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Background: John M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, Opitz's early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics. Main body: A testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz's teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues. Conclusion: John M. Opitz's towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth—a symbol of resilience, humanity, and scientific excellence. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the diagnostic yield from prior genetic testing in a 20-year cohort of pediatric patients with congenital cataracts. A retrospective review of patients with congenital cataracts who underwent genetic testing was completed from 2003–2022. The diagnostic yield of the test was determined by variant classification and inheritance pattern. Variants from initial testing underwent reclassification in accordance with ACMG-AMP (American College of Medical Genetics and Genomics—American Association of Molecular Pathology) 2015 or 2020 ACMG CNV guidelines. A total of 95 variants were identified in 52 patients with congenital cataracts (42 bilateral, 10 unilateral); 42 % were White, 37% were Hispanic, 8% were Black, and 6% were Asian. The majority of patients (92%) did not have a family history of congenital cataracts but did have systemic illnesses (77%). Whole exome sequencing and targeted congenital cataract panels showed diagnostic yields of 46.2% and 37.5%, respectively. Microarray had the lowest yield at 11%. Compared to the initial classification, 16% (15 of 92 variants) had discrepant reclassifications. More testing is needed, and an increased focus is warranted in the field of ocular genetics on congenital cataracts, particularly in those with systemic illnesses and no family history, to advance our knowledge of this potentially blinding condition. [ABSTRACT FROM AUTHOR]

The literature on neurofibromatosis (NF) has never been systematically assessed using bibliometric analytic methodologies. We quantitatively analyzed the major trends and scientific output regarding NF, highlighting potential avenues for research. An Elsevier's Scopus database search was performed for all indexed studies related to NF from 1898 to 2021. Validated bibliometric parameters were analyzed using productivity, citation, and keyword analysis, including text mining, content analysis, and collaboration network mapping from inception to date on R 4.1.2. Our search yielded 15,024 documents. Annual scientific production has grown at a compounded rate of 5.86%, with the largest occurring in 2021 (n = 626). Journals with the most publications on NF include the Journal of Medical Genetics (n = 117) and Neurology (n = 113). The topmost cited author was Gutmann DH (n = 295). The United States had the most international collaboration (n = 435; multiple country publications). Identification of citation classics revealed a shift in recent decades towards understanding genetic and molecular pathways of NF tumorigenesis. Macro-level and micro-level text mining revealed the top 20 genetic and molecular pathways, and syndromes, associated with NF. Our study exemplifies a quantitative method for understanding the historical and current state of academic efforts regarding NF. There has been a shift of treatment strategies towards targeting specific pathways involved in tumorigenesis. We highlight the top 20 genetic and molecular pathways in the literature as well as the top 20 associated syndromes. This data is encouraging as increased research in molecular targeted therapies aimed at NF pathogenesis may allow advances in disease control. [ABSTRACT FROM AUTHOR]

In the science communication literature, we can easily notice the persistence of the knowledge-attitudes model (or the deficit model) that attributes the lack of public support to a lack of scientific knowledge. However, there has also been a continuing debate over the roles of scientific knowledge in explaining public attitudes towards specific controversial science and technologies. Using the data from an American nationwide survey, this study examined the variety of antecedents of the public acceptance of human gene editing (HGE), including scientific knowledge, attitudes towards science, risk-benefit perceptions of HGE, and belief in human evolution. Our findings illuminate how scientific knowledge indirectly influenced the public acceptance of HGE through a variety of mediating variables (such as attitudes towards science, risk perceptions of HGE, and benefit perceptions of HGE), though it did not directly influence this acceptance. The findings also reveal some moderating effects of belief in human evolution on the relationships among the above variables, serving as a 'perceptual filter' in the case of HGE. These findings revisit and extend the persistent but simplified knowledge-attitudes model and provide new insights into the complicated process of public attitude formation about such controversial technologies as HGE. [ABSTRACT FROM AUTHOR]

