Genetic Testing Technologies Research Articles

Management of Gynecologic Cancers In Relation to Genetic Predisposition.

To review hereditary gynecologic cancer syndromes and outline current clinical management considerations. Retrieved articles and guidelines dated 2013-2018 from PubMed, National Comprehensive Cancer Network, American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and National Institutes of Health databases. Advances in genetic testing technology have allowed for the identification of a growing number of patients with genetic mutations associated with hereditary cancer. Individuals with a hereditary predisposition to cancer may qualify for targeted drug therapies, risk-reducing surgeries, and/or high-risk cancer surveillance depending on the specific gene mutation(s) they harbor. Furthermore, there are clinical implications for relatives. This article is an educational guide for oncology nurses who often play a key role in identifying patients at risk for hereditary cancer, prompting referrals for genetic evaluation, and providing follow-up care for these patients.

Cardiovascular genomics and sudden cardiac death in the young.

Sudden cardiac death (SCD) in the young is a rare but tragic consequence of a number of genetic cardiovascular disorders. The care of survivors of cardiac arrest and families affected bySCD seeks to prevent further SCD events through family screening. The aim of this article is to review the genetic basis of SCD in the young and outline the clinical aspects of caring for families affected by SCD. Inherited cardiomyopathies and primary arrhythmia syndromes are important causes of SCD in young people. Over the past 30 years, there has been an explosion of knowledge regarding the underlying genetic mechanisms of these disorders and dramatic advances in genetic testing technologies. Family screening with thorough multidisciplinary clinical assessment and genetic testing allows for the initiation of preventive strategies in high-risk relatives and ultimately a reduction in SCD events.

Sport Nutrigenomics: Personalized Nutrition for Athletic Performance.

An individual's dietary and supplement strategies can influence markedly their physical performance. Personalized nutrition in athletic populations aims to optimize health, body composition, and exercise performance by targeting dietary recommendations to an individual's genetic profile. Sport dietitians and nutritionists have long been adept at placing additional scrutiny on the one-size-fits-all general population dietary guidelines to accommodate various sporting populations. However, generic “one-size-fits-all” recommendations still remain. Genetic differences are known to impact absorption, metabolism, uptake, utilization and excretion of nutrients and food bioactives, which ultimately affects a number of metabolic pathways. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients and other food components. Although there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to an ergogenic aid, there is a growing foundation of research linking gene-diet interactions on biomarkers of nutritional status, which impact exercise and sport performance. This foundation forms the basis from which the field of sport nutrigenomics continues to develop. We review the science of genetic modifiers of various dietary factors that impact an athlete's nutritional status, body composition and, ultimately athletic performance.

Cost-Effectiveness Analysis of Non-invasive Prenatal Testing for Down Syndrome in China.

There is little evidence in China regarding the cost-effectiveness of non-invasive prenatal testing (NIPT) for Down syndrome (DS). This study aims to evaluate the cost-effectiveness of NIPT and provide evidence to inform decision-making. To determine the cost-effectiveness of NIPT for DS, a decision-analytic model was developed using the TreeAge Pro software from a societal perspective in a simulated cohort of 10 000 pregnant women. Main indicators were based on field surveys from sampled hospitals in four locations in China and a literature review. The conventional maternal serum screening (CMSS) strategy, contingent screening strategy (NIPT delivered to high risk pregnant women after CMSS), and universal screening strategy could prevent 3.02, 7.53, and 9.97 DS births, respectively. NIPT would decrease unnecessary invasive procedures, resulting in fewer procedure-related miscarriages. The cost-effectiveness ratio of the contingent screening strategy was the lowest. When compared with the CMSS strategy, the incremental cost per DS birth averted by the contingent screening strategy and universal screening strategy were USD 20,160 and 352,388, respectively. One-way sensitivity analysis showed that, if the cost of NIPT could be decreased to USD 76.92, the cost-effectiveness ratio of the universal screening strategy would be lower than the CMSS strategy. Although NIPT has the merits of greater effectiveness and safety, CMSS is unlikely to be replaced by NIPT at this time because of NIPT's higher cost. Contingent screening may be an appropriate strategy to balance the effectiveness and cost factors of the new genetic testing technology.

