particle swarm optimization has been developed and tested for trajectory optimization problems with multi-constraints and a multi-objective cost function. The technique is used to calculate control settings for two types for ascending trajectories (constant dynamic pressure and minimum-fuel-minimum-heat) for a two-dimensional model of an aerospace plane. A thorough statistical analysis is done on the hybrid technique to make comparisons with both basic genetic algorithms and particle swarm optimization techniques with respect to convergence and execution time. Genetic algorithm optimization showed better execution time performance while particle swarm optimization showed better convergence performance. The hybrid optimization technique, benefiting from both techniques, showed superior robust performance compromising convergence trends and execution time.

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

PubMed

Amstutz, Ursula; Shear, Neil H; Rieder, Michael J; Hwang, Soomi; Fung, Vincent; Nakamura, Hidefumi; Connolly, Mary B; Ito, Shinya; Carleton, Bruce C

2014-04-01

To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Gene-Based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions.

PubMed

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y; Chen, Wei

2016-02-01

Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. © 2016 WILEY PERIODICALS, INC.

Gene-based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions

PubMed Central

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E.; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y.; Chen, Wei

2015-01-01

Summary Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, we develop here Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT) which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. PMID:26782979

Empirical valence bond models for reactive potential energy surfaces: a parallel multilevel genetic program approach.

PubMed

Bellucci, Michael A; Coker, David F

2011-07-28

We describe a new method for constructing empirical valence bond potential energy surfaces using a parallel multilevel genetic program (PMLGP). Genetic programs can be used to perform an efficient search through function space and parameter space to find the best functions and sets of parameters that fit energies obtained by ab initio electronic structure calculations. Building on the traditional genetic program approach, the PMLGP utilizes a hierarchy of genetic programming on two different levels. The lower level genetic programs are used to optimize coevolving populations in parallel while the higher level genetic program (HLGP) is used to optimize the genetic operator probabilities of the lower level genetic programs. The HLGP allows the algorithm to dynamically learn the mutation or combination of mutations that most effectively increase the fitness of the populations, causing a significant increase in the algorithm's accuracy and efficiency. The algorithm's accuracy and efficiency is tested against a standard parallel genetic program with a variety of one-dimensional test cases. Subsequently, the PMLGP is utilized to obtain an accurate empirical valence bond model for proton transfer in 3-hydroxy-gamma-pyrone in gas phase and protic solvent. © 2011 American Institute of Physics

Estimation of genetic parameters for heat stress, including dominance gene effects, on milk yield in Thai Holstein dairy cattle.

PubMed

Boonkum, Wuttigrai; Duangjinda, Monchai

2015-03-01

Heat stress in tropical regions is a major cause that strongly negatively affects to milk production in dairy cattle. Genetic selection for dairy heat tolerance is powerful technique to improve genetic performance. Therefore, the current study aimed to estimate genetic parameters and investigate the threshold point of heat stress for milk yield. Data included 52 701 test-day milk yield records for the first parity from 6247 Thai Holstein dairy cattle, covering the period 1990 to 2007. The random regression test day model with EM-REML was used to estimate variance components, genetic parameters and milk production loss. A decline in milk production was found when temperature and humidity index (THI) exceeded a threshold of 74, also it was associated with the high percentage of Holstein genetics. All variance component estimates increased with THI. The estimate of heritability of test-day milk yield was 0.231. Dominance variance as a proportion to additive variance (0.035) indicated that non-additive effects might not be of concern for milk genetics studies in Thai Holstein cattle. Correlations between genetic and permanent environmental effects, for regular conditions and due to heat stress, were - 0.223 and - 0.521, respectively. The heritability and genetic correlations from this study show that simultaneous selection for milk production and heat tolerance is possible. © 2014 Japanese Society of Animal Science.

Genomic testing interacts with reproductive surplus in reducing genetic lag and increasing economic net return.

PubMed

Hjortø, L; Ettema, J F; Kargo, M; Sørensen, A C

2015-01-01

Until now, genomic information has mainly been used to improve the accuracy of genomic breeding values for breeding animals at a population level. However, we hypothesize that the use of information from genotyped females also opens up the possibility of reducing genetic lag in a dairy herd, especially if genomic tests are used in combination with sexed semen or a high management level for reproductive performance, because both factors provide the opportunity for generating a reproductive surplus in the herd. In this study, sexed semen is used in combination with beef semen to produce high-value crossbred beef calves. Thus, on average there is no surplus of and selection among replacement heifers whether to go into the herd or to be sold. In this situation, the selection opportunities arise when deciding which cows to inseminate with sexed semen, conventional semen, or beef semen. We tested the hypothesis by combining the results of 2 stochastic simulation programs, SimHerd and ADAM. SimHerd estimates the economic effect of different strategies for use of sexed semen and beef semen at 3 levels of reproductive performance in a dairy herd. Besides simulating the operational return, SimHerd also simulates the parity distribution of the dams of heifer calves. The ADAM program estimates genetic merit per year in a herd under different strategies for use of sexed semen and genomic tests. The annual net return per slot was calculated as the sum of operational return and value of genetic lag minus costs of genomic tests divided by the total number of slots. Our results showed that the use of genomic tests for decision making decreases genetic lag by as much as 0.14 genetic standard deviation units of the breeding goal and that genetic lag decreases even more (up to 0.30 genetic standard deviation units) when genomic tests are used in combination with strategies for increasing and using a reproductive surplus. Thus, our hypothesis was supported. We also observed that genomic tests are used most efficiently to decrease genetic lag when the genomic information is used more than once in the lifetime of an animal and when as many selection decisions as possible are based on genomic information. However, all breakeven prices were lower than or equal to €50, which is the current price of low-density chip genotyping in Denmark, Finland, and Sweden, so in the vast majority of cases, it is not profitable to genotype routinely for management purposes under the present price assumptions. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A Smart Itsy Bitsy Spider for the Web.

ERIC Educational Resources Information Center

Chen, Hsinchun; Chung, Yi-Ming; Ramsey, Marshall; Yang, Christopher C.

1998-01-01

This study tested two Web personal spiders (i.e., agents that take users' requests and perform real-time customized searches) based on best first-search and genetic-algorithm techniques. Both results were comparable and complementary, although the genetic algorithm obtained higher recall value. The Java-based interface was found to be necessary…

Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose

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

Niroomand-Rad, A.; Cumberlin, R.

The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm[sup 3] dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimatedmore » doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs.« less

Automation of diagnostic genetic testing: mutation detection by cyclic minisequencing.

PubMed

Alagrund, Katariina; Orpana, Arto K

2014-01-01

The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.

Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

PubMed

Yang, Hang; Luo, Mingyao; Chen, Qianlong; Fu, Yuanyuan; Zhang, Jing; Qian, Xiangyang; Sun, Xiaogang; Fan, Yuxin; Zhou, Zhou; Chang, Qian

2016-08-01

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder typically involving the ocular, skeletal and cardiovascular systems, and aortic aneurysms/dissection mainly contributes to its mortality. Here, we performed genetic testing of the FBN1 gene in 39 Chinese probands with Marfan/Marfan-like syndrome and their related family members by Sanger sequencing. In total, 29 pathogenic/likely pathogenic FBN1 mutations, including 17 novel ones, were identified. In addition, most MFS patients with aortic disease (62%) had a truncating or splicing mutation. These results expand the FBN1 mutation spectrum and enrich our knowledge of genotype-phenotype correlations. Genetic testing for MFS and its related aortic diseases is increasingly important for early intervention and treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

The challenge of juvenile Huntington disease: to test or not to test.

PubMed

Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

2013-03-12

In a cohort of patients with suspected juvenile-onset Huntington disease (HD), we compared HD expansion-positive and -negative cases in order to identify parameters that may allow differentiating between them and may act as a guide to clinicians contemplating genetic testing. We analyzed the clinical and genetic characteristics of 76 juvenile-onset patients referred consecutively for HD genetic testing over a 16-year period. In total, 24 patients were positive for the HD expansion (7.8% of our HD cohort). Mean age at onset of expanded cases was similar to unexpanded cases. All expanded cases had a family history of genetically confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000). Clinical symptoms at onset or at presentation could not differentiate between expanded and unexpanded patients. Although criteria suggested by previous reports allowed statistical differentiation between the 2 groups, they were not sufficiently sensitive and specific to be used in clinical context and performed less satisfactorily than presence of a family history of HD alone. A diagnosis of juvenile HD should be primarily contemplated in symptomatic children with a family history of HD, although a proportion of these will test negative. With no family history of HD, juvenile HD is very unlikely and genetic testing should never delay searching for other causes. The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test.

For your interest? The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'.

PubMed

Deans, Zuzana; Clarke, Angus J; Newson, Ainsley J

2015-01-01

Non-invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely 'for information'. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT 'purely for information', including the competing interests of the prospective parents and the future child, and the acceptability of testing for 'frivolous' reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable. © 2014 John Wiley & Sons Ltd.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study.

PubMed

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-10-01

Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. 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/

Effect of genetic testing for risk of type 2 diabetes mellitus on health behaviors and outcomes: study rationale, development and design.

PubMed

Cho, Alex H; Killeya-Jones, Ley A; O'Daniel, Julianne M; Kawamoto, Kensaku; Gallagher, Patrick; Haga, Susanne; Lucas, Joseph E; Trujillo, Gloria M; Joy, Scott V; Ginsburg, Geoffrey S

2012-01-18

Type 2 diabetes is a prevalent chronic condition globally that results in extensive morbidity, decreased quality of life, and increased health services utilization. Lifestyle changes can prevent the development of diabetes, but require patient engagement. Genetic risk testing might represent a new tool to increase patients' motivation for lifestyle changes. Here we describe the rationale, development, and design of a randomized controlled trial (RCT) assessing the clinical and personal utility of incorporating type 2 diabetes genetic risk testing into comprehensive diabetes risk assessments performed in a primary care setting. Patients are recruited in the laboratory waiting areas of two primary care clinics and enrolled into one of three study arms. Those interested in genetic risk testing are randomized to receive either a standard risk assessment (SRA) for type 2 diabetes incorporating conventional risk factors plus upfront disclosure of the results of genetic risk testing ("SRA+G" arm), or the SRA alone ("SRA" arm). Participants not interested in genetic risk testing will not receive the test, but will receive SRA (forming a third, "no-test" arm). Risk counseling is provided by clinic staff (not study staff external to the clinic). Fasting plasma glucose, insulin levels, body mass index (BMI), and waist circumference are measured at baseline and 12 months, as are patients' self-reported behavioral and emotional responses to diabetes risk information. Primary outcomes are changes in insulin resistance and BMI after 12 months; secondary outcomes include changes in diet patterns, physical activity, waist circumference, and perceived risk of developing diabetes. The utility, feasibility, and efficacy of providing patients with genetic risk information for common chronic diseases in primary care remain unknown. The study described here will help to establish whether providing type 2 diabetes genetic risk information in a primary care setting can help improve patients' clinical outcomes, risk perceptions, and/or their engagement in healthy behavior change. In addition, study design features such as the use of existing clinic personnel for risk counseling could inform the future development and implementation of care models for the use of individual genetic risk information in primary care. ClinicalTrials.gov: NCT00849563.

A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems.

PubMed

Araújo, Luciano V; Malkowski, Simon; Braghetto, Kelly R; Passos-Bueno, Maria R; Zatz, Mayana; Pu, Calton; Ferreira, João E

2011-12-22

Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.

A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems

PubMed Central

2011-01-01

Background Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. Results This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. Conclusions This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces. PMID:22369688

A genetic analysis of post-weaning feedlot performance and profitability in Bonsmara cattle.

PubMed

van der Westhuizen, R R; van der Westhuizen, J; Schoeman, S J

2009-02-25

The aim of this study was to identify factors influencing profitability in a feedlot environment and to estimate genetic parameters for and between a feedlot profit function and productive traits measured in growth tests. The heritability estimate of 0.36 for feedlot profitability shows that this trait is genetically inherited and that it can be selected for. The genetic correlations between feedlot profitability and production and efficiency varied from negligible to high. The genetic correlation estimate of -0.92 between feed conversion ratio and feedlot profitability is largely due to the part-whole relationship between these two traits. Consequently, a multiple regression equation was developed to estimate a feed intake value for all performance-tested Bonsmara bulls, which were group fed and whose feed intakes were unknown. These predicted feed intake values enabled the calculation of a post-weaning growth or feedlot profitability value for all tested bulls, even where individual feed intakes were unknown. Subsequently, a feedlot profitability value for each bull was calculated in a favorable economic environment, an average economic environment and in an unfavorable economic environment. The high Pearson and Spearman correlations between the estimate breeding values based on the average economic environment and the other two environments suggested that the average economic environment could be used to calculate estimate breeding values for feedlot profitability. It is therefore not necessary to change the carcass, weaned calf or feed price on a regular basis to allow for possible re-rankings based on estimate breeding values.

Polygenic risk for psychiatric disorders correlates with executive function in typical development.

PubMed

Schork, A J; Brown, T T; Hagler, D J; Thompson, W K; Chen, C-H; Dale, A M; Jernigan, T L; Akshoomoff, N

2018-04-16

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Prioritization based on neutral genetic diversity may fail to conserve important characteristics in cattle breeds.

PubMed

Hall, S J G; Lenstra, J A; Deeming, D C

2012-06-01

Conservation of the intraspecific genetic diversity of livestock species requires protocols that assess between-breed genetic variability and also take into account differences among individuals within breeds. Here, we focus on variation between breeds. Conservation of neutral genetic variation has been seen as promoting, through linkage processes, the retention of useful and potentially useful variation. Using public information on beef cattle breeds, with a total of 165 data sets each relating to a breed comparison of a performance variable, we have tested this paradigm by calculating the correlations between pairwise breed differences in performance and pairwise genetic distances deduced from biochemical and immunological polymorphisms, microsatellites and single-nucleotide polymorphisms. As already observed in floral and faunal biodiversity, significant positive correlations (n=54) were found, but many correlations were non-significant (n=100) or significantly negative (n=11). This implies that maximizing conserved neutral genetic variation with current techniques may conserve breed-level genetic variation in some traits but not in others and supports the view that genetic distance measurements based on neutral genetic variation are not sufficient as a determinant of conservation priority among breeds. © 2011 Blackwell Verlag GmbH.

Nuclear fuel management optimization using genetic algorithms

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

DeChaine, M.D.; Feltus, M.A.

1995-07-01

The code independent genetic algorithm reactor optimization (CIGARO) system has been developed to optimize nuclear reactor loading patterns. It uses genetic algorithms (GAs) and a code-independent interface, so any reactor physics code (e.g., CASMO-3/SIMULATE-3) can be used to evaluate the loading patterns. The system is compared to other GA-based loading pattern optimizers. Tests were carried out to maximize the beginning of cycle k{sub eff} for a pressurized water reactor core loading with a penalty function to limit power peaking. The CIGARO system performed well, increasing the k{sub eff} after lowering the peak power. Tests of a prototype parallel evaluation methodmore » showed the potential for a significant speedup.« less

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 comparison of fitness-case sampling methods for genetic programming

NASA Astrophysics Data System (ADS)

Martínez, Yuliana; Naredo, Enrique; Trujillo, Leonardo; Legrand, Pierrick; López, Uriel

2017-11-01

Genetic programming (GP) is an evolutionary computation paradigm for automatic program induction. GP has produced impressive results but it still needs to overcome some practical limitations, particularly its high computational cost, overfitting and excessive code growth. Recently, many researchers have proposed fitness-case sampling methods to overcome some of these problems, with mixed results in several limited tests. This paper presents an extensive comparative study of four fitness-case sampling methods, namely: Interleaved Sampling, Random Interleaved Sampling, Lexicase Selection and Keep-Worst Interleaved Sampling. The algorithms are compared on 11 symbolic regression problems and 11 supervised classification problems, using 10 synthetic benchmarks and 12 real-world data-sets. They are evaluated based on test performance, overfitting and average program size, comparing them with a standard GP search. Comparisons are carried out using non-parametric multigroup tests and post hoc pairwise statistical tests. The experimental results suggest that fitness-case sampling methods are particularly useful for difficult real-world symbolic regression problems, improving performance, reducing overfitting and limiting code growth. On the other hand, it seems that fitness-case sampling cannot improve upon GP performance when considering supervised binary classification.

Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: findings from the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Stone, William S; Giuliano, Anthony J; Tsuang, Ming T; Braff, David L; Cadenhead, Kristin S; Calkins, Monica E; Dobie, Dorcas J; Faraone, Stephen V; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Mintz, Jim; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Roe, Andrea H; Schork, Nicholas J; Siever, Larry J; Silverman, Jeremy M; Swerdlow, Neal R; Thomas, Alison R; Tsuang, Debby W; Turetsky, Bruce I; Seidman, Larry J

2011-05-01

Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

Multiple testing and power calculations in genetic association studies.

PubMed

So, Hon-Cheong; Sham, Pak C

2011-01-01

Modern genetic association studies typically involve multiple single-nucleotide polymorphisms (SNPs) and/or multiple genes. With the development of high-throughput genotyping technologies and the reduction in genotyping cost, investigators can now assay up to a million SNPs for direct or indirect association with disease phenotypes. In addition, some studies involve multiple disease or related phenotypes and use multiple methods of statistical analysis. The combination of multiple genetic loci, multiple phenotypes, and multiple methods of evaluating associations between genotype and phenotype means that modern genetic studies often involve the testing of an enormous number of hypotheses. When multiple hypothesis tests are performed in a study, there is a risk of inflation of the type I error rate (i.e., the chance of falsely claiming an association when there is none). Several methods for multiple-testing correction are in popular use, and they all have strengths and weaknesses. Because no single method is universally adopted or always appropriate, it is important to understand the principles, strengths, and weaknesses of the methods so that they can be applied appropriately in practice. In this article, we review the three principle methods for multiple-testing correction and provide guidance for calculating statistical power.

Clinical audit of genetic testing and referral patterns for fragile X and associated conditions.

PubMed

Cotter, Megan; Archibald, Alison D; McClaren, Belinda J; Burgess, Trent; Francis, David; Hills, Louise; Martyn, Melissa; Oertel, Ralph; Slater, Howard; Cohen, Jonathan; Metcalfe, Sylvia A

2016-06-01

An audit was conducted of laboratory/clinical databases of genetic tests performed between January 2003 and December 2009, and for 2014, as well as referrals to the clinical service and a specialist multidisciplinary clinic, to determine genetic testing request patterns for fragile X syndrome and associated conditions and referrals for genetic counseling/multidisciplinary management in Victoria, Australia. An expanded allele (full mutation, premutation or intermediate) was found in 3.7% of tests. Pediatricians requested ∼70% of test samples, although fewer general practitioners and more obstetricians/gynecologists ordered tests in 2014. Median age at testing for individuals with a full mutation seeking a diagnosis without a fragile X family history was 4.3 years (males) and 9.4 years (females); these ages were lower when pediatricians ordered the tests (2.1 years and 6.1 years, respectively). Individuals with a premutation were generally tested at a later age (median age: males, 33.2 years; females, 36.4 years). Logistic regression showed that a family history of ID (OR 3.28 P = 0.005, CI 1.77-5.98) was the only indication to independently increase the likelihood of a test-positive (FM or PM) result. Following testing, ∼25% of full mutation or premutation individuals may not have attended clinical services providing genetic counseling or multidisciplinary management for these families. The apparent delay in fragile X syndrome diagnosis and lack of appropriate referrals for some may result in less than optimal management for these families. These findings suggest continued need for awareness and education of health professionals around diagnosis and familial implications of fragile X syndrome and associated conditions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Hearing Loss

PubMed Central

Chandrasekharan, Subhashini; Fiffer, Melissa

2011-01-01

Genetic testing for heritable hearing loss involves a mix of patented and unpatented genes, mutations and testing methods. More than half of all hearing loss is linked to inherited mutations, and five genes are most commonly tested in the United States. There are no patents on three of these genes, but Athena Diagnostics holds exclusive licenses to test for a common mutation in the GJB2 gene associated with about 50% of all cases, as well as mutations in the MTRNR1 gene. This fragmented intellectual property landscape made hearing loss a useful case study for assessing whether patent rights in genetic testing can proliferate or overlap, and whether it is possible to gather the rights necessary to perform testing. Testing for hearing loss is widely available, primarily from academic medical centers. Based on literature reviews and interviews with researchers, research on the genetics of hearing loss has generally not been impeded by patents. There is no consistent evidence of a premium in testing prices attributable to patent status. Athena Diagnostics has, however, used its intellectual property to discourage other providers from offering some tests. There is no definitive answer about the suitability of current patenting and licensing of commonly tested genes because of continuing legal uncertainty about the extent of enforcement of patent rights. Clinicians have also expressed concerns that multiplex tests will be difficult to develop because of overlapping intellectual property and conflict with Athena’s sole provider business model. PMID:20393307

A Simple Test of Class-Level Genetic Association Can Reveal Novel Cardiometabolic Trait Loci.

PubMed

Qian, Jing; Nunez, Sara; Reed, Eric; Reilly, Muredach P; Foulkes, Andrea S

2016-01-01

Characterizing the genetic determinants of complex diseases can be further augmented by incorporating knowledge of underlying structure or classifications of the genome, such as newly developed mappings of protein-coding genes, epigenetic marks, enhancer elements and non-coding RNAs. We apply a simple class-level testing framework, termed Genetic Class Association Testing (GenCAT), to identify protein-coding gene association with 14 cardiometabolic (CMD) related traits across 6 publicly available genome wide association (GWA) meta-analysis data resources. GenCAT uses SNP-level meta-analysis test statistics across all SNPs within a class of elements, as well as the size of the class and its unique correlation structure, to determine if the class is statistically meaningful. The novelty of findings is evaluated through investigation of regional signals. A subset of findings are validated using recently updated, larger meta-analysis resources. A simulation study is presented to characterize overall performance with respect to power, control of family-wise error and computational efficiency. All analysis is performed using the GenCAT package, R version 3.2.1. We demonstrate that class-level testing complements the common first stage minP approach that involves individual SNP-level testing followed by post-hoc ascribing of statistically significant SNPs to genes and loci. GenCAT suggests 54 protein-coding genes at 41 distinct loci for the 13 CMD traits investigated in the discovery analysis, that are beyond the discoveries of minP alone. An additional application to biological pathways demonstrates flexibility in defining genetic classes. We conclude that it would be prudent to include class-level testing as standard practice in GWA analysis. GenCAT, for example, can be used as a simple, complementary and efficient strategy for class-level testing that leverages existing data resources, requires only summary level data in the form of test statistics, and adds significant value with respect to its potential for identifying multiple novel and clinically relevant trait associations.

Testing natural selection vs. genetic drift in phenotypic evolution using quantitative trait locus data.

PubMed Central

Orr, H A

1998-01-01

Evolutionary biologists have long sought a way to determine whether a phenotypic difference between two taxa was caused by natural selection or random genetic drift. Here I argue that data from quantitative trait locus (QTL) analyses can be used to test the null hypothesis of neutral phenotypic evolution. I propose a sign test that compares the observed number of plus and minus alleles in the "high line" with that expected under neutrality, conditioning on the known phenotypic difference between the taxa. Rejection of the null hypothesis implies a role for directional natural selection. This test is applicable to any character in any organism in which QTL analysis can be performed. PMID:9691061

Genetic and developmental factors in spontaneous selective attention: a study of normal twins.

PubMed

Myles-Worsley, M; Coon, H

1997-08-08

The Spontaneous Selective Attention Task (SSAT) is a visual word identification task designed to measure the type of selective attention that occurs spontaneously when there are multiple stimuli, all potentially relevant, and insufficient time to process each of them fully. These are conditions which are common in everyday life. SSAT performance is measured by word identification accuracy, first under a baseline divided attention condition with no predictability, then under a selective attention condition with partial predictability introduced via word repetition. Accuracy to identify novel words in the upper location which becomes partially predictable (P words) vs. the lower location which remains non-predictable (N words) can be used to calculate a baseline performance index and a P/N ratio measure of selective attention. The SSAT has been shown to identify an attentional abnormality that may be useful in the development of an attentional endophenotype for family-genetic studies of schizophrenia. This study examined age and genetic effects on SSAT performance in normal children in order to evaluate whether the SSAT has the potential to qualify as a candidate endophenotype for schizophrenia in studies of at-risk children. A total of 59 monozygotic twin pairs and 33 same-sex dizygotic twin pairs ranging from 10 to 18 years of age were tested on the SSAT, a Continuous Performance Test. (CPT), a Span of Apprehension Test (SPAN) and a full-scale IQ test. Baseline performance on the SSAT, which was correlated with verbal IQ and SPAN performance, improved with age but showed no significant heritability. The P/N selectivity ratio was stable over the 10-18-year age range, was not significantly correlated with IQ, CPT, or SPAN performance, and its heritability was estimated to be 0.41. These findings suggest that the P/N selectivity ratio measured by the SSAT may be useful as a vulnerability marker in studies of children born into families segregating schizophrenia.

From phenotyping towards breeding strategies: using in vivo indicator traits and genetic markers to improve meat quality in an endangered pig breed.

PubMed

Biermann, A D M; Yin, T; König von Borstel, U U; Rübesam, K; Kuhn, B; König, S

2015-06-01

In endangered and local pig breeds of small population sizes, production has to focus on alternative niche markets with an emphasis on specific product and meat quality traits to achieve economic competiveness. For designing breeding strategies on meat quality, an adequate performance testing scheme focussing on phenotyped selection candidates is required. For the endangered German pig breed 'Bunte Bentheimer' (BB), no breeding program has been designed until now, and no performance testing scheme has been implemented. For local breeds, mainly reared in small-scale production systems, a performance test based on in vivo indicator traits might be a promising alternative in order to increase genetic gain for meat quality traits. Hence, the main objective of this study was to design and evaluate breeding strategies for the improvement of meat quality within the BB breed using in vivo indicator traits and genetic markers. The in vivo indicator trait was backfat thickness measured by ultrasound (BFiv), and genetic markers were allele variants at the ryanodine receptor 1 (RYR1) locus. In total, 1116 records of production and meat quality traits were collected, including 613 in vivo ultrasound measurements and 713 carcass and meat quality records. Additionally, 700 pigs were genotyped at the RYR1 locus. Data were used (1) to estimate genetic (co)variance components for production and meat quality traits, (2) to estimate allele substitution effects at the RYR1 locus using a selective genotyping approach and (3) to evaluate breeding strategies on meat quality by combining results from quantitative-genetic and molecular-genetic approaches. Heritability for the production trait BFiv was 0.27, and 0.48 for backfat thickness measured on carcass. Estimated heritabilities for meat quality traits ranged from 0.14 for meat brightness to 0.78 for the intramuscular fat content (IMF). Genetic correlations between BFiv and IMF were higher than estimates based on carcass backfat measurements (0.39 v. 0.25). The presence of the unfavorable n allele was associated with increased electric conductivity, paler meat and higher drip loss. The allele substitution effect on IMF was unfavorable, indicating lower IMF when the n allele is present. A breeding strategy including the phenotype (BFiv) combined with genetic marker information at the RYR1 locus from the selection candidate, resulted in a 20% increase in accuracy and selection response when compared with a breeding strategy without genetic marker information.

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices.

PubMed

Michaud, Katarzyna; Mangin, Patrice; Elger, Bernice S

2011-05-01

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.

Genetic testing improves identification of transthyretin amyloid (ATTR) subtype in cardiac amyloidosis.

PubMed

Brown, Emily E; Lee, Yi Zhen Joan; Halushka, Marc K; Steenbergen, Charles; Johnson, Nicole M; Almansa, Johana; Tedford, Ryan J; Cingolani, Oscar; Russell, Stuart D; Sharma, Kavita; Judge, Daniel P

2017-06-01

Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC-MS/MS has not been evaluated. A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR amyloidosis, and 56 of these patients underwent both genetic testing and LC-MS/MS. LC-MS/MS and proteomics correctly reported the mutant peptide and heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who were homozygous for the ATTRV122I mutation and failed to detect the following mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and ATTRV122I. Therefore, LC-MS/MS is not sufficient to rule out a pathogenic mutation in cases of ATTR amyloid, and genetic testing should be performed in most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR amyloidosis is important for estimating prognosis, proper familial counselling and guiding use of therapies, such as liver transplantation.

Effects of normalization on quantitative traits in association test

PubMed Central

2009-01-01

Background Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies. Results We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate. Conclusion For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest. PMID:20003414

A statistical assessment of differences and equivalences between genetically modified and reference plant varieties

PubMed Central

2011-01-01

Background Safety assessment of genetically modified organisms is currently often performed by comparative evaluation. However, natural variation of plant characteristics between commercial varieties is usually not considered explicitly in the statistical computations underlying the assessment. Results Statistical methods are described for the assessment of the difference between a genetically modified (GM) plant variety and a conventional non-GM counterpart, and for the assessment of the equivalence between the GM variety and a group of reference plant varieties which have a history of safe use. It is proposed to present the results of both difference and equivalence testing for all relevant plant characteristics simultaneously in one or a few graphs, as an aid for further interpretation in safety assessment. A procedure is suggested to derive equivalence limits from the observed results for the reference plant varieties using a specific implementation of the linear mixed model. Three different equivalence tests are defined to classify any result in one of four equivalence classes. The performance of the proposed methods is investigated by a simulation study, and the methods are illustrated on compositional data from a field study on maize grain. Conclusions A clear distinction of practical relevance is shown between difference and equivalence testing. The proposed tests are shown to have appropriate performance characteristics by simulation, and the proposed simultaneous graphical representation of results was found to be helpful for the interpretation of results from a practical field trial data set. PMID:21324199

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 ...