Gene-editing technologies, such as CRISPR/Cas9, are internationally ethically fraught. In the United States, policy surrounding gene-editing has yet to be implemented, while the science continues to speed ahead. However, it is not enough that policy be implemented: in order for policy to establish limits for the technology such that benefits are possible while threats are kept at bay, such policy must be ethical. In turn, the ethics of gene-editing is a culturally determined field of inquiry. This piece presents a proposal for a study whose goal is to arrive at ethical policy recommendations for policymakers. To achieve this goal, this study proposes, what needs to be done is, first, to understand the full history and foundation of gene-editing by conducting a thorough legal, bioethical, and policy review for precedent assisted reproductive technologies and genetic reproductive technologies. Following this effort, an empirical study must be conducted involving careful surveys of key stakeholder groups on their knowledge and opinions of gene-editing. Such stakeholder groups must include bioethicists, medical geneticists, and lay persons, including those in the disability community. [ABSTRACT FROM AUTHOR]

In this article, I offer historical, jurisprudential, and moral analyses of racial eugenics campaigns against African American, Native American, and Hispanic American women. I argue that African American, Native American, and Hispanic American women were sterilized at a time in US history when doctors working for/with the Department of Health, Education, and Welfare, the Indian Health Service, and Medicaid engaged in forced and coerced sterilizations with impunity. As a result, Black and Brown women did not have equal protection of the laws nor unimpeded access to the courts. Therefore, they had few options for protecting themselves from harm or redressing their grievances against the state. For these reasons, I conclude that African American, Native American, and Hispanic American women who were sterilized without their knowledge or consent by doctors working for public health agencies ought to be awarded reparations by the United States Congress. Additionally, I conclude that federal prosecutors and the American Medical Association ought to bring criminal charges and professional sanctions against the doctors and healthcare workers involved. Finally, I conclude that medical professionals ought to engage in a nationwide effort to reconcile people in Black and Brown communities with the healthcare community in the United States. [ABSTRACT FROM AUTHOR]

Background: Hereditary cancer susceptibility syndrome (HCSS) contributes to the cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and refer the patients and their families for genetic counselling. The study aimed to identify ALL patients who meet the American College of Medical Genetics (ACMG) criteria and refer them for the genetic testing for HCSS as hereditary leukemia and hematologic malignancy syndrome, and to elucidate the significance of high consanguinity with the prevalence of inherited leukemia in Pakistani population.Methods: A total of 300 acute lymphoblastic leukemia patients were recruited from the Children's Hospital, Lahore, Pakistan from December 2018 to September 2019. A structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection.Results: In our cohort, 60.40% of ALL patients were identified to meet ACMG criteria. Among them, a large number of patients (40.65%) solely fulfil the criteria due to the presence of parental consanguinity. However, parental consanguinity showed protective impact on the onset at early age of disease [OD = 0.44 (0.25-0.77), p-value = 0.00] while, a family history of cancer increased the risk of cardiotoxicity [OD = 2.46 (1.15-5.24), p-value = 0.02]. Parental consanguinity shows no significant impact on the family history of cancer and the number of relatives with cancer.Conclusions: More than 50% of the ALL patients were considered the strong candidates' for genetic testing of HCSS in the Pakistani population, and parental consanguinity was the leading criteria fulfilled by the individuals when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines, especially for the criterion of parental consanguinity, and formulating the score based criteria based on; genetic research, the toxicology profile, physical features, personal and family history of cancer for the identification of patients for the genetic testing. [ABSTRACT FROM AUTHOR]

Mutations in NFkB pathway genes can cause inborn errors of immunity (IEI), with NFKB1 haploinsufficiency being a significant etiology for common variable immunodeficiency (CVID). Indeed, mutations in NFKB1 are found in 4 to 5% of in European and United States CVID cohorts, respectively; CVID representing almost ¼ of IEI patients in European countries registries. This case study presents a 49-year-old patient with respiratory infections, chronic diarrhea, immune thrombocytopenia, hypogammaglobulinemia, and secondary lymphoma. Comprehensive genetic analysis, including high-throughput sequencing of 300 IEI-related genes and copy number variation analysis, identified a critical 2.6-kb deletion spanning the first untranslated exon and its upstream region. The region's importance was confirmed through genetic markers indicative of enhancers and promoters. The deletion was also found in the patient's brother, who displayed similar but milder symptoms. Functional analysis supported haploinsufficiency with reduced mRNA and protein expression in both patients. This case underscores the significance of copy number variation (CNV) analysis and targeting noncoding exons within custom gene panels, emphasizing the broader genomic approaches needed in medical genetics. • NFKB1 haploinsufficiency can be caused by a deletion restricted to an untranslated region. • Deletion in the promoter region can only be detected using custom targeted NGS or whole genome sequencing. • Untranslated exons and promoter regions should be included in NGS panel design. • Pathogenic variations in untranslated regions are likely underdiagnosed in patients with inborn errors of immunity. [ABSTRACT FROM AUTHOR]

