Medical Education - General

The following resources are general examples that illustrate the application of genomics information to our understanding disease susceptibilities, prevention, diagnosis and treatment relative to one's individualized genetic makeup.  In addition, several resources reflect the increasing requirement for genetics/genomics training in medical education.  Other, more detailed resources can be found in the folders listed in the left navigation panel.

Contemporary Issues in Medicine: Genetics Education

Am. Assn. Med. Colleges Report VI, 2004, pp. 1-12

Preamble

Although genetic factors have been recognized to play a role in health and disease since the beginning of the twentieth century, until recently the contribution of genetics to medical practice was limited to a set of important, but rare, disorders. Recent events, especially the sequencing of the human genome, have introduced new approaches to diagnosis and therapy, and have broadened the scope of genetics to include common disorders and preventative strategies of public health significance. With the general recognition that genetic medicine will play a much larger – indeed, central - role in the work and knowledge of the practicing physician of the future, the challenge to medical education today is to determine the level of knowledge about genetics that students graduating from medical school need to acquire. Genetics cuts across all areas of medical practice, creating a challenge in providing coherent exposure and an opportunity to integrate learning across multiple disciplines. Furthermore, practical applications of genetics in medical practice are only beginning to emerge, and will likely mature at different rates in different areas. Genetic medicine, therefore, presents a rapidly moving educational target, with great promise, but relatively few examples of current application. Two groups, The National Coalition for Health Professional Education in Genetics and The Association of Professors of Human and Medical Genetics/American Society of Human Genetics (NCHPEG and APHMG/ASHG), have given considerable thought to the core competencies required of the generalist health provider. The task here is to give that same consideration to the education of the general physician.

Journal Link

Comments

If you (or, more likely, your administrators and other faculty) need convincing that genomics is useful in medical education, this AAMC report is the place to start.  This short report details the needs for genomics education not only for current students in their clinical rotations, but also for their residency in 5 years and practice in 10 years.  The table on page 9 (What Do Physicians Need to Know, and When Do They Need to Know It?) is especially useful.  Hardcopies can be obtained from the AAMC.

Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications.

Bernard, S. N., K. A.; Nguyen, A. T.; Flockhart, D. A. (2006).  Oncologist 11(2): 126-35.

Abstract

DNA polymorphisms have been identified in the genes encoding a number of the cytochrome P450 (CYP) enzymes, leading to wide inter-individual variation in drug clearance. CYP2D6 metabolizes a significant number of clinically used medications, and genetic variants of the CYP2D6 isozyme that result in varying levels of metabolic activity are of clinical importance in some settings. The exact nature of the clinical effect caused by polymorphisms of the gene depends on the drug in question and the specific variant alleles expressed, as individual variants result in differing phenotypes with a range of levels of enzymatic activity. Compromised drug efficacy due to CYP2D6 variation has been documented with a variety of agents, and this review considers a number of examples, including the 5-HT(3)-receptor antagonists, which are used in oncology supportive care for the prophylaxis of nausea and vomiting. CYP2D6 is involved in the metabolism of all of the most commonly available agents, except granisetron, and their efficacy and side effects may therefore be affected by the CYP2D6 polymorphism. Significant interethnic differences in CYP2D6 allele frequencies have been demonstrated from studies across many countries. However, incidences of polymorphisms in the U.S. population have been challenging to characterize because of the country's wide ethnic diversity. The CYP2D6 polymorphism may become more important as robust clinical tests become widely available and as the use of multiple medications and the attendant risk for drug-drug interactions increases.

Journal Link  | PMID

Comment

This review has three learning objectives, and it achieves them well. in addition to a general introduction these include understanding the four genotypes for CYP2D6 polymorphisms, the potential effects of CYP2D6 polymorphism on the efficacy and safety for drugs metabolized via this enzyme, and a useful listing of the ethnic groups that are most frequently affected by genetic variation of the CYP2D6 enzyme.  Although focused on the this single enzyme and its variants, this article is a good introduction/review for other clinical important enzymes and proteins encoded by polymorphic genes.

Genomics and the family physician: Realizing the potential.

Collins, F, 2004. Am.Fam.Physician 70:1637-1640.

Intro. Comment:

The dawning of the genome era is changing the scope of care for family physicians, with significant implications for the design of future health care delivery systems. Many consider the imminent introduction of genomics into clinical medicine to be the most significant advance in health care since antibiotics were introduced. Being able to build on the strengths of the physician-patient-family relationship enhances the potential for family physicians to realize the benefits of genomic technology. Knowledge of the individual patient across his or her lifespan provides an excellent foundation from which to begin integrating genomics information to improve health outcomes.