Heritability in Cognitive Performance: Evidence Using Computer-Based Testing

ERIC Educational Resources Information Center

Hervey, Aaron S.; Greenfield, Kathryn; Gualtieri, C. Thomas

2012-01-01

There is overwhelming evidence of genetic influence on cognition. The effect is seen in general cognitive ability, as well as in specific cognitive domains. A conventional assessment approach using face-to-face paper and pencil testing is difficult for large-scale studies. Computerized neurocognitive testing is a suitable alternative. A total of…

Assessing the cost of implementing the 2011 Society of Obstetricians and Gynecologists of Canada and Canadian College of Medical Genetics practice guidelines on the detection of fetal aneuploidies.

PubMed

Lilley, Margaret; Hume, Stacey; Karpoff, Nina; Maire, Georges; Taylor, Sherry; Tomaszewski, Robert; Yoshimoto, Maisa; Christian, Susan

2017-09-01

The Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics published guidelines, in 2011, recommending replacement of karyotype with quantitative fluorescent polymerase chain reaction when prenatal testing is performed because of an increased risk of a common aneuploidy. This study's objective is to perform a cost analysis following the implementation of quantitative fluorescent polymerase chain reaction as a stand-alone test. A total of 658 samples were received between 1 April 2014 and 31 August 2015: 576 amniocentesis samples and 82 chorionic villi sampling. A chromosome abnormality was identified in 14% (93/658) of the prenatal samples tested. The implementation of the 2011 Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics guidelines in Edmonton and Northern Alberta resulted in a cost savings of $46 295.80. The replacement of karyotype with chromosomal microarray for some indications would be associated with additional costs. The implementation of new test methods may provide cost savings or added costs. Cost analysis is important to consider during the implementation of new guidelines or technologies. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Development of a Novel and Rapid Fully Automated Genetic Testing System.

PubMed

Uehara, Masayuki

2016-01-01

We have developed a rapid genetic testing system integrating nucleic acid extraction, purification, amplification, and detection in a single cartridge. The system performs real-time polymerase chain reaction (PCR) after nucleic acid purification in a fully automated manner. RNase P, a housekeeping gene, was purified from human nasal epithelial cells using silica-coated magnetic beads and subjected to real-time PCR using a novel droplet-real-time-PCR machine. The process was completed within 13 min. This system will be widely applicable for research and diagnostic uses.

The micropolitics of responsibility vis-à-vis autonomy: parental accounts of childhood genetic testing and (non)disclosure.

PubMed

Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus

2008-03-01

Genetic testing and (non)disclosure of genetic information present ethical and moral dilemmas for the management of parental responsibility vis-à-vis the child's autonomy. Ethical guidelines aimed at professionals currently seek to defer childhood testing where there is no clear medical or psychosocial benefit. This version of autonomy is derived from a bioethical paradigm which brackets the individual rights and capacities of the child. In this paper we focus on situated parental accounts of responsibility/autonomy to understand the complex forms of relational work -i.e. the micropolitics of balancing rights and responsibilities - involving a range of inherited genetic disorders. Interviews (n= 20) were conducted with parents whose genetic condition may have had consequences for their children. Using rhetorical discourse analysis, we show how parents draw upon a number of rhetorical/discoursal devices to produce accounts where genetic responsibility is actually or potentially transmitted to the child. We identify three kinds of accounting practice: (1) aligned responsibility; (2) deferred responsibility; and (3) misaligned responsibility. Each of these practices demonstrates how parents position themselves responsibly by foregrounding figures and events onto which the child's autonomy is selectively mapped. Rather than simple representations, we regard these accounts as complex moral performances that seek alignment with broader bioethical discourses.

Genetic Difference in Height Growth and Survival of Cottonwood Full-Sib Families

Treesearch

D. T. Cooper; W. K. Randall

1973-01-01

Sixteen full-sib families from crosses between four fast-growing female and four fast-growing male clones of cottonwood (Populus deltoides Bartr.) were clonally evaluated for 1 year in a replicated field test. Seedling size had no effect on clonal performance. Approximately 70 percent of the genetic variance for height and 20 percent of that for...

Acoustic Impedance Inversion of Seismic Data Using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Eladj, Said; Djarfour, Noureddine; Ferahtia, Djalal; Ouadfeul, Sid-Ali

2013-04-01

The inversion of seismic data can be used to constrain estimates of the Earth's acoustic impedance structure. This kind of problem is usually known to be non-linear, high-dimensional, with a complex search space which may be riddled with many local minima, and results in irregular objective functions. We investigate here the performance and the application of a genetic algorithm, in the inversion of seismic data. The proposed algorithm has the advantage of being easily implemented without getting stuck in local minima. The effects of population size, Elitism strategy, uniform cross-over and lower mutation are examined. The optimum solution parameters and performance were decided as a function of the testing error convergence with respect to the generation number. To calculate the fitness function, we used L2 norm of the sample-to-sample difference between the reference and the inverted trace. The cross-over probability is of 0.9-0.95 and mutation has been tested at 0.01 probability. The application of such a genetic algorithm to synthetic data shows that the inverted acoustic impedance section was efficient. Keywords: Seismic, Inversion, acoustic impedance, genetic algorithm, fitness functions, cross-over, mutation.

Fuzzy Mixed Assembly Line Sequencing and Scheduling Optimization Model Using Multiobjective Dynamic Fuzzy GA

PubMed Central

Tahriri, Farzad; Dawal, Siti Zawiah Md; Taha, Zahari

2014-01-01

A new multiobjective dynamic fuzzy genetic algorithm is applied to solve a fuzzy mixed-model assembly line sequencing problem in which the primary goals are to minimize the total make-span and minimize the setup number simultaneously. Trapezoidal fuzzy numbers are implemented for variables such as operation and travelling time in order to generate results with higher accuracy and representative of real-case data. An improved genetic algorithm called fuzzy adaptive genetic algorithm (FAGA) is proposed in order to solve this optimization model. In establishing the FAGA, five dynamic fuzzy parameter controllers are devised in which fuzzy expert experience controller (FEEC) is integrated with automatic learning dynamic fuzzy controller (ALDFC) technique. The enhanced algorithm dynamically adjusts the population size, number of generations, tournament candidate, crossover rate, and mutation rate compared with using fixed control parameters. The main idea is to improve the performance and effectiveness of existing GAs by dynamic adjustment and control of the five parameters. Verification and validation of the dynamic fuzzy GA are carried out by developing test-beds and testing using a multiobjective fuzzy mixed production assembly line sequencing optimization problem. The simulation results highlight that the performance and efficacy of the proposed novel optimization algorithm are more efficient than the performance of the standard genetic algorithm in mixed assembly line sequencing model. PMID:24982962

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/

A quantitative test of population genetics using spatiogenetic patterns in bacterial colonies.

PubMed

Korolev, Kirill S; Xavier, João B; Nelson, David R; Foster, Kevin R

2011-10-01

It is widely accepted that population-genetics theory is the cornerstone of evolutionary analyses. Empirical tests of the theory, however, are challenging because of the complex relationships between space, dispersal, and evolution. Critically, we lack quantitative validation of the spatial models of population genetics. Here we combine analytics, on- and off-lattice simulations, and experiments with bacteria to perform quantitative tests of the theory. We study two bacterial species, the gut microbe Escherichia coli and the opportunistic pathogen Pseudomonas aeruginosa, and show that spatiogenetic patterns in colony biofilms of both species are accurately described by an extension of the one-dimensional stepping-stone model. We use one empirical measure, genetic diversity at the colony periphery, to parameterize our models and show that we can then accurately predict another key variable: the degree of short-range cell migration along an edge. Moreover, the model allows us to estimate other key parameters, including effective population size (density) at the expansion frontier. While our experimental system is a simplification of natural microbial community, we argue that it constitutes proof of principle that the spatial models of population genetics can quantitatively capture organismal evolution.

Mating tactics determine patterns of condition dependence in a dimorphic horned beetle.

PubMed

Knell, Robert J; Simmons, Leigh W

2010-08-07

The persistence of genetic variability in performance traits such as strength is surprising given the directional selection that such traits experience, which should cause the fixation of the best genetic variants. One possible explanation is 'genic capture' which is usually considered as a candidate mechanism for the maintenance of high genetic variability in sexual signalling traits. This states that if a trait is 'condition dependent', with expression being strongly influenced by the bearer's overall viability, then genetic variability can be maintained via mutation-selection balance. Using a species of dimorphic beetle with males that gain matings either by fighting or by 'sneaking', we tested the prediction of strong condition dependence for strength, walking speed and testes mass. Strength was strongly condition dependent only in those beetles that fight for access to females. Walking speed, with less of an obvious selective advantage, showed no condition dependence, and testes mass was more condition dependent in sneaks, which engage in higher levels of sperm competition. Within a species, therefore, condition dependent expression varies between morphs, and corresponds to the specific selection pressures experienced by that morph. These results support genic capture as a general explanation for the maintenance of genetic variability in traits under directional selection.

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.

Preimplantation genetic testing for aneuploidy: what technology should you use and what are the differences?

PubMed

Brezina, Paul R; Anchan, Raymond; Kearns, William G

2016-07-01

The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a clear and balanced manner the various strengths and weaknesses of these technologies. A systematic literature review was conducted. We used the terms "preimplantation genetic testing," "preimplantation genetic diagnosis," "preimplantation genetic screening," "preimplantation genetic diagnosis for aneuploidy," "PGD," "PGS," and "PGD-A" to search through PubMed, ScienceDirect, and Google Scholar from the year 2000 to April 2016. Bibliographies of articles were also searched for relevant studies. When possible, larger randomized controlled trials were used. However, for some emerging data, only data from meeting abstracts were available. PGS is emerging as one of the most valuable tools to enhance pregnancy success with assisted reproductive technologies. While all of the current diagnostic platforms currently available have various advantages and disadvantages, some platforms, such as next-generation sequencing (NGS), are capable of evaluating far more data points than has been previously possible. The emerging complexity of different technologies, especially with the utilization of more sophisticated tools such as NGS, requires an understanding by clinicians in order to request the best test for their patients.. Ultimately, the choice of which diagnostic platform is utilized should be individualized to the needs of both the clinic and the patient. Such a decision must incorporate the risk tolerance of both the patient and provider, fiscal considerations, and other factors such as the ability to counsel patients on their testing results and how these may or may not impact clinical outcomes.

Quality of Life and Psychological State in Chinese Breast Cancer Patients Who Received BRCA1/2 Genetic Testing

PubMed Central

Qiu, Jiajia; Guan, Jiaqin; Yang, Xiaochen; Wu, Jiong; Liu, Guangyu; Di, Genhong; Chen, Canming; Hou, Yifeng; Han, Qixia; Shen, Zhenzhou; Shao, Zhimin; Hu, Zhen

2016-01-01

Background This study aims to understand the quality of life (QOL) and psychological state (PS) of Chinese breast cancer patients who received BRCA1/2 genetic testing; to examine the psychological changes between BRCA1/2 mutation carriers and non-carriers; and to further explore the psychological experience of BRCA1/2 mutation carriers. Methods This study was combined with quantitative and qualitative designs. First, we performed a quantitative investigation using FACT-B (Chinese version) and Irritability, Depression and Anxiety scale (IDA) to assess the QOL and PS in breast cancer patients who received BRCA1/2 genetic testing. Then semi-structured in-depth qualitative interviews among 13 mutation carriers were conducted in hospital. Results Results from the quantitative study showed QOL scores were relatively high and the IDA scores were relatively low among the patients, and there was no significant difference in the QOL or IDA scores between non-carriers and carriers. Based on the qualitative analysis, four main themes emerged: (1) Finding the reason for having breast cancer; (2) Negative emotions; (3) Behavioral changes; (4) Lack of information. Conclusions The present study showed that QOL and PS are good among the breast cancer patients who received genetic testing. Genetic testing itself does not cause long psychosocial effects. BRCA1/2 mutation carriers may have certain negative emotions at the first stage they knew the testing results and may initiate behavioral and lifestyle changes. The patients with a BRCA1/2 mutation desire knowledge with regard to genetic aspects in mainland China. Professional information and advice can be provided to relieve the patients’ negative emotions when they were informed of gene defect. PMID:27428375

A Comparison Study of Multivariate Fixed Models and Gene Association with Multiple Traits (GAMuT) for Next-Generation Sequencing

PubMed Central

Chiu, Chi-yang; Jung, Jeesun; Wang, Yifan; Weeks, Daniel E.; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Amos, Christopher I.; Mills, James L.; Boehnke, Michael; Xiong, Momiao; Fan, Ruzong

2016-01-01

In this paper, extensive simulations are performed to compare two statistical methods to analyze multiple correlated quantitative phenotypes: (1) approximate F-distributed tests of multivariate functional linear models (MFLM) and additive models of multivariate analysis of variance (MANOVA), and (2) Gene Association with Multiple Traits (GAMuT) for association testing of high-dimensional genotype data. It is shown that approximate F-distributed tests of MFLM and MANOVA have higher power and are more appropriate for major gene association analysis (i.e., scenarios in which some genetic variants have relatively large effects on the phenotypes); GAMuT has higher power and is more appropriate for analyzing polygenic effects (i.e., effects from a large number of genetic variants each of which contributes a small amount to the phenotypes). MFLM and MANOVA are very flexible and can be used to perform association analysis for: (i) rare variants, (ii) common variants, and (iii) a combination of rare and common variants. Although GAMuT was designed to analyze rare variants, it can be applied to analyze a combination of rare and common variants and it performs well when (1) the number of genetic variants is large and (2) each variant contributes a small amount to the phenotypes (i.e., polygenes). MFLM and MANOVA are fixed effect models which perform well for major gene association analysis. GAMuT can be viewed as an extension of sequence kernel association tests (SKAT). Both GAMuT and SKAT are more appropriate for analyzing polygenic effects and they perform well not only in the rare variant case, but also in the case of a combination of rare and common variants. Data analyses of European cohorts and the Trinity Students Study are presented to compare the performance of the two methods. PMID:27917525

Results from a large-scale epidemiologic look-back investigation of improperly reprocessed endoscopy equipment.

PubMed

Holodniy, Mark; Oda, Gina; Schirmer, Patricia L; Lucero, Cynthia A; Khudyakov, Yury E; Xia, Guoliang; Lin, Yulin; Valdiserri, Ronald; Duncan, William E; Davey, Victoria J; Cross, Gerald M

2012-07-01

To determine whether improper high-level disinfection practices during endoscopy procedures resulted in bloodborne viral infection transmission.  Retrospective cohort study.  Four Veterans Affairs medical centers (VAMCs).  Veterans who underwent colonoscopy and laryngoscopy (ear, nose, and throat [ENT]) procedures from 2003 to 2009.  Patients were identified through electronic health record searches and serotested for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Newly discovered case patients were linked to a potential source with known identical infection, whose procedure occurred no more than 1 day prior to the case patient's procedure. Viral genetic testing was performed for case/proximate pairs to determine relatedness.  Of 10,737 veterans who underwent endoscopy at 4 VAMCs, 9,879 patients agreed to viral testing. Of these, 90 patients were newly diagnosed with 1 or more viral bloodborne pathogens (BBPs). There were no case/proximate pairings found for patients with either HIV or HBV; 24 HCV case/proximate pairings were found, of which 7 case patients and 8 proximate patients had sufficient viral load for further genetic testing. Only 2 of these cases, both of whom underwent laryngoscopy, and their 4 proximates agreed to further testing. None of the 4 remaining proximate patients who underwent colonoscopy agreed to further testing. Mean genetic distance between the 2 case patients and 4 proximate patients ranged from 13.5% to 19.1%.  Our investigation revealed that exposure to improperly reprocessed ENT endoscopes did not result in viral transmission in those patients who had viral genetic analysis performed. Any potential transmission of BBPs from colonoscopy remains unknown.

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.

Modification of neurobehavioral effects of mercury by a genetic polymorphism of coproporphyrinogen oxidase in children.

PubMed

Woods, James S; Heyer, Nicholas J; Echeverria, Diana; Russo, Joan E; Martin, Michael D; Bernardo, Mario F; Luis, Henrique S; Vaz, Lurdes; Farin, Federico M

2012-01-01

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

[Prenatal genetic counseling and instruction for deaf families by genetic test].

PubMed

Han, Ming-yu; Huang, Sha-sha; Wang, Guo-jian; Yuan, Yong-yi; Kang, Dong-yang; Zhang, Xin; Dai, Pu

2011-11-01

Analyzed the molecular pathogenesis of probands by means of genetic test and assisted the local Family Planning Institute by providing prenatal genetic counseling and instruction for deaf families who eager to have more baby. Total of forty-three deaf families were recruited by two institutes for family planning from Guangzhou and Weifang. Forty-two families had one deaf child with normal hearing parents. One family was that parents and their child were all deaf. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) 12SrRNA were firstly performed in probands and their parents, following medical history, physical examination, auditory test and CT scan of temporal bone were completed. And then the genetic information and instruction were provided to each deaf family. Fifteen of these 43 families had positive results of genetic test. In fifteen families, one family was confirmed that the parents and their child all carried homozygous GJB2 mutations and the recurrence risk was 100%. Twelve families were confirmed that the probands carried homozygous/compound GJB2 or SLC26A4 mutations while their parents were GJB2 or SLC26A4 carriers, and the recurrence risk was 25%. One family was confirmed that the proband, diagnosed with enlarged vestibular aqueduct syndrome (EVAS) by CT scan, carried heterozygous SLC26A4 mutation from the mother, and the recurrence risk was still 25% based on the hereditary pattern of EVAS although another SLC26A4 mutation from the father was not found. One family was confirmed that the proband carried a heterozygous GJB2 mutation from the mother and the possibility to be GJB2 carrier for offsprings was 50%. The rest 28 families were that all probands and their parents did not carry GJB2, SLC26A4 and mtDNA 12SrRNA pathological mutation. Genetic testing can provide more accurate and useful prenatal genetic counseling and instruction to deaf families. Meanwhile, it is an ideal way to develop a cooperative relationship with the institute for family planning.

How is genetic testing evaluated? A systematic review of the literature.

PubMed

Pitini, Erica; De Vito, Corrado; Marzuillo, Carolina; D'Andrea, Elvira; Rosso, Annalisa; Federici, Antonio; Di Maria, Emilio; Villari, Paolo

2018-05-01

Given the rapid development of genetic tests, an assessment of their benefits, risks, and limitations is crucial for public health practice. We performed a systematic review aimed at identifying and comparing the existing evaluation frameworks for genetic tests. We searched PUBMED, SCOPUS, ISI Web of Knowledge, Google Scholar, Google, and gray literature sources for any documents describing such frameworks. We identified 29 evaluation frameworks published between 2000 and 2017, mostly based on the ACCE Framework (n = 13 models), or on the HTA process (n = 6), or both (n = 2). Others refer to the Wilson and Jungner screening criteria (n = 3) or to a mixture of different criteria (n = 5). Due to the widespread use of the ACCE Framework, the most frequently used evaluation criteria are analytic and clinical validity, clinical utility and ethical, legal and social implications. Less attention is given to the context of implementation. An economic dimension is always considered, but not in great detail. Consideration of delivery models, organizational aspects, and consumer viewpoint is often lacking. A deeper analysis of such context-related evaluation dimensions may strengthen a comprehensive evaluation of genetic tests and support the decision-making process.

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.

Performance of full-sib families of Douglas-fir in pure-family and mixed-family deployments

Treesearch

Peter J. Gould; J. Bradley St.Clair; Paul D. Anderson

2011-01-01

A major objective of tree improvement programs is to identify genotypes that will perform well in operational deployments. Relatively little is known, however, about how the competitive environment affects performance in different types of deployments. We tested whether the genetic composition and density of deployments affect the performance of full-sib families of...

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

Entropy Based Genetic Association Tests and Gene-Gene Interaction Tests

PubMed Central

de Andrade, Mariza; Wang, Xin

2011-01-01

In the past few years, several entropy-based tests have been proposed for testing either single SNP association or gene-gene interaction. These tests are mainly based on Shannon entropy and have higher statistical power when compared to standard χ2 tests. In this paper, we extend some of these tests using a more generalized entropy definition, Rényi entropy, where Shannon entropy is a special case of order 1. The order λ (>0) of Rényi entropy weights the events (genotype/haplotype) according to their probabilities (frequencies). Higher λ places more emphasis on higher probability events while smaller λ (close to 0) tends to assign weights more equally. Thus, by properly choosing the λ, one can potentially increase the power of the tests or the p-value level of significance. We conducted simulation as well as real data analyses to assess the impact of the order λ and the performance of these generalized tests. The results showed that for dominant model the order 2 test was more powerful and for multiplicative model the order 1 or 2 had similar power. The analyses indicate that the choice of λ depends on the underlying genetic model and Shannon entropy is not necessarily the most powerful entropy measure for constructing genetic association or interaction tests. PMID:23089811

Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.

PubMed

Xu, C; Lang-Muritano, M; Phan-Hug, F; Dwyer, A A; Sykiotis, G P; Cassatella, D; Acierno, J; Mohammadi, M; Pitteloud, N

2017-08-01

Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exploring links among imitation, mental development, and temperament

PubMed Central

Fenstermacher, Susan K.; Saudino, Kimberly J.

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children’s imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique. PMID:27840593

Exploring links among imitation, mental development, and temperament.

PubMed

Fenstermacher, Susan K; Saudino, Kimberly J

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children's imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique.

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) ...

Genetic Algorithm Optimization of a Cost Competitive Hybrid Rocket Booster

NASA Technical Reports Server (NTRS)

Story, George

2015-01-01

Performance, reliability and cost have always been drivers in the rocket business. Hybrid rockets have been late entries into the launch business due to substantial early development work on liquid rockets and solid rockets. Slowly the technology readiness level of hybrids has been increasing due to various large scale testing and flight tests of hybrid rockets. One remaining issue is the cost of hybrids versus the existing launch propulsion systems. This paper will review the known state-of-the-art hybrid development work to date and incorporate it into a genetic algorithm to optimize the configuration based on various parameters. A cost module will be incorporated to the code based on the weights of the components. The design will be optimized on meeting the performance requirements at the lowest cost.

Genetic Algorithm Optimization of a Cost Competitive Hybrid Rocket Booster

NASA Technical Reports Server (NTRS)

Story, George

2014-01-01

Performance, reliability and cost have always been drivers in the rocket business. Hybrid rockets have been late entries into the launch business due to substantial early development work on liquid rockets and later on solid rockets. Slowly the technology readiness level of hybrids has been increasing due to various large scale testing and flight tests of hybrid rockets. A remaining issue is the cost of hybrids vs the existing launch propulsion systems. This paper will review the known state of the art hybrid development work to date and incorporate it into a genetic algorithm to optimize the configuration based on various parameters. A cost module will be incorporated to the code based on the weights of the components. The design will be optimized on meeting the performance requirements at the lowest cost.

Meta-analysis of gene-level tests for rare variant association.

PubMed

Liu, Dajiang J; Peloso, Gina M; Zhan, Xiaowei; Holmen, Oddgeir L; Zawistowski, Matthew; Feng, Shuang; Nikpay, Majid; Auer, Paul L; Goel, Anuj; Zhang, He; Peters, Ulrike; Farrall, Martin; Orho-Melander, Marju; Kooperberg, Charles; McPherson, Ruth; Watkins, Hugh; Willer, Cristen J; Hveem, Kristian; Melander, Olle; Kathiresan, Sekar; Abecasis, Gonçalo R

2014-02-01

The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays.

A 100-Year Review: Methods and impact of genetic selection in dairy cattle-From daughter-dam comparisons to deep learning algorithms.

PubMed

Weigel, K A; VanRaden, P M; Norman, H D; Grosu, H

2017-12-01

In the early 1900s, breed society herdbooks had been established and milk-recording programs were in their infancy. Farmers wanted to improve the productivity of their cattle, but the foundations of population genetics, quantitative genetics, and animal breeding had not been laid. Early animal breeders struggled to identify genetically superior families using performance records that were influenced by local environmental conditions and herd-specific management practices. Daughter-dam comparisons were used for more than 30 yr and, although genetic progress was minimal, the attention given to performance recording, genetic theory, and statistical methods paid off in future years. Contemporary (herdmate) comparison methods allowed more accurate accounting for environmental factors and genetic progress began to accelerate when these methods were coupled with artificial insemination and progeny testing. Advances in computing facilitated the implementation of mixed linear models that used pedigree and performance data optimally and enabled accurate selection decisions. Sequencing of the bovine genome led to a revolution in dairy cattle breeding, and the pace of scientific discovery and genetic progress accelerated rapidly. Pedigree-based models have given way to whole-genome prediction, and Bayesian regression models and machine learning algorithms have joined mixed linear models in the toolbox of modern animal breeders. Future developments will likely include elucidation of the mechanisms of genetic inheritance and epigenetic modification in key biological pathways, and genomic data will be used with data from on-farm sensors to facilitate precision management on modern dairy farms. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Multiplex Ligation - dependent Probe Amplification (MLPA) as a screening test in children with developmental defects and intellectual disability of unknown etiology].

PubMed

Laczmańska, Izabela; Jakubiak, Aleksandra; Slęzak, Ryszard; Pesz, Karolina; Stembalska, Agnieszka; Laczmański, Lukasz; Sąsiadek, Maria M; Smigiel, Robert

2011-01-01

Developmental delay and intellectual disability are significant medical and social problems which concern 1-3% of population. The etiology remains unknown in over half of the cases. To evaluate the efficiency of MLPA (Multiplex Ligation-dependent Probe Amplification) as a screening test in diagnosis of patients with developmental delay and/or intellectual disability. 313 MLPA tests were performed in 256 patients with developmental delay and/ or intellectual disability with unknown etiology. MLPA test was made after exclusion of genetic disorders possible to diagnose by dysmorphological examination or using specifi c genetic tests. Positive results were confirmed by FISH analysis with appropriate probes. Chromosomal microaberrations were identifi ed in 15 patients (4,8%): deletions of 1p36 in 4 cases, in one case deletion of 22q11.21, 22q13.33, SNRPN1, 4ptel, 6qtel, 7q11.23, 16ptel, 18qtel as well as one ca se of deletion 3ptel/duplication 15qtel; deletion 18qtel/duplication Xqtel, and also duplication 7q11.23. Detail clinical analysis was performed in patients with diagnosed microaberrations in MLPA test. The molecular MLPA test, screening for chromosomal microaberration syndromes, should be performed in each patient with developmental delay and/or intellectual disability of unknown etiology and normal cytogenetic analysis, even if congenital defects and positive familial history do not exist.

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®: ...

Genetic Counselling, BRCA1/2 Status and Clinico-pathologic Characteristics of Patients with Ovarian Cancer before 50 Years of Age

PubMed Central

Cvelbar, Mirjam; Hocevar, Marko; Novakovic, Srdjan; Stegel, Vida; Perhavec, Andraz

2017-01-01

Abstract Background In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered. PMID:28740454

Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

PubMed Central

Kloek, Anne T.; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L.; Asselbergs, Folkert W.; Serón, Mercedes Valls; Brouwer, Matthijs C.; van de Beek, Diederik; Ferwerda, Bart

2016-01-01

Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

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.

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

Communication with patients during the prenatal testing procedure: an explorative qualitative study.

PubMed

van Zwieten, Myra; Willems, Dick; Knegt, Lia; Leschot, Nico

2006-10-01

While generally two phases of prenatal genetic counseling are distinguished, i.e. pre- and post-test counseling, we revealed a third form of communication during the testing procedure. The content of this intermediate communication was explored. A secondary analysis was performed on data obtained in another observational study, which was focussed on how indefinite testing results are clarified. Thirteen testing trajectories in which communication with parents took place during the testing procedure were further analysed. In the majority of cases the content of intermediate communication was similar to the content of pre-test counseling. In four cases the content was different, because the communication involved the parents in decision-making about a testing result, which was still being processed. Communication in (prenatal) genetic testing is not always restricted to separate phases, but can be an ongoing process occurring parallel to, and sometimes even intertwined with, the testing process. The advocated model of shared decision-making might work better once it is determined if the decision concerns the area wherein the provider is the expert, or the patient. Further research into the process of continuing decision-making could clarify how providers' and patients' responsibilities regarding the diagnostic process are distributed. Meanwhile, the possible occurrence of continuous decision-making should be mentioned in (prenatal) genetic counseling.

Field of Genes: An Investigation of Sports-Related Genetic Testing

PubMed Central

Wagner, Jennifer K.; Royal, Charmaine D.

2012-01-01

Sports-related genetic testing is a sector of the diverse direct-to-consumer (DTC) industry that has not yet been examined thoroughly by academic scholars. A systematic search was used to identify companies in this sector and content analysis of online information was performed. More than a dozen companies were identified. Marketing practices observed generally did not target parents for child testing, and marketing images were mild compared to images used in popular media. Information was provided at a high reading level (industry-wide Flesh-Kincaid Grade Levels > 11). While ~75% of companies provide privacy policies and terms of service prior to purchase and ~40% provide scientific citations for their tests, <25% reported using American Association of Blood Banks (AABB) accredited or the Clinical Laboratory Improvement Amendments of 1988 (CLIA) certified laboratories. Tests ranged considerably in price (~$100–$1,100) and were substantively diverse. These findings highlight the need to appreciate nuances and avoid broad generalizations of this and other DTC sectors. Utilization of consumer protections available for e-commerce generally may adequately protect DTC genetics consumers without new federal legislation or regulation. PMID:25562204

Predictive genomics DNA profiling for athletic performance.