Background and Aims: The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). Design Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Setting: Six sites in the United States. Participants: European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. Measurements Outcomes included criterion counts for DSM‐5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM‐5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears‐GPS) using summary statistics from a large (> 1 million) genome‐wide association study of educational attainment. Findings In polygenic association analyses, higher EduYears‐GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears‐GPS predicted all three SUDs (P < 0.05, R2 0.13–0.20%). Conclusions: Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio‐economic status, urban–rural residency and parental education). [ABSTRACT FROM AUTHOR]

The article discusses what the author refers to as the potential impact that human genetic prediction will have on America's insurance markets, and it mentions coverage for preexisting conditions under the U.S. Patient Protection and Affordable Care Act, as well as DNA analyses. Artificial intelligence (AI)-informed insurance pricing and an individual's polygenic score (PGS) are examined, along with body mass index and America's Genetic Information NonDiscrimination Act.

Background: A large number of SCN5A variants have been reported to underlie Brugada syndrome (BrS). However, the evidence supporting individual variants is highly heterogeneous. Objective: We systematically re‐evaluated all SCN5A variants reported in BrS using the 2015 American college of medical genetics and genomics and the association for molecular pathology (ACMG‐AMP) guidelines. Methods: A PubMed/Embase search was performed to identify all reported SCN5A variants in BrS. Standardized bioinformatic re‐analysis (SIFT, PolyPhen, Mutation Taster, Mutation assessor, FATHMM, GERP, PhyloP, and SiPhy) and re‐evaluation of frequency in the gnomAD database were performed. Fourteen ACMG‐AMP rules were deemed applicable for SCN5A variant analysis. Results: Four hundred and eighty unique SCN5A variants were identified, the majority of which 425 (88%) were coding variants. One hundred and fifty‐six of 425 (37%) variants were classified as pathogenic/likely pathogenic. Two hundred and fifty‐eight (60%) were classified as variants of uncertain significance, while a further 11 (3%) were classified as benign/likely benign. When considering the subset of variants that were considered "null" variants separately, 95% fulfilled criteria for pathogenicity/likely pathogenicity. In contrast, only 17% of missense variants fulfilled criteria for pathogenicity/likely pathogenicity. Importantly, however, only 25% of missense variants had available functional data, which was a major score driver for pathogenic classification. Conclusion: Based on contemporary ACMG‐AMP guidelines, only a minority of SCN5A variants implicated in BrS fulfill the criteria for pathogenicity or likely pathogenicity. [ABSTRACT FROM AUTHOR]

The Genetics Society of America (GSA) Medal recognizes researchers who have made outstanding contributions to the field of genetics in the past 15 years. The 2019 GSA Medal is awarded to Bonnie L. Bassler of Princeton University and the Howard Hughes Medical Institute in recognition of her groundbreaking studies of bacterial chemical communication and regulation of group behaviors. [ABSTRACT FROM AUTHOR]

The Genetic Information Nondiscrimination Act of 2008 (GINA) provides federal safeguards to prohibit employer or insurance discrimination based on personal or familial genetic information or conditions. Awareness of the implications of genetic testing in individuals and families and of state and federal legislation in place for their protection is an essential component of oncology nursing practice. This article discusses the critical role of the oncology nurse in interacting with and providing information about GINA to patients in a cancer care setting engaged in genetic assessment. [ABSTRACT FROM AUTHOR]