Journal Link  |  PMID

Genetics and Genomics:  A Call for Papers

DeAngelis, CD et al., 2007. JAMA 298(2):228

Intro. Paragraph:

The October 15, 1997, issue of JAMA was devoted to genetics and featured articles on genomic screening in late-onset familial Alzheimer disease, BRCA1 sequence analysis, hereditary prostate cancer 1 locus, chromosome 19 single locus, and multilocus haplotype associations with multiple sclerosis, cancer incidence after retinoblastoma, prenatal genetic carrier testing, molecular diagnosis and carrier screening for beta-thalassemia, genetic testing in hereditary colorectal cancer, molecular neurogenetics, family history and genetic risk factors, and preparing health professionals for the genetic revolution.

Journal Link | PMID

Genomic competencies for the public health worker.

National Office of Public Health Genomics, at http://www.cdc.gov/genomics/training/competencies/default.htm

Information about the role of genes in health and disease is evolving rapidly because of the mapping of all human genes by the Human Genome Project. The number and types of genetic tests and services now available commercially are growing exponentially, and public health workers are increasingly aware of the potential role of genetic information in preventing common diseases. Everyone involved in public health should become aware of these advances and begin to incorporate genomic competencies into their public health specialties.

Website

The genomics gold rush.

Topol, EJ et al. 2007. JAMA 298(2):218-221

Intro. Paragraph:

In recent weeks there has been an unprecedented  chain of discoveries in the genomics of complex traits.  The studies identified DNA markers associated with susceptibility to many of the most common diseases, ranging from acute lymphoblastic leukemia, the most important pediatric cancer, to obesity, type 2 diabetes mellitus, and coronary heart disease, which collectively affect nearly a billion individuals worldwide. The breakneck pace of discovery will be continuing in the months ahead, with anticipated findings for many cancers, cardiovascular diseases, and neurological diseases. In aggregate, these studies have the potential to radically change medicine. This Commentary is intended to provide perspective for the medical community, to understand the limitations of the work that has thus far been completed, and to outline the challenges that lie ahead.

Journal Link | PMID

Comment:

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Inheritance and drug response

Weinshilboum, R. 2003. N. Eng. J. Med. 348(6):529-537

Abstract

The promise of pharmacogenetics, the study of the role of inheritance in the individual variation in drug response, lies in its potential to identify the right drug and dose for each patient. Even though individual differences in drug response can result from the effects of age, sex, disease, or drug interactions, genetic factors also influence both the efficacy of a drug and the likelihood of an adverse reaction. This article briefly reviews concepts that underlie the emerging fields of pharmacogenetics and pharmacogenomics, with an emphasis on the pharmacogenetics of drug metabolism. Although only a few examples will be provided to illustrate concepts and to demonstrate the potential contribution of pharmacogenetics to medical practice, it is now clear that virtually every pathway of drug metabolism will eventually be found to have genetic variation. The accompanying article by Evans and McLeod expands on many of the themes introduced here. Once a drug is administered, it is absorbed and distributed to its site of action, where it interacts with targets (such as receptors and enzymes), undergoes metabolism, and is then excreted. Each of these processes could potentially involve clinically significant genetic variation. However, pharmacogenetics originated as a result of the observation that there are clinically important inherited variations in drug metabolism. Therefore, this article - and the examples highlighted - focuses on the pharmacogenetics of drug metabolism. However, similar principles apply to clinically significant inherited variation in the transport and distribution of drugs and their interaction with their therapeutic targets. The underlying message is that inherited variations in drug effect are common and that some tests that incorporate pharmacogenetics into clinical practice are now available, with many more to follow. The concept of pharmacogenetics originated from the clinical observation that there were patients with very high or very low plasma or urinary drug concentrations, followed by the realization that the biochemical traits leading to this variation were inherited. Only later were the drug-metabolizing enzymes identified, and this discovery was followed by the identification of the genes that encoded the proteins and the DNA-sequence variation within the genes that was associated with the inherited trait. Most of the pharmacogenetic traits that were first identified were monogenic - that is, they involved only a single gene - and most were due to genetic polymorphisms; in other words, the allele or alleles responsible for the variation were relatively common. Although drug effect is a complex phenotype that depends on many factors, early and often dramatic examples involving succinylcholine and isoniazid facilitated acceptance of the fact that inheritance can have an important influence on the effect of a drug. Today there is a systematic search to identify functionally significant variations in DNA sequences in genes that influence the effects of various drugs.

Journal Link | PMID

Comment

Although somewhat dated, this remains a very good introduction to medical genomics.  In addition, it reviews several of the major enzyme systems (i.e., Cytochrome P₄₅₀'s, N-acetyltransferase, thiopurine S-methyltransferase) involved in common clinical situations, and includes some population frequency data.