PubMed

Kambouris, Marios; Ntalouka, Foteini; Ziogas, Georgios; Maffulli, Nicola

2012-12-01

Genes control biological processes such as muscle, cartilage and bone formation, muscle energy production and metabolism (mitochondriogenesis, lactic acid removal), blood and tissue oxygenation (erythropoiesis, angiogenesis, vasodilatation), all essential in sport and athletic performance. DNA sequence variations in such genes confer genetic advantages that can be exploited, or genetic 'barriers' that could be overcome to achieve optimal athletic performance. Predictive Genomic DNA Profiling for athletic performance reveals genetic variations that may be associated with better suitability for endurance, strength and speed sports, vulnerability to sports-related injuries and individualized nutritional requirements. Knowledge of genetic 'suitability' in respect to endurance capacity or strength and speed would lead to appropriate sport and athletic activity selection. Knowledge of genetic advantages and barriers would 'direct' an individualized training program, nutritional plan and nutritional supplementation to achieving optimal performance, overcoming 'barriers' that results from intense exercise and pressure under competition with minimum waste of time and energy and avoidance of health risks (hypertension, cardiovascular disease, inflammation, and musculoskeletal injuries) related to exercise, training and competition. Predictive Genomics DNA profiling for Athletics and Sports performance is developing into a tool for athletic activity and sport selection and for the formulation of individualized and personalized training and nutritional programs to optimize health and performance for the athlete. Human DNA sequences are patentable in some countries, while in others DNA testing methodologies [unless proprietary], are non patentable. On the other hand, gene and variant selection, genotype interpretation and the risk and suitability assigning algorithms based on the specific Genomic variants used are amenable to patent protection.

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®: ...

Cryptic genetic diversity, population structure, and gene flow in the Mojave rattlesnake (Crotalus scutulatus).

PubMed

Schield, Drew R; Adams, Richard H; Card, Daren C; Corbin, Andrew B; Jezkova, Tereza; Hales, Nicole R; Meik, Jesse M; Perry, Blair W; Spencer, Carol L; Smith, Lydia L; García, Gustavo Campillo; Bouzid, Nassima M; Strickland, Jason L; Parkinson, Christopher L; Borja, Miguel; Castañeda-Gaytán, Gamaliel; Bryson, Robert W; Flores-Villela, Oscar A; Mackessy, Stephen P; Castoe, Todd A

2018-06-15

The Mojave rattlesnake (Crotalus scutulatus) inhabits deserts and arid grasslands of the western United States and Mexico. Despite considerable interest in its highly toxic venom and the recognition of two subspecies, no molecular studies have characterized range-wide genetic diversity and population structure or tested species limits within C. scutulatus. We used mitochondrial DNA and thousands of nuclear loci from double-digest restriction site associated DNA sequencing to infer population genetic structure throughout the range of C. scutulatus, and to evaluate divergence times and gene flow between populations. We find strong support for several divergent mitochondrial and nuclear clades of C. scutulatus, including splits coincident with two major phylogeographic barriers: the Continental Divide and the elevational increase associated with the Central Mexican Plateau. We apply Bayesian clustering, phylogenetic inference, and coalescent-based species delimitation to our nuclear genetic data to test hypotheses of population structure. We also performed demographic analyses to test hypotheses relating to population divergence and gene flow. Collectively, our results support the existence of four distinct lineages within C. scutulatus, and genetically defined populations do not correspond with currently recognized subspecies ranges. Finally, we use approximate Bayesian computation to test hypotheses of divergence among multiple rattlesnake species groups distributed across the Continental Divide, and find evidence for co-divergence at this boundary during the mid-Pleistocene. Copyright © 2018 Elsevier Inc. All rights reserved.

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, ...

The genetics of muscle atrophy and growth: the impact and implications of polymorphisms in animals and humans.

PubMed

Gordon, Erynn S; Gordish Dressman, Heather A; Hoffman, Eric P

2005-10-01

Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.

Genetics-based methods for detection of Salmonella spp. in foods.

PubMed

Mozola, Mark A

2006-01-01

Genetic methods are now at the forefront of foodborne pathogen testing. The sensitivity, specificity, and inclusivity advantages offered by deoxyribonucleic acid (DNA) probe technology have driven an intense effort in methods development over the past 20 years. DNA probe-based methods for Salmonella spp. and other pathogens have progressed from time-consuming procedures involving the use of radioisotopes to simple, high throughput, automated assays. The analytical sensitivity of nucleic acid amplification technology has facilitated a reduction in analysis time by allowing enriched samples to be tested for previously undetectable quantities of analyte. This article will trace the evolution of the development of genetic methods for detection of Salmonella in foods, review the basic assay formats and their advantages and limitations, and discuss method performance characteristics and considerations for selection of methods.

Assessment of Genetics Understanding. Under What Conditions Do Situational Features Have an Impact on Measures?

NASA Astrophysics Data System (ADS)

Schmiemann, Philipp; Nehm, Ross H.; Tornabene, Robyn E.

2017-12-01

Understanding how situational features of assessment tasks impact reasoning is important for many educational pursuits, notably the selection of curricular examples to illustrate phenomena, the design of formative and summative assessment items, and determination of whether instruction has fostered the development of abstract schemas divorced from particular instances. The goal of our study was to employ an experimental research design to quantify the degree to which situational features impact inferences about participants' understanding of Mendelian genetics. Two participant samples from different educational levels and cultural backgrounds (high school, n = 480; university, n = 444; Germany and USA) were used to test for context effects. A multi-matrix test design was employed, and item packets differing in situational features (e.g., plant, animal, human, fictitious) were randomly distributed to participants in the two samples. Rasch analyses of participant scores from both samples produced good item fit, person reliability, and item reliability and indicated that the university sample displayed stronger performance on the items compared to the high school sample. We found, surprisingly, that in both samples, no significant differences in performance occurred among the animal, plant, and human item contexts, or between the fictitious and "real" item contexts. In the university sample, we were also able to test for differences in performance between genders, among ethnic groups, and by prior biology coursework. None of these factors had a meaningful impact upon performance or context effects. Thus some, but not all, types of genetics problem solving or item formats are impacted by situational features.

Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.

PubMed

Hamada, Motoharu; Doisaki, Sayoko; Okuno, Yusuke; Muramatsu, Hideki; Hama, Asahito; Kawashima, Nozomu; Narita, Atsushi; Nishio, Nobuhiro; Yoshida, Kenichi; Kanno, Hitoshi; Manabe, Atsushi; Taga, Takashi; Takahashi, Yoshiyuki; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji

2018-06-23

Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

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

A new compound arithmetic crossover-based genetic algorithm for constrained optimisation in enterprise systems

NASA Astrophysics Data System (ADS)

Jin, Chenxia; Li, Fachao; Tsang, Eric C. C.; Bulysheva, Larissa; Kataev, Mikhail Yu

2017-01-01

In many real industrial applications, the integration of raw data with a methodology can support economically sound decision-making. Furthermore, most of these tasks involve complex optimisation problems. Seeking better solutions is critical. As an intelligent search optimisation algorithm, genetic algorithm (GA) is an important technique for complex system optimisation, but it has internal drawbacks such as low computation efficiency and prematurity. Improving the performance of GA is a vital topic in academic and applications research. In this paper, a new real-coded crossover operator, called compound arithmetic crossover operator (CAC), is proposed. CAC is used in conjunction with a uniform mutation operator to define a new genetic algorithm CAC10-GA. This GA is compared with an existing genetic algorithm (AC10-GA) that comprises an arithmetic crossover operator and a uniform mutation operator. To judge the performance of CAC10-GA, two kinds of analysis are performed. First the analysis of the convergence of CAC10-GA is performed by the Markov chain theory; second, a pair-wise comparison is carried out between CAC10-GA and AC10-GA through two test problems available in the global optimisation literature. The overall comparative study shows that the CAC performs quite well and the CAC10-GA defined outperforms the AC10-GA.

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.

Community and ecosystem effects of intraspecific genetic diversity in grassland microcosms of varying species diversity.

PubMed

Fridley, Jason D; Grime, J Philip

2010-08-01

Studies of whether plant community structure and ecosystem properties depend on the genetic diversity of component populations have been largely restricted to species monocultures and have involved levels of genetic differentiation that do not necessarily correspond to that exhibited by neighboring mature individuals in the field. We established experimental communities of varying intraspecific genetic diversity, using genotypes of eight species propagated from clonal material of individuals derived from a small (100-m2) limestone grassland community, and tested whether genetic diversity (one, four, and eight genotypes per species) influenced community composition and annual aboveground productivity across communities of one, four, and eight species. Eight-species communities were represented by common grass, sedge, and forb species, and four- and one-species communities were represented by four graminoids and the dominant grass Festuca ovina, respectively. After three years of community development, there was a marginal increase of species diversity with increased genetic diversity in four- and eight-species communities, and genetic diversity altered the performance of genotypes in monospecific communities of F. ovina. However, shifts in composition from genetic diversity were not sufficient to alter patterns of community productivity. Neighborhood models describing pairwise interactions between species indicated that genetic diversity decreased the intensity of competition between species in four-species mixtures, thereby promoting competitive equivalency and enhancing species equitability. In F. ovina monocultures, neighborhood models revealed both synergistic and antagonistic interactions between genotypes that were reduced in intensity on more stressful shallow soils. Although the dependence of F. ovina genotype performance on neighborhood genetic composition did not influence total productivity, such dependence was sufficient to uncouple genotype performance in genetic mixtures and monocultures. Our results point to an important connection between local genetic diversity and species diversity in this species-rich ecosystem but suggest that such community-level dependence on genetic diversity may not feedback to ecosystem productivity.

Genetic counseling and presymptomatic testing programs for Machado-Joseph Disease: lessons from Brazil and Portugal

PubMed Central

Schuler-Faccini, Lavínia; Osorio, Claudio Maria; Romariz, Flavia; Paneque, Milena; Sequeiros, Jorge; Jardim, Laura Bannach

2014-01-01

Machado-Joseph disease (MJD) is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA) worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST) can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the decision-making process. In this study, we present the protocol used in PST for MJD and the relevant observations from two centers: Brazil (Porto Alegre) and Portugal (Porto). We provide a case report that illustrates the significant ethical and psychological issues related to PST in late-onset neurological disorders. In both centers, counseling and PST are performed by a multidisciplinary team, and genetic testing is conducted at the same institutions. From 1999 to 2012, 343 individuals sought PST in Porto Alegre; 263 (77%) of these individuals were from families with MJD. In Porto, 1,530 individuals sought PST between 1996 and 2013, but only 66 (4%) individuals were from families with MJD. In Brazil, approximately 50% of the people seeking PST eventually took the test and received their results, whereas 77% took the test in Portugal. In this case report, we highlight several issues that might be raised by the consultand and how the team can extract significant information. Literature about PST testing for MJD and other SCAs is scarce, and we hope this report will encourage similar studies and enable the implementation of PST protocols in other populations, mainly in Latin America. PMID:24764760

Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls

PubMed Central

Ripke, Stephan; van den Berg, Leonard; Buchbinder, Susan; Carrington, Mary; Cossarizza, Andrea; Dalmau, Judith; Deeks, Steven G.; Delaneau, Olivier; De Luca, Andrea; Goedert, James J.; Haas, David; Herbeck, Joshua T.; Kathiresan, Sekar; Kirk, Gregory D.; Lambotte, Olivier; Luo, Ma; Mallal, Simon; van Manen, Daniëlle; Martinez-Picado, Javier; Meyer, Laurence; Miro, José M.; Mullins, James I.; Obel, Niels; O'Brien, Stephen J.; Pereyra, Florencia; Plummer, Francis A.; Poli, Guido; Qi, Ying; Rucart, Pierre; Sandhu, Manj S.; Shea, Patrick R.; Schuitemaker, Hanneke; Theodorou, Ioannis; Vannberg, Fredrik; Veldink, Jan; Walker, Bruce D.; Weintrob, Amy; Winkler, Cheryl A.; Wolinsky, Steven; Telenti, Amalio; Goldstein, David B.; de Bakker, Paul I. W.; Zagury, Jean-François; Fellay, Jacques

2013-01-01

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size. PMID:23935489

Ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries: protocol for a systematic review.

PubMed

Zhong, Adrina; Darren, Benedict; Dimaras, Helen

2017-07-11

There has been little focus in the literature on how to build genetic testing and counseling services in low- and middle-income countries in a responsible, ethical, and culturally appropriate manner. It is unclear to what extent this area is being explored and what form further research should take. The proposed knowledge synthesis aims to fill this gap in knowledge and mine the existing data to determine the breadth of work in this area and identify ethical, social, and cultural issues that have emerged. An integrated knowledge translation approach will be undertaken by engaging knowledge users throughout the review to ensure relevance to their practice. Electronic databases encompassing various disciplines, such as healthcare, social sciences, and public health, will be searched. Studies that address clinical genetic testing and/or counseling and ethical, social, and/or cultural issues of these genetic services, and are performed in low- and middle-income countries as defined by World Bank will be considered for inclusion. Two independent reviewers will be involved in a two-stage literature screening process, data extraction, and quality appraisal. Studies included in the review will be analyzed by thematic analysis. A narrative synthesis guided by the social ecological model will be used to summarize findings. This systematic review will provide a foundation of evidence regarding ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries. Using the social ecological model as a conceptual framework will facilitate the understanding of broader influences of the sociocultural context on an individual's experience with clinical genetic testing and counseling, thereby informing interdisciplinary sectors in future recommendations for practice and policy. PROSPERO CRD42016042894.

Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.

PubMed

Song, Minsun; Wheeler, William; Caporaso, Neil E; Landi, Maria Teresa; Chatterjee, Nilanjan

2018-03-01

Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large-scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta-analysis of "one-step" maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package. © 2017 WILEY PERIODICALS, INC.

Splice site mutations in GH1 detected in previously (Genetically) undiagnosed families with congenital isolated growth hormone deficiency type II.

PubMed

Kempers, M J E; van der Crabben, S N; de Vroede, M; Alfen-van der Velden, J; Netea-Maier, R T; Duim, R A J; Otten, B J; Losekoot, M; Wit, J M

2013-01-01

Congenital isolated growth hormone deficiency (IGHD) is a rare endocrine disorder that presents with severe proportionate growth failure. Dominant (type II) IGHD is usually caused by heterozygous mutations of GH1. The presentation of newly affected family members in 3 families with dominant IGHD in whom previous genetic testing had not demonstrated a GH1 mutation or had not been performed, prompted us to identify the underlying genetic cause. GH1 was sequenced in 3 Caucasian families with a clinical autosomal dominant IGHD. All affected family members had severe growth hormone (GH) deficiency that became apparent in the first 2 years of life. GH treatment led to a marked increase in height SDS. So far, no other pituitary dysfunctions have become apparent. In the first family a novel splice site mutation in GH1 was identified (c.172-1G>C, IVS2-1G>C). In two other families a previously reported splice site mutation (c.291+1G>A, IVS3+1G>A) was found. These data show that several years after negative genetic testing it was now possible to make a genetic diagnosis in these families with a well-defined, clearly heritable, autosomal dominant IGHD. This underscores the importance of clinical and genetic follow-up in a multidisciplinary setting. It also shows that even without a positive family history, genetic testing should be considered if the phenotype is strongly suggestive for a genetic syndrome. Identification of pathogenic mutations, like these GH1 mutations, has important clinical implications for the surveillance and genetic counseling of patients and expands our knowledge on the genotype-phenotype correlation. © 2013 S. Karger AG, Basel.

Progeny testing: proceedings of servicewide genetics workshop

Treesearch

Dick Miller

1984-01-01

The primary objective of this workshop was to discuss in detail the state- of-the-art of progeny testing. All aspects, from setting objectives through data collection and analysis, was be covered. We all know progeny testing is a highly technical phase of our tree improvement programs. Each task is critical and must be performed accurately and within a prescribed time...

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

Contrasting effects of chloride on growth, reproduction, and toxicant sensitivity in two genetically distinct strains of Hyalella azteca.

PubMed

Soucek, David J; Mount, David R; Dickinson, Amy; Hockett, J Russell; McEwen, Abigail R

2015-10-01

The strain of Hyalella azteca (Saussure: Amphipoda) commonly used for aquatic toxicity testing in the United States has been shown to perform poorly in some standardized reconstituted waters frequently used for other test species. In 10-d and 42-d experiments, the growth and reproduction of the US laboratory strain of H. azteca was shown to vary strongly with chloride concentration in the test water, with declining performance observed below 15 mg/L to 20 mg/L. In contrast to the chloride-dependent performance of the US laboratory strain of H. azteca, growth of a genetically distinct strain of H. azteca obtained from an Environment Canada laboratory in Burlington, Ontario, Canada, was not influenced by chloride concentration. In acute toxicity tests with the US laboratory strain of H. azteca, the acute toxicity of sodium nitrate increased with decreasing chloride in a pattern similar not only to that observed for control growth, but also to previous acute toxicity testing with sodium sulfate. Subsequent testing with the Burlington strain showed no significant relationship between chloride concentration and the acute toxicity of sodium nitrate or sodium sulfate. These findings suggest that the chloride-dependent toxicity shown for the US laboratory strain may be an unusual feature of that strain and perhaps not broadly representative of aquatic organisms as a whole. © 2015 SETAC.

Improved classification accuracy by feature extraction using genetic algorithms

NASA Astrophysics Data System (ADS)

Patriarche, Julia; Manduca, Armando; Erickson, Bradley J.

2003-05-01

A feature extraction algorithm has been developed for the purposes of improving classification accuracy. The algorithm uses a genetic algorithm / hill-climber hybrid to generate a set of linearly recombined features, which may be of reduced dimensionality compared with the original set. The genetic algorithm performs the global exploration, and a hill climber explores local neighborhoods. Hybridizing the genetic algorithm with a hill climber improves both the rate of convergence, and the final overall cost function value; it also reduces the sensitivity of the genetic algorithm to parameter selection. The genetic algorithm includes the operators: crossover, mutation, and deletion / reactivation - the last of these effects dimensionality reduction. The feature extractor is supervised, and is capable of deriving a separate feature space for each tissue (which are reintegrated during classification). A non-anatomical digital phantom was developed as a gold standard for testing purposes. In tests with the phantom, and with images of multiple sclerosis patients, classification with feature extractor derived features yielded lower error rates than using standard pulse sequences, and with features derived using principal components analysis. Using the multiple sclerosis patient data, the algorithm resulted in a mean 31% reduction in classification error of pure tissues.

Effects of UGT1A9 genetic polymorphisms on monohydroxylated derivative of oxcarbazepine concentrations and oxcarbazepine monotherapeutic efficacy in Chinese patients with epilepsy.

PubMed

Lu, Yao; Fang, Youxin; Wu, Xunyi; Ma, Chunlai; Wang, Yue; Xu, Lan

2017-03-01

The human UDP-glucuronosyltransferase which is genetically polymorphic catalyzes glucuronidations of various drugs. The interactions among UGT1A4, UGT1A6, UGT1A9, and UGT2B15 genetic polymorphisms, monohydroxylated derivative (MHD) of oxcarbazepine (OXC) plasma concentrations, and OXC monotherapeutic efficacy were explored in 124 Chinese patients with epilepsy receiving OXC monotherapy. MHD is the major active metabolite of OXC, and its plasma concentration was measured using high-performance liquid chromatography when patients reached their maintenance dose of OXC. Genomic DNA was extracted from whole blood and SNP genotyping performed using PCR followed by dideoxy chain termination sequencing. We followed the patients for at least 1 year to evaluate the OXC monotherapy efficacy. Patients were divided into two groups according to their therapeutic outcome: group 1, seizure free; group 2, not seizure free. The data were analyzed using T test, one-way analysis of variance (ANOVA), Kruskal-Wallis test, chi-square test, Fisher's exact test, correlation analysis, and multivariate regression analysis. T test analysis showed that MHD plasma concentrations were significantly different between the two groups (p = 0.002). One-way ANOVA followed by Bonferroni post hoc testing of four candidate SNPs revealed that carriers of the UGT1A9 variant allele I399 C > T (TT 13.28 ± 7.44 mg/L, TC 16.41 ± 6.53 mg/L) had significantly lower MHD plasma concentrations and poorer seizure control than noncarriers (CC 22.24 ± 8.49 mg/L, p < 0.05). In our study, we have demonstrated the effects of UGT1A9 genetic polymorphisms on MHD plasma concentrations and OXC therapeutic efficacy. Through MHD monitoring, we can predict OXC therapeutic efficacy, which may be useful for the personalization of OXC therapy in epileptic patients.

Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline.

PubMed

Pappas, Derek J; Marin, Wesley; Hollenbach, Jill A; Mack, Steven J

2016-03-01

Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Estimates of genetic parameters and environmental effects for measures of hunting performance in Finnish hounds.

PubMed

Liinamo, A E; Karjalainen, L; Ojala, M; Vilva, V

1997-03-01

Data from field trials of Finnish Hounds between 1988 and 1992 in Finland were used to estimate genetic parameters and environmental effects for measures of hunting performance using REML procedures and an animal model. The original data set included 28,791 field trial records from 5,666 dogs. Males and females had equal hunting performance, whereas experience acquired by age improved trial results compared with results for young dogs (P < .001). Results were mostly better on snow than on bare ground (P < .001), and testing areas, years, months, and their interactions affected results (P < .001). Estimates of heritabilities and repeatabilities were low for most of the 28 measures, mainly due to large residual variances. The highest heritabilities were for frequency of tonguing (h2 = .15), pursuit score (h2 = .13), tongue score (h2 = .13), ghost trailing score (h2 = .12), and merit and final score (both h2 = .11). Estimates of phenotypic and genetic correlations were positive and moderate or high for search scores, pursuit scores, and final scores but lower for other studied measures. The results suggest that, due to low heritabilities, evaluation of breeding values for Finnish Hounds with respect to their hunting ability should be based on animal model BLUP methods instead of mere performance testing. The evaluation system of field trials should also be revised for more reliability.

OPATs: Omnibus P-value association tests.

PubMed

Chen, Chia-Wei; Yang, Hsin-Chou

2017-07-10

Combining statistical significances (P-values) from a set of single-locus association tests in genome-wide association studies is a proof-of-principle method for identifying disease-associated genomic segments, functional genes and biological pathways. We review P-value combinations for genome-wide association studies and introduce an integrated analysis tool, Omnibus P-value Association Tests (OPATs), which provides popular analysis methods of P-value combinations. The software OPATs programmed in R and R graphical user interface features a user-friendly interface. In addition to analysis modules for data quality control and single-locus association tests, OPATs provides three types of set-based association test: window-, gene- and biopathway-based association tests. P-value combinations with or without threshold and rank truncation are provided. The significance of a set-based association test is evaluated by using resampling procedures. Performance of the set-based association tests in OPATs has been evaluated by simulation studies and real data analyses. These set-based association tests help boost the statistical power, alleviate the multiple-testing problem, reduce the impact of genetic heterogeneity, increase the replication efficiency of association tests and facilitate the interpretation of association signals by streamlining the testing procedures and integrating the genetic effects of multiple variants in genomic regions of biological relevance. In summary, P-value combinations facilitate the identification of marker sets associated with disease susceptibility and uncover missing heritability in association studies, thereby establishing a foundation for the genetic dissection of complex diseases and traits. OPATs provides an easy-to-use and statistically powerful analysis tool for P-value combinations. OPATs, examples, and user guide can be downloaded from http://www.stat.sinica.edu.tw/hsinchou/genetics/association/OPATs.htm. © The Author 2017. Published by Oxford University Press.

What is in a cause? Exploring the relationship between genetic cause and felt stigma

PubMed Central

Sankar, Pamela; Cho, Mildred K.; Wolpe, Paul Root; Schairer, Cynthia

2008-01-01

Purpose Concern over stigma as a consequence of genetic testing has grown in response to the recent increase in genetic research and testing resulting from the Human Genome Project. However, whether a genetic or hereditary basis necessarily confers a stigma to a condition remains unexamined. Methods We performed a qualitative interview study with 86 individuals with one of four conditions: deafness or hearing loss, breast cancer, sickle cell disease, and cystic fibrosis. The first two groups were divided approximately between people who ascribed their conditions to a genetic or hereditary cause and those who did not. Results Respondents interpreted genetic or hereditary causes and nongenetic causes in a variety of ways. Subjects with breast cancer reported the most consistently negative interpretation of genetic cause. This response concerned future ill health, not an enduring sense of stigma. Deaf and hard of hearing subjects provided the most consistently positive comments about a genetic or hereditary basis to their condition, casting familial hearing loss as a vital component of group and individual identity. Respondents with sickle cell disease and cystic fibrosis offered similar and positive interpretations of the genetic cause of their condition insofar as it meant their conditions were not contagious. Conclusions Although some subjects report feeling stigmatized as a result of their condition, this stigmatization is not uniformly associated with the condition’s cause, genetic or otherwise. Instead, stigma emerges from a variety of sources in the context of the lived experience of a particular condition. PMID:16418597

Discriminatory power of common genetic variants in personalized breast cancer diagnosis

NASA Astrophysics Data System (ADS)

Wu, Yirong; Abbey, Craig K.; Liu, Jie; Ong, Irene; Peissig, Peggy; Onitilo, Adedayo A.; Fan, Jun; Yuan, Ming; Burnside, Elizabeth S.

2016-03-01

Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine.

Effects of canine parvovirus strain variations on diagnostic test results and clinical management of enteritis in dogs.

PubMed

Markovich, Jessica E; Stucker, Karla M; Carr, Alaina H; Harbison, Carole E; Scarlett, Janet M; Parrish, Colin R

2012-07-01

To estimate the prevalence of canine parvovirus (CPV) strains among dogs with enteritis admitted to a referral hospital in the southwestern United States during an 11-month period and to compare diagnostic test results, disease severity, and patient outcome among CPV strains. Prospective observational study. 72 dogs with histories and clinical signs of parvoviral enteritis. For each dog, a fecal sample or rectal swab specimen was evaluated for CPV antigen via an ELISA. Subsequently, fecal samples (n = 42 dogs) and pharyngeal swab specimens (16) were obtained and tested for CPV antigen via an ELISA and CPV DNA via a PCR assay. For specimens with CPV-positive results via PCR assay, genetic sequencing was performed to identify the CPV strain. 56 dogs tested positive for CPV via ELISA or PCR assay. For 42 fecal samples tested via both ELISA and PCR assay, 27 had positive results via both assays, whereas 6 had positive PCR assay results only. Ten pharyngeal swab specimens yielded positive PCR assay results. Genetic sequencing was performed on 34 fecal or pharyngeal swab specimens that had CPV-positive PCR assay results; 25 (73.5%) were identified as containing CPV type-2c, and 9 (26.5%) were identified as containing CPV type-2b. No association was found between CPV strain and disease severity or clinical outcome. CPV type-2b and CPV type-2c posed similar health risks for dogs; therefore, genetic sequencing of CPV does not appear necessary for clinical management of infected patients. The diagnostic tests used could detect CPV type-2c.

Familial aggregation patterns in mathematical ability.

PubMed

Wijsman, Ellen M; Robinson, Nancy M; Ainsworth, Kathryn H; Rosenthal, Elisabeth A; Holzman, Ted; Raskind, Wendy H

2004-01-01

Mathematical talent is an asset in modern society both at an individual and a societal level. Environmental factors such as quality of mathematics education undoubtedly affect an individual's performance, and there is some evidence that genetic factors also may play a role. The current study was performed to investigate the feasibility of undertaking genetics studies on mathematical ability. Because the etiology of low ability in mathematics is likely to be multifactorial and heterogeneous, we evaluated families ascertained through a proband with high mathematical performance in grade 7 on the SAT to eliminate, to some degree, adverse environmental factors. Families of sex-matched probands, selected for high verbal performance on the SAT, served as the comparison group. We evaluated a number of proxy measures for their usefulness in the study of clustering of mathematical talent. Given the difficulty of testing mathematics performance across developmental ages, especially with the added complexity of decreasing exposure to formal mathematics concepts post schooling, we also devised a semiquantitative scale that incorporated educational, occupational, and avocational information as a surrogate for an academic mathematics measure. Whereas several proxy measures showed no evidence of a genetic basis, we found that the semiquantitative scale of mathematical talent showed strong evidence of a genetic basis, with a differential response as a function of the performance measure used to select the proband. This observation suggests that there may be a genetic basis to specific mathematical talent, and that specific, as opposed to proxy, investigative measures that are designed to measure such talent in family members could be of benefit for this purpose.

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.

Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity.

PubMed

Shapiro, Lucy; Chatterjee, Sumana; Ramadan, Dina G; Davies, Kate M; Savage, Martin O; Metherell, Louise A; Storr, Helen L

2017-12-01

GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown. To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect. We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS. A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver-Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in FANCA and PHKB in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect. Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres. © 2017 European Society of Endocrinology.

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 ...

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

PubMed

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

2015-12-01

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

Can the ability to adapt to exercise be considered a talent-and if so, can we test for it?