Background: The relationship between obesity and health expenditures is not well understood. We examined the relationship between genetic predisposition to obesity measured by a polygenic risk score for body mass index (BMI) and Medicare expenditures.Methods: Biennial interview data from the Health and Retirement Survey for a nationally representative sample of older adults enrolled in fee-for-service Medicare were obtained from 1991 through 2010 and linked to Medicare claims for the same period and to Genome-Wide Association Study (GWAS) data. The study included 6,628 Medicare beneficiaries who provided 68,627 complete person-year observations during the study period. Outcomes were total and service-specific Medicare expenditures and indicators for expenditures exceeding the 75th and 90th percentiles. The BMI polygenic risk score was derived from GWAS data. Regression models were used to examine how the BMI polygenic risk score was related to health expenditures adjusting for demographic factors and GWAS-derived ancestry.Results: Greater genetic predisposition to obesity was associated with higher Medicare expenditures. Specifically, a 1 SD increase in the BMI polygenic risk score was associated with a $805 (p < .001) increase in annual Medicare expenditures per person in 2010 dollars (~15% increase), a $370 (p < .001) increase in inpatient expenses, and a $246 (p < .001) increase in outpatient services. A 1 SD increase in the polygenic risk score was also related to increased likelihood of expenditures exceeding the 75th percentile by 18% (95% CI: 10%-28%) and the 90th percentile by 27% (95% CI: 15%-40%).Conclusion: Greater genetic predisposition to obesity is associated with higher Medicare expenditures. [ABSTRACT FROM AUTHOR]

Review of genetics in the United States with emphasis on the prenatal, metabolic, genetic counseling, and training aspects of the field. [ABSTRACT FROM AUTHOR]

The article discusses what the author refers to as the evolution of the ethical standards that are associated with clinical medical care-based human genomic sequencing in America as of 2017, and it mentions policy statements from the American College of Medical Genetics and Genomics. The ethical aspects of genomic medicine are addressed, along with opt-out policies and the risks associated with cancer and cardiovascular disease.

Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease. [ABSTRACT FROM AUTHOR]

Objectives To describe the incidence of cardiovascular risk factors, or race-related disparities in incidence, across the age spectrum in adults. Design Longitudinal cohort. Setting National sample. Participants Community-dwelling black and white adults recruited between 2003 and 2007. Measurements Incident hypertension, diabetes mellitus, dyslipidemia and atrial fibrillation over 10 years of follow-up in 10,801 adults, stratified according to age (45-54, 55-64, 65-74, ≥75). Results There was no evidence ( P ≥ .68) of an age-related difference in the incidence of hypertension for white men (average incidence 38%), black men (48%), or black women (54%), although for white women incidence increased with age (45-54, 27%; ≥75, 40%). Incidence of diabetes mellitus was lower at older ages for white men (45-54, 15%; ≥75, 8%), black men (45-54, 29%; ≥75, 13%), and white women (45-54, 11%; ≥75, 4%), although there was no evidence ( P = .11) of age-related changes for black women (average incidence 21%). For dyslipidemia, incidence for all race-sex groups was approximately 20% for aged 45 to 54 but approximately 30% for aged 54 to 64 and 65 to 74 and approximately 22% for aged 75 and older. Incidence of atrial fibrillation was low at age 45 to 54 (<5%) but for aged 75 and older was approximately 20% for whites and 11% for blacks. The incidence of hypertension, diabetes mellitus, and dyslipidemia was higher in blacks across the age spectrum but lower for atrial fibrillation. Conclusion Incidence of risk factors remains high in older adults. Blacks have a higher incidence of hypertension, diabetes mellitus, and dyslipidemia after age 45, underscoring the ongoing importance of prevention of all three conditions in mid- to later life. [ABSTRACT FROM AUTHOR]

The article projects the future of cardiovascular genomics and genetics in the U.S. Topics discussed include an overview of cardiovascular genetics, the gap of phenotype in precision medicine, the impact of cardiovascular genomics and genetics on health, and the genetic architecture of cardiovascular system.