A Key Role for the Genetic Counsellor in the Genomics Era

New genetic testing technologies such as microarrays and whole exome sequencing mean the diagnostic potential for a child with a development disorder is greatly increased over traditional testing techniques. With this increased potential comes increased expectations from families and professionals about the answers a diagnosis will provide. However, limitations remain and a proportion of individuals will continue to remain undiagnosed. In addition, some individuals will receive novel or very rare diagnoses about which very little is known in terms of prognosis and effective treatments. In this paper, I present an argument for why these families would benefit from additional Genetic Counsellor support and how Clinical Genetics services in the UK could provide this support. I acknowledge that resources are limited, but as demands on services increase and interactions with families become shorter, I argue that this kind of service should be prioritised, for the benefit of these families.

Knowledge and Information Need for Prenatal Genetic Screening and Diagnosis and Attitude toward Terminating Pregnancy among Pregnant Women in South Korea

Purpose: This study identifies correlations among information needs and knowledge about prenatal genetic screening and diagnosis (I-PGSD & K-PGSD), and attitude toward terminating pregnancy (ATP) among pregnant women in South Korea. Methods: A descriptive survey was conducted from January 2013 to April 2014 in South Korea. 222 pregnant women responded to three questionnaires developed by the authors. The questionnaire for I-PGSD consisted of 19 questions; 18 questions for K-PGSD; and 10 questions for ATP. Results: Mean scores were $80.46{pm}11.73$ for I-PGSD; $14.86{pm}3.74$ for K-PGSD; and $33.71{pm}6.13$ for ATP. The ATP score was positively correlated with the I-PGSD and K-PGSD scores, but statistically significant with only I-PGSD (p=.006). I-PGSD scores were higher than average on three genetic syndromes (Down, Patau, and Edwards syndrome), on management after the diagnosis of positive fetal aneuploidy, and on test result interpretation after the amniocentesis and level II fetal ultrasonogram. Conclusions: In light of current legal and moral controversy regarding terminating pregnancy and rapidly advancing prenatal genetic testing technology, more prenatal genetic education for nurses and nursing students who teach pregnant women is needed. In addition, more professional counseling services provided by trained nurses are also required.

Investigating the child with intellectual disability.

The search for causation is a key component of the assessment of the child with intellectual disability. Historically, a specific diagnosis has been achievable in only a small minority of these children, but over the last decade, this has changed dramatically such that a specific diagnosis is now possible in about half of all children with intellectual disability. This improvement has been driven by major advances in genetic-testing technologies, the most important of which are chromosome microarray and whole exome sequencing. Simultaneously, these technological advances have revealed many new genetic syndromes that had previously escaped clinical recognition, and demonstrated that the majority of severe intellectual disability is caused by pathogenic gene variants that arise de novo in the child. Although access to genomic testing is currently limited, evidence from health economic studies suggests that this testing is most cost effective when performed early in the patient's diagnostic journey.

Towards Cultural Competence in the Genomic Age: a Review of Current Health Care Provider Educational Trainings and Interventions

The increasing diversity of the USA brings opportunities and challenges for health care providers, health care systems, and policymakers to create and maintain culturally aware services. To reduce health disparities and reflect societal changes, the medical community must evaluate how it is addressing cultural competence in all areas. A focus on genomics is a particular need as the increased availability of and access to genetic testing technologies has led to a new level of understanding of human genetic variation and advances in the individualized care of patients. However, there is a justified concern that these technologies could perpetuate or even widen existing health disparities among patients from historically underrepresented groups. This article reviews the impact of cultural influences on the medical genomics and genetic counseling processes, as well as educational and interventional strategies available for health care professionals. While cultural competence training and educational opportunities are available to most health care providers, there is limited published literature on the utilization and effectiveness of these interventions. Recent reviews acknowledge the equal importance of awareness, knowledge, and skills within cultural competence training and interventions; however, there is a lack of understanding of how a cultural competence framework should be developed and adopted in an increasingly diverse society. This suggests an opportunity to re-evaluate current practices through measured outcomes research. The most beneficial cultural competence training likely occurs when traditional coursework is complemented by cultural awareness and self-reflection activities intimately woven into training and patient encounters. Cultural competence is a complex, multidimensional process that includes cultural awareness, knowledge, and skills. A lifelong commitment to understanding and embracing culture is central to effective practice. Suggestions for promoting cultural competence within the health care professions are presented.

A Key Role for the Genetic Counsellor in the Genomics Era

New genetic testing technologies such as microarrays and whole exome sequencing mean the diagnostic potential for a child with a development disorder is greatly increased over traditional testing techniques. With this increased potential comes increased expectations from families and professionals about the answers a diagnosis will provide. However, limitations remain and a proportion of individuals will continue to remain undiagnosed. In addition, some individuals will receive novel or very rare diagnoses about which very little is known in terms of prognosis and effective treatments. In this paper, I present an argument for why these families would benefit from additional Genetic Counsellor support and how Clinical Genetics services in the UK could provide this support. I acknowledge that resources are limited, but as demands on services increase and interactions with families become shorter, I argue that this kind of service should be prioritised, for the benefit of these families.