PubMed

Pickering, Craig; Kiely, John

2017-11-29

Talent identification (TI) is a popular and hugely important topic within sports performance, with an ever-increasing amount of resources dedicated to unveiling the next sporting star. However, at present, most TI processes appear to select high-performing individuals at the present point in time, as opposed to identifying those individuals with the greatest capacity to improve. This represents a potential inefficiency within the TI process, reducing its effectiveness. In this article, we discuss whether the ability to adapt favorably, and with a large magnitude, to physical training can be considered a talent, testing it against proposed criteria. We also discuss whether, if such an ability can be considered a talent, being able to test for it as part of the TI process would be advantageous. Given that such a capacity is partially heritable, driven by genetic variation between individuals that mediate the adaptive response, we also explore whether the information gained from genetic profiling can be used to identify those with the greatest capacity to improve. Although there are some ethical hurdles which must be considered, the use of genetic information to identify those individuals with the greatest capacity appears to hold promise and may improve both the efficiency and effectiveness of contemporary TI programmes.

Genetic progress in multistage dairy cattle breeding schemes using genetic markers.

PubMed

Schrooten, C; Bovenhuis, H; van Arendonk, J A M; Bijma, P

2005-04-01

The aim of this paper was to explore general characteristics of multistage breeding schemes and to evaluate multistage dairy cattle breeding schemes that use information on quantitative trait loci (QTL). Evaluation was either for additional genetic response or for reduction in number of progeny-tested bulls while maintaining the same response. The reduction in response in multistage breeding schemes relative to comparable single-stage breeding schemes (i.e., with the same overall selection intensity and the same amount of information in the final stage of selection) depended on the overall selection intensity, the selection intensity in the various stages of the breeding scheme, and the ratio of the accuracies of selection in the various stages of the breeding scheme. When overall selection intensity was constant, reduction in response increased with increasing selection intensity in the first stage. The decrease in response was highest in schemes with lower overall selection intensity. Reduction in response was limited in schemes with low to average emphasis on first-stage selection, especially if the accuracy of selection in the first stage was relatively high compared with the accuracy in the final stage. Closed nucleus breeding schemes in dairy cattle that use information on QTL were evaluated by deterministic simulation. In the base scheme, the selection index consisted of pedigree information and own performance (dams), or pedigree information and performance of 100 daughters (sires). In alternative breeding schemes, information on a QTL was accounted for by simulating an additional index trait. The fraction of the variance explained by the QTL determined the correlation between the additional index trait and the breeding goal trait. Response in progeny test schemes relative to a base breeding scheme without QTL information ranged from +4.5% (QTL explaining 5% of the additive genetic variance) to +21.2% (QTL explaining 50% of the additive genetic variance). A QTL explaining 5% of the additive genetic variance allowed a 35% reduction in the number of progeny tested bulls, while maintaining genetic response at the level of the base scheme. Genetic progress was up to 31.3% higher for schemes with increased embryo production and selection of embryos based on QTL information. The challenge for breeding organizations is to find the optimum breeding program with regard to additional genetic progress and additional (or reduced) cost.

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

Understanding Individual Differences in Spatial Ability within Females: A Nature/Nurture Interactionist Framework.

ERIC Educational Resources Information Center

Casey, M. Beth

1996-01-01

Identified subjects' handedness and family handedness (genetic variables) and college major (environmental variable); and tested subjects on the Vandenberg Mental Rotation Test. Found that right-handed females with non-right-handed relatives and with science or math majors outperformed other females and equaled the performance of males on the…

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.

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.

EvolQG - An R package for evolutionary quantitative genetics

PubMed Central

Melo, Diogo; Garcia, Guilherme; Hubbe, Alex; Assis, Ana Paula; Marroig, Gabriel

2016-01-01

We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the \\textbf{EvolQG} package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification. PMID:27785352

GenoCore: A simple and fast algorithm for core subset selection from large genotype datasets.

PubMed

Jeong, Seongmun; Kim, Jae-Yoon; Jeong, Soon-Chun; Kang, Sung-Taeg; Moon, Jung-Kyung; Kim, Namshin

2017-01-01

Selecting core subsets from plant genotype datasets is important for enhancing cost-effectiveness and to shorten the time required for analyses of genome-wide association studies (GWAS), and genomics-assisted breeding of crop species, etc. Recently, a large number of genetic markers (>100,000 single nucleotide polymorphisms) have been identified from high-density single nucleotide polymorphism (SNP) arrays and next-generation sequencing (NGS) data. However, there is no software available for picking out the efficient and consistent core subset from such a huge dataset. It is necessary to develop software that can extract genetically important samples in a population with coherence. We here present a new program, GenoCore, which can find quickly and efficiently the core subset representing the entire population. We introduce simple measures of coverage and diversity scores, which reflect genotype errors and genetic variations, and can help to select a sample rapidly and accurately for crop genotype dataset. Comparison of our method to other core collection software using example datasets are performed to validate the performance according to genetic distance, diversity, coverage, required system resources, and the number of selected samples. GenoCore selects the smallest, most consistent, and most representative core collection from all samples, using less memory with more efficient scores, and shows greater genetic coverage compared to the other software tested. GenoCore was written in R language, and can be accessed online with an example dataset and test results at https://github.com/lovemun/Genocore.

Generalist genes and learning disabilities: a multivariate genetic analysis of low performance in reading, mathematics, language and general cognitive ability in a sample of 8000 12-year-old twins.

PubMed

Haworth, Claire M A; Kovas, Yulia; Harlaar, Nicole; Hayiou-Thomas, Marianna E; Petrill, Stephen A; Dale, Philip S; Plomin, Robert

2009-10-01

Our previous investigation found that the same genes influence poor reading and mathematics performance in 10-year-olds. Here we assess whether this finding extends to language and general cognitive disabilities, as well as replicating the earlier finding for reading and mathematics in an older and larger sample. Using a representative sample of 4000 pairs of 12-year-old twins from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between internet-based batteries of language and general cognitive ability tests in addition to tests of reading and mathematics for the bottom 15% of the distribution using DeFries-Fulker extremes analysis. We compared these results to those for the entire distribution. All four traits were highly correlated at the low extreme (average group phenotypic correlation = .58). and in the entire distribution (average phenotypic correlation = .59). Genetic correlations for the low extreme were consistently high (average = .67), and non-shared environmental correlations were modest (average = .23). These results are similar to those seen across the entire distribution (.68 and .23, respectively). The 'Generalist Genes Hypothesis' holds for language and general cognitive disabilities, as well as reading and mathematics disabilities. Genetic correlations were high, indicating a strong degree of overlap in genetic influences on these diverse traits. In contrast, non-shared environmental influences were largely specific to each trait, causing phenotypic differentiation of traits.

Genetic Variation in Taste Sensitivity to Sugars in Drosophila melanogaster.

PubMed

Uchizono, Shun; Tanimura, Teiichi

2017-05-01

Taste sensitivity plays a major role in controlling feeding behavior, and alterations in feeding habit induced by changes in taste sensitivity can drive speciation. We investigated variability in taste preferences in wild-derived inbred lines from the Drosophila melanogaster Genetic Reference Panel. Preferences for different sugars, which are essential nutrients for fruit flies, were assessed using two-choice preference tests that paired glucose with fructose, sucrose, or trehalose. The two-choice tests revealed that individual lines have differential and widely variable sugar preferences, and that sugar taste sensitivity is polygenic in the inbred population tested. We focused on 2 strains that exhibited opposing preferences for glucose and fructose, and performed proboscis extension reflex tests and electrophysiological recordings on taste sensilla upon exposure to fructose and glucose. The results indicated that taste sensitivity to fructose is dimorphic between the 2 lines. Genetic analysis showed that high sensitivity to fructose is autosomal dominant over low sensitivity, and that multiple loci on chromosomes 2 and 3 influence sensitivity. Further genetic complementation tests for fructose sensitivity on putative gustatory receptor (Gr) genes for sugars suggested that the Gr64a-Gr64f locus, not the fructose receptor gene Gr43a, might contribute to the dimorphic sensitivity to fructose between the 2 lines. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A systematic analysis of online marketing materials used by providers of expanded carrier screening.

PubMed

Chokoshvili, Davit; Borry, Pascal; Vears, Danya F

2017-12-14

PurposeExpanded carrier screening (ECS) for a large number of recessive disorders is available to prospective parents through commercial providers. This study aimed to analyze the content of marketing materials on ECS providers' websites.MethodsTo identify providers of ECS tests, we undertook a comprehensive online search, reviewed recent academic literature on commercial carrier screening, and consulted with colleagues familiar with the current ECS landscape. The identified websites were archived in April 2017, and inductive content analysis was performed on website text, brochures and educational materials, and video transcripts.ResultsWe identified 18 ECS providers, including 16 commercial genetic testing companies. Providers typically described ECS as an important family planning tool. The content differed in both the tone used to promote ECS and the accuracy and completeness of the test information provided. We found that most providers offered complimentary genetic counseling to their consumers, although this was often optional, limited to the posttest context, and, in some cases, appeared to be available only to test-positive individuals.ConclusionThe quality of ECS providers' websites could be improved by offering more complete and accurate information about ECS and their tests. Providers should also ensure that all carrier couples receive posttest genetic counseling to inform their subsequent reproductive decision making.Genet Med advance online publication, 14 December 2017; doi:10.1038/gim.2017.222.

Pharmacogenetics of clopidogrel: comparison between a standard and a rapid genetic testing.

PubMed

Saracini, Claudia; Vestrini, Anna; Galora, Silvia; Armillis, Alessandra; Abbate, Rosanna; Giusti, Betti

2012-06-01

CYP2C19 variant alleles are independent predictors of clopidogrel response variability and occurrence of major adverse cardiovascular events in high-risk vascular patients on clopidogrel therapy. Increasing evidence suggests a combination of platelet function testing with CYP2C19 genetic testing may be more effective in identifying high-risk individuals for alternative antiplatelet therapeutic strategies. A crucial point in evaluating the use of these polymorphisms in clinical practice, besides test accuracy, is the cost of the genetic test and rapid availability of the results. One hundred acute coronary syndrome patients were genotyped for CYP2C19*2,*3,*4,*5, and *17 polymorphisms with two platforms: Verigene(®) and the TaqMan(®) system. Genotyping results obtained by the classical TaqMan approach and the rapid Verigene approach showed a 100% concordance for all the five polymorphisms investigated. The Verigene system had shorter turnaround time with respect to TaqMan. The cost of reagents for TaqMan genotyping was lower than that for the Verigene system, but the effective manual staff involvement and the relative cost resulted in higher cost for TaqMan than for Verigene. The Verigene system demonstrated good performance in terms of turnaround time and cost for the evaluation of the clopidogrel poor metabolizer status, giving genetic information in suitable time (206 min) for a therapeutic strategy decision.

Genetic variability and resistance of cultivars of cowpea [Vigna unguiculata (L.) Walp] to cowpea weevil (Callosobruchus maculatus Fabr.).

PubMed

Vila Nova, M X; Leite, N G A; Houllou, L M; Medeiros, L V; Lira Neto, A C; Hsie, B S; Borges-Paluch, L R; Santos, B S; Araujo, C S F; Rocha, A A; Costa, A F

2014-03-31

The cowpea weevil (Callosobruchus maculatus Fabr.) is the most destructive pest of the cowpea bean; it reduces seed quality. To control this pest, resistance testing combined with genetic analysis using molecular markers has been widely applied in research. Among the markers that show reliable results, the inter-simple sequence repeats (ISSRs) (microsatellites) are noteworthy. This study was performed to evaluate the resistance of 27 cultivars of cowpea bean to cowpea weevil. We tested the resistance related to the genetic variability of these cultivars using ISSR markers. To analyze the resistance of cultivars to weevil, a completely randomized test design with 4 replicates and 27 treatments was adopted. Five pairs of the insect were placed in 30 grains per replicate. Analysis of variance showed that the number of eggs and emerged insects were significantly different in the treatments, and the means were compared by statistical tests. The analysis of the large genetic variability in all cultivars resulted in the formation of different groups. The test of resistance showed that the cultivar Inhuma was the most sensitive to both number of eggs and number of emerged adults, while the TE96-290-12-G and MNC99-537-F4 (BRS Tumucumaque) cultivars were the least sensitive to the number of eggs and the number of emerged insects, respectively.

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

Genetic testing of newborns for type 1 diabetes susceptibility: a prospective cohort study on effects on maternal mental health

PubMed Central

2010-01-01

Background Concerns about the general psychological impact of genetic testing have been raised. In the Environmental Triggers of Type 1 Diabetes (MIDIA) study, genetic testing was performed for HLA-conferred type 1 diabetes susceptibility among Norwegian newborns. The present study assessed whether mothers of children who test positively suffer from poorer mental health and well-being after receiving genetic risk information about their children. Methods The study was based on questionnaire data from the Norwegian Mother and Child Cohort (MoBa) study conducted by the Norwegian Institute of Public Health. Many of the mothers in the MoBa study also took part in the MIDIA study, in which their newborn children were tested for HLA-conferred genetic susceptibility for type 1 diabetes. We used MoBa questionnaire data from the 30th week of pregnancy (baseline) and 6 months post-partum (3-3.5 months after disclosure of test results). We measured maternal symptoms of anxiety and depression (SCL-8), maternal self-esteem (RSES), and satisfaction with life (SWLS). The mothers also reported whether they were seriously worried about their child 6 months post-partum. We compared questionnaire data from mothers who had received information about having a newborn with high genetic risk for type 1 diabetes (N = 166) with data from mothers who were informed that their baby did not have a high-risk genotype (N = 7224). The association between genetic risk information and maternal mental health was analysed using multiple linear regression analysis, controlling for baseline mental health scores. Results Information on genetic risk in newborns was found to have no significant impact on maternal symptoms of anxiety and depression (p = 0.9), self-esteem (p = 0.2), satisfaction with life (p = 0.2), or serious worry about their child (OR = 0.98, 95% CI 0.64-1.48). Mental health before birth was strongly associated with mental health after birth. In addition, an increased risk of maternal worry was found if the mother herself had type 1 diabetes (OR = 2.39, 95% CI 1.2-4.78). Conclusions This study did not find evidence supporting the notion that genetic risk information about newborns has a negative impact on the mental health of Norwegian mothers. PMID:20630116

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PubMed

Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Probability of Positive Genetic Testing Results in Patients with Family History of Primary Hyperparathyroidism.

PubMed

El Lakis, Mustapha; Nockel, Pavel; Gaitanidis, Apostolos; Guan, Bin; Agarwal, Sunita; Welch, James; Simonds, William F; Weinstein, Lee; Marx, Stephen; Nilubol, Naris; Patel, Dhaval; Merkel, Roxanne; Tirosh, Amit; Kebebew, Electron

2018-05-01

Approximately 10% of patients with primary hyperparathyroidism (PHPT) have hereditary disease. Hereditary PHPT may be syndromic (MEN1, 2, and 4 and hyperparathyroidism-jaw tumor syndrome) or non-syndromic (familial isolated PHPT). There are limited data on the probability of testing positive for genetic mutation based on clinical presentation. The aim of this study was to determine potential associations between clinical and biochemical features and mutation in susceptibility genes for PHPT in patients with a family history of PHPT. A retrospective analysis of 657 patients who had an initial parathyroidectomy for PHPT at a tertiary referral center. Logistic regression analyses were performed in 205 patients with a family history of PHPT to identify factors associated with a positive genetic test. Of 657 patients, 205 (31.2%) had a family history of PHPT. Of those 205 patients, 123 (60%) had a germline mutation detected (91 MEN1, 14 CDC73, and 18 GCM2). In univariate analysis, younger age (45 years and younger), male sex, multigland disease, and parathyroid carcinoma were associated with positive germline mutation; biochemical cure after an initial parathyroidectomy was less frequent in patients with familial PHPT (96.2% vs 89.2%; p = 0.005). In multivariable analysis, age 45 years and younger, male sex, and multigland disease were independent factors associated with positive genetic testing. In addition to a family history of PHPT, male sex, age 45 years and younger, and presence of multigland disease, should prompt physicians to offer the opportunity for genetic counseling and testing, as it could influence the management of patients with PHPT. Published by Elsevier Inc.

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.

Awareness of Cancer Susceptibility Genetic Testing

PubMed Central

Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.

2014-01-01

Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (p<0.001) between 2000 and 2005, and increased to 47.0% (p<0.001) in 2010. Awareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633

Awareness of cancer susceptibility genetic testing: the 2000, 2005, and 2010 National Health Interview Surveys.

PubMed

Mai, Phuong L; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S; Wideroff, Louise; Graubard, Barry I

2014-05-01

Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000-2005 and 2005-2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Awareness decreased from 44.4% to 41.5% (p<0.001) between 2000 and 2005, and increased to 47.0% (p<0.001) in 2010. Awareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (pinteraction=0.03) or with a usual place of care (pinteraction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25-39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. Published by Elsevier Inc.

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

Pitfalls in genetic testing: the story of missed SCN1A mutations.

PubMed

Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa; Guerrini, Renzo; Hämäläinen, Eija; Hartmann, Corinna; Hernandez-Hernandez, Laura; Hjalgrim, Helle; Koeleman, Bobby P C; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R; Leu, Costin; Marini, Carla; McMahon, Jacinta M; Mei, Davide; Møller, Rikke S; Muhle, Hiltrud; Myers, Candace T; Nava, Caroline; Serratosa, Jose M; Sisodiya, Sanjay M; Stephani, Ulrich; Striano, Pasquale; van Kempen, Marjan J A; Verbeek, Nienke E; Usluer, Sunay; Zara, Federico; Palotie, Aarno; Mefford, Heather C; Scheffer, Ingrid E; De Jonghe, Peter; Helbig, Ingo; Suls, Arvid

2016-07-01

Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. We sent out a survey to 16 genetic centers performing SCN1A testing. We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.

Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation

PubMed Central

Ferguson, John; Wheeler, William; Fu, YiPing; Prokunina-Olsson, Ludmila; Zhao, Hongyu; Sampson, Joshua

2013-01-01

With recent advances in sequencing, genotyping arrays, and imputation, GWAS now aim to identify associations with rare and uncommon genetic variants. Here, we describe and evaluate a class of statistics, generalized score statistics (GSS), that can test for an association between a group of genetic variants and a phenotype. GSS are a simple weighted sum of single-variant statistics and their cross-products. We show that the majority of statistics currently used to detect associations with rare variants are equivalent to choosing a specific set of weights within this framework. We then evaluate the power of various weighting schemes as a function of variant characteristics, such as MAF, the proportion associated with the phenotype, and the direction of effect. Ultimately, we find that two classical tests are robust and powerful, but details are provided as to when other GSS may perform favorably. The software package CRaVe is available at our website (http://dceg.cancer.gov/bb/tools/crave). PMID:23092956

A Genetic Interaction Screen for Breast Cancer Progression Driver Genes

DTIC Science & Technology

2013-06-01

analysis of genetic alterations in human breast cancers has revealed that individual tumors accumulate mutations in approximately ninety different genes ...cancer. We performed a screen to test the roles of seventy breast cancer mutated genes in mouse mammary tumorigenesis using the MMTV-PyVT mouse breast...cancer model and piggyBac insertional mutation strains. We found that insertional mutations in 23 genes altered the onset of tumor formation and four

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.

The psychological impact of genetic testing on parents.

PubMed

Dinc, Leyla; Terzioglu, Fusun

2006-01-01

The aim of this descriptive study was to explore the psychological impact of genetic testing on parents whose children have been referred for genetic testing. Genetic tests enable individuals to be informed about their health status and to have the opportunity of early diagnosis and treatment of their diseases. However undergoing genetic testing and receiving a positive test result may also cause stress and anxiety. This descriptive study was carried out at the genetic departments of two university hospitals in Ankara. The sample of this study consisted of 128 individuals whose children have been referred for chromosomal analysis. Data were collected through using a semi-structured interview method with a data collection form and the anxiety inventory and analysed using the percentages and independent samples t-test. The majority of our participants experienced distress before genetic testing. Their general trait anxiety score before receiving the test results was 47.38, and following the test results the state anxiety score was 50.65. Having a previous child with an abnormality, a positive test result, and being a mother elevated the anxiety of individuals. This paper supports the findings of previous studies, which indicated that genetic test results might lead to anxiety in individuals and reveals the importance of genetic counselling. As the results of this study indicated, genetic testing causes distress and anxiety in individuals. Nurses can play an important role in minimizing anxiety of parents whose children undergo genetic testing by providing information about genetic testing and by taking part in the counselling process.

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.

Estimation of Genetic Parameters from Longitudinal Records of Body Weight of Berkshire Pigs

PubMed Central

Lee, Dong-Hee; Do, Chang-Hee

2012-01-01

Direct and maternal genetic heritabilities and their correlations with body weight at 5 stages in the life span of purebred Berkshire pigs, from birth to harvest, were estimated to scrutinize body weight development with the records for 5,088 purebred Berkshire pigs in a Korean farm, using the REML based on an animal model. Body weights were measured at birth (Birth), at weaning (Weaning: mean 22.9 d), at the beginning of a performance test (On: mean 72.7 d), at the end of a performance test (Off: mean 152.4 d), and at harvest (Finish: mean 174.3 d). Ordinary polynomials and Legendre with order 1, 2, and 3 were adopted to adjust body weight with age in the multivariate animal models. Legendre with order 3 fitted best concerning prediction error deviation (PED) and yielded the lowest AIC for multivariate analysis of longitudinal body weights. Direct genetic correlations between body weight at Birth and body weight at Weaning, On, Off, and Finish were 0.48, 0.36, 0.10, and 0.10, respectively. The estimated maternal genetic correlations of body weight at Finish with body weight at Birth, Weaning, On, and Off were 0.39, 0.49, 0.65, and 0.90, respectively. Direct genetic heritabilities progressively increased from birth to harvest and were 0.09, 0.11, 0.20, 0.31, and 0.43 for body weight at Birth, Weaning, On, Off, and Finish, respectively. Maternal genetic heritabilities generally decreased and were 0.26, 0.34, 0.15, 0.10, and 0.10 for body weight at Birth, Weaning, On, Off, and Finish, respectively. As pigs age, maternal genetic effects on growth are reduced and pigs begin to rely more on the expression of their own genes. Although maternal genetic effects on body weight may not be large, they are sustained through life. PMID:25049624

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

PubMed

Witt, S H; Streit, F; Jungkunz, M; Frank, J; Awasthi, S; Reinbold, C S; Treutlein, J; Degenhardt, F; Forstner, A J; Heilmann-Heimbach, S; Dietl, L; Schwarze, C E; Schendel, D; Strohmaier, J; Abdellaoui, A; Adolfsson, R; Air, T M; Akil, H; Alda, M; Alliey-Rodriguez, N; Andreassen, O A; Babadjanova, G; Bass, N J; Bauer, M; Baune, B T; Bellivier, F; Bergen, S; Bethell, A; Biernacka, J M; Blackwood, D H R; Boks, M P; Boomsma, D I; Børglum, A D; Borrmann-Hassenbach, M; Brennan, P; Budde, M; Buttenschøn, H N; Byrne, E M; Cervantes, P; Clarke, T-K; Craddock, N; Cruceanu, C; Curtis, D; Czerski, P M; Dannlowski, U; Davis, T; de Geus, E J C; Di Florio, A; Djurovic, S; Domenici, E; Edenberg, H J; Etain, B; Fischer, S B; Forty, L; Fraser, C; Frye, M A; Fullerton, J M; Gade, K; Gershon, E S; Giegling, I; Gordon, S D; Gordon-Smith, K; Grabe, H J; Green, E K; Greenwood, T A; Grigoroiu-Serbanescu, M; Guzman-Parra, J; Hall, L S; Hamshere, M; Hauser, J; Hautzinger, M; Heilbronner, U; Herms, S; Hitturlingappa, S; Hoffmann, P; Holmans, P; Hottenga, J-J; Jamain, S; Jones, I; Jones, L A; Juréus, A; Kahn, R S; Kammerer-Ciernioch, J; Kirov, G; Kittel-Schneider, S; Kloiber, S; Knott, S V; Kogevinas, M; Landén, M; Leber, M; Leboyer, M; Li, Q S; Lissowska, J; Lucae, S; Martin, N G; Mayoral-Cleries, F; McElroy, S L; McIntosh, A M; McKay, J D; McQuillin, A; Medland, S E; Middeldorp, C M; Milaneschi, Y; Mitchell, P B; Montgomery, G W; Morken, G; Mors, O; Mühleisen, T W; Müller-Myhsok, B; Myers, R M; Nievergelt, C M; Nurnberger, J I; O'Donovan, M C; Loohuis, L M O; Ophoff, R; Oruc, L; Owen, M J; Paciga, S A; Penninx, B W J H; Perry, A; Pfennig, A; Potash, J B; Preisig, M; Reif, A; Rivas, F; Rouleau, G A; Schofield, P R; Schulze, T G; Schwarz, M; Scott, L; Sinnamon, G C B; Stahl, E A; Strauss, J; Turecki, G; Van der Auwera, S; Vedder, H; Vincent, J B; Willemsen, G; Witt, C C; Wray, N R; Xi, H S; Tadic, A; Dahmen, N; Schott, B H; Cichon, S; Nöthen, M M; Ripke, S; Mobascher, A; Rujescu, D; Lieb, K; Roepke, S; Schmahl, C; Bohus, M; Rietschel, M

2017-06-20

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10 -7 ) and PKP4 (P=8.67 × 10 -7 ); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r g =0.28 [P=2.99 × 10 -3 ]), SCZ (r g =0.34 [P=4.37 × 10 -5 ]) and MDD (r g =0.57 [P=1.04 × 10 -3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Functional linear models for association analysis of quantitative traits.

PubMed

Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

2013-11-01

Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY PERIODICALS, INC.

MHC class II is an important genetic risk factor for canine systemic lupus erythematosus (SLE)-related disease: implications for reproductive success.

PubMed

Wilbe, M; Andersson, G

2012-01-01

Major histocompatibility complex (MHC) class II genes are important genetic risk factors for development of immune-mediated diseases in mammals. Recently, the dog (Canis lupus familiaris) has emerged as a useful model organism to identify critical MHC class II genotypes that contribute to development of these diseases. Therefore, a study aimed to evaluate a potential genetic association between the dog leukocyte antigen (DLA) class II region and an immune-mediated disease complex in dogs of the Nova Scotia duck tolling retriever breed was performed. We show that DLA is one of several genetic risk factors for this disease complex and that homozygosity of the risk haplotype is disadvantageous. Importantly, the disease is complex and has many genetic risk factors and therefore we cannot provide recommendations for breeders exclusively on the basis of genetic testing for DLA class II genotype. © 2012 Blackwell Verlag GmbH.

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

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

PubMed

Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

Sports genetics moving forward: lessons learned from medical research.

PubMed

Mattsson, C Mikael; Wheeler, Matthew T; Waggott, Daryl; Caleshu, Colleen; Ashley, Euan A

2016-03-01

Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy. Copyright © 2016 the American Physiological Society.

Working memory training promotes general cognitive abilities in genetically heterogeneous mice.

PubMed

Light, Kenneth R; Kolata, Stefan; Wass, Christopher; Denman-Brice, Alexander; Zagalsky, Ryan; Matzel, Louis D

2010-04-27

In both humans and mice, the efficacy of working memory capacity and its related process, selective attention, are each strongly predictive of individuals' aggregate performance in cognitive test batteries [1-9]. Because working memory is taxed during most cognitive tasks, the efficacy of working memory may have a causal influence on individuals' performance on tests of "intelligence" [10, 11]. Despite the attention this has received, supporting evidence has been largely correlational in nature (but see [12]). Here, genetically heterogeneous mice were assessed on a battery of five learning tasks. Animals' aggregate performance across the tasks was used to estimate their general cognitive abilities, a trait that is in some respects analogous to intelligence [13, 14]. Working memory training promoted an increase in animals' selective attention and their aggregate performance on these tasks. This enhancement of general cognitive performance by working memory training was attenuated if its selective attention demands were reduced. These results provide evidence that the efficacy of working memory capacity and selective attention may be causally related to an animal's general cognitive performance and provide a framework for behavioral strategies to promote those abilities. Furthermore, the pattern of behavior reported here reflects a conservation of the processes that regulate general cognitive performance in humans and infrahuman animals. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Genetic control of wheat quality: interactions between chromosomal regions determining protein content and composition, dough rheology, and sponge and dough baking properties.

PubMed

Mann, Gulay; Diffey, Simon; Cullis, Brian; Azanza, Fermin; Martin, David; Kelly, Alison; McIntyre, Lynne; Schmidt, Adele; Ma, Wujun; Nath, Zena; Kutty, Ibrahim; Leyne, P Emmett; Rampling, Lynette; Quail, Ken J; Morell, Matthew K

2009-05-01

While the genetic control of wheat processing characteristics such as dough rheology is well understood, limited information is available concerning the genetic control of baking parameters, particularly sponge and dough (S&D) baking. In this study, a quantitative trait loci (QTL) analysis was performed using a population of doubled haploid lines derived from a cross between Australian cultivars Kukri x Janz grown at sites across different Australian wheat production zones (Queensland in 2001 and 2002 and Southern and Northern New South Wales in 2003) in order to examine the genetic control of protein content, protein expression, dough rheology and sponge and dough baking performance. The study highlighted the inconsistent genetic control of protein content across the test sites, with only two loci (3A and 7A) showing QTL at three of the five sites. Dough rheology QTL were highly consistent across the 5 sites, with major effects associated with the Glu-B1 and Glu-D1 loci. The Glu-D1 5 + 10 allele had consistent effects on S&D properties across sites; however, there was no evidence for a positive effect of the high dough strength Glu-B1-al allele at Glu-B1. A second locus on 5D had positive effects on S&D baking at three of five sites. This study demonstrated that dough rheology measurements were poor predictors of S&D quality. In the absence of robust predictive tests, high heritability values for S&D demonstrate that direct selection is the current best option for achieving genetic gain in this product category.

