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Genetics and ethics

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https://www.readbyqxmd.com/read/29348295/tuning%C3%A2-crispr-cas9-gene-drives-in-saccharomyces-cerevisiae
#1
Emily Roggenkamp, Rachael M Giersch, Madison N Schrock, Emily Turnquist, Megan Halloran, Gregory C Finnigan
Control of biological populations is an ongoing challenge in many fields including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g. malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR/Cas9 gene editing technology, a unique arrangement of this system-a nuclease based "gene drive"-allows for the Super-Mendelian spread and forced propagation of a genetic element through a population...
January 18, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29342286/the-ethics-of-general-population-preventive-genomic-sequencing-rights-and-social-justice
#2
Clair Morrissey, Rebecca L Walker
Advances in DNA sequencing technology open new possibilities for public health genomics, especially in the form of general population preventive genomic sequencing (PGS). Such screening programs would sit at the intersection of public health and preventive health care, and thereby at once invite and resist the use of clinical ethics and public health ethics frameworks. Despite their differences, these ethics frameworks traditionally share a central concern for individual rights. We examine two putative individual rights-the right not to know, and the child's right to an open future-frequently invoked in discussions of predictive genetic testing, in order to explore their potential contribution to evaluating this new practice...
January 12, 2018: Journal of Medicine and Philosophy
https://www.readbyqxmd.com/read/29340884/-i-would-like-to-discuss-it-further-with-an-expert-a-focus-group-study-of-finnish-adults-perspectives-on-genetic-secondary-findings
#3
M Vornanen, K Aktan-Collan, N Hallowell, H Konttinen, H Kääriäinen, A Haukkala
Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people's support needs after receiving SFs have received less attention. We explored Finnish adults' perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome...
January 16, 2018: Journal of Community Genetics
https://www.readbyqxmd.com/read/29333086/ethical-and-safety-issues-of-stem-cell-based-therapy
#4
REVIEW
Vladislav Volarevic, Bojana Simovic Markovic, Marina Gazdic, Ana Volarevic, Nemanja Jovicic, Nebojsa Arsenijevic, Lyle Armstrong, Valentin Djonov, Majlinda Lako, Miodrag Stojkovic
Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29326429/responsible-innovation-in-human-germline-gene-editing-background-document-to-the-recommendations-of-eshg-and-eshre
#5
Guido De Wert, Björn Heindryckx, Guido Pennings, Angus Clarke, Ursula Eichenlaub-Ritter, Carla G van El, Francesca Forzano, Mariëtte Goddijn, Heidi C Howard, Dragica Radojkovic, Emmanuelle Rial-Sebbag, Wybo Dondorp, Basil C Tarlatzis, Martina C Cornel
Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29326428/human-germline-gene-editing-recommendations-of-eshg-and-eshre
#6
Guido de Wert, Guido Pennings, Angus Clarke, Ursula Eichenlaub-Ritter, Carla G van El, Francesca Forzano, Mariëtte Goddijn, Björn Heindryckx, Heidi C Howard, Dragica Radojkovic, Emmanuelle Rial-Sebbag, Basil C Tarlatzis, Martina C Cornel
Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if GLGE would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique can help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29325614/ethical-issues-in-neurogenetics
#7
Wendy R Uhlmann, J Scott Roberts
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...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29318647/realizing-effectiveness-across-continents-with-hydroxyurea-enrollment-and-baseline-characteristics-of-the-multicenter-reach-study-in-sub-saharan-africa
#8
Patrick T McGann, Thomas N Williams, Peter Olupot-Olupot, George A Tomlinson, Adam Lane, José Luís Reis da Fonseca, Robert Kitenge, George Mochamah, Ham Wabwire, Susan Stuber, Thad A Howard, Kathryn McElhinney, Banu Aygun, Teresa Latham, Brígida Santos, Léon Tshilolo, Russell E Ware
Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries...