Cardiovascular (CV) disease is a leading cause of death worldwide, accounting for approximately 31.4% of deaths globally in 2012. It is estimated that, from 1980 to 2000, reduction in total cholesterol accounted for a 33% decrease in coronary heart disease (CHD) deaths in the United States. In other developed countries, similar decreases in CHD deaths (ranging from 19%–46%) have been attributed to reduction in total cholesterol. Low-density lipoprotein cholesterol (LDL-C) has now largely replaced total cholesterol as a risk marker and the primary treatment target for hyperlipidemia. Reduction in LDL-C levels by statin-based therapies has been demonstrated to result in a reduction in the risk of nonfatal CV events and mortality in a continuous and graded manner over a wide range of baseline risk and LDL-C levels. This article provides a review of (1) the relationship between LDL-C and CV risk from a biologic, epidemiologic, and genetic standpoint; (2) evidence-based strategies for LDL-C lowering; (3) lipid-management guidelines; (4) new strategies to further reduce CV risk through LDL-C lowering; and (5) population-level and health-system initiatives aimed at identifying, treating, and lowering lifetime LDL-C exposure. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including role of physicians in balancing social and medical services of disability, use of noninvasive prenatal testing and issues of discrimination against patients with mental disabilities.

Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score (GRS) based on 17 established IR variants and effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (β = -0.754 [SE = 0.229] log-ISI per unit, P = 0.001 in fully adjusted models). There was no differential effect of treatment for the association between the IR-GRS on the change in ISI; higher IR-GRS was associated with an attenuation in ISI improvement over 1 year (β = -0.520 [SE = 0.233], P = 0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin treatment improved the ISI, regardless of the genetic burden of IR variants. [ABSTRACT FROM AUTHOR]

The Basque Diaspora in Western USA and Argentina represents two populations which have maintained strong Basque cultural and social roots in a completely different geographic context. Hence, they provide an exceptional opportunity to study the maternal genetic legacy from the ancestral Basque population and assess the degree of genetic introgression from the host populations in two of the largest Basque communities outside the Basque Country. For this purpose, we analyzed the complete mitochondrial DNA control region of Basque descendants living in Western USA (n = 175) and in Argentina (n = 194). The Diaspora populations studied here displayed a genetic diversity in their European maternal input which was similar to that of the Basque source populations, indicating that not important founder effects would have occurred. Actually, the genetic legacy of the Basque population still prevailed in their present-day maternal pools, by means of a haplogroup distribution similar to the source population characterized by the presence of autochthonous Basque lineages, such as U5b1f1a and J1c5c1. However, introgression of non-Basque lineages, mostly Native American, has been observed in the Diaspora populations, particularly in Argentina, where the quick assimilation of the newcomers would have favored a wider admixture with host populations. In contrast, a longer isolation of the Diaspora groups in USA, because of language and cultural differences, would have limited the introgression of local lineages. This study reveals important differences in the maternal evolutionary histories of these Basque Diaspora populations, which have to be taken into consideration in forensic and medical genetic studies. [ABSTRACT FROM AUTHOR]

The Genetic Information Nondiscrimination Act (GINA) is a federal law that became fully effective in 2009 and is intended to prevent employers and health insurers from discriminating against individuals based on their genetic or family history. The article discusses the sections of GINA, what information constitutes genetic information, who enforces GINA, and scenarios in which GINA does not apply. Also discussed are the instances in which an employer may request genetic information from employees, including wellness or genetic monitoring programs. Finally, the article offers a look at how GINA affects nurses who are administering wellness or genetic monitoring programs on behalf of employers. [ABSTRACT FROM AUTHOR]

The article discusses the U.S. consumer genetics company 23andMe's role in collecting DNA samples and analyzing them for their relations with diseases, including the company's efforts to develop drugs to treat diseases. An overview of 23andMe's co-founder and chief executive officer (CEO) Anne Wojcicki is provided.

This paper examines three possible justifications for original ACMG recommendations to return incidental findings from whole exome or genome sequencing independent of patient preferences. The first two potential justifications, based on a patient's authentic values, then on harms to others, are founding lacking as a basis of justification for these recommendations. The third, grounded in analogous professional practices, might serve as a potential justification if several controversies can be avoided. However, given the nature of these controversies and the need to instill public trust in this newly emerging science, the paper finds that updated ACMG recommendations that recognize opt-out rights on behalf of patients is the most prudent, and justifiable, approach. [ABSTRACT FROM AUTHOR]