GAPscreener: an automatic tool for screening human genetic association literature in PubMed using the support vector machine technique.

PubMed

Yu, Wei; Clyne, Melinda; Dolan, Siobhan M; Yesupriya, Ajay; Wulf, Anja; Liu, Tiebin; Khoury, Muin J; Gwinn, Marta

2008-04-22

Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.

A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.

PubMed

Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Chung, Daniel C

2017-03-01

To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, P<0.01). However, a hybrid approach that reserves MLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

Hierarchical Naive Bayes for genetic association studies.

PubMed

Malovini, Alberto; Barbarini, Nicola; Bellazzi, Riccardo; de Michelis, Francesca

2012-01-01

Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability.

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

Adaptation to climate change? Moving coast redwood seedlings northward and inland

Treesearch

Christa M. Dagley; John-Pascal Berrill; Forrest T. Johnson; Lucy P. Kerhoulas

2017-01-01

Insight into genetic variation in trees may provide opportunities to select for genotypes that are better adapted to new locations and future climate conditions. We established a field test at two sites in Humboldt County, California to study the performance of coast redwood (Sequoia sempervirens (D. Don) Endl.) under assisted migration. Both test...

Genetic variance and covariance components for feed intake, average daily gain, and postweaning gain in growing beef cattle

USDA-ARS?s Scientific Manuscript database

Feed is the single most expensive cost related to a beef cattle production enterprise. Data collection to determine feed efficient animals is also costly. Currently a 70 d performance test is recommended for accurate calculation of efficiency. Previous research has suggested intake tests can be l...

Recombinant DNA Paper Model Simulation: The Genetic Engineer.

ERIC Educational Resources Information Center

Wagner, Joan

1998-01-01

Describes a course for talented high school students that focuses on DNA science and technology. Employs Cold Spring Harbor's DNA Science laboratory manual. Engages students in performing sickle-cell anemia and thalassemia tests in rabbits. (DDR)

GENOTOXICITY RISK ASSESSMENT: A PROPOSED CLASSIFICATION STRATEGY

EPA Science Inventory

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines fo...

PRESAGE: PRivacy-preserving gEnetic testing via SoftwAre Guard Extension.

PubMed

Chen, Feng; Wang, Chenghong; Dai, Wenrui; Jiang, Xiaoqian; Mohammed, Noman; Al Aziz, Md Momin; Sadat, Md Nazmus; Sahinalp, Cenk; Lauter, Kristin; Wang, Shuang

2017-07-26

Advances in DNA sequencing technologies have prompted a wide range of genomic applications to improve healthcare and facilitate biomedical research. However, privacy and security concerns have emerged as a challenge for utilizing cloud computing to handle sensitive genomic data. We present one of the first implementations of Software Guard Extension (SGX) based securely outsourced genetic testing framework, which leverages multiple cryptographic protocols and minimal perfect hash scheme to enable efficient and secure data storage and computation outsourcing. We compared the performance of the proposed PRESAGE framework with the state-of-the-art homomorphic encryption scheme, as well as the plaintext implementation. The experimental results demonstrated significant performance over the homomorphic encryption methods and a small computational overhead in comparison to plaintext implementation. The proposed PRESAGE provides an alternative solution for secure and efficient genomic data outsourcing in an untrusted cloud by using a hybrid framework that combines secure hardware and multiple crypto protocols.

An empirical evaluation of genetic distance statistics using microsatellite data from bear (Ursidae) populations.

PubMed

Paetkau, D; Waits, L P; Clarkson, P L; Craighead, L; Strobeck, C

1997-12-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data.

An Empirical Evaluation of Genetic Distance Statistics Using Microsatellite Data from Bear (Ursidae) Populations

PubMed Central

Paetkau, D.; Waits, L. P.; Clarkson, P. L.; Craighead, L.; Strobeck, C.

1997-01-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data. PMID:9409849

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.

Impact of a randomized controlled educational trial to improve physician practice behaviors around screening for inherited breast cancer.

PubMed

Bell, Robert A; McDermott, Haley; Fancher, Tonya L; Green, Michael J; Day, Frank C; Wilkes, Michael S

2015-03-01

Many primary care physicians (PCPs) are ill-equipped to provide screening and counseling for inherited breast cancer. To evaluate the outcomes of an interactive web-based genetics curriculum versus text curriculum for primary care physicians. Randomized two-group design. 121 California and Pennsylvania community physicians. Web-based interactive genetics curriculum, evaluated against a control group of physicians who studied genetics review articles. After education, physicians interacted with an announced standardized patient (SP) at risk for inherited breast cancer. Transcripts of visit discussions were coded for presence or absence of 69 topics relevant to inherited breast cancer. Across all physicians, history-taking, discussions of test result implications, and exploration of ethical and legal issues were incomplete. Approximately half of physicians offered a genetic counseling referral (54.6%), and fewer (43.8%) recommended testing. Intervention physicians were more likely than controls to explore genetic counseling benefits (78.3% versus 60.7%, P = 0.048), encourage genetic counseling before testing (38.3% versus 21.3%, P = 0.048), ask about a family history of prostate cancer (25.0% versus 6.6%, P = 0.006), and report that a positive result indicated an increased risk of prostate cancer for male relatives (20.0% versus 1.6%, P = 0.001). Intervention-group physicians were less likely than controls to ask about Ashkenazi heritage (13.3% versus 34.4%, P = 0.01) or to reply that they would get tested when asked, "What would you do?" (33.3% versus 54.1%, P = 0.03). Physicians infrequently performed key counseling behaviors, and this was true regardless of whether they had completed the web-based interactive training or read clinical reviews.

Irradiation influence on the detection of genetic-modified soybeans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H.; Araújo, M. M.; Baldasso, J. G.; Aquino, S.; Konietzny, U.; Greiner, R.

2004-09-01

Three soybean varieties were analyzed to evaluate the irradiation influence on the detection of genetic modification. Samples were treated in a 60Co facility at dose levels of 0, 500, 800, and 1000Gy. The seeds were at first analyzed by Comet Assay as a rapid screening irradiation detection method. Secondly, germination test was performed to detect the viability of irradiated soybeans. Finally, because of its high sensitivity, its specificity and rapidity the polimerase chain reaction was the method applied for genetic modified organism detection. The analysis of DNA by the single technique of microgel electrophoresis of single cells (DNA Comet Assay) showed that DNA damage increased with increasing radiation doses. No negative influence of irradiation on the genetic modification detection was found.

Yield-trait performance landscapes: from theory to application in breeding maize for drought tolerance.

PubMed

Messina, Carlos D; Podlich, Dean; Dong, Zhanshan; Samples, Mitch; Cooper, Mark

2011-01-01

The effectiveness of breeding strategies to increase drought resistance in crops could be increased further if some of the complexities in gene-to-phenotype (G → P) relations associated with epistasis, pleiotropy, and genotype-by-environment interactions could be captured in realistic G → P models, and represented in a quantitative manner useful for selection. This paper outlines a promising methodology. First, the concept of landscapes was extended from the study of fitness landscapes used in evolutionary genetics to the characterization of yield-trait-performance landscapes for agricultural environments and applications in plant breeding. Second, the E(NK) model of trait genetic architecture was extended to incorporate biophysical, physiological, and statistical components. Third, a graphical representation is proposed to visualize the yield-trait performance landscape concept for use in selection decisions. The methodology was demonstrated at a particular stage of a maize breeding programme with the objective of improving the drought tolerance of maize hybrids for the US Western Corn-Belt. The application of the framework to the genetic improvement of drought tolerance in maize supported selection of Doubled Haploid (DH) lines with improved levels of drought tolerance based on physiological genetic knowledge, prediction of test-cross yield within the target population of environments, and their predicted potential to sustain further genetic progress with additional cycles of selection. The existence of rugged yield-performance landscapes with multiple peaks and intervening valleys of lower performance, as shown in this study, supports the proposition that phenotyping strategies, and the directions emphasized in genomic selection can be improved by creating knowledge of the topology of yield-trait performance landscapes.

Independent test assessment using the extreme value distribution theory.

PubMed

Almeida, Marcio; Blondell, Lucy; Peralta, Juan M; Kent, Jack W; Jun, Goo; Teslovich, Tanya M; Fuchsberger, Christian; Wood, Andrew R; Manning, Alisa K; Frayling, Timothy M; Cingolani, Pablo E; Sladek, Robert; Dyer, Thomas D; Abecasis, Goncalo; Duggirala, Ravindranath; Blangero, John

2016-01-01

The new generation of whole genome sequencing platforms offers great possibilities and challenges for dissecting the genetic basis of complex traits. With a very high number of sequence variants, a naïve multiple hypothesis threshold correction hinders the identification of reliable associations by the overreduction of statistical power. In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic associations. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being performed in whole genome association project by the use of an extreme value distribution and a set of phenotype simulations. Given the familiar nature of the GAW19 data and the finite number of pedigree founders in the sample, the number of correlations between genotypes is greater than in a set of unrelated samples. Using our procedure, we estimate that the effective number represents only 15 % of the total number of independent tests performed. However, even using this corrected significance threshold, no genome-wide significant association could be detected for systolic and diastolic blood pressure traits. The second approach implements a biological relevance-driven hypothesis tested by exploiting prior computational predictions on the effect of nonsynonymous genetic variants detected in a whole genome sequencing association study. This guided testing approach was able to identify 2 promising single-nucleotide polymorphisms (SNPs), 1 for each trait, targeting biologically relevant genes that could help shed light on the genesis of the human hypertension. The first gene, PFH14 , associated with systolic blood pressure, interacts directly with genes involved in calcium-channel formation and the second gene, MAP4 , encodes a microtubule-associated protein and had already been detected by previous genome-wide association study experiments conducted in an Asian population. Our results highlight the necessity of the development of alternative approached to improve the efficiency on the detection of reasonable candidate associations in whole genome sequencing studies.

Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe.

PubMed

Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew

2017-06-19

Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity. A wider literature search was performed to provide a fuller assessment of the pharmacogenetic test and variants were matched to FDA recommendations. Additional evidence from CPIC guidelines, PharmGKB, and Dutch Pharmacogenetics Working Group was reviewed to determine current clinical practice. The value of the tests across ethnic groups was determined, including information on linkage disequilibrium between the tested SNP and causal pharmacogenetic variant, where relevant. 23andMe offers 12 pharmacogenetic tests to their UK customers, some of which are in standard clinical practice, and others which are less widely applied. The clinical validity and clinical utility varies extensively between tests. The variants tested are likely to have different degrees of sensitivity due to different risk allele frequencies and linkage disequilibrium patterns across populations. The clinical relevance depends on the ethnicity of the individual and variability of pharmacogenetic markers. Further research is required to determine causal variants and provide more complete assessment of drug response and side effects. 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful intermediate step to integrate pharmacogenetic testing into clinical practice.

Integrating environmental and genetic effects to predict responses of tree populations to climate.

PubMed

Wang, Tongli; O'Neill, Gregory A; Aitken, Sally N

2010-01-01

Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate.

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.

Oncogenetics service and the Brazilian public health system: the experience of a reference Cancer Hospital.

PubMed

Palmero, Edenir I; Galvão, Henrique C R; Fernandes, Gabriela C; Paula, André E de; Oliveira, Junea C; Souza, Cristiano P; Andrade, Carlos E; Romagnolo, Luis G C; Volc, Sahlua; C Neto, Maximiliano; Sabato, Cristina; Grasel, Rebeca; Mauad, Edmundo; Reis, Rui M; Michelli, Rodrigo A D

2016-05-13

The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper-middle class population, but also to the people whose only possibility is the public health system.

Assessment of genetic and nongenetic interactions for the prediction of depressive symptomatology: an analysis of the Wisconsin Longitudinal Study using machine learning algorithms.

PubMed

Roetker, Nicholas S; Page, C David; Yonker, James A; Chang, Vicky; Roan, Carol L; Herd, Pamela; Hauser, Taissa S; Hauser, Robert M; Atwood, Craig S

2013-10-01

We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors-13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors-18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naïve Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic-environmental-sociobehavioral interactions in depressive symptoms.

[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 diversity among Angus, American Brahman, Senepol and Romosinuano cattle breeds.

PubMed

Brenneman, R A; Chase, C C; Olson, T A; Riley, D G; Coleman, S W

2007-02-01

The objective of this study was to quantify the genetic diversity among breeds under evaluation for tropical adaptability traits that affect the performance of beef cattle at the USDA/ARS SubTropical Agricultural Research Station (STARS) near Brooksville, FL, USA. Twenty-six microsatellite loci were used to estimate parameters of genetic diversity among the breeds American Brahman, Angus, Senepol and Romosinuano; the latter was comprised of two distinct bloodlines (Costa Rican and Venezuelan). Genotypes of 47 animals from each of these STARS herds were analysed for genetic diversity and genetic distance. Using two methods, the greatest genetic distance was detected between the Costa Rican line of Romosinuano and the Senepol. Gene diversity ranged between 0.64 (Costa Rican line of Romosinuano) and 0.75 (American Brahman). The breed relationship inferences, which are based on genetic distance, provide additional tools for consideration in future crossbreeding studies and for testing the relationship between quantified breed diversity and observed heterosis.

Equine performance genes and the future of doping in horseracing.

PubMed

Wilkin, Tessa; Baoutina, Anna; Hamilton, Natasha

2017-09-01

A horse's success on the racetrack is determined by genetics, training and nutrition, and their translation into physical traits such as speed, endurance and muscle strength. Advances in genetic technologies are slowly explaining the roles of specific genes in equine performance, and offering new insights into the development of novel therapies for diseases and musculoskeletal injuries that cause early retirement of many racehorses. Gene therapy approaches may also soon provide new means to artificially enhance the physical performance of racehorses. Gene doping, the misuse of gene therapies for performance enhancement, is predicted to be the next phase of doping faced by horseracing. The risk of gene doping to human sports has been recognised for almost 15 years, and the introduction of the first gene doping detection tests for doping control in human athletes is imminent. Gene doping is also a threat to horseracing, but there are currently no methods to detect it. Efficient and accurate detection methods need to be developed to deter those looking to use gene doping in horses and to maintain the integrity of the sport. Methods developed for human athletes could offer an avenue for detection in racehorses. Development of an equine equivalent test will first require identification of equine genes that will likely be targeted by gene doping attempts. This review focuses on genes that have been linked to athletic performance in horses and, therefore, could be targeted for genetic manipulation. The risks associated with gene doping and approaches to detect gene doping are also discussed. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy.

PubMed

Kohn, Taylor P; Kohn, Jaden R; Darilek, Sandra; Ramasamy, Ranjith; Lipshultz, Larry

2016-05-01

The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities. The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE. Sperm fluorescence in situ hybridization (FISH) can be used to determine if disomy or unbalanced chromosomal translocations are present. In men with aneuploidy in sperm or who carry a chromosomal translocation, pre-implantation genetic screening (PGS) combined with in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) can increase chances of live birth. In men with abnormal sperm FISH results, the degree of increased risk of abnormal pregnancy remains unclear. Genetic counselors can provide information to couples about the risk for potential trisomies and sex chromosome aneuploidies and discuss their reproductive and testing options such as PGS, use of donor sperm, and adoption. The provision of genetic counseling also allows a couple to be educated about recommended prenatal testing since pregnancies conceived with a partner who has had abnormal sperm FISH are considered to be at increased risk for aneuploidy. We review the literature and discuss genetic counseling for couples with RPL or recurrent implantation failure due to increased sperm aneuploidy.

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.

A Novel Hybrid Classification Model of Genetic Algorithms, Modified k-Nearest Neighbor and Developed Backpropagation Neural Network

PubMed Central

Salari, Nader; Shohaimi, Shamarina; Najafi, Farid; Nallappan, Meenakshii; Karishnarajah, Isthrinayagy

2014-01-01

Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models. PMID:25419659

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.

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.

An SNP within the Angiotensin-Converting Enzyme Distinguishes between Sprint and Distance Performing Alaskan Sled Dogs in a Candidate Gene Analysis

PubMed Central

Huson, Heather J.; Byers, Alexandra M.; Runstadler, Jonathan

2011-01-01

The Alaskan sled dog offers a unique mechanism for studying the genetics of elite athletic performance. They are a group of mixed breed dogs, comprised of multiple common breeds, and a unique breed entity seen only as a part of the sled dog mix. Alaskan sled dogs are divided into 2 primary groups as determined by their racing skills. Distance dogs are capable of running over 1000 miles in 10 days, whereas sprint dogs run much shorter distances, approximately 30 miles, but in faster times, that is, 18–25 mph. Finding the genes that distinguish these 2 types of performers is likely to illuminate genetic contributors to human athletic performance. In this study, we tested for association between polymorphisms in 2 candidate genes; angiotensin-converting enzyme (ACE) and myostatin (MSTN) and enhanced speed and endurance performance in 174 Alaskan sled dogs. We observed 81 novel genetic variants within the ACE gene and 4 within the MSTN gene, including a polymorphism within the ACE gene that significantly (P value 2.38 × 10−5) distinguished the sprint versus distance populations. PMID:21846742

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 ( ...

Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

PubMed

Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

2013-09-01

Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also contributed substantially to micro-environmental sensitivity. Addition of random regressions to the mean model did not reduce heterogeneity in residual variance and that genetic heterogeneity of residual variance was not simply an effect of an incomplete mean model. Copyright © 2013 American Dairy Science Association. 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.

Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

PubMed

Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

2009-10-01

Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

Worldwide analysis of multiple microsatellites: language diversity has a detectable influence on DNA diversity.

PubMed

Belle, Elise M S; Barbujani, Guido

2007-08-01

Previous studies of the correlations between the languages spoken by human populations and the genes carried by the members of those populations have been limited by the small amount of genetic markers available and by approximations in the treatment of linguistic data. In this study we analyzed a large collection of polymorphic microsatellite loci (377), distributed on all autosomes, and used Ruhlen's linguistic classification, to investigate the relative roles of geography and language in shaping the distribution of human DNA diversity at a worldwide scale. For this purpose, we performed three different kinds of analysis: (i) we partitioned genetic variances at three hierarchical levels of population subdivision according to language group by means of a molecular analysis of variance (AMOVA); (ii) we quantified by a series of Mantel's tests the correlation between measures of genetic and linguistic differentiation; and (iii) we tested whether linguistic differences are increased across known zones of increased genetic change between populations. Genetic differences appear to more closely reflect geographic than linguistic differentiation. However, our analyses show that language differences also have a detectable effect on DNA diversity at the genomic level, above and beyond the effects of geographic distance. (c) 2007 Wiley-Liss, Inc.

The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants.

PubMed

Fadista, João; Manning, Alisa K; Florez, Jose C; Groop, Leif

2016-08-01

Genome-wide association studies (GWAS) have long relied on proposed statistical significance thresholds to be able to differentiate true positives from false positives. Although the genome-wide significance P-value threshold of 5 × 10(-8) has become a standard for common-variant GWAS, it has not been updated to cope with the lower allele frequency spectrum used in many recent array-based GWAS studies and sequencing studies. Using a whole-genome- and -exome-sequencing data set of 2875 individuals of European ancestry from the Genetics of Type 2 Diabetes (GoT2D) project and a whole-exome-sequencing data set of 13 000 individuals from five ancestries from the GoT2D and T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) projects, we describe guidelines for genome- and exome-wide association P-value thresholds needed to correct for multiple testing, explaining the impact of linkage disequilibrium thresholds for distinguishing independent variants, minor allele frequency and ancestry characteristics. We emphasize the advantage of studying recent genetic isolate populations when performing rare and low-frequency genetic association analyses, as the multiple testing burden is diminished due to higher genetic homogeneity.

Physics-Based Image Segmentation Using First Order Statistical Properties and Genetic Algorithm for Inductive Thermography Imaging.

PubMed

Gao, Bin; Li, Xiaoqing; Woo, Wai Lok; Tian, Gui Yun

2018-05-01

Thermographic inspection has been widely applied to non-destructive testing and evaluation with the capabilities of rapid, contactless, and large surface area detection. Image segmentation is considered essential for identifying and sizing defects. To attain a high-level performance, specific physics-based models that describe defects generation and enable the precise extraction of target region are of crucial importance. In this paper, an effective genetic first-order statistical image segmentation algorithm is proposed for quantitative crack detection. The proposed method automatically extracts valuable spatial-temporal patterns from unsupervised feature extraction algorithm and avoids a range of issues associated with human intervention in laborious manual selection of specific thermal video frames for processing. An internal genetic functionality is built into the proposed algorithm to automatically control the segmentation threshold to render enhanced accuracy in sizing the cracks. Eddy current pulsed thermography will be implemented as a platform to demonstrate surface crack detection. Experimental tests and comparisons have been conducted to verify the efficacy of the proposed method. In addition, a global quantitative assessment index F-score has been adopted to objectively evaluate the performance of different segmentation algorithms.

Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

PubMed Central

Rubio-Cabezas, Oscar; Patch, Ann-Marie; Minton, Jayne A. L.; Flanagan, Sarah E.; Edghill, Emma L.; Hussain, Khalid; Balafrej, Amina; Deeb, Asma; Buchanan, Charles R.; Jefferson, Ian G.; Mutair, Angham; Hattersley, Andrew T.; Ellard, Sian

2009-01-01

Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. PMID:19837917

Reproductive health and genetic testing in the Third World.

PubMed

Penchaszadeh, V B

1993-09-01

New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.

Genetic programming and serial processing for time series classification.

PubMed

Alfaro-Cid, Eva; Sharman, Ken; Esparcia-Alcázar, Anna I

2014-01-01

This work describes an approach devised by the authors for time series classification. In our approach genetic programming is used in combination with a serial processing of data, where the last output is the result of the classification. The use of genetic programming for classification, although still a field where more research in needed, is not new. However, the application of genetic programming to classification tasks is normally done by considering the input data as a feature vector. That is, to the best of our knowledge, there are not examples in the genetic programming literature of approaches where the time series data are processed serially and the last output is considered as the classification result. The serial processing approach presented here fills a gap in the existing literature. This approach was tested in three different problems. Two of them are real world problems whose data were gathered for online or conference competitions. As there are published results of these two problems this gives us the chance to compare the performance of our approach against top performing methods. The serial processing of data in combination with genetic programming obtained competitive results in both competitions, showing its potential for solving time series classification problems. The main advantage of our serial processing approach is that it can easily handle very large datasets.

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.

Genetic testing in the European Union: does economic evaluation matter?

PubMed

Antoñanzas, Fernando; Rodríguez-Ibeas, R; Hutter, M F; Lorente, R; Juárez, C; Pinillos, M

2012-10-01

We review the published economic evaluation studies applied to genetic technologies in the EU to know the main diseases addressed by these studies, the ways the studies were conducted and to assess the efficiency of these new technologies. The final aim of this review was to understand the possibilities of the economic evaluations performed up to date as a tool to contribute to decision making in this area. We have reviewed a set of articles found in several databases until March 2010. Literature searches were made in the following databases: PubMed; Euronheed; Centre for Reviews and Dissemination of the University of York-Health Technology Assessment, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database; and Scopus. The algorithm was "(screening or diagnosis) and genetic and (cost or economic) and (country EU27)". We included studies if they met the following criteria: (1) a genetic technology was analysed; (2) human DNA must be tested for; (3) the analysis was a real economic evaluation or a cost study, and (4) the articles had to be related to any EU Member State. We initially found 3,559 papers on genetic testing but only 92 articles of economic analysis referred to a wide range of genetic diseases matched the inclusion criteria. The most studied diseases were as follows: cystic fibrosis (12), breast and ovarian cancer (8), hereditary hemochromatosis (6), Down's syndrome (7), colorectal cancer (5), familial hypercholesterolaemia (5), prostate cancer (4), and thrombophilia (4). Genetic tests were mostly used for screening purposes, and cost-effectiveness analysis is the most common type of economic study. The analysed gene technologies are deemed to be efficient for some specific population groups and screening algorithms according to the values of their cost-effectiveness ratios that were below the commonly accepted threshold of 30,000€. Economic evaluation of genetic technologies matters but the number of published studies is still rather low as to be widely used for most of the decisions in different jurisdictions across the EU. Further, the decision bodies across EU27 are fragmented and the responsibilities are located at different levels of the decision process for what it is difficult to find out whether a given decision on genetic tests was somehow supported by the economic evaluation results.

Supervised chaos genetic algorithm based state of charge determination for LiFePO4 batteries in electric vehicles

NASA Astrophysics Data System (ADS)

Shen, Yanqing

2018-04-01

LiFePO4 battery is developed rapidly in electric vehicle, whose safety and functional capabilities are influenced greatly by the evaluation of available cell capacity. Added with adaptive switch mechanism, this paper advances a supervised chaos genetic algorithm based state of charge determination method, where a combined state space model is employed to simulate battery dynamics. The method is validated by the experiment data collected from battery test system. Results indicate that the supervised chaos genetic algorithm based state of charge determination method shows great performance with less computation complexity and is little influenced by the unknown initial cell state.

Genetic prediction of type 2 diabetes using deep neural network.

PubMed

Kim, J; Kim, J; Kwak, M J; Bajaj, M

2018-04-01

Type 2 diabetes (T2DM) has strong heritability but genetic models to explain heritability have been challenging. We tested deep neural network (DNN) to predict T2DM using the nested case-control study of Nurses' Health Study (3326 females, 45.6% T2DM) and Health Professionals Follow-up Study (2502 males, 46.5% T2DM). We selected 96, 214, 399, and 678 single-nucleotide polymorphism (SNPs) through Fisher's exact test and L1-penalized logistic regression. We split each dataset randomly in 4:1 to train prediction models and test their performance. DNN and logistic regressions showed better area under the curve (AUC) of ROC curves than the clinical model when 399 or more SNPs included. DNN was superior than logistic regressions in AUC with 399 or more SNPs in male and 678 SNPs in female. Addition of clinical factors consistently increased AUC of DNN but failed to improve logistic regressions with 214 or more SNPs. In conclusion, we show that DNN can be a versatile tool to predict T2DM incorporating large numbers of SNPs and clinical information. Limitations include a relatively small number of the subjects mostly of European ethnicity. Further studies are warranted to confirm and improve performance of genetic prediction models using DNN in different ethnic groups. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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.

Genetic causes of intellectual disability in a birth cohort: a population-based study.

PubMed

Karam, Simone M; Riegel, Mariluce; Segal, Sandra L; Félix, Têmis M; Barros, Aluísio J D; Santos, Iná S; Matijasevich, Alicia; Giugliani, Roberto; Black, Maureen

2015-06-01

Intellectual disability affects approximately 1-3% of the population and can be caused by genetic and environmental factors. Although many studies have investigated the etiology of intellectual disability in different populations, few studies have been performed in middle-income countries. The present study estimated the prevalence of genetic causes related to intellectual disability in a cohort of children from a city in south Brazil who were followed from birth. Children who showed poor performance in development and intelligence tests at the ages of 2 and 4 were included. Out of 4,231 liveborns enrolled in the cohort, 214 children fulfilled the inclusion criteria. A diagnosis was established in approximately 90% of the children evaluated. Genetic causes were determined in 31 of the children and 19 cases remained unexplained even after extensive investigation. The overall prevalence of intellectual disability in this cohort due to genetic causes was 0.82%. Because this study was nested in a cohort, there were a large number of variables related to early childhood and the likelihood of information bias was minimized by collecting information with a short recall time. This study was not influenced by selection bias, allowing identification of intellectual disability and estimation of the prevalence of genetic causes in this population, thereby increasing the possibility of providing appropriate management and/or genetic counseling. © 2015 Wiley Periodicals, Inc.

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.

PubMed

Partemi, Sara; Vidal, Monica Coll; Striano, Pasquale; Campuzano, Oscar; Allegue, Catarina; Pezzella, Marianna; Elia, Maurizio; Parisi, Pasquale; Belcastro, Vincenzo; Casellato, Susanna; Giordano, Lucio; Mastrangelo, Massimo; Pietrafusa, Nicola; Striano, Salvatore; Zara, Federico; Bianchi, Amedeo; Buti, Daniela; La Neve, Angela; Tassinari, Carlo Alberto; Oliva, Antonio; Brugada, Ramon

2015-05-01

Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.

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.

Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.

PubMed

Li, Ge; Millard, Steven P; Peskind, Elaine R; Zhang, Jing; Yu, Chang-En; Leverenz, James B; Mayer, Cynthia; Shofer, Jane S; Raskind, Murray A; Quinn, Joseph F; Galasko, Douglas R; Montine, Thomas J

2014-06-01

Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury). Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31). Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.

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.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Genetic and environmental correlates of topiramate-induced cognitive impairment

PubMed Central

Cirulli, Elizabeth T.; Urban, Thomas J.; Marino, Susan E.; Linney, Kristen N.; Birnbaum, Angela K.; Depondt, Chantal; Attix, Deborah K.; Radtke, Rodney A.; Goldstein, David B.

2011-01-01

Topiramate is an antiepileptic drug that has marked, treatment-limiting side effects on specific aspects of cognitive performance in both patients and healthy volunteers. As these severe side-effects occur only in certain individuals, identifying genetic or environmental variables that influence cognitive response would be of great utility in determining whether to administer this drug to a patient. We gave an acute 100 mg oral dose of topiramate to 158 healthy volunteers and measured how the drug changed their performance on a diverse battery of cognitive tests. We found a wide range of responses to topiramate and demonstrated that not all tests in the battery were equally affected. There was no correlation between the effect of topiramate and either education level or baseline cognitive performance. Interestingly, there was up to 55-fold variation in the topiramate plasma levels of the participants. Our genome-wide association study (GWAS) of cognitive response did not reveal any genome-wide significant associations; the study was powered to find variants explaining at least 25% of the variation in cognitive response. Combining the results of this GWAS with a retrospective study of cognitive complaints in 290 epilepsy patients who received topiramate as part of their treatment also did not result in a significant association. Our results support the need for additional genetic studies of topiramate that utilize larger sample sizes. PMID:22091778

Genetic and environmental correlates of topiramate-induced cognitive impairment.