The possible implications of advances in genetic testing technologies for Genetic Counsellors working with families of children with developmental disorders

New genetic testing technologies such as microarrays and whole exome sequencing mean the diagnostic potential for a child with a development disorder is greatly increased over traditional testing techniques. With this increased potential comes increased expectations from families and professionals about the answers a diagnosis will provide. However, limitations remain and a proportion of individuals will continue to remain undiagnosed. In addition, some individuals will receive novel or very rare diagnoses about which very little is known in terms of prognosis and effective treatments. In this paper, I present an argument for why these families would benefit from additional Genetic Counsellor support and how Clinical Genetics services in the UK could provide this support. I acknowledge that resources are limited, but as demands on services increase and interactions with families become shorter, I argue that these resources should be fought for, for the benefit of these families.

Research of pollution-free and precision cultivation system of Chinese herbal medicines

The issues of disordering production and non-standard pesticide application are common in the production of Chinese herbal medicines. Aimed to above problems, research groups built the pollution-free and precision cultivation system of medicinal plants. This system mainly included the precise site selection of medicinal plants based on the GIS technology, modern omics-assisted breeding, metagenomics guiding the soil complex improvement, and the precise field management based on rational application of fertilizer and comprehensive control of disease. At present, the production and distribution of medicinal plants were performed in the many poor counties of the whole nation. The breeding platform of resistant varieties was built, and certificates of new and well-bred varieties were received, in the base of genetic backgrounds of the original species of medicinal plants. The disease incidences were declined after application of these resistant varieties. Additionally, chemical pesticide consumption of medicinal plants (such as Panax ginseng, P. notoginseng, Salvia miltiorrhiza, P. quinquefolium, Schisandra chinensis, Platycodon grandiflorum and P. grandiflorus etc.) reduced by 20%-80% based on the genetic testing technologies of plant diseases and insect pests and safety evaluation of pollution-free pesticides. The application of pollution-free and precision cultivation system of Chinese herbal medicines achieve significantly social, economic and ecological benefits.

The use of droplet digital PCR and high resolution melt for detection of low level mosaicism

Diagnostic testing and screening for a number of genetic conditions can be complicated by presence of low level mosaicism (LLM) that arises post-zygotically, termed somatic mosaicism. While improvements in genetic testing technologies have significantly increased diagnostic yield in children with intellectual disability (ID), more than half of these children still remain undiagnosed. Many pathogenic variants contributing to ID may go unnoticed if present in a small proportion of cells, below the analytical sensitivity of standard methods in wide use. Importantly, mosaic variants may be present in the brain without being readily detectable in the tissues commonly sampled for genetic analysis, including blood and saliva. Some of these may be copy number and/or epigenetic changes such as DNA methylation involved in regulation of gene expression. This presentation highlights these issues in the context of syndromic forms of ID, including examples of well-characterised cohorts of children affected with fragile X syndrome (FXS), Rett syndrome and chromosome 15 imprinting disorders, as well as in developmental delay referrals. Potential solutions are described that use novel methodologies that utilise droplet digital PCR and high resolution melt to detect LLM in blood, buccal, saliva, and dried blood spots, significantly increasing diagnostic yield.

Germline mutations in hereditary diffuse gastric cancer.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%-3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer (HDGC). Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network (NCCN) guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team (MDT) are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.

The known unknown: the challenges of genetic variants of uncertain significance in clinical practice.

As genetic testing technology has advanced, allowing scientists to obtain much of the raw data from our DNA, their ability to interpret these data has struggled to keep up. The result is the ubiquity of variants of uncertain significance (VUSs): findings from genetic testing for which the clinical significance is currently unresolved. What to do when these results are found is a problem that has vexed laboratories, clinicians, and patients alike. In this paper, I focus on the issues raised by VUSs in clinical practice, and suggest paths forward.

The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer

Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

Medical Genetics Ethics Case Collection: Discussion Materials for Medical Students in the Genomic Era.