Sperm donor profiles in catalogues exhibited in commercial sperm bank websites provide health information about each donor, both explicitly and implicitly. Donors' anonymity poses a great challenge to signalling credibility. Inspired by both Spence's signalling theory and Walther and Park's warranting theory, the study explores the way sperm donors add credibility to their self-presentations. Profiles of 135 donors from nine sperm banks in Europe and North America were content analysed; 36 of these donors' baby photos were visually analysed. Donors compensated for the paucity of usable warrants by adding intensified emotional context to the profile and inviting potential recipients to join a fantasy family. The article concludes with some practical recommendations aimed at facilitating the process of donor selection for the benefit of donor insemination users, as well as fertility practitioners, and sperm donors. [ABSTRACT FROM AUTHOR]

Before about 1990, insofar as diagnostic and other medical tests were subject to regulatory oversight, it was chiefly to ensure that they met appropriate standards of analytic and clinical validity. Over the course of the 1990s, however, regulatory reformers in the United States began to argue that genetic tests, specifically, should also be assessed to determine whether or not they actually benefit those undergoing testing—whether they possess "clinical utility", as they put it. The present paper asks why this shift in regulatory focus occurred specifically in relation to genetic tests, and why clinical utility became a key object of assessment. It answers these questions by situating concerns about genetic tests in the longer history of medical genetics. Looking back to the 1970s and medical geneticists' efforts to distance themselves from their earlier association with eugenics, it shows that they adopted a particular framing of the dangers of genetic testing which would inform their response to the proliferation of new genetic tests and the growth of commercial testing in the 1990s. In a series of policy committees convened over the course of that decade, medical geneticists called for regulatory measures to be implemented to ensure that genetic tests were only introduced into medical practice if they had been shown to be beneficial to those tested. The paper follows the deliberations of those committees to show in detail how geneticists worked within this framing to accommodate new technical capacities and regulatory opportunities. In the course of these deliberations, they adopted the idea of clinical utility to signify the need for evidence of benefit specifically to those tested. The paper concludes with some observations regarding how this framing of genetic tests relates to current understandings of "genetic exceptionalism" and to more recent articulations of clinical utility. • Calls to regulate genetic tests on grounds of "clinical utility" first emerged in the 1990s. • They were informed by a framing of the risks of genetic testing that dated back to the 1970s. • That framing stressed the need for tests to benefit the individuals undergoing testing. • Calls for formal regulation reflected geneticists' declining control over genetic testing. • More recent versions of "clinical utility" neglect the need for testing to benefit those tested. [ABSTRACT FROM AUTHOR]

The article offers information on an report of National Academies of Sciences, Engineering, and Medicine committee, according to which clinical trials for human genome editing is permissible under stringent oversight, and discusses the requirement of ethical framework for human genome editing.

Clinical next generation sequencing (NGS) technologies are challenging existing regulatory paradigms. We advocate a coordinate policy approach, which first requires a comprehensive understanding of the existing regulatory and legal structures. This paper introduces four key policy domains - including quality assurance, insurance coverage, intellectual property management, and data sharing - that must be addressed to ensure high quality clinical NGS. In bringing these policy issues into conversation through this special issue for the Journal of Law, Medicine & Ethics, we hope to lay the foundation for further discussion by a range of stakeholder groups with diverse and strong interests in the governance of NGS. [ABSTRACT FROM AUTHOR]

Next generation sequencing raises new questions within the context of an existing and still evolving regulatory landscape for device manufacturers and clinical laboratories. FDA cleared the first NGS sequencing platform in November 2013, but it is unclear what lies ahead for this technology. NGS will require new types of training and expertise to interpret the vast quantities of genetic data so as to provide meaningful clinical information to physicians and patients. This paper will describe the current regulatory landscape for NGS technologies, identify the regulatory challenges they present, and consider whether new regulatory paradigms are needed to accommodate NGS technologies and services. [ABSTRACT FROM AUTHOR]

Some claims in patents on individual genes and methods of detecting variations appear to be infringed by whole-genome and all-exome sequencing and genomic analysis. But what is the real risk of infringement liability? The risk is probably low. This is partly because it will rarely make sense to sue, but also because the patent-holder may well lose if they do sue. Courts have recently narrowed standards of patentable subject matter, invalidating broad method claims and DNA-based claims for sequences that would be found in nature. Moreover, claims broad enough to cover WGS are likely to be invalid on other grounds, and not worth risking a lawsuit to enforce. [ABSTRACT FROM AUTHOR]