PubMed

Cirulli, Elizabeth T; Urban, Thomas J; Marino, Susan E; Linney, Kristen N; Birnbaum, Angela K; Depondt, Chantal; Attix, Deborah K; Radtke, Rodney A; Goldstein, David B

2012-01-01

Topiramate is an antiepileptic drug that has marked treatment-limiting side effects on specific aspects of cognitive performance in both patients and healthy volunteers. Because these severe side effects occur only in certain individuals, identifying genetic or environmental variables that influence cognitive response would be of great utility in determining whether to administer this drug to a patient. We gave an acute 100 mg oral dose of topiramate to 158 healthy volunteers and measured how the drug changed their performance on a diverse battery of cognitive tests. We found a wide range of responses to topiramate, and we demonstrated that not all tests in the battery were equally affected. There was no correlation between the effect of topiramate and either education level or baseline cognitive performance. Of interest, there was an up to 55-fold variation in the topiramate plasma levels of the participants. Our genome-wide association study (GWAS) of cognitive response did not reveal any genome-wide significant associations; the study was powered to find variants explaining at least 25% of the variation in cognitive response. Combining the results of this GWAS with a retrospective study of cognitive complaints in 290 epilepsy patients who received topiramate as part of their treatment also did not result in a significant association. Our results support the need for additional genetic studies of topiramate that use larger sample sizes. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Measuring the Effectiveness of a Genetic Counseling Supervision Training Conference.

PubMed

Atzinger, Carrie L; He, Hua; Wusik, Katie

2016-08-01

Genetic counselors who receive formal training report increased confidence and competence in their supervisory roles. The effectiveness of specific formal supervision training has not been assessed previously. A day-long GC supervision conference was designed based on published supervision competencies and was attended by 37 genetic counselors. Linear Mixed Model and post-hoc paired t-test was used to compare Psychotherapy Supervisor Development Scale (PSDS) scores among/between individuals pre and post conference. Generalized Estimating Equation (GEE) model and post-hoc McNemar's test was used to determine if the conference had an effect on GC supervision competencies. PSDS scores were significantly increased 1 week (p < 0.001) and 6 months (p < 0.001) following the conference. For three supervision competencies, attendees were more likely to agree they were able to perform them after the conference than before. These effects remained significant 6 months later. For the three remaining competencies, the majority of supervisors agreed they could perform these before the conference; therefore, no change was found. This exploratory study showed this conference increased the perceived confidence and competence of the supervisors who attended and increased their self-reported ability to perform certain supervision competencies. While still preliminary, this supports the idea that a one day conference on supervision has the potential to impact supervisor development.

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.

Estimating genetic effects and quantifying missing heritability explained by identified rare-variant associations.

PubMed

Liu, Dajiang J; Leal, Suzanne M

2012-10-05

Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner's curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study where the association is identified. This is because there can be substantial heterogeneity of RV sites and frequencies even among closely related populations. In order to obtain an unbiased estimate for aggregated RV analysis, we developed bootstrap-sample-split algorithms to reduce the bias of the winner's curse. The unbiased estimates are greatly important for understanding the population-specific contribution of RVs to the heritability of complex traits. We also demonstrate both theoretically and via simulations that for aggregate RV analysis the genetic variance for a gene or region will always be underestimated, sometimes substantially, because of the presence of noncausal variants or because of the presence of causal variants with effects of different magnitudes or directions. Therefore, even if RVs play a major role in the complex-trait etiologies, a portion of the heritability will remain missing, and the contribution of RVs to the complex-trait etiologies will be underestimated. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetic parameters for first lactation test-day milk flow in Holstein cows.

PubMed

Laureano, M M M; Bignardi, A B; El Faro, L; Cardoso, V L; Albuquerque, L G

2012-01-01

Genetic parameters for test-day milk flow (TDMF) of 2175 first lactations of Holstein cows were estimated using multiple-trait and repeatability models. The models included the direct additive genetic effect as a random effect and contemporary group (defined as the year and month of test) and age of cow at calving (linear and quadratic effect) as fixed effects. For the repeatability model, in addition to the effects cited, the permanent environmental effect of the animal was also included as a random effect. Variance components were estimated using the restricted maximum likelihood method in single- and multiple-trait and repeatability analyses. The heritability estimates for TDMF ranged from 0.23 (TDMF 6) to 0.32 (TDMF 2 and TDMF 4) in single-trait analysis and from 0.28 (TDMF 7 and TDMF 10) to 0.37 (TDMF 4) in multiple-trait analysis. In general, higher heritabilities were observed at the beginning of lactation until the fourth month. Heritability estimated with the repeatability model was 0.27 and the coefficient of repeatability for first lactation TDMF was 0.66. The genetic correlations were positive and ranged from 0.72 (TDMF 1 and 10) to 0.97 (TDMF 4 and 5). The results indicate that milk flow should respond satisfactorily to selection, promoting rapid genetic gains because the estimated heritabilities were moderate to high. Higher genetic gains might be obtained if selection was performed in the TDMF 4. Both the repeatability model and the multiple-trait model are adequate for the genetic evaluation of animals in terms of milk flow, but the latter provides more accurate estimates of breeding values.

Genetic Analysis of Milk Yield in First-Lactation Holstein Friesian in Ethiopia: A Lactation Average vs Random Regression Test-Day Model Analysis

PubMed Central

Meseret, S.; Tamir, B.; Gebreyohannes, G.; Lidauer, M.; Negussie, E.

2015-01-01

The development of effective genetic evaluations and selection of sires requires accurate estimates of genetic parameters for all economically important traits in the breeding goal. The main objective of this study was to assess the relative performance of the traditional lactation average model (LAM) against the random regression test-day model (RRM) in the estimation of genetic parameters and prediction of breeding values for Holstein Friesian herds in Ethiopia. The data used consisted of 6,500 test-day (TD) records from 800 first-lactation Holstein Friesian cows that calved between 1997 and 2013. Co-variance components were estimated using the average information restricted maximum likelihood method under single trait animal model. The estimate of heritability for first-lactation milk yield was 0.30 from LAM whilst estimates from the RRM model ranged from 0.17 to 0.29 for the different stages of lactation. Genetic correlations between different TDs in first-lactation Holstein Friesian ranged from 0.37 to 0.99. The observed genetic correlation was less than unity between milk yields at different TDs, which indicated that the assumption of LAM may not be optimal for accurate evaluation of the genetic merit of animals. A close look at estimated breeding values from both models showed that RRM had higher standard deviation compared to LAM indicating that the TD model makes efficient utilization of TD information. Correlations of breeding values between models ranged from 0.90 to 0.96 for different group of sires and cows and marked re-rankings were observed in top sires and cows in moving from the traditional LAM to RRM evaluations. PMID:26194217

Successful application of preimplantation genetic diagnosis for Leigh syndrome.

PubMed

Unsal, Evrim; Aktaş, Yasemin; Uner, Ozge; BaltacI, Aysun; Ozcan, Sarp; Turhan, Feriba; Baltaci, Volkan

2008-11-01

To perform preimplantation genetic diagnosis (PGD) for a SURF1 gene mutation of the Leigh syndrome to transfer unaffected or carrier embryo/embryos. Case report. Clinical IVF laboratory. A couple carrying an nt769 G/A mutation that is associated with Leigh syndrome. Oocytes were fertilized by means of intracytoplasmic sperm injection. The resulting embryos were biopsied 3 days after fertilization. One blastomere was taken and whole-genome amplification was performed. Amplification of the mutation site was achieved by polymerase chain reaction (PCR) and restriction digestion was completed. Gel Imager was used to measure the digests of normal and mutant load. Embryo testing by means of PGD-PCR and pregnancy. Successful preimplantation genetic diagnosis for a SURF1 gene mutation and transfer of healthy or carrier embryos. Successful singleton pregnancy resulting in the delivery of healthy baby girl. We report the first case of successful PGD for Leigh syndrome resulting in delivery of a healthy newborn.

Genetic causes of intellectual disability in a birth cohort: A population‐based study

PubMed Central

Riegel, Mariluce; Segal, Sandra L.; Félix, Têmis M.; Barros, Aluísio J. D.; Santos, Iná S.; Matijasevich, Alicia; Giugliani, Roberto; Black, Maureen

2015-01-01

Intellectual disability affects approximately 1–3% of the population and can be caused by genetic and environmental factors. Although many studies have investigated the etiology of intellectual disability in different populations, few studies have been performed in middle‐income countries. The present study estimated the prevalence of genetic causes related to intellectual disability in a cohort of children from a city in south Brazil who were followed from birth. Children who showed poor performance in development and intelligence tests at the ages of 2 and 4 were included. Out of 4,231 liveborns enrolled in the cohort, 214 children fulfilled the inclusion criteria. A diagnosis was established in approximately 90% of the children evaluated. Genetic causes were determined in 31 of the children and 19 cases remained unexplained even after extensive investigation. The overall prevalence of intellectual disability in this cohort due to genetic causes was 0.82%. Because this study was nested in a cohort, there were a large number of variables related to early childhood and the likelihood of information bias was minimized by collecting information with a short recall time. This study was not influenced by selection bias, allowing identification of intellectual disability and estimation of the prevalence of genetic causes in this population, thereby increasing the possibility of providing appropriate management and/or genetic counseling. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:25728503

Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals.

PubMed

Morgante, Fabio; Huang, Wen; Maltecca, Christian; Mackay, Trudy F C

2018-06-01

Predicting complex phenotypes from genomic data is a fundamental aim of animal and plant breeding, where we wish to predict genetic merits of selection candidates; and of human genetics, where we wish to predict disease risk. While genomic prediction models work well with populations of related individuals and high linkage disequilibrium (LD) (e.g., livestock), comparable models perform poorly for populations of unrelated individuals and low LD (e.g., humans). We hypothesized that low prediction accuracies in the latter situation may occur when the genetics architecture of the trait departs from the infinitesimal and additive architecture assumed by most prediction models. We used simulated data for 10,000 lines based on sequence data from a population of unrelated, inbred Drosophila melanogaster lines to evaluate this hypothesis. We show that, even in very simplified scenarios meant as a stress test of the commonly used Genomic Best Linear Unbiased Predictor (G-BLUP) method, using all common variants yields low prediction accuracy regardless of the trait genetic architecture. However, prediction accuracy increases when predictions are informed by the genetic architecture inferred from mapping the top variants affecting main effects and interactions in the training data, provided there is sufficient power for mapping. When the true genetic architecture is largely or partially due to epistatic interactions, the additive model may not perform well, while models that account explicitly for interactions generally increase prediction accuracy. Our results indicate that accounting for genetic architecture can improve prediction accuracy for quantitative traits.

Breast cancer in high-risk Afrikaner families: Is BRCA founder mutation testing sufficient?

PubMed

Seymour, Heather Jessica; Wainstein, Tasha; Macaulay, Shelley; Haw, Tabitha; Krause, Amanda

2016-02-03

Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified. To investigate the uptake and type of molecular testing performed on patients for HBOCS, to determine the prevalence of the three Afrikaner founder BRCA mutations as well as non-founder BRCA mutations in the study population, and to analyse the utility of two mutation prediction models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and Manchester scoring method) in assisting with the decision for the most cost-effective testing option. A retrospective file review was performed on counsellees of self-reported Afrikaner ancestry from Johannesburg, SA (2001 - 2014), with a personal or family history of breast and/or ovarian cancer. Demographic and family history information was recorded and Manchester and BOADICEA scores were calculated for each patient. Of 86 unrelated counsellees whose files were reviewed, 54 (62.8%) underwent BRCA genetic testing; 18 (33.3%) tested positive for a mutation, and 14 of these (77.8%) for an Afrikaner founder mutation. Twelve counsellees had the BRCA2 c.7934delG mutation. Four non-founder mutations were identified. BOADICEA scores were significantly higher in counsellees who tested positive for a mutation than in those who tested negative. Founder mutation testing should be performed as a first-line option. BOADICEA is very useful in identifying counsellees at high risk for a BRCA mutation and also assists with the decision to pursue further testing following a negative founder mutation result. These findings assist in guiding an informed genetic counselling service for at-risk individuals with an Afrikaner background.

Quality in genetic counselling for presymptomatic testing--clinical guidelines for practice across the range of genetic conditions.

PubMed

Skirton, Heather; Goldsmith, Lesley; Jackson, Leigh; Tibben, Aad

2013-03-01

Presymptomatic testing (PST) is the performance of a genetic test on an asymptomatic individual at risk of a condition to determine whether the person has inherited the disease-causing mutation. Although relevant guidelines exist for specific diseases, there is no overarching protocol that can be adapted to any disorder or clinical setting in which such testing is offered. The objective of this European project was to develop a set of coherent guidelines for PST (for adult-onset monogenic conditions) for use by health professionals working in a range of disciplines, countries or contexts. To ensure the guidelines were appropriate and practice based, we organised a workshop attended by an expert group of practitioners with relevant health professional backgrounds from 11 countries. Models of service for offering PST were presented, the group then discussed different aspects of testing and the standard of care required to ensure that patients were prepared to make decisions and deal with results and consequences. After the workshop, several rounds of consultation were used with a wider group of professionals to refine the guidelines. The guidelines include general principles governing the offer of testing (eg, autonomous choice of the patient), objectives of genetic counselling in this context (eg, facilitation of decision making), logistical considerations (eg, use of trained staff) and topics to be included during counselling discussion with the patient (eg, consequences of both positive and negative outcomes). We recommend the adoption of these guidelines to provide an equitable structure for those seeking PST in any country.

Psychological Distress, Anxiety, and Depression of Cancer-Affected BRCA1/2 Mutation Carriers: a Systematic Review.

PubMed

Ringwald, Johanna; Wochnowski, Christina; Bosse, Kristin; Giel, Katrin Elisabeth; Schäffeler, Norbert; Zipfel, Stephan; Teufel, Martin

2016-10-01

Understanding the intermediate- and long-term psychological consequences of genetic testing for cancer patients has led to encouraging research, but a clear consensus of the psychosocial impact and clinical routine for cancer-affected BRCA1 and BRCA2 mutation carriers is still missing. We performed a systematic review of intermediate- and long-term studies investigating the psychological impact like psychological distress, anxiety, and depression in cancer-affected BRCA mutation carriers compared to unaffected mutation carriers. This review included the screening of 1243 studies. Eight intermediate- and long-term studies focusing on distress, anxiety, and depression symptoms among cancer-affected mutation carriers at least six months after the disclosure of genetic testing results were included. Studies reported a great variety of designs, methods, and patient outcomes. We found evidence indicating that cancer-affected mutation carriers experienced a negative effect in relation to psychological well-being in terms of an increase in symptoms of distress, anxiety, and depression in the first months after test disclosure. In the intermediate- and long-term, no significant clinical relevant symptoms occurred. However, none of the included studies used specific measurements, which can clearly identify psychological burdens of cancer-affected mutation carriers. We concluded that current well-implemented distress screening instruments are not sufficient for precisely identifying the psychological burden of genetic testing. Therefore, future studies should implement coping strategies, specific personality structures, the impact of genetic testing, supportive care needs and disease management behaviour to clearly screen for the possible intermediate- and long-term psychological impact of a positive test disclosure.

Clinical and Genetic Diagnosis of Nonischemic Sudden Cardiac Death.

PubMed

Jiménez-Jáimez, Juan; Alcalde Martínez, Vicente; Jiménez Fernández, Miriam; Bermúdez Jiménez, Francisco; Rodríguez Vázquez Del Rey, María Del Mar; Perin, Francesca; Oyonarte Ramírez, José Manuel; López Fernández, Silvia; de la Torre, Inmaculada; García Orta, Rocío; González Molina, Mercedes; Cabrerizo, Elisa María; Álvarez Abril, Beatriz; Álvarez, Miguel; Macías Ruiz, Rosa; Correa, Concepción; Tercedor, Luis

2017-10-01

Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P=.53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P=.21). There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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.

[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.

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.

[Hereditary fructose intolerance].

PubMed

Rumping, Lynne; Waterham, Hans R; Kok, Irene; van Hasselt, Peter M; Visser, Gepke

2014-01-01

Hereditary fructose intolerance (HFI) is a rare metabolic disease affecting fructose metabolism. After ingestion of fructose, patients may present with clinical symptoms varying from indefinite gastrointestinal symptoms to life-threatening hypoglycaemia and hepatic failure. A 13-year-old boy was referred to the department of metabolic diseases because of an abnormal fructose loading test. He was known with persistent gastrointestinal symptoms since infancy. His dietary history revealed an avoidance of fruit and sweets. Because malabsorption was suspected, an oral fructose loading test was performed. During this test, he developed severe vagal symptoms which were probably caused by a potentially fatal hypoglycaemia. The diagnosis of HFI was confirmed by genetic analysis. A good dietary history may be of important help in the diagnosis of HFI. On suspicion of HFI, genetic analysis is easy and the first choice in the diagnostic work-up. With timely diagnosis and adequate dietary treatment patients have an excellent prognosis. Fructose loading tests as part of the diagnostics can be dangerous.

Generalist genes and high cognitive abilities.

PubMed

Haworth, Claire M A; Dale, Philip S; Plomin, Robert

2009-07-01

The concept of generalist genes operating across diverse domains of cognitive abilities is now widely accepted. Much less is known about the etiology of the high extreme of performance. Is there more specialization at the high extreme? Using a representative sample of 4,000 12-year-old twin pairs from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between web-based tests of general cognitive ability, reading, mathematics and language performance for the top 15% of the distribution using DF extremes analysis. Generalist genes are just as evident at the high extremes of performance as they are for the entire distribution of abilities and for cognitive disabilities. However, a smaller proportion of the phenotypic intercorrelations appears to be explained by genetic influences for high abilities.

Generalist genes and high cognitive abilities

PubMed Central

Haworth, Claire M.A.; Dale, Philip S.; Plomin, Robert

2014-01-01

The concept of generalist genes operating across diverse domains of cognitive abilities is now widely accepted. Much less is known about the etiology of the high extreme of performance. Is there more specialization at the high extreme? Using a representative sample of 4000 12-year-old twin pairs from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between web-based tests of general cognitive ability, reading, mathematics and language performance for the top 15% of the distribution using DF extremes analysis. Generalist genes are just as evident at the high extremes of performance as they are for the entire distribution of abilities and for cognitive disabilities. However, a smaller proportion of the phenotypic intercorrelations appears to be explained by genetic influences for high abilities. PMID:19377870

[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.

College of American Pathologists/American College of Medical Genetics proficiency testing for constitutional cytogenomic microarray analysis.

PubMed

Brothman, Arthur R; Dolan, Michelle M; Goodman, Barbara K; Park, Jonathan P; Persons, Diane L; Saxe, Debra F; Tepperberg, James H; Tsuchiya, Karen D; Van Dyke, Daniel L; Wilson, Kathleen S; Wolff, Daynna J; Theil, Karl S

2011-09-01

To evaluate the feasibility of administering a newly established proficiency test offered through the College of American Pathologists and the American College of Medical Genetics for genomic copy number assessment by microarray analysis, and to determine the reproducibility and concordance among laboratory results from this test. Surveys were designed through the Cytogenetic Resource Committee of the two colleges to assess the ability of testing laboratories to process DNA samples provided and interpret results. Supplemental questions were asked with each Survey to determine laboratory practice trends. Twelve DNA specimens, representing 2 pilot and 10 Survey challenges, were distributed to as many as 74 different laboratories, yielding 493 individual responses. The mean consensus for matching result interpretations was 95.7%. Responses to supplemental questions indicate that the number of laboratories offering this testing is increasing, methods for analysis and evaluation are becoming standardized, and array platforms used are increasing in probe density. The College of American Pathologists/American College of Medical Genetics proficiency testing program for copy number assessment by cytogenomic microarray is a successful and efficient mechanism for assessing interlaboratory reproducibility. This will provide laboratories the opportunity to evaluate their performance and assure overall accuracy of patient results. The high level of concordance in laboratory responses across all testing platforms by multiple facilities highlights the robustness of this technology.

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.

Integrating evolutionary and functional approaches to infer adaptation at specific loci.

PubMed

Storz, Jay F; Wheat, Christopher W

2010-09-01

Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally,population-genetic evidence for positive selection serves as a stepping-off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population-genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness-related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.

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.

Ethical issues in the use of genetic testing of patients with schizophrenia and their families.

PubMed

DeLisi, Lynn E

2014-05-01

This review outlines the positive and negative aspects of DNA testing and provides an account of the issues particularly relevant to schizophrenia. Modern technology has changed the field of medicine so rapidly that patients and their families have become much more independent in their healthcare decisions than in the previous decade. Simply by finding information on the Internet, they gain knowledge about disease diagnosis, treatment options and their side-effects. No medical field likely has been more affected and more controversial than that of genetics. It is now possible to sequence the individual human genome and detect single nucleotide variations, microdeletions and duplications within it. Commercial companies have sprung up in a similar manner to the software or electronic industries and have begun to market direct-to-consumer DNA testing. Much of this may be performed to satisfy curiosity about one's ancestry; but commercially available results that appear incidentally can also be distributed to the consumer. Ethicists, genetics researchers, clinicians and government agencies are currently in discussion about concerns raised about commercially available DNA testing, while at the same time recognizing its value in some instances to be able to predict very serious disabilities.

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 ...

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)

An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures.

PubMed

Kang, Eun Yong; Lee, Cue Hyunkyu; Furlotte, Nicholas A; Joo, Jong Wha J; Kostem, Emrah; Zaitlen, Noah; Eskin, Eleazar; Han, Buhm

2018-05-11

Over the past few years, genome-wide association studies have identified many trait-associated loci that have different effects on females and males, which increased attention to the genetic architecture differences between the sexes. The between-sex differences in genetic architectures can cause a variety of phenomena such as differences in the effect sizes at trait-associated loci, differences in the magnitudes of polygenic background effects, and differences in the phenotypic variances. However, current association testing approaches for dealing with sex, such as including sex as a covariate, cannot fully account for these phenomena and can be suboptimal in statistical power. We present a novel association mapping framework, MetaSex, that can comprehensively account for the genetic architecture differences between the sexes. Through simulations and applications to real data, we show that our framework has superior performance than previous approaches in association mapping. Copyright © 2018, Genetics.

Genetic and environmental contributions to the associations between intraindividual variability in reaction time and cognitive function.

PubMed

Finkel, Deborah; Pedersen, Nancy L

2014-01-01

Intraindividual variability (IIV) in reaction time has been related to cognitive decline, but questions remain about the nature of this relationship. Mean and range in movement and decision time for simple reaction time were available from 241 individuals aged 51-86 years at the fifth testing wave of the Swedish Adoption/Twin Study of Aging. Cognitive performance on four factors was also available: verbal, spatial, memory, and speed. Analyses indicated that range in reaction time could be used as an indicator of IIV. Heritability estimates were 35% for mean reaction and 20% for range in reaction. Multivariate analysis indicated that the genetic variance on the memory, speed, and spatial factors is shared with genetic variance for mean or range in reaction time. IIV shares significant genetic variance with fluid ability in late adulthood, over and above and genetic variance shared with mean reaction time.

eSensor: an electrochemical detection-based DNA microarray technology enabling sample-to-answer molecular diagnostics

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Longiaru, Mathew

2009-05-01

DNA microarrays are becoming a widespread tool used in life science and drug screening due to its many benefits of miniaturization and integration. Microarrays permit a highly multiplexed DNA analysis. Recently, the development of new detection methods and simplified methodologies has rapidly expanded the use of microarray technologies from predominantly gene expression analysis into the arena of diagnostics. Osmetech's eSensor® is an electrochemical detection platform based on a low-to- medium density DNA hybridization array on a cost-effective printed circuit board substrate. eSensor® has been cleared by FDA for Warfarin sensitivity test and Cystic Fibrosis Carrier Detection. Other genetic-based diagnostic and infectious disease detection tests are under development. The eSensor® platform eliminates the need for an expensive laser-based optical system and fluorescent reagents. It allows one to perform hybridization and detection in a single and small instrument without any fluidic processing and handling. Furthermore, the eSensor® platform is readily adaptable to on-chip sample-to-answer genetic analyses using microfluidics technology. The eSensor® platform provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus have a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

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,…

A case report and literature review of Fanconi Anemia (FA) diagnosed by genetic testing.

PubMed

Solomon, Ponnumony John; Margaret, Priya; Rajendran, Ramya; Ramalingam, Revathy; Menezes, Godfred A; Shirley, Alph S; Lee, Seung Jun; Seong, Moon-Woo; Park, Sung Sup; Seol, Dodam; Seo, Soo Hyun

2015-05-08

Fanconi anemia (FA) is a genetically heterogeneous rare autosomal recessive disorder characterized by congenital malformations, hematological problems and predisposition to malignancies. The genes that have been found to be mutated in FA patients are called FANC. To date 16 distinct FANC genes have been reported. Among these, mutations in FANCA are the most frequent among FA patients worldwide which account for 60- 65%. In this study, a nine years old male child was brought to our hospital one year ago for opinion and advice. He was the third child born to consanguineous parents. The mutation analyses were performed for proband, parents, elder sibling and the relatives [maternal aunt and maternal aunt's son (cousin)]. Molecular genetic testing [targeted next-generation sequencing (MiSeq, Illumina method)] was performed by mutation analysis in 15 genes involved. Entire coding exons and their flanking regions of the genes were analysed. Sanger sequencing [(ABI 3730 analyzer by Applied Biosystems)] was performed using primers specific for 43 coding exons of the FANCA gene. A novel splice site mutation, c.3066 + 1G > T, (IVS31 + 1G > T), homozygote was detected by sequencing in the patient. The above sequence variant was identified in heterozygous state in his parents. Further, the above sequence variant was not identified in other family members (elder sibling, maternal aunt and cousin). It is concluded that genetic study should be done if possible in all the cases of suspected FA, including siblings, parents and close blood relatives. It will help us to plan appropriate treatment and also to select suitable donor for hematopoietic stem cell transplantation and to plan for genetic counseling. In addition to the case report, the main focus of this manuscript was to review literature on role of FANCA gene in FA since large number of FANCA mutations and polymorphisms have been identified.

Electroencephalogram Signal Classification for Automated Epileptic Seizure Detection Using Genetic Algorithm

PubMed Central

Nanthini, B. Suguna; Santhi, B.

2017-01-01

Background: Epilepsy causes when the repeated seizure occurs in the brain. Electroencephalogram (EEG) test provides valuable information about the brain functions and can be useful to detect brain disorder, especially for epilepsy. In this study, application for an automated seizure detection model has been introduced successfully. Materials and Methods: The EEG signals are decomposed into sub-bands by discrete wavelet transform using db2 (daubechies) wavelet. The eight statistical features, the four gray level co-occurrence matrix and Renyi entropy estimation with four different degrees of order, are extracted from the raw EEG and its sub-bands. Genetic algorithm (GA) is used to select eight relevant features from the 16 dimension features. The model has been trained and tested using support vector machine (SVM) classifier successfully for EEG signals. The performance of the SVM classifier is evaluated for two different databases. Results: The study has been experimented through two different analyses and achieved satisfactory performance for automated seizure detection using relevant features as the input to the SVM classifier. Conclusion: Relevant features using GA give better accuracy performance for seizure detection. PMID:28781480

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.

A New Primer Set to Amplify the Mitochondrial Cytochrome C Oxidase Subunit I (COI) Gene in the DHA-Rich Microalgae, the Genus Aurantiochytrium.

PubMed

Nishitani, Goh; Yoshida, Masaki

2018-06-01

This study was performed in order to develop a primer set for mitochondrial cytochrome c oxidase subunit I (COI) in the DHA-rich microalgae of the genus Aurantiochytrium. The performance of the primer set was tested using 12 Aurantiochytrium strains and other thraustochytrid species. There were no genetic polymorphisms in the mitochondrial sequences from the Aurantiochytrium strains, in contrast to the nuclear 18S rRNA gene sequence. This newly developed primer set amplified sequences from Aurantiochytrium and closely related genera, and may be useful for species identification and clarifying the genetic diversity of Aurantiochytrium in the field.

Underestimation of Risk of a BRCA1 or BRCA2 Mutation in Women With High-Grade Serous Ovarian Cancer by BRCAPRO: A Multi-Institution Study

PubMed Central

Daniels, Molly S.; Babb, Sheri A.; King, Robin H.; Urbauer, Diana L.; Batte, Brittany A.L.; Brandt, Amanda C.; Amos, Christopher I.; Buchanan, Adam H.; Mutch, David G.; Lu, Karen H.

2014-01-01

Purpose Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. Methods BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. Results One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). Conclusion Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history. PMID:24638001

Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy.

