Genomics education for advance practice nurses: Staying cutting edge.

ABSTRACT: As we celebrate the 20th anniversary of sequencing of the human genome and the rapid integration of genetics in health care, we pause to reflect on the status of genomic competency in nursing. The literature provides evidence that nurses do not feel prepared or confident in genomics. Genomic education for nurses and other health care professionals can support access and equity in the integration of genomics into practice. Resources are provided to support genomic education and clinical support.

Genomics of aging: Reactive oxidation and inefficient mitochondria.

ABSTRACT: Many things are associated with decreased health and lifespan, including cancer, diabetes, atherosclerosis, high blood pressure, and chronic inflammatory conditions. Clinicians may not be familiar with the role that mitochondrial mutations and associated mitochondrial dysfunction play in a shortened lifespan. This article, the fifth in the JAANP Genomics of Aging series, describes the role that mitochondrial dysfunction plays in the development of age-related diseases such as Alzheimer disease, Parkinson disease, cancer, heart disease, and stroke.

The genomics of COVID.

ABSTRACT: Coronaviruses, named for their crown-like appearance, are relative newcomers to the human viral encyclopedia, but they are anything but new to the viral landscape. Initially thought to cause relatively mild disease in humans, it is now clear that coronaviruses can cause significant morbidity and mortality. COVID-19 provided a ringside seat from which to watch scientists use genomics in hundreds of ways to learn about, protect against, and ultimately control the effects of this novel virus. This article provides an overview of how genomics was used from the very first reported case in Wuhan, China to the development of at-home test kits, vaccines, and understanding the genetic association with increased risk for severe illness.

Genomics update 2022: Clinician and patient hot topics.

ABSTRACT: Advances in genomics research and clinical applications continue to accelerate. Coupled with the availability of direct-to-consumer (DTC) marketing of genetic testing and new discoveries, patients are increasingly coming into primary care with genomic questions. This article offers a snapshot of the kinds of questions patients are asking and that providers should be prepared to discuss such as what to do with DTC results or whether pharmacogenetics testing would help make sure "the right" medication is prescribed. Clinicians should understand the value of clinical guidelines (and where to find them), how to find a genetic specialist, what's happening with gene editing (to include gene sequencing), what's on the horizon in cancer care, and what the future might hold.

Genomics of aging: The role of sirtuin and metabolic health.

ABSTRACT: Healthy aging is not the result of a single factor. Genes, dietary choices/options, exercise, and environmental exposures all play a role. A family of seven nicotinamide adenine dinucleotide (NAD)-dependent sirtuin proteins are very involved in various metabolic functions, such as glucose and fat regulation, and polymorphisms in these genes have been associated with the development of obesity, type 2 diabetes, cancer, cardiovascular disease, and longevity. Nutraceuticals (i.e., resveratrol, quercetin, kaempferol, and curcumin) and other therapies (i.e., synthetic sirtuin-activating compounds, NAD, nicotinamide mononucleotide) are all being explored as in potential therapies in the sirtuin pathway and point to promising treatments to promote metabolic health and reduce obesity and age-related disease. For the clinician looking to reduce the risk of age-related metabolic disorders, evidence points to these supplements and appropriate food choices as the next generation of pharmaceutical grade therapies continue to be researched for human use.

Genomics of aging: Glycosylation.

ABSTRACT: This third article in the Genomics of Aging series explores the process of glycosylation and how abnormal glycosylation contributes to aging and disease (i.e., diabetes, cardiovascular disease [CVD], neurological disorder, and cancer). Glycosylation is an important posttranslational process that contributes to normal protein folding, cell adhesion, protein stability, and motility. Gradual accumulation of molecular errors contributes to the aging process, and specific genetic variants in this pathway have been identified in cancer, CVD, aging, and vulnerability to disease progression. Manipulating glycosylation pathways may be beneficial in reducing disease risk in the future. Smoking cessation has been shown to reverse epigenetic changes in glycosylation pathways that increase cancer, CVD, and all-cause mortality risk, and CVD risk may be reduced if a dimeric glycosylated fusion protein pathway can be regulated. Selective food sources and synthetic vitamins and antioxidants have been shown to support normal glycosylation and help in the cell repair process.

Genomics of aging: Decreased immune defenses.

There are multiple factors that contribute to aging. In this second series of Genomics of Aging, decreased immune defenses and the effects of unregulated inflammation on the aging process of cells, and the body as a whole, are reviewed from the perspective of genomics and the microbiome. Healthy lifestyle choices and foods can slow down this aging process, and clinical implications are described here.

Genomics of aging: Genes, adducts, and telomeres.

Genomics influences the aging process in many different ways. This 10-part series of articles describes what is known about genetics and aging, including genes, adducts, and telomeres, decreased immune defenses, oxidation and inefficient mitochondria, toxins and radiation, glycosylation, caloric intake and sirtuin production, neurotransmitter imbalance, hormone mechanisms, reduced nitric oxide, and stem cell slowdown. This first article explores gene adducts as an epigenetic "sludge," the influence of telomeres and other mutations that contribute to DNA dysfunction, cell stress, and premature aging. Factors that contribute to adduct formation and reduced telomere length are presented along with some changes in behavior, environmental exposure, food/supplement use, weight, sleep, and exercise that have been found to reduce damage, potentially increasing longevity. Adherence to a Mediterranean diet that contains fruits and whole grains along with fiber, antioxidants (e.g., beta-carotene, vitamins C and E), omega-3 fatty acids, and soy protein may reduce DNA adducts and protect telomeres. So providers may want to recommend these simple but key clinical and individual changes to enhance DNA health, wellness, and longevity.