This collection of cases in medical genetics focuses on ethical dimensions of genetic testing. Given the recent and continuing revolution in genetic testing technologies, understanding the nuances of genetic tests and the implications of their outcomes for patients is a critical learning goal for medical students. This case collection was developed for first-year medical students. The cases fall into two types: discussion cases that lend themselves to both small-group and lecture settings and brief audience-response clicker cases to be used in larger lecture settings. The cases span topics such as direct-to-consumer genetic testing, patient privacy, economic and legal issues of genetic testing, and secondary findings in whole exome/genome sequencing. The clicker cases can be used to punctuate class sessions on the related science, while the discussion cases can be deployed as a single 2-hour session focusing on ethics. The associated materials include teaching notes on the scientific and ethical dimensions of the cases, a slide presentation of the cases, and implementation advice. Students found that engaging with these cases was very stimulating and eye-opening. Student comments indicated that they appreciated the opportunity to grapple with the ethical dimensions of the genetic testing technologies and that the challenges brought to light highlighted the complexity of medical practice in the genomic era. Although these cases were originally developed for use with medical students, they could easily be adapted for use in postgraduate and CME settings to explore complex ethical scenarios on which even the experts disagree.

Appropriate Use of Genetic Testing in Congenital Heart Disease Patients

Congenital heart disease (CHD) remains the most common birth defect, occurring in 1% of all births. Although the exact etiology of CHD is still largely unknown, it is thought to be an interaction of genetic and non-genetic factors. The purposes of this review are to summarize recent advances in CHD genetics and testing and to present a suggested algorithm for appropriate use of genetic testing in patients with CHD. Advances in genetic testing technology are rapidly expanding the options for screening and are providing further insights into the genetic and molecular background of non-syndromic CHD. As the field advances, the role of the geneticist and genetic counselor will continue to expand as the testing becomes more complex and interpretation of results becomes increasingly challenging. Coordination of practice between cardiologists and geneticists using a shared clinical structure is essential and will help improve cost utilization and facilitate individualized patient care.

The Need to Protect Employees with Genetic Predisposition to Mental Illness? The UN Convention on the Rights of Persons with Disabilities and the Case for Regulation

Abstract Ground-breaking genetic discoveries and technological advances have opened up a new era in genetic exploration, and technological advances have enabled geneticists to successfully uncover the genetic basis of a wide range of diseases. Although currently of limited predictive value, genetic testing promises to potentially revolutionise health care and medical treatment. Among other things, genetic testing technology may offer the prospect of being able to detect the onset of future disabilities, including mental illness. In light of advances in genetic science and technology, questions arise as to whether an appropriate framework exists to protect the interests of individuals and also to acknowledge competing commercial considerations for the use of genetic testing, particularly in the employment context. Against the backdrop of rapidly advancing genetic technologies, this article considers whether it is necessary to regulate genetic testing of employees for mental illness. This article examines the regulation of genetic testing in this area from the perspective of the social model of disability and the UN Convention on the Rights of Persons with Disabilities. It makes recommendations for addressing the competing interests and argues for the need to regulate genetic testing for mental illnesses in employment, with individual rights at the forefront.

Current Approach to Breast Cancer Risk Reduction for Women with Hereditary Predispositions to Breast Cancer

Risk reduction strategies for women at an increased risk for breast cancer include prophylactic mastectomy, prophylactic salpingo-oophorectomy, and chemoprevention. These techniques have been well studied in certain high-risk populations such as women with significant family histories of breast cancer and women with BRCA1 and BRCA2 mutations. Rapid evolution in genetic testing technology has enabled increased access and ability to analyze genes associated with an increased risk for breast cancer. These genes include but are not limited to BRCA1 and BRCA2. This technological progress has expanded the definition and number of women classified as having a genetic predisposition to breast cancer; however, literature specifically evaluating efficacy of breast cancer risk reduction strategies in this expanded population does not yet exist. In order to appreciate the effectiveness of risk-reducing strategies for women with a hereditary predisposition to breast cancer, we provide an overview of current literature and recommendations for risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, and chemoprevention in the high-risk breast cancer population.

Progress in genetic basis of congenital heart disease

Congenital heart disease (CHD) is the most common human congenital malformation, which is the biggest cause of infant morbidity and mortality.Even though it can be corrected by surgical operation, the patient also faces a variety of surgical complications and even the risk of disease recurrence, which brings huge economic pressure to the society.At present, the occurrence of CHD is related to the gene mutation, chromosome variation, environmental factors and epigenetic inheritance.This paper focuses on the genetic basis of CHD and genetic testing technology, to deepen the understanding of the genetic basis of the disease, to provide the basis for the prevention of disease and early diagnosis. Key words: Congenital heart disease; Genetics; Genetic testing technology