PubMed

Dudley, Beth; Karloski, Eve; Monzon, Federico A; Singhi, Aatur D; Lincoln, Stephen E; Bahary, Nathan; Brand, Randall E

2018-04-15

Approximately 10% of pancreatic adenocarcinoma (PC) cases are attributed to hereditary causes. Individuals with PC and a personal history of another cancer associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) may be more likely to carry germline mutations. Participants with PC and a history of cancer were selected from a pancreatic disease registry. Of 1296 individuals with PC, 149 had a relevant history of cancer. If banked DNA was available, a multigene panel was performed for individuals who had not 1) previously had a mutation identified through clinical testing or 2) undergone clinical multigene panel testing with no mutations detected. Twenty-two of 124 individuals with PC and another HBOC- or LS-related cancer who underwent genetic testing had a mutation identified in a PC susceptibility gene (18%). If prostate cancer is excluded, the mutation prevalence increased to 23% (21/93). Mutation carriers were more likely to have more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN) genetic testing criteria (P < .001). Approximately 23% of mutation carriers did not meet NCCN HBOC or LS testing guidelines based on their personal cancer history and reported cancer history in first-degree relatives. At least 18% of individuals with PC and a personal history of other HBOC- or LS-related cancers carry mutations in a PC susceptibility gene based on our data, suggesting that criteria for genetic testing in individuals with PC should include consideration of previous cancer history. Cancer 2018;124:1691-700. © 2018 American Cancer Society. © 2018 American Cancer Society.

Genetic testing in combination with preventive donepezil treatment for patients with amnestic mild cognitive impairment: an exploratory economic evaluation of personalized medicine.

PubMed

Djalalov, Sandjar; Yong, Jean; Beca, Jaclyn; Black, Sandra; Saposnik, Gustavo; Musa, Zahra; Siminovitch, Katherine; Moretti, Myla; Hoch, Jeffrey S

2012-12-01

To evaluate the cost effectiveness of genetic screening for the apolipoprotein (APOE) ε4 allele in combination with preventive donepezil treatment in comparison with the standard of care for amnestic mild cognitive impairment (AMCI) patients in Canada. We performed a cost-effectiveness analysis using a Markov model with a societal perspective and a time horizon of 30 years. For each strategy, we calculated quality-adjusted life-years (QALYs), using utilities from the literature. Costs were also based on the literature and, when appropriate, Ontario sources. One-way and probabilistic sensitivity analyses were performed. Expected value of perfect information (EVPI) analysis was conducted to explore the value of future research. The base case results in our exploratory study suggest that the combination of genetic testing and preventive donepezil treatment resulted in a gain of 0.027 QALYs and an incremental cost of $1,015 (in 2009 Canadian dollars [Can$]), compared with the standard of care. The incremental cost-effectiveness ratio (ICER) for the base case was Can$38,016 per QALY. The ICER was sensitive to the effectiveness of donepezil in slowing the rate of progression to Alzheimer's disease (AD), utility in AMCI patients, and AD and donepezil treatment costs. EVPI analysis showed that additional information on these parameters would be of value. Using presently available clinical evidence, this exploratory study illustrates that genetic testing combined with preventive donepezil treatment for AMCI patients may be economically attractive. Since our results were based on a secondary post hoc analysis, our study alone is insufficient to warrant recommending APOE genotyping in AMCI patients. Future research on the effectiveness of preventive donepezil as a targeted therapy is recommended.

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.

Pathway-based variant enrichment analysis on the example of dilated cardiomyopathy.

PubMed

Backes, Christina; Meder, Benjamin; Lai, Alan; Stoll, Monika; Rühle, Frank; Katus, Hugo A; Keller, Andreas

2016-01-01

Genome-wide association (GWA) studies have significantly contributed to the understanding of human genetic variation and its impact on clinical traits. Frequently only a limited number of highly significant associations were considered as biologically relevant. Increasingly, network analysis of affected genes is used to explore the potential role of the genetic background on disease mechanisms. Instead of first determining affected genes or calculating scores for genes and performing pathway analysis on the gene level, we integrated both steps and directly calculated enrichment on the genetic variant level. The respective approach has been tested on dilated cardiomyopathy (DCM) GWA data as showcase. To compute significance values, 5000 permutation tests were carried out and p values were adjusted for multiple testing. For 282 KEGG pathways, we computed variant enrichment scores and significance values. Of these, 65 were significant. Surprisingly, we discovered the "nucleotide excision repair" and "tuberculosis" pathways to be most significantly associated with DCM (p = 10(-9)). The latter pathway is driven by genes of the HLA-D antigen group, a finding that closely resembles previous discoveries made by expression quantitative trait locus analysis in the context of DCM-GWA. Next, we implemented a sub-network-based analysis, which searches for affected parts of KEGG, however, independent on the pre-defined pathways. Here, proteins of the contractile apparatus of cardiac cells as well as the FAS sub-network were found to be affected by common polymorphisms in DCM. In this work, we performed enrichment analysis directly on variants, leveraging the potential to discover biological information in thousands of published GWA studies. The applied approach is cutoff free and considers a ranked list of genetic variants as input.

Exome Array Analysis of Nuclear Lens Opacity.

PubMed

Loomis, Stephanie J; Klein, Alison P; Lee, Kristine E; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K; Klein, Ronald; Klein, Barbara E K; Duggal, Priya

2018-06-01

Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10 -6 ; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10 -5 ). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10 -6 ) and among never smokers (N = 790, p = 2.67 × 10 -6 ). This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

Does the Genetic Cause of Prader-Willi Syndrome Explain the Highly Variable Phenotype?

PubMed

Dobrescu, Andreea-Iulia; Chirita-Emandi, Adela; Andreescu, Nicoleta; Farcas, Simona; Puiu, Maria

2016-09-01

Prader-Willi syndrome (PWS) is characterized by extensive clinical and genetic variability caused by lack of expression of imprinted genes of the chromosomal region 15q11.2-q13. The genotye-phenotype correlation has not been yet fully elucidated. To analyze these correlations in order to determine the role of specifi c geneic alterations in the development of clinical symptoms in PWS. We retrospectively analyzed data routinely collected as part of the clinical care of 52 patients with clinical suspicion of PWS. FISH test was performed in all patients; in case of negative results, methylation test was performed. PWS was confi rmed in 35 patients that were divided in two groups according to the genetic cause of PWS: group A-21 patients with 15q11-q13 region deletion, mean age at evaluation 8.1 years (SD= 5.6) and mean of clinical score 9.4 ± 1.8; group B-14 patients with positive methylation test, with mean age at evaluation 6.7 years (SD= 4.6) and mean of clinical score 10.1 ± 1.9. Facial dysmorphism and neonatal hypotonia were present in all evaluated patients; while, higher frequency of major and minor PWS criteria were noted in the group A. Onset of hyperphagia, was around the age of 2 years in most patients, however one patient from group B had normal eating behavior and normal weight beyond age 5 years. In our study, the various genotypes did not seem to explain the diff erence in phenotype in PWS patients. We found a delayed time until diagnosis in these patients, although all had neonatal hypotonia and other suggestive phenotypic features, underlining once more the need for increased awareness of this syndrome, as well as easier accessibility to genetic counseling.

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.

Linear score tests for variance components in linear mixed models and applications to genetic association studies.

PubMed

Qu, Long; Guennel, Tobias; Marshall, Scott L

2013-12-01

Following the rapid development of genome-scale genotyping technologies, genetic association mapping has become a popular tool to detect genomic regions responsible for certain (disease) phenotypes, especially in early-phase pharmacogenomic studies with limited sample size. In response to such applications, a good association test needs to be (1) applicable to a wide range of possible genetic models, including, but not limited to, the presence of gene-by-environment or gene-by-gene interactions and non-linearity of a group of marker effects, (2) accurate in small samples, fast to compute on the genomic scale, and amenable to large scale multiple testing corrections, and (3) reasonably powerful to locate causal genomic regions. The kernel machine method represented in linear mixed models provides a viable solution by transforming the problem into testing the nullity of variance components. In this study, we consider score-based tests by choosing a statistic linear in the score function. When the model under the null hypothesis has only one error variance parameter, our test is exact in finite samples. When the null model has more than one variance parameter, we develop a new moment-based approximation that performs well in simulations. Through simulations and analysis of real data, we demonstrate that the new test possesses most of the aforementioned characteristics, especially when compared to existing quadratic score tests or restricted likelihood ratio tests. © 2013, The International Biometric Society.

The genetic basis of female reproductive disorders: Etiology and clinical testing ☆

PubMed Central

Layman, Lawrence C.

2013-01-01

With the advent of improved molecular biology techniques, the genetic basis of an increasing number of reproductive disorders has been elucidated. Mutations in at least 20 genes cause hypogonadotropic hypogonadism including Kallmann syndrome in about 35–40% of patients. The two most commonly involved genes are FGFR1 and CHD7. When combined pituitary hormone deficiency includes hypogonadotropic hypogonadism as a feature, PROP1 mutations are the most common of the six genes involved. For hypergonadotropic hypogonadism, mutations in 14 genes cause gonadal failure in 15% of affected females, most commonly in FMR1. In eugonadal disorders, activating FSHR mutations have been identified for spontaneous ovarian hyperstimulation syndrome; and WNT4 mutations have been described in mullerian aplasia. For other eugonadal disorders, such as endometriosis, polycystic ovary syndrome, and leiomyomata, specific germline gene mutations have not been identified, but some chromosomal regions are associated with the corresponding phenotype. Practical genetic testing is possible to perform in both hypogonadotropic and hypergonadotropic hypogonadism and spontaneous ovarian hyperstimulation syndrome. However, clinical testing for endometriosis, polycystic ovary syndrome, and leiomyomata is not currently practical for the clinician. PMID:23499866

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.

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.

Genetic testing for hereditary cancer: effects of alexithymia and coping strategies on variations in anxiety before and after result disclosure.

PubMed

Fantini-Hauwel, Carole; Dauvier, Bruno; Arciszewski, Thomas; Antoine, Pascal; Manouvrier, Sylvie

2011-07-01

This study assessed the impact of the results of genetic testing for hereditary cancer from a multifactorial health psychology perspective, considering that emotional expression plays a key role in psychological adjustment. Measures of dispositional and transactional coping strategies, anxiety and alexithymia were filled out by 77 participants in a longitudinal study design. Statistical analyses were performed using general linear models and partial least squares path modelling, low-constraint methods that are particularly useful in the behavioural sciences. While anxiety levels prior to the result announcement were predictive of the distress experienced by noncarriers, considerable variability was observed for mutation carriers. Some subjects who had lower anxiety levels before the test displayed greater anxiety afterwards, but others seemed to anticipate the distress they would experience with the result that they showed a decrease in anxiety. The mutation carriers behaved as though their adaptive functioning were reshaped by the test result, independent of their disposition and previous emotional state, except in the case of alexithymia. Difficulty expressing emotions prior to genetic testing contributed to a similar difficulty after receiving the result, adding to the latter's emotional impact by promoting emotion-focused coping strategies and increasing distress. © 2011 Taylor & Francis

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

PubMed

Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

2016-11-01

To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

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.

Health Orientation, Knowledge, and Attitudes toward Genetic Testing and Personalized Genomic Services: Preliminary Data from an Italian Sample.

PubMed

Oliveri, Serena; Masiero, Marianna; Arnaboldi, Paola; Cutica, Ilaria; Fioretti, Chiara; Pravettoni, Gabriella

2016-01-01

Objective . The study aims at assessing personality tendencies and orientations that could be closely correlated with knowledge, awareness, and interest toward undergoing genetic testing. Methods. A sample of 145 subjects in Italy completed an online survey, investigating demographic data, health orientation, level of perceived knowledge about genetic risk, genetic screening, and personal attitudes toward direct to consumer genetic testing (DTCGT). Results . Results showed that respondents considered genetic assessment to be helpful for disease prevention, but they were concerned that results could affect their life planning with little clinical utility. Furthermore, a very high percentage of respondents (67%) had never heard about genetic testing directly available to the public. Data showed that personality tendencies, such as personal health consciousness, health internal control, health esteem, and confidence, motivation to avoid unhealthiness and motivation for healthiness affected the uptake of genetic information and the interest in undergoing genetic testing. Conclusions . Public knowledge and attitudes toward genetic risk and genetic testing among European countries, along with individual personality and psychological tendencies that could affect these attitudes, remain unexplored. The present study constitutes one of the first attempts to investigate how such personality tendencies could motivation to undergo genetic testing and engagement in lifestyle changes.

Health Orientation, Knowledge, and Attitudes toward Genetic Testing and Personalized Genomic Services: Preliminary Data from an Italian Sample

PubMed Central

Arnaboldi, Paola; Cutica, Ilaria; Fioretti, Chiara

2016-01-01

Objective. The study aims at assessing personality tendencies and orientations that could be closely correlated with knowledge, awareness, and interest toward undergoing genetic testing. Methods. A sample of 145 subjects in Italy completed an online survey, investigating demographic data, health orientation, level of perceived knowledge about genetic risk, genetic screening, and personal attitudes toward direct to consumer genetic testing (DTCGT). Results. Results showed that respondents considered genetic assessment to be helpful for disease prevention, but they were concerned that results could affect their life planning with little clinical utility. Furthermore, a very high percentage of respondents (67%) had never heard about genetic testing directly available to the public. Data showed that personality tendencies, such as personal health consciousness, health internal control, health esteem, and confidence, motivation to avoid unhealthiness and motivation for healthiness affected the uptake of genetic information and the interest in undergoing genetic testing. Conclusions. Public knowledge and attitudes toward genetic risk and genetic testing among European countries, along with individual personality and psychological tendencies that could affect these attitudes, remain unexplored. The present study constitutes one of the first attempts to investigate how such personality tendencies could motivation to undergo genetic testing and engagement in lifestyle changes. PMID:28105428

Mutation extraction tools can be combined for robust recognition of genetic variants in the literature

PubMed Central

Jimeno Yepes, Antonio; Verspoor, Karin

2014-01-01

As the cost of genomic sequencing continues to fall, the amount of data being collected and studied for the purpose of understanding the genetic basis of disease is increasing dramatically. Much of the source information relevant to such efforts is available only from unstructured sources such as the scientific literature, and significant resources are expended in manually curating and structuring the information in the literature. As such, there have been a number of systems developed to target automatic extraction of mutations and other genetic variation from the literature using text mining tools. We have performed a broad survey of the existing publicly available tools for extraction of genetic variants from the scientific literature. We consider not just one tool but a number of different tools, individually and in combination, and apply the tools in two scenarios. First, they are compared in an intrinsic evaluation context, where the tools are tested for their ability to identify specific mentions of genetic variants in a corpus of manually annotated papers, the Variome corpus. Second, they are compared in an extrinsic evaluation context based on our previous study of text mining support for curation of the COSMIC and InSiGHT databases. Our results demonstrate that no single tool covers the full range of genetic variants mentioned in the literature. Rather, several tools have complementary coverage and can be used together effectively. In the intrinsic evaluation on the Variome corpus, the combined performance is above 0.95 in F-measure, while in the extrinsic evaluation the combined recall performance is above 0.71 for COSMIC and above 0.62 for InSiGHT, a substantial improvement over the performance of any individual tool. Based on the analysis of these results, we suggest several directions for the improvement of text mining tools for genetic variant extraction from the literature. PMID:25285203

Kernel-Based Measure of Variable Importance for Genetic Association Studies.

PubMed

Gallego, Vicente; Luz Calle, M; Oller, Ramon

2017-06-17

The identification of genetic variants that are associated with disease risk is an important goal of genetic association studies. Standard approaches perform univariate analysis where each genetic variant, usually Single Nucleotide Polymorphisms (SNPs), is tested for association with disease status. Though many genetic variants have been identified and validated so far using this univariate approach, for most complex diseases a large part of their genetic component is still unknown, the so called missing heritability. We propose a Kernel-based measure of variable importance (KVI) that provides the contribution of a SNP, or a group of SNPs, to the joint genetic effect of a set of genetic variants. KVI can be used for ranking genetic markers individually, sets of markers that form blocks of linkage disequilibrium or sets of genetic variants that lie in a gene or a genetic pathway. We prove that, unlike the univariate analysis, KVI captures the relationship with other genetic variants in the analysis, even when measured at the individual level for each genetic variable separately. This is specially relevant and powerful for detecting genetic interactions. We illustrate the results with data from an Alzheimer's disease study and show through simulations that the rankings based on KVI improve those rankings based on two measures of importance provided by the Random Forest. We also prove with a simulation study that KVI is very powerful for detecting genetic interactions.

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.

Knowledge, attitudes and preferences regarding genetic testing for smoking cessation. A cross-sectional survey among Dutch smokers

PubMed Central

Smerecnik, Chris; van Schooten, Frederik J; de Vries, Hein; van Schayck, Constant P

2012-01-01

Objectives Recent research strongly suggests that genetic variation influences smokers' ability to stop. Therefore, the use of (pharmaco) genetic testing may increase cessation rates. This study aims to assess the intention of smokers concerning undergoing genetic testing for smoking cessation and their knowledge, attitudes and preferences about this subject. Design Online cross-sectional survey. Setting Database internet research company of which every inhabitant of the Netherlands of ≥12 years with an email address and capable of understanding Dutch can become a member. Participants 587 of 711 Dutch smokers aged ≥18 years, daily smokers for ≥5 years and smoke on average ≥10 cigarettes/day (response rate=83%). Primary and secondary outcome measures Smokers' knowledge, attitudes and preferences and their intention to undergo genetic testing for smoking cessation. Results Knowledge on the influence of genetic factors in smoking addiction and cessation was found to be low. Smokers underestimated their chances of having a genetic predisposition and the influence of this on smoking cessation. Participants perceived few disadvantages, some advantages and showed moderate self-efficacy towards undergoing a genetic test and dealing with the results. Smokers were mildly interested in receiving information and participating in genetic testing, especially when offered by their general practitioner (GP). Conclusions For successful implementation of genetic testing for smoking in general practice, several issues should be addressed, such as the knowledge on smoking cessation, genetics and genetic testing (including advantages and disadvantages) and the influence of genetics on smoking addiction and cessation. Furthermore, smokers allocate their GPs a crucial role in the provision of information and the delivery of a genetic test for smoking; however, it is unclear whether GPs will be able and willing to take on this role. PMID:22223839

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 .

Parent-offspring conflict and the genetic trade-offs shaping parental investment.

PubMed

Kölliker, Mathias; Boos, Stefan; Wong, Janine W Y; Röllin, Lilian; Stucki, Dimitri; Raveh, Shirley; Wu, Min; Meunier, Joël

2015-04-16

The genetic conflict between parents and their offspring is a cornerstone of kin selection theory and the gene-centred view of evolution, but whether it actually occurs in natural systems remains an open question. Conflict operates only if parenting is driven by genetic trade-offs between offspring performance and the parent's ability to raise additional offspring, and its expression critically depends on the shape of these trade-offs. Here we investigate the occurrence and nature of genetic conflict in an insect with maternal care, the earwig Forficula auricularia. Specifically, we test for a direct response to experimental selection on female future reproduction and correlated responses in current offspring survival, developmental rate and growth. The results demonstrate genetic trade-offs that differ in shape before and after hatching. Our study not only provides direct evidence for parent-offspring conflict but also highlights that conflict is not inevitable and critically depends on the genetic trade-offs shaping parental investment.

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

PubMed

Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

2010-07-01

Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

The population structure and recent colonization history of Oregon threespine stickleback determined using RAD-seq

PubMed Central

Catchen, Julian; Bassham, Susan; Wilson, Taylor; Currey, Mark; O’Brien, Conor; Yeates, Quick; Cresko, William A.

2013-01-01

Understanding how genetic variation is partitioned across genomes within and among populations is a fundamental problem in ecological and evolutionary genetics. To address this problem we are studied the threespine stickleback fish, which has repeatedly undergone parallel phenotypic and genetic differentiation when oceanic fish have invaded freshwater habitats. While significant evolutionary genetic research has been performed using stickleback from geographic regions that have been de-glaciated in the last 20,000 years, less research has focused on freshwater populations that predate the last glacial maximum. We performed RAD-seq based population genomic analyses on stickleback from across Oregon, which was not glaciated during the last maximum. We sampled stickleback from coastal, Willamette Basin, and central Oregon sites, analyzed their genetic diversity using RAD-seq, performed STRUCTURE analyses, reconstructed their phylogeographic history, and tested the hypothesis of recent stickleback introduction into central Oregon, where incidence of this species was only recently documented. Our results showed a clear phylogeographic break between coastal and inland populations, with oceanic populations exhibiting the lowest levels of divergence from one another. Willamette Basin and central Oregon populations formed a clade of closely related populations, a finding consistent with a recent introduction of stickleback into central Oregon. Finally, genome wide analysis of genetic diversity (π) and correlations of alleles within individuals in subpopulations (FIS) supported a role for introgressive hybridization in coastal populations and a recent expansion in central Oregon. Our results exhibit the power of next generation sequencing genomic approaches such as RAD-seq to identify both historical population structure and recent colonization history. PMID:23718143

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.

QTLs associated with dry matter intake, metabolic mid-test weight, growth and feed efficiency have little overlap across 4 beef cattle studies.

PubMed

Saatchi, Mahdi; Beever, Jonathan E; Decker, Jared E; Faulkner, Dan B; Freetly, Harvey C; Hansen, Stephanie L; Yampara-Iquise, Helen; Johnson, Kristen A; Kachman, Stephen D; Kerley, Monty S; Kim, JaeWoo; Loy, Daniel D; Marques, Elisa; Neibergs, Holly L; Pollak, E John; Schnabel, Robert D; Seabury, Christopher M; Shike, Daniel W; Snelling, Warren M; Spangler, Matthew L; Weaber, Robert L; Garrick, Dorian J; Taylor, Jeremy F

2014-11-20

The identification of genetic markers associated with complex traits that are expensive to record such as feed intake or feed efficiency would allow these traits to be included in selection programs. To identify large-effect QTL, we performed a series of genome-wide association studies and functional analyses using 50 K and 770 K SNP genotypes scored in 5,133 animals from 4 independent beef cattle populations (Cycle VII, Angus, Hereford and Simmental×Angus) with phenotypes for average daily gain, dry matter intake, metabolic mid-test body weight and residual feed intake. A total of 5, 6, 11 and 10 significant QTL (defined as 1-Mb genome windows with Bonferroni-corrected P-value<0.05) were identified for average daily gain, dry matter intake, metabolic mid-test body weight and residual feed intake, respectively. The identified QTL were population-specific and had little overlap across the 4 populations. The pleiotropic or closely linked QTL on BTA 7 at 23 Mb identified in the Angus population harbours a promising candidate gene ACSL6 (acyl-CoA synthetase long-chain family member 6), and was the largest effect QTL associated with dry matter intake and mid-test body weight explaining 10.39% and 14.25% of the additive genetic variance, respectively. Pleiotropic or closely linked QTL associated with average daily gain and mid-test body weight were detected on BTA 6 at 38 Mb and BTA 7 at 93 Mb confirming previous reports. No QTL for residual feed intake explained more than 2.5% of the additive genetic variance in any population. Marker-based estimates of heritability ranged from 0.21 to 0.49 for residual feed intake across the 4 populations. This GWAS study, which is the largest performed for feed efficiency and its component traits in beef cattle to date, identified several large-effect QTL that cumulatively explained a significant percentage of additive genetic variance within each population. Differences in the QTL identified among the different populations may be due to differences in power to detect QTL, environmental variation, or differences in the genetic architecture of trait variation among breeds. These results enhance our understanding of the biology of growth, feed intake and utilisation in beef cattle.

Cardiac Channel Molecular Autopsy: Insights From 173 Consecutive Cases of Autopsy-Negative Sudden Unexplained Death Referred for Postmortem Genetic Testing

PubMed Central

Tester, David J.; Medeiros-Domingo, Argelia; Will, Melissa L.; Haglund, Carla M.; Ackerman, Michael J.

2012-01-01

Objective To perform long QT syndrome and catecholaminergic polymorphic ventricular tachycardia cardiac channel postmortem genetic testing (molecular autopsy) for a large cohort of cases of autopsy-negative sudden unexplained death (SUD). Methods From September 1, 1998, through October 31, 2010, 173 cases of SUD (106 males; mean ± SD age, 18.4±12.9 years; age range, 1-69 years; 89% white) were referred by medical examiners or coroners for a cardiac channel molecular autopsy. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, a comprehensive mutational analysis of the long QT syndrome susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) and a targeted analysis of the catecholaminergic polymorphic ventricular tachycardia type 1–associated gene (RYR2) were conducted. Results Overall, 45 putative pathogenic mutations absent in 400 to 700 controls were identified in 45 autopsy-negative SUD cases (26.0%). Females had a higher yield (26/67 [38.8%]) than males (19/106 [17.9%]; P<.005). Among SUD cases with exercise-induced death, the yield trended higher among the 1- to 10-year-olds (8/12 [66.7%]) compared with the 11- to 20-year-olds (4/27 [14.8%]; P=.002). In contrast, for those who died during a period of sleep, the 11- to 20-year-olds had a higher yield (9/25 [36.0%]) than the 1- to 10-year-olds (1/24 [4.2%]; P=.01). Conclusion Cardiac channel molecular autopsy should be considered in the evaluation of autopsy-negative SUD. Several interesting genotype-phenotype observations may provide insight into the expected yields of postmortem genetic testing for SUD and assist in selecting cases with the greatest potential for mutation discovery and directing genetic testing efforts. PMID:22677073

Assessment of Geographic and Host-Associated Population Variations of the Carob Moth, Ectomyelois ceratoniae, on Pomegranate, Fig, Pistachio and Walnut, Using AFLP Markers

PubMed Central

Mozaffarian, Fariba; Mardi, Mohsen; Sarafrazi, Alimorad; Nouri Ganbalani, Gadir

2008-01-01

The carob moth, Ectomyelois ceratoniae (Zeller 1839) (Lepidoptera: Pyralidae) is the most important pest of pomegranate, Punica granatum L. (Myrtales: Ponicaceae), in Iran. In this study, 6 amplified fragment length polymorphism primer combinations were used to survey the genetic structure of the geographic and putative host-associated populations of this pest in Iran. An AMOVA was performed on test populations. Pairwise differences, Mantel test, multidimensional analysis, cluster analysis and migration rate were calculated for 5 geographic populations of E. ceratoniae sharing the same host, pomegranate. In another part of the study, 3 comparisons were performed on pairwise populations that were collected on different hosts (pomegranate, fig, pistachio and walnut) in same geographic regions. The results showed high within population variation (85.51% of total variation), however geographic populations differed significantly. The Mantel test did not show correlations between genetic and geographic distances. The probable factors that affect genetic distances are discussed. Multidimensional scaling analysis, migration rate and cluster analysis on geographic populations showed that the Arsanjan population was the most different from the others while the Saveh population was more similar to the Sabzevar population. The comparisons didn't show any host fidelity in test populations. It seems that the ability of E. ceratoniae to broaden its host range with no fidelity to hosts can decrease the efficiency of common control methods that are used on pomegranate. The results of this study suggest that in spite of the effects of geographic barriers, high within-population genetic variation, migration rate and gene flow can provide the opportunity for emerging new phenotypes or behaviors in pest populations, such as broadening host range, changing egg lying places, or changing over-wintering sites to adapt to difficult conditions such as those caused by intensive control methods. PMID:20345296

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 ...

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.

Conditional Tests for Localizing Trait Genes

PubMed Central

Di, Yanming; Thompson, Elizabeth A.

2009-01-01

Background/Aims With pedigree data, genetic linkage can be detected using inheritance vector tests, which explore the discrepancy between the posterior distribution of the inheritance vectors given observed trait values and the prior distribution of the inheritance vectors. In this paper, we propose conditional inheritance vector tests for linkage localization. These conditional tests can also be used to detect additional linkage signals in the presence of previously detected causal genes. Methods For linkage localization, we propose to perform inheritance vector tests conditioning on the inheritance vectors at two positions bounding a test region. We can detect additional linkage signals by conducting a further conditional test in a region with no previously detected genes. We use randomized p values to extend the marginal and conditional tests when the inheritance vectors cannot be completely determined from genetic marker data. Results We conduct simulation studies to compare and contrast the marginal and the conditional tests and to demonstrate that randomized p values can capture both the significance and the uncertainty in the test results. Conclusions The simulation results demonstrate that the proposed conditional tests provide useful localization information, and with informative marker data, the uncertainty in randomized marginal and conditional test results is small. PMID:19439976

Clinical and genetic analysis of Indian patients with NDP-related retinopathies.

PubMed

Sudha, Dhandayuthapani; Ganapathy, Aparna; Mohan, Puja; Mannan, Ashraf U; Krishna, Shuba; Neriyanuri, Srividya; Swaminathan, Meenakshi; Rishi, Pukhraj; Chidambaram, Subbulakshmi; Arunachalam, Jayamuruga Pandian

2017-06-10

NDP-related retinopathies are a group of X-linked disorders characterized by degenerative and proliferative changes of the neuroretina, occasionally accompanied with varying degrees of mental retardation and sensorineural hearing loss. NDP is the predominant gene associated with NDP-related retinopathies. The purpose of this study was to report the clinical and genetic findings in three unrelated patients diagnosed with NDP-related retinopathies. The patients underwent complete ophthalmic examination followed by genetic analyses. NDP gene was screened by direct sequencing approach. Targeted resequencing of several other ocular genes was carried out in patient samples that either indicated NDP gene deletion or tested negative for NDP mutation. Gene quantitation analysis was performed using real-time PCR. The whole NDP gene was deleted in patient I, while a missense NDP mutation, c.205T>C, was identified in patient II, and both had classical Norrie disease ocular phenotype (with no other systemic defects). Patient III who was diagnosed with familial exudative vitreoretinopathy did not show any mutation in the known candidate genes as well as in other ocular genes tested. The patient with whole NDP gene deletion did not exhibit any apparent extraocular defects (like mental retardation or sensorineural hearing loss) during his first decade of life, and this is considered to be a notable finding. Our study also provides evidence emphasizing the need for genetic testing which could eliminate ambiguities in clinical diagnosis and detect carrier status, thereby aiding the patient and family members during genetic counseling.