January 10, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29317129/introduction-reproductive-genetics-bringing-clarity-to-a-foreign-language
#9
Anthony R Gregg, Steven R Lindheim
Genomic based technologies are firmly implanted into clinical medicine. They arrived rapidly and their uses continue to evolve in both the pre and postconception periods. These technologies migrated from the prenatal arena into the domain of the reproductive endocrinology and infertility specialists in some cases nearly simultaneously (expanded carrier screening), in others more slowly (chromosome microarrays), and for some technologies the ethical and cost concerns have resulted in a slower diffusion across the disciplines...
January 6, 2018: Fertility and Sterility
https://www.readbyqxmd.com/read/29316410/environmental-warming-and-feminization-of-one-of-the-largest-sea-turtle-populations-in-the-world
#10
Michael P Jensen, Camryn D Allen, Tomoharu Eguchi, Ian P Bell, Erin L LaCasella, William A Hilton, Christine A M Hof, Peter H Dutton
Climate change affects species and ecosystems around the globe [1]. The impacts of rising temperature are particularly pertinent in species with temperature-dependent sex determination (TSD), where the sex of an individual is determined by incubation temperature during embryonic development [2]. In sea turtles, the proportion of female hatchlings increases with the incubation temperature. With average global temperature predicted to increase 2.6°C by 2100 [3], many sea turtle populations are in danger of high egg mortality and female-only offspring production...
January 8, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29315221/introduction-of-exogenous-hsv-tk-suicide-gene-increases-safety-of-keratinocyte-derived-induced-pluripotent-stem-cells-by-providing-genetic-emergency-exit-switch
#11
Maciej Sułkowski, Paweł Konieczny, Paula Chlebanowska, Marcin Majka
Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29308742/autoantibodies-and-gastrointestinal-symptoms-in-colombian-children-with-juvenile-idiopathic-arthritis
#12
Tatiana Gonzalez, Clara Malagon, Pilar Guarnizo, Angela Catalina Mosquera, Lorena Chila-Moreno, Consuelo Romero-Sanchez
BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common inflammatory joint disease in children. JIA and autoimmune inflammatory diseases of the gastrointestinal (GI) mucosa share common etiologic mechanisms, including genetic predisposition and environmental influences. OBJECTIVE: To determine the presence of autoantibodies associated with inflammatory diseases of the GI mucosa in patients with JIA and its relationship to GI symptoms. METHODOLOGY: In a cross-sectional study of patients with JIA, GI symptoms and autoantibody expression were evaluated with respect to their association with JIA disease activity indices...
January 7, 2018: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/29308663/gain-of-function-mutant-of-complement-factor-b-k323e-mimics-pathogenic-c3nef-autoantibodies-in-convertase-assays
#13
Aleksandra Urban, Anna Borowska, Anna Felberg, Lambertus van den Heuvel, Grzegorz Stasiłojć, Elena Volokhina, Marcin Okrój
Complement convertases are enzymatic complexes, which play a critical role in propagation and amplification of the complement cascade. Under physiological conditions, convertases decay shortly after being formed in either spontaneous or inhibitor-driven process. Prolongation of their half-life by C3NeF autoantibodies that prevent convertase dissociation results in pathogenic condition often manifested by renal diseases. However, the diagnosis of convertase abnormalities is difficult due to the labile nature of these enzymes and low credibility of existing methods...
January 8, 2018: Autoimmunity
https://www.readbyqxmd.com/read/29307893/genomic-medicine-for-kidney-disease
#14
REVIEW
Emily E Groopman, Hila Milo Rasouly, Ali G Gharavi
Technologies such as next-generation sequencing and chromosomal microarray have advanced the understanding of the molecular pathogenesis of a variety of renal disorders. Genetic findings are increasingly used to inform the clinical management of many nephropathies, enabling targeted disease surveillance, choice of therapy, and family counselling. Genetic analysis has excellent diagnostic utility in paediatric nephrology, as illustrated by sequencing studies of patients with congenital anomalies of the kidney and urinary tract and steroid-resistant nephrotic syndrome...