Pharmacogenomics in clinical care.

Health care designed specifically for a person based on their genetic makeup ("personalized" or "precision" medicine) is expanding rapidly, especially in the area of drug selection. Pharmacogenomic (PGx) testing, when drugs and doses are selected based on an individual's genetic profile, is increasingly being used to guide the selection of drugs or therapies to optimize outcomes and minimize side effects. Based on an individual's genetic blueprint, health care providers now have important information about how a drug is likely to behave in that individual's body. Pharmacogenomic information on drug labels is now available for nearly 250 drugs. Health care organizations are also increasingly making this information available to customers to reduce emergency department visits, improve outcomes (selecting the right chemotherapy doses), and reduce cost. This study reviews some of the challenges and benefits on using PGx testing to improve clinical outcomes.

Direct to consumer versus clinical genetic testing.

There are approximately 250 direct to consumer (DTC) genetic testing companies marketing different testing options such as genetic health risk, carrier status, ancestry, wellness, traits, noninvasive prenatal genetic testing, athleticism, and many others. As a result, choosing the most appropriate test may be daunting when compared with a focused genetic test ordered by a clinician. A wealth of information may be discovered and care must be taken by both consumers and clinicians when deciphering test results. This column highlights considerations when proceeding forward with a DTC genetic test.

Lung Disease and Genomics.

Research and application of genomic medicine in lung disease during the past century has clarified our understanding and focus on specific phenotypes, helping clinicians tailor treatment for individual patients. Cystic fibrosis and lung cancer have been researched extensively; specific genotypes have been instrumental in precision medicine to treat these lung diseases. Asthma and chronic obstructive pulmonary disease are more complex and heterogeneous in their pathogenesis, genotypic profile, and phenotypic expression, making treatment more difficult with increasing disease severity. This article focuses on the evolving state of the science of precision medicine in lung cancer, chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The body of knowledge in lung disease is growing related to pharmacogenomics, clinical guidelines, genome editing, and approaches to genomic health that will guide clinical treatment options, reduce risk, and promote health.

Epigenome variation in severe asthma.

BACKGROUND: Asthma is a complex heterogeneous disease process with mild, moderate, and severe classifications. Although the science of genomics has opened our understanding of the molecular underpinnings of asthma, epigenetics is emerging as a mechanism whereby the expression of disease-risk genes may be influenced by environmental exposure. OBJECTIVES: The purpose of this article is to discuss the methodology of data collection and evaluation involved in genome-wide methylation profiling (epigenomic) through presentation of data generated for a population presenting with severe asthma. METHOD: Over 14,000 gene promoter sites were analyzed for methylation status among six subjects with severe asthma and four normal controls in this pilot study. Two duplicate samples were used as technical replicates. Nonsmoking case/control subjects were chosen based on similar gender and age. Blood samples were used for DNA extraction, and methylation data were collected utilizing the Illumina Infinium HumanMethylation27BeadChip platform. RESULTS: Technical replicates were highly concordant, and statistically significant differences were found in methylation profiles between subjects with severe asthma and normal controls (p < 10(-8)), some previously reported with pulmonary function and others never before reported. After correction for multiple testing, three gene promoter regions remained statistically different: FAM181A, ZNF718, and MRI1. DISCUSSION: This research supports the internal validity of the Illumina platform in methylation analysis of DNA from stored blood samples. Although significant differences in methylation were noted between subjects with severe asthma and controls, the small sample size warrants further investigation into these results.

Diseasome: an approach to understanding gene-disease interactions.

Using bioinformatics computational tools, network maps that integrate the complex interactions of genetics and diseases have been developed. The purpose of this review is to introduce the reader to new approaches in understanding disease-gene associations using network maps, with an emphasis on how the human disease network (HDN) map (or diseasome) was constructed. A search was conducted in PubMed using the years 1999-2011 and using key words diseasome, molecular interaction, interactome, protein-protein interaction, and gene. The information reviewed included journal reviews, open source and web-based databases, and open source computational tools. A review of the literature revealed the complexity of molecular, genetic, and protein structures that contribute to cellular function and possible disease, and how network mapping can help the clinician and scientist gain a better understanding of this complexity Using computational tools and databases of genetics, protein interactions, and diseases, scientists have developed a network map of human genes and human diseases referred to as a diseasome. The diseasome is composed of 22 disease classes represented in different colored circular nodes. Lines connecting nodes indicate shared genes among diseases. Thus, the diseasome map provides a colorfully visual display that helps the user conceptualize gene-disease relationships. This review provides an overview of the use of network maps to understand the interrrelationships of genomics and disease. One such map, the diseasome, could be used as a reference for biomedical researchers and multidiscipline health care providers, including nurse practitioners and genetic counselors, to enhance their conceptualization and understanding of the genetic origins of disease.