Genetics of pulmonary hypertension in the clinic.

PubMed

Girerd, Barbara; Lau, Edmund; Montani, David; Humbert, Marc

2017-09-01

Heritable pulmonary arterial hypertension (PAH) is an autosomal dominant disease with incomplete penetrance because of mutations in bone morphogenetic protein receptor-II (BMPR2), activin A receptor type II-like kinase 1, endoglin, caveolin-1, potassium channel subfamily K, member 3, and T-box gene 4 genes. Heritable pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH) is an autosomal recessive disease because of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene. The 2015 european society of cardiology (ESC) and european respiratory society (ERS) pulmonary hypertension guidelines recommend genetic counselling and testing to adults and children with PAH or PVOD/PCH as well as in adult relatives at risk of carrying a predisposing mutation. In France, genetic counseling and testing are offered to all patients displaying sporadic or familial form of PAH or PVOD/PCH and to their relatives at high risk of carrying a predisposing mutation. Patients with a heritable form of PAH are younger at diagnosis with a worse hemodynamic and a dismal prognosis. Patients with a heritable form of PVOD/PCH are younger at diagnosis with a worse response to specific PAH therapies. A program to detect PAH in an early phase was offered to all asymptomatic BMPR2 mutation carriers, according to the 2015 ESC/ERS guidelines. Finally, preimplantation genetic diagnosis has been performed in families with a history of BMPR2 mutations. Genetic counseling and testing has to be implemented in pulmonary hypertension centers.

[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.

Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets

PubMed Central

Olsson, Anders H.; Volkov, Petr; Bacos, Karl; Dayeh, Tasnim; Hall, Elin; Nilsson, Emma A.; Ladenvall, Claes; Rönn, Tina; Ling, Charlotte

2014-01-01

Genetic and epigenetic mechanisms may interact and together affect biological processes and disease development. However, most previous studies have investigated genetic and epigenetic mechanisms independently, and studies examining their interactions throughout the human genome are lacking. To identify genetic loci that interact with the epigenome, we performed the first genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human pancreatic islets. We related 574,553 single nucleotide polymorphisms (SNPs) with genome-wide DNA methylation data of 468,787 CpG sites targeting 99% of RefSeq genes in islets from 89 donors. We identified 67,438 SNP-CpG pairs in cis, corresponding to 36,783 SNPs (6.4% of tested SNPs) and 11,735 CpG sites (2.5% of tested CpGs), and 2,562 significant SNP-CpG pairs in trans, corresponding to 1,465 SNPs (0.3% of tested SNPs) and 383 CpG sites (0.08% of tested CpGs), showing significant associations after correction for multiple testing. These include reported diabetes loci, e.g. ADCY5, KCNJ11, HLA-DQA1, INS, PDX1 and GRB10. CpGs of significant cis-mQTLs were overrepresented in the gene body and outside of CpG islands. Follow-up analyses further identified mQTLs associated with gene expression and insulin secretion in human islets. Causal inference test (CIT) identified SNP-CpG pairs where DNA methylation in human islets is the potential mediator of the genetic association with gene expression or insulin secretion. Functional analyses further demonstrated that identified candidate genes (GPX7, GSTT1 and SNX19) directly affect key biological processes such as proliferation and apoptosis in pancreatic β-cells. Finally, we found direct correlations between DNA methylation of 22,773 (4.9%) CpGs with mRNA expression of 4,876 genes, where 90% of the correlations were negative when CpGs were located in the region surrounding transcription start site. Our study demonstrates for the first time how genome-wide genetic and epigenetic variation interacts to influence gene expression, islet function and potential diabetes risk in humans. PMID:25375650

Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

PubMed

Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

2016-04-01

To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes.

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis.

PubMed

Ammann, Sandra; Lehmberg, Kai; Zur Stadt, Udo; Klemann, Christian; Bode, Sebastian F N; Speckmann, Carsten; Janka, Gritta; Wustrau, Katharina; Rakhmanov, Mirzokhid; Fuchs, Ilka; Hennies, Hans C; Ehl, Stephan

2017-11-01

We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years.

Should I Perform Genetic Testing? A Qualitative Look into the Decision Making Considerations of Religious Israeli Undergraduate Students.

PubMed

Siani, Merav; Assaraf, Orit Ben-Zvi

2016-10-01

The aim of this study is to draw a picture of the concerns that guide the decision making of Israeli religious undergraduate students and the complex considerations they take into account while facing the need to have genetic testing or to attend a genetic counseling session. We examined how the religious affiliation of the students influences their perceptions toward genetics and how these are expressed. Qualitative data were collected from 51 semi-structured interviews with students, in which recurring themes were identified using 'thematic analysis.' The codes from the thematic analysis were obtained according to 'grounded theory'. Our results show that religious undergraduate students' decision making in these issues is influenced by factors that fall under three main categories: knowledge and perceptions, values, and norms. In order to include all the components of influence, we created the Triple C model: "Culture influences Choices towards genetic Counseling" which aims to generalize the complex decision making considerations that we detected. Our model places religion, as part of culture, as its central point of influence that impacts all three of the main categories we detected. It also traces the bidirectional influences that each of these main categories have on one another. Using this model may help identify the sociocultural differences between different types of patients, helping genetic counselors to better assist them in addressing their genetic status by tailoring the counseling more specifically to the patient's cultural uniqueness.

Testcross additive and dominance effects in best linear unbiased prediction of maize single-cross performance.

PubMed

Bernardo, R

1996-11-01

Best linear unbiased prediction (BLUP) has been found to be useful in maize (Zea mays L.) breeding. The advantage of including both testcross additive and dominance effects (Intralocus Model) in BLUP, rather than only testcross additive effects (Additive Model), has not been clearly demonstrated. The objective of this study was to compare the usefulness of Intralocus and Additive Models for BLUP of maize single-cross performance. Multilocation data from 1990 to 1995 were obtained from the hybrid testing program of Limagrain Genetics. Grain yield, moisture, stalk lodging, and root lodging of untested single crosses were predicted from (1) the performance of tested single crosses and (2) known genetic relationships among the parental inbreds. Correlations between predicted and observed performance were obtained with a delete-one cross-validation procedure. For the Intralocus Model, the correlations ranged from 0.50 to 0.66 for yield, 0.88 to 0.94 for moisture, 0.47 to 0.69 for stalk lodging, and 0.31 to 0.45 for root lodging. The BLUP procedure was consistently more effective with the Intralocus Model than with the Additive Model. When the Additive Model was used instead of the Intralocus Model, the reductions in the correlation were largest for root lodging (0.06-0.35), smallest for moisture (0.00-0.02), and intermediate for yield (0.02-0.06) and stalk lodging (0.02-0.08). The ratio of dominance variance (v D) to total genetic variance (v G) was highest for root lodging (0.47) and lowest for moisture (0.10). The Additive Model may be used if prior information indicates that VD for a given trait has little contribution to VG. Otherwise, the continued use of the Intralocus Model for BLUP of single-cross performance is recommended.

New frontiers in sport training: genetics and artistic gymnastics.

PubMed

Morucci, Gabriele; Punzi, Tiziana; Innocenti, Giovanni; Gulisano, Massimo; Ceroti, Marco; Pacini, Stefania

2014-02-01

The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

Compliance between clinical and genetic diagnosis of choroidal hypoplasia in 103 Norwegian Border Collie puppies.

PubMed

Grosås, Siv; Lingaas, Frode; Prestrud, Kristin Wear; Ropstad, Ernst-Otto

2017-11-07

To describe the frequency of the nonhomologous end-joining factor 1 (NHEJ1) mutation and the compliance between clinical and genetic diagnosis of choroidal hypoplasia (CH) in a group of Norwegian Border Collies. Border collie puppies in the age from 5 to 8 weeks. Puppies included in the study had a complete ophthalmological examination. All findings were recorded, and an ECVO scheme form was issued for each puppy. DNA samples were achieved from buccal swabs. Genetic typing was performed for the 7.8-kb deletion in the gene encoding NHEJ1. Dogs with none, one, or two copies of the mutated allele were classified as free, carriers, and affected, respectively. 103 Border Collie puppies from 16 litters, 52 females and 51 males, were included in the study. Ages ranged from 5.1 to 8.9 weeks. One puppy had clinical findings consistent with CH and optic nerve coloboma compatible with the diagnosis Collie Eye Anomaly (CEA). Findings on ophthalmological examination of the remaining puppies were within normal limits. On genetic testing, 85 puppies were clear of the mutation in the NHEJ1 gene, 17 puppies were carriers, and one puppy was genetically affected. A good compliance between the clinical diagnosis and the genetic test results was found in all of the puppies examined. The allele frequency of the mutation was 6.3%. © 2017 American College of Veterinary Ophthalmologists.

Maintenance of genetic variation in sexual ornaments: a review of the mechanisms.

PubMed

Radwan, Jacek

2008-09-01

Female preferences for elaborate male sexual traits have been documented in a number of species in which males contribute only genes to the next generation. In such systems, mate choice has been hypothesised to benefit females genetically. For the genetic benefits to be possible there must be additive genetic variation (V A) for sexual ornaments, such that highly ornamented males can pass fitter genes on to the progeny of choosy females. Here, I review the mechanisms that can contribute to the maintenance of this variation. The variation may be limited to sexual ornaments, resulting in Fisherian benefits in terms of the increased reproductive success of male progeny produced by choosy females. Alternatively, ornaments may capture V A in other life-history traits. In the latter case, "good genes" benefits may apply in terms of improved performance of the progeny of either sex. Some mechanisms, however, such as negative pleiotropy, sexually antagonistic variation or overdominance, can maintain V A in ornaments and other life-history traits with little variation in total fitness, leaving little room for any genetic benefits of mate choice. Distinguishing between these mechanisms has consequences not only for the theory of sexual selection, but also for evolution of sex and for biological conservation. I discuss how the traditional ways of testing for genetic benefits can usefully be supplemented by tests detecting benefits resulting from specific mechanisms maintaining V A in sexual ornaments.

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.

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.

Use of noninvasive ‘bug-eggs’ to enable comparative inferences on genetic mating system with and without parental information: A study in a cattle egret colony

PubMed Central

de Souza, Elaine Dantas; Moralez-Silva, Emmanuel; Valdes, Talita Alvarenga; Cortiço Corrêa Rodrigues, Vera Lúcia

2017-01-01

Colonial waterbirds such as herons, egrets and spoonbills exhibit ecological characteristics that could have promoted the evolution of conspecific brood parasitism and extra-pair copulation. However, an adequate characterization of the genetic mating systems of this avian group has been hindered by the lack of samples of elusive candidate parents which precluded conducting conventional parentage allocation tests. Here, we investigate the genetic mating system of the invasive cattle egret using hematophagous insects contained in fake eggs to collect blood from incubating adults in a wild breeding colony. We tested a protocol with a previously unused Neotropical Triatominae, Panstrongylus megistus, obtained blood samples from males and females in 31 nests built on trees, drew blood from 89 nestlings at those nests, and genotyped all samples at 14 microsatellite loci, including six new species-specific loci. We comparatively addressed the performance of parentage allocation versus kinship classification of nestlings to infer the genetic mating system of cattle egrets. In line with previous behavioral observations, we found evidence in support of a non-monogamous genetic mating system, including extra-pair paternity (EPP) and conspecific brood parasitism (CBP). Parentage allocation tests detected a higher percentage of nests with alternative reproductive tactics (EPP: 61.7%; CBP: 64.5%) than the kinship classification method (EPP: 50.0%; CBP: 43.3%). Overall, these results indicate that rates of alternative reproductive tactics inferred in the absence of parental genetic information could be underestimated and should be interpreted with caution. This study highlights the importance of incorporating samples from candidate parents to adequately determine the genetic mating system of a species. We expand knowledge on the reproductive tactics of colonial waterbirds, contributing novel data on the genetic mating system of the cattle egret, valuable for the design of management strategies for this invasive bird. PMID:28854191

Use of noninvasive 'bug-eggs' to enable comparative inferences on genetic mating system with and without parental information: A study in a cattle egret colony.

PubMed

Miño, Carolina Isabel; de Souza, Elaine Dantas; Moralez-Silva, Emmanuel; Valdes, Talita Alvarenga; Cortiço Corrêa Rodrigues, Vera Lúcia; Del Lama, Sílvia Nassif

2017-01-01

Colonial waterbirds such as herons, egrets and spoonbills exhibit ecological characteristics that could have promoted the evolution of conspecific brood parasitism and extra-pair copulation. However, an adequate characterization of the genetic mating systems of this avian group has been hindered by the lack of samples of elusive candidate parents which precluded conducting conventional parentage allocation tests. Here, we investigate the genetic mating system of the invasive cattle egret using hematophagous insects contained in fake eggs to collect blood from incubating adults in a wild breeding colony. We tested a protocol with a previously unused Neotropical Triatominae, Panstrongylus megistus, obtained blood samples from males and females in 31 nests built on trees, drew blood from 89 nestlings at those nests, and genotyped all samples at 14 microsatellite loci, including six new species-specific loci. We comparatively addressed the performance of parentage allocation versus kinship classification of nestlings to infer the genetic mating system of cattle egrets. In line with previous behavioral observations, we found evidence in support of a non-monogamous genetic mating system, including extra-pair paternity (EPP) and conspecific brood parasitism (CBP). Parentage allocation tests detected a higher percentage of nests with alternative reproductive tactics (EPP: 61.7%; CBP: 64.5%) than the kinship classification method (EPP: 50.0%; CBP: 43.3%). Overall, these results indicate that rates of alternative reproductive tactics inferred in the absence of parental genetic information could be underestimated and should be interpreted with caution. This study highlights the importance of incorporating samples from candidate parents to adequately determine the genetic mating system of a species. We expand knowledge on the reproductive tactics of colonial waterbirds, contributing novel data on the genetic mating system of the cattle egret, valuable for the design of management strategies for this invasive bird.

Strong genetic influences on measures of behavioral-regulation among inbred rat strains

PubMed Central

Richards, Jerry B.; Lloyd, David R.; Kuehlewind, Brandon; Militello, Leah; Paredez, Marita; Solberg -Woods, Leah; Palmer, Abraham A.

2013-01-01

A fundamental challenge for any complex nervous system is to regulate behavior in response to environmental challenges. Three measures of behavioral regulation were tested in a panel of 8 inbred rat strains. These measures were; 1) sensation seeking as assessed by locomotor response to novelty and the sensory reinforcing effects of light onset, 2) attention and impulsivity, as measured by a choice reaction time task, and 3) impulsivity as measured by a delay discounting task. Deficient behavioral regulation has been linked to a number of psychopathologies, including ADHD, Schizophrenia, Autism, drug abuse and eating disorders. Eight inbred rat strains (August Copenhagen Irish, Brown Norway, Buffalo, Fischer 344, Wistar Kyoto, Spontaneous Hypertensive Rat, Lewis, Dahl Salt Sensitive) were tested. With n=9 for each strain, we observed robust strain differences for all tasks; heritability was estimated between 0.43 and 0.66. Performance of the 8 inbred rat strains on the choice reaction time task was compared to the performance of out bred Sprague Dawley (n=28) and Heterogeneous strain rats (n=48). The results indicate a strong genetic influence on complex tasks related to behavioral regulation and indicate that some of measures tap common genetically-driven processes. Furthermore, our results establish the potential for future studies aimed at identifying specific alleles that influence variability for these traits. Identification of such alleles could contribute to our understanding of the molecular genetic basis of behavioral regulation, which is of fundamental importance and likely contributes to multiple psychiatric disorders. PMID:23710681

Longitudinal Assessment of Intellectual Abilities of Children with Williams Syndrome: Multilevel Modeling of Performance on the Kaufman Brief Intelligence Test--Second Edition

ERIC Educational Resources Information Center

Mervis, Carolyn B.; Kistler, Doris J.; John, Angela E.; Morris, Colleen A.

2012-01-01

Multilevel modeling was used to address the longitudinal stability of standard scores (SSs) measuring intellectual ability for children with Williams syndrome (WS). Participants were 40 children with genetically confirmed WS who completed the Kaufman Brief Intelligence Test--Second Edition (KBIT-2; A. S. Kaufman & N. L. Kaufman, 2004) 4-7…

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.

Genetic antimicrobial susceptibility testing in Gram-negative sepsis - impact on time to results in a routine laboratory.

PubMed

Kommedal, Øyvind; Aasen, Johanne Lind; Lindemann, Paul Christoffer

2016-07-01

Diagnostic testing of positive blood cultures is among the most critical tasks performed by clinical microbiology laboratories, and the total analysis time from sampling to results should be kept as short as possible. By providing identification of pelleted bacteria directly from positive blood-cultures, MALDI-TOF MS opens for relatively low-complex species-adjusted genetic susceptibility testing from the same bacterial pellet. In our lab routine, we prospectively evaluated a rapid in-house real-time PCR targeting the most common aminoglycoside and cephalosporin resistance genes in Escherichia coli and Klebsiella pneumoniae and measured time to preliminary susceptibility reporting for 138 samples. The results were compared to direct phenotypic susceptibility testing with interpretation after 6 h and overnight incubation respectively. Results from the genetic susceptibility testing were available for 69.5% (96/138) of the positive blood cultures within 24 h after sample collection. No phenotypic susceptibility results were available at this time. Compared to overnight direct susceptibility testing, the average time from sample collection to preliminary susceptibility reporting was reduced with 43%, from 45 h and 5 min to 25 h and 44 min, providing an earlier adjustment of antimicrobial therapy for 12 patients. Minor logistic adjustments have the potential to save yet another 4 h. © 2016 APMIS. Published by John Wiley & Sons Ltd.

View-Invariant Gait Recognition Through Genetic Template Segmentation

NASA Astrophysics Data System (ADS)

Isaac, Ebenezer R. H. P.; Elias, Susan; Rajagopalan, Srinivasan; Easwarakumar, K. S.

2017-08-01

Template-based model-free approach provides by far the most successful solution to the gait recognition problem in literature. Recent work discusses how isolating the head and leg portion of the template increase the performance of a gait recognition system making it robust against covariates like clothing and carrying conditions. However, most involve a manual definition of the boundaries. The method we propose, the genetic template segmentation (GTS), employs the genetic algorithm to automate the boundary selection process. This method was tested on the GEI, GEnI and AEI templates. GEI seems to exhibit the best result when segmented with our approach. Experimental results depict that our approach significantly outperforms the existing implementations of view-invariant gait recognition.

A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

PubMed

Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S; Brhane, Yonathan; Amos, Christopher I; Kraft, Peter; Hung, Rayjean J; Sellers, Thomas A; Witte, John S; Pharoah, Paul; Henderson, Brian E; Gruber, Stephen B; Hunter, David J; Garber, Judy E; Joshi, Amit D; McDonnell, Kevin; Easton, Doug F; Eeles, Ros; Kote-Jarai, Zsofia; Muir, Kenneth; Doherty, Jennifer A; Schildkraut, Joellen M

2016-01-01

DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10(-6)), MSH5 (P < 5.09 × 10(-6)), and BRCA2 (P = 5.70 × 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. ©2015 American Association for Cancer Research.

Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.

PubMed

Li, Bian; Mendenhall, Jeffrey L; Kroncke, Brett M; Taylor, Keenan C; Huang, Hui; Smith, Derek K; Vanoye, Carlos G; Blume, Jeffrey D; George, Alfred L; Sanders, Charles R; Meiler, Jens

2017-10-01

An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity. In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred. Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools. © 2017 American Heart Association, Inc.

Controversies in colorectal cancer screening.

PubMed

Pox, Christian P

2014-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only have an effect on distal cancers. Colonoscopy is more invasive but enables inspection of the whole colon. The role of CT-C, capsule endoscopy, genetic stool tests, blood tests and M2-PK is currently unknown. © 2014 S. Karger AG, Basel.

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.

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

GENETIC BASIS OF ACTIVITY METABOLISM. I. INHERITANCE OF SPEED, STAMINA, AND ANTIPREDATOR DISPLAYS IN THE GARTER SNAKE THAMNOPHIS SIRTALIS.

PubMed

Garland, Theodore

1988-03-01

Recent conceptual advances in physiological ecology emphasize the potential selective importance of whole-animal performance. Empirical studies of locomotor performance in reptiles have revealed surprising amounts of individual variation in speed and stamina. The present study is the first in a series examining the genetic basis of variation in locomotor performance, activity metabolism, and associated behaviors in garter snakes. Maximal sprint crawling speed, treadmill endurance, and antipredator displays (Arnold and Bennett, 1984; exhibited as snakes reached exhaustion on the treadmill) were measured for approximately six offspring (presumed to be full siblings) from each of 46 wild-caught gravid garter snakes (Thamnophis sirtalis). Each character was measured on two days; all were individually repeatable. Correlations of these characters with body mass, snout-vent length, age at testing, litter size, dam mass, and dam snout-vent length were removed by computing residuals from multiple-regression equations. These residuals were used in subsequent genetic analyses. Approximate coefficients of variation of residuals were 17% for speed, 48% for endurance, and 31% for antipredator displays. Broad-sense heritabilities were significant for all characters: speed h 2 = 0.58; stamina h 2 = 0.70; antipredator display h 2 = 0.42. All three residual characters showed positive and statistically significant phenotypic correlations (r = 0.19-0.36). Genetic correlations (estimated and tested by restricted maximum likelihood) among residuals were positive and highly significant between speed and endurance (0.58), but nonsignificant between speed and antipredator display (0.43), and between endurance and antipredator display (0.26). All environmental correlations were nonsignificant. These data suggest that, contrary to expectations based on previous physiological studies, there may be no necessary evolutionary trade-off between speed and stamina in these animals. This tentative conclusion will have important implications for future theoretical studies of the evolution of locomotor performance and associated antipredator behaviors. © 1988 The Society for the Study of Evolution.

Modification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in children.

PubMed

Woods, James S; Heyer, Nicholas J; Russo, Joan E; Martin, Michael D; Pillai, Pradeep B; Farin, Federico M

2013-01-01

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that genetic variants of metallothionein (MT) that are reported to affect Hg toxicokinetics in adults would modify the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the completion of the clinical trial, we performed genotyping assays for variants of MT isoforms MT1M (rs2270837) and MT2A (rs10636) on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant interactions or independent main effects for Hg exposure and either of the MT gene variants were observed. In contrast, among boys, numerous significant interaction effects between variants of MT1M and MT2A, alone and combined, with Hg exposure were observed spanning multiple domains of neurobehavioral function. All dose-response associations between Hg exposure and test performance were restricted to boys and were in the direction of impaired performance. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with relatively common genetic variants of MT, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure. We note that because urinary Hg reflects a composite exposure index that cannot be attributed to a specific source, these findings do not support an association between Hg in dental amalgams specifically and the adverse neurobehavioral outcomes observed. © 2013.

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.

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

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.

Clustering of Staphylococcus aureus bovine mastitis strains from regions of Central-Eastern Poland based on their biochemical and genetic characteristics.

PubMed

Puacz, E; Ilczyszyn, W M; Kosecka, M; Buda, A; Dudziak, W; Polakowska, K; Panz, T; Białecka, A; Kasprowicz, A; Lisowski, A; Krukowski, H; Cuteri, V; Międzobrodzki, J

2015-01-01

Staphylococcus aureus strains were isolated from mastitic milk of cows with infected mammary glands. The animals were living in 12 different farms near Lublin, in Central-Eastern Poland. A biochemical identification method based on enzymatic assay was performed, followed by haemolytic and proteolytic tests. PCR-RFLP targeted on the gap gene allowed the genetic identification of strains at the species level and verified phenotypic identification results. A molecular typing method using triplex PCR was performed to recognize the genetic similarity of the analyzed strains. DNA microarray hybridization (StaphyType, Alere Technologies) was used for detection of antibiotic resistance and virulence associated markers. The results obtained indicate high genetic similarity in strains isolated from the same sites. High genetic similarities were also detected between strains isolated from cows from different farms of the same region. A slightly lower similarity was noted however, in strains from various regions indicating that the strains are herd specific and that the cow's infections caused by S. aureus were of a clonal character. In 21 representative isolates selected for DNA-microarray testing, only fosfomycin (fosB) and penicillin resistance markers (blaZ, blaI, blaR) were detected. The presence of genes coding for haemolysins (lukF, lukS, hlgA, hla, hld, hlb), proteases (aur, sspA, sspB, sspP), enterotoxins (entA, entD, entG, entI, entJ, entM, entN, entO, entR, entU, egc-cluster), adhesins (icaA, icaC, icaD, bbp, clfA, clfB, fib, fnbA, map, vwb) or immune evasion proteins (scn, chp, sak) was common and, with exceptions, matched triplex PCR-defined clusters.

Stable genetic diversity despite parasite and pathogen spread in honey bee colonies.

PubMed

Jara, Laura; Muñoz, Irene; Cepero, Almudena; Martín-Hernández, Raquel; Serrano, José; Higes, Mariano; De la Rúa, Pilar

2015-10-01

In the last decades, the rapid spread of diseases, such as varroosis and nosemosis, associated with massive honey bee colonies mortality around the world has significantly decreased the number and size of honey bee populations and possibly their genetic diversity. Here, we compare the genetic diversity of Iberian honey bee colonies in two samplings performed in 2006 and 2010 in relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae, and Varroa destructor in order to determine whether parasite and pathogen spread in honey bee colonies reflects changes in genetic diversity. We found that the genetic diversity remained similar, while the incidence of N. ceranae increased and the incidence of N. apis and V. destructor decreased slightly. These results indicate that the genetic diversity was not affected by the presence of these pathogenic agents in the analyzed period. However, the two groups of colonies with and without Nosema/Varroa detected showed significant genetic differentiation (G test). A detailed analysis of the allelic segregation of microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones revealed two outlier loci related to genes involved in immune response.

Stable genetic diversity despite parasite and pathogen spread in honey bee colonies

NASA Astrophysics Data System (ADS)

Jara, Laura; Muñoz, Irene; Cepero, Almudena; Martín-Hernández, Raquel; Serrano, José; Higes, Mariano; De la Rúa, Pilar

2015-10-01

In the last decades, the rapid spread of diseases, such as varroosis and nosemosis, associated with massive honey bee colonies mortality around the world has significantly decreased the number and size of honey bee populations and possibly their genetic diversity. Here, we compare the genetic diversity of Iberian honey bee colonies in two samplings performed in 2006 and 2010 in relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae, and Varroa destructor in order to determine whether parasite and pathogen spread in honey bee colonies reflects changes in genetic diversity. We found that the genetic diversity remained similar, while the incidence of N. ceranae increased and the incidence of N. apis and V. destructor decreased slightly. These results indicate that the genetic diversity was not affected by the presence of these pathogenic agents in the analyzed period. However, the two groups of colonies with and without Nosema/Varroa detected showed significant genetic differentiation (G test). A detailed analysis of the allelic segregation of microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones revealed two outlier loci related to genes involved in immune response.

Genetic parameters for growth performance, fillet traits, and fat percentage of male Nile tilapia (Oreochromis niloticus).

PubMed

Garcia, André Luiz Seccatto; de Oliveira, Carlos Antonio Lopes; Karim, Hanner Mahmud; Sary, César; Todesco, Humberto; Ribeiro, Ricardo Pereira

2017-11-01

Improvement of fillet traits and flesh quality attributes are of great interest in farmed tilapia and other aquaculture species. The main objective of this study was to estimate genetic parameters for fillet traits (fillet weight and fillet yield) and the fat content of fillets from 1136 males combined with 2585 data records on growth traits (body weight at 290 days, weight at slaughter, and daily weight gain) of 1485 males and 1100 females from a third generation of the Aquaamerica tilapia strain. Different models were tested for each trait, and the best models were used to estimate genetic parameters for the fat content, fillet, and growth traits. Genetic and phenotypic correlations were estimated using two-trait animal models. The heritability estimates were moderate for the fat content of fillets and fillet yield (0.2-0.32) and slightly higher for body weight at slaughter (0.41). The genetic correlation between fillet yield and fat was significant (0.6), but the genetic correlations were not significant between body weight and fillet yield, body weight and fat content, daily weight gain and fillet yield, and daily weight gain and fat content (- 0.032, - 0.1, - 0.09, and - 0.4, respectively). Based on the genetic correlation estimates, it is unlikely that changes in fillet yield and fat content will occur when using growth performance as a selection criterion, but indirect changes may be expected in fat content if selecting for higher fillet yield.

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.

Rotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial ability

PubMed Central

Shakeshaft, Nicholas G.; Rimfeld, Kaili; Schofield, Kerry L.; Selzam, Saskia; Malanchini, Margherita; Rodic, Maja; Kovas, Yulia; Plomin, Robert

2016-01-01

Spatial abilities–defined broadly as the capacity to manipulate mental representations of objects and the relations between them–have been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are “mental rotation” (rotating mental models) and “visualisation” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel “Bricks” test battery, designed to tap these abilities in isolation. The results suggest substantial genetic influence unique to spatial ability as a whole, but indicate that dissociations between the more specific constructs (rotation and visualisation, in 2D and 3D) disappear when tested under identical conditions: they are highly correlated phenotypically, perfectly correlated genetically (indicating that the same genetic influences underpin performance), and are related similarly to other abilities. This has important implications for the structure of spatial ability, suggesting that the proliferation of apparent sub-domains may sometimes reflect idiosyncratic tasks rather than meaningful dissociations. PMID:27476554