January 8, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29305293/beyond-screening-for-chromosomal-abnormalities-advances-in-non-invasive-diagnosis-of-single-gene-disorders-and-fetal-exome-sequencing
#15
REVIEW
Jane Hayward, Lyn S Chitty
Emerging genomic technologies, largely based around next generation sequencing (NGS), are offering new promise for safer prenatal genetic diagnosis. These innovative approaches will improve screening for fetal aneuploidy, allow definitive non-invasive prenatal diagnosis (NIPD) of single gene disorders at an early gestational stage without the need for invasive testing, and improve our ability to detect monogenic disorders as the aetiology of fetal abnormalities. This presents clinicians and scientists with novel challenges as well as opportunities...
January 2, 2018: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29300981/chromosome-screening-using-noninvasive-prenatal-testing-beyond-trisomy-21-what-to-screen-for-and-why-it-matters
#16
Kristien Hens
With the new and highly accurate noninvasive prenatal test (NIPT), new options for screening become available. I contend that the current state of the art of NIPT is already in need of a thorough ethical investigation and that there are different points to consider before any chromosomal or subchromosomal condition is added to the screening panel of a publicly funded screening program. Moreover, the application of certain ethical principles makes the inclusion of some conditions unethical in a privately funded scheme, even if such screening would enhance a woman's reproductive autonomy...
December 29, 2017: Journal of Medicine and Philosophy
https://www.readbyqxmd.com/read/29298459/embolisation-for-pulmonary-arteriovenous-malformation
#17
REVIEW
Charlie C-T Hsu, Gigi Nc Kwan, Hannah Evans-Barns, Mieke L van Driel
BACKGROUND: Pulmonary arteriovenous malformations are abnormal direct connections between the pulmonary artery and pulmonary vein which result in a right-to-left shunt. They are associated with substantial morbidity and mortality mainly from the effects of paradoxical emboli. Potential complications include stroke, cerebral abscess, pulmonary haemorrhage and hypoxaemia. Embolisation is an endovascular intervention based on the occlusion of the feeding arteries the pulmonary arteriovenous malformations thus eliminating the abnormal right-to-left-shunting...
January 4, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29275226/reverse-engineering-organogenesis-through-feedback-loops-between-model-systems
#18
REVIEW
Cody Narciso, Jeremiah Zartman
Biological complexity and ethical limitations necessitate models of human development. Traditionally, genetic model systems have provided inexpensive routes to define mechanisms governing organ development. Recent progress has led to 3D human organoid models of development and disease. However, robust methods to control the size and morphology of organoids for high throughput studies need to be developed. Additionally, insights from multiple developmental contexts are required to reveal conserved genes and processes regulating organ growth and development...
December 21, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29259530/%C3%A2-an-appreciation-of-the-gene-an-intimate-history-by-siddhartha-mukherjee-and-a-call-for-expanded-training-in-the-responsible-conduct-of-research%C3%A2
#19
REVIEW
Evan D Morris
The Gene: An Intimate History by Siddhartha Mukherjee, first published in 2016, is a comprehensive and fascinating recounting of the discovery of the gene and genetics research from wrinkled peas to CRISPR/Cas9 and all the details in between. In Mukherjee's sweeping history, the science is clearly depicted but also tightly integrated into the political movements and world events that it spawned, both hopeful and detestable. Two stories from The Gene are the central focuses of this article. One story is driven by the desire of Eugenicists in early 20th century America to rid the population of defective traits...
December 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/29259526/science-and-bioethics-of-crispr-cas9-gene-editing-an-analysis-towards-separating-facts-and-fiction%C3%A2
#20
REVIEW
Adam P Cribbs, Sumeth M W Perera
Since its emergence in 2012, the genome editing technique known as CRISPR-Cas9 and its scientific use have rapidly expanded globally within a very short period of time. The technique consists of using an RNA guide molecule to bind to complementary DNA sequences, which simultaneously recruits the endonuclease Cas9 to introduce double-stranded breaks in the target DNA. The resulting double-stranded break is then repaired, allowing modification or removal of specific DNA bases. The technique has gained momentum in the laboratory because it is cheap, quick, and easy to use...
December 2017: Yale Journal of Biology and Medicine
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