Recent advances in next generation sequencing along with high hopes for genomic medicine have inspired interest in genomic research with the newly dead. However, applicable law does not adequately determine ethical or policy responses to such research. In this paper we propose that such research stands at a crossroads between other more established biomedical clinical and research practices. In addressing the ethical and policy issues raised by a particular research project within our institution comparatively with these other practices, we illustrate the moral significance of paying careful heed to where one looks for guidance in responding to ethical questions raised by a novel endeavor. [ABSTRACT FROM AUTHOR]

The article discusses a reported effort to define the scope of public engagement in regards to a "right not to know" in public health genomics as of March 2014. Autonomy and an individual's rights are addressed in relation to bioethics, personal genetic information, and the promotion of the common good. Transparency and communication are mentioned in regards to democratic participation in health policy decision-making. Disease development and genetic susceptibility are also examined.

An introduction is presented in which the author discusses various reports within the journal on topics including personal autonomy, public engagement, and an individual's right to know and a right not to know about genetic research results in America.

The article discusses a right not to know and a duty to tell in relation to human genetic information sharing and potential conflicts of interest between U.S. medical patients (index-persons) and their families and relatives as of 2014. Genetic predispositions for disorders or diseases are mentioned, along with the reported hereditary nature of genes. Anxiety, depression, and stigmatization are examined in relation to self-image and autonomy. Direct-to-consumer genetic testing is assessed.

Much of what has been written about the history of medical genetics in North America has focused on physician involvement in eugenics and the transition from heredity counseling to genetic counseling in the United States. What are typically missing in these accounts are details concerning the formation of a new medical specialty, i.e., medical genetics, and Canada's involvement in specialty formation. Accordingly, this paper begins to fill in gaps by investigating, on the one hand, the history of American and Canadian geneticists working together to support the creation of examining and teaching positions in human genetics in North American medical schools and, on the other, working independently of one another to monitor the rate and direction of workloads and patient access to local genetic counseling and laboratory services and, subsequently, achieve recognition for medical genetics as a medical specialty at the national level., (© 2022. Springer Nature Switzerland AG.)

The research and publication practices by which scientists produce biomedical knowledge about race and ethnicity remain largely unexamined, and most of the existing research looks at the knowledge production process at a single point in time. In light of this, we specifically focus on the questions of whether and in what ways researchers' discussions of race and ethnicity change over the course of the research process by comparing grant proposals to published articles. Using content analysis, we investigated the use of race and ethnicity in 72 grants funded by the National Cancer Institute of the National Institutes of Health between 1990 and 1999 and 144 matched articles published between 1996 and 2010, tracing the production of biomedical knowledge from study design to published findings. This is also the first study to look at whether the NIH Inclusion Mandate, which went into effect in June of 1994, changed the way investigators research and write about racial and ethnic differences. In following this knowledge production process, we explore how scientists "deliver" on their research proposal goals. In addition, we provide insight into whether and how state policies directed at guiding research practices can shape output. [ABSTRACT FROM AUTHOR]

The article offers information on how pharmacogenomics can aid nurses provide better care for patients. It illustrates an example of a lady aged 62 who experienced an acute myocardial infarction and was prescribed with genetic testing which resulted in better outcome. It discusses pharmacogenomic implications with warfarin drug, including antiplatelet therapy, mental health, human immunodeficiency virus (HIV) therapy, and oncology. Further discussed are limitations of genetic testing.

The Genetic Information Nondiscrimination Act of 2008 (GINA) was passed to encourage patients to seek genetic testing that could improve health outcomes and provide opportunities for preventive measures. GINA protects individuals from discrimination based upon genetic information, but not upon manifested diseases and conditions. Because the manifestation of a disease establishes a threshold of protection for individuals under GINA, the definition of manifestation is crucial to understanding the scope of the bill. This paper examines the range of possible legal definitions of disease manifestation and explores the historical struggle that courts have faced when trying to apply these different definitions. Specifically, the paper examines three frameworks that courts have used in the past to interpret the manifestation of a disease; 'manifestation as apparent symptoms,''manifestation as patient action,' and 'manifestation as physician action.' We argue that the 'manifestation as physician action' is the best framework to utilize in this law generally, but that the definition of manifestation should be read in the light most favorable to a plaintiff in order to achieve the underlying goals of GINA. [ABSTRACT FROM AUTHOR]

Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective To characterise genetic and clinical findings in individuals with SHH mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). Individuals with truncating mutations were significantly more likely to have frank HPE than those with non-truncating mutations (49% vs 35%, respectively; p=0.012). While mutations were significantly more common in the N-terminus than in the C-terminus (including accounting for the relative size of the coding regions, p=0.00010), no specific genotype-phenotype correlations could be established regarding mutation location. Conclusions SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive. [ABSTRACT FROM AUTHOR]

African Americans have higher rates of cardiovascular disease (CVD) than Whites and the racial gap in heart disease is widening over time. There are especially striking patterns of the earlier onset of disease, greater severity of illness and large racial differences in CVD even when Blacks and Whites are compared at the same level of economic status. This paper outlines critical research opportunities for the Jackson Heart Study to advance the science base for understanding and effectively addressing racial disparities in CVD. These include: 1) the study of CVD by using a life course perspective; 2) comprehensively characterizing social stressors; 3) expanding our analysis of how racism affects health; 4) explicating variation in the levels and impact of risk factors; 5) advancing our understanding of the contribution of genetics to CVD; 6) understanding resilience and its effects on CVD; and 7) identifying how economic crises can shape CVD risk. [ABSTRACT FROM AUTHOR]

The article provides information related to the Cuba's public health care system. It is mentioned that the Cuba have low infant mortality and low rate of birth defects. It is further mentioned that the rate of child health in Cuba indicates the high rate of immunization and high cost spend in autonomy. It is discussed that the U.S and Cuba has several social, educational and medical opportunities which needs to be explored.

OBJECTIVE--To test the association of family history of diabetes with the adoption of diabetes risk--reducing behaviors and whether this association is strengthened by physician advice or commonly known factors associated with diabetes risk. RESEARCH DESIGN AND METHODS--We used cross-sectional data from the 2005-- 2008 National Health and Nutrition Examination Survey (NHANES) to examine the effects of family history of diabetes on the adoption of selected risk-reducing behaviors in 8,598 adults (aged ≥20 years) without diabetes. We used multiple logistic regression to model three risk reduction behaviors (controlling or losing weight, increasing physical activity, and reducing the amount of dietary fat or calories) with family history of diabetes. RESULTS--Overall, 36.2% of U.S. adults without diabetes had a family history of diabetes. Among them, ∼39.8% reported receiving advice from a physician during the past year regarding any of the three selected behaviors compared with 29.2% of participants with no family history (P < 0.01). In univariate analysis, adults with a family history of diabetes were more likely to perform these risk-reducing behaviors compared with adults without a family history. Physician advice was strongly associated with each of the behavioral changes (P < 0.01), and this did not differ by family history of diabetes. CONCLUSIONS--Familial risk for diabetes and physician advice both independently influence the adoption of diabetes risk--reducing behaviors. However, fewer than half of participants with familial risk reported receiving physician advice for adopting these behaviors. [ABSTRACT FROM AUTHOR]

In this article the authors reflect on regulations which have been developed to protect research subjects and data in research which uses human subjects. They suggest that regulations related to informed consent and privacy protection are burdensome in research which uses human subjects. They argue that a new category of research risk must be established which informs research subjects of the level of risk that they will be exposed to by participating in the research.

The collection and analysis of genomic data has the potential to reveal novel druggable targets by providing insight into the genetic basis of disease. However, the number of drugs targeting new molecular entities, approved by the US Food and Drug Administration has not increased in the years since the collection of genomic data has become commonplace. The paucity of translatable results can be partly attributed to conventional analysis methods that test one gene at a time in an effort to identify disease-associated factors as candidate drug targets. By disengaging genetic factors from their position within the genetic regulatory system, much of the information stored within the genomic data set is lost. Here we discuss how genomic data is used to identify disease-associated genes or genomic regions, how disease-associated regions are validated as functional targets, and the role network analysis can play in bridging the gap between data generation and effective drug target identification. [ABSTRACT FROM AUTHOR]