David L Eaton
Addresses current DNA sequencing and genotyping approaches, and basic concepts of pharmacogenetics and toxicogenomics. Emphasis placed on applications of genomic technologies to the understanding of "gene-environment interactions" that cause diseases of public health importance, including cancer, chronic neurological diseases, and adverse drug reactions. Offered: jointly with ENV H 513/PCEUT 513; W.
This course will draw from multiple disciplines to provide a general understanding of molecular approaches to genotyping, as well as the understanding of genotype/phenotype relationships and gene-environment interactions as determinants of disease susceptibility. Instruction will cover the application of array technologies for the identification of low penetrance disease susceptibility genes and the identification of potential gene targets for novel pharmacotherapeutic treatments of disease. It will also examine the molecular basis for interindividual differences in drug/xenobiotic disposition and application of that information for individualized drug treatment regimens and disease prevention strategies.
Student learning goals
Studentw will: be able to explain the various technologies used to identify genetic polymorphisms, with particular emphasis on genes of pharmacological and environmental relevance.
be able to identify and understand the conceptual basis behind basic methodologies used to identify genetic variability in human DNA samples
explain the significance of genetic polymorphisms in the development, progression, and treatment of human disease.
appreciate the public health importance of genetic variability in specific multigene families of enzymes involved in metabolism of drugs and non-drug chemicals in the environment
describe the connection between environmental exposures, genetic polymorphisms, and risk for diseases of public health importance, and understand the role of genetic polymorphisms as determinants of adverse drug reactions and pharmacological efficacy.
have the technical background necessary to appreciate the ethical, legal and social implications that arise out of pharmaco- and toxicogenomic research, and write professionally about one area of ‘gene-environment’ interaction with public health importance; integrate basic concepts of ethics into arguments for and against genotyping of populations for ‘environmental susceptibility’ genes.
General method of instruction
didactic course lectures with discussion. Read assigned readings. Textbook: We recommend that students use the textbook, “Gene-Environment Interactions: Fundamentals of Ecogenetics (LG Costa and DL Eaton, Editors, Wiley Press, 2006) for selected background reading, although it is not required. Some reading assignments will be from this textbook, although some additional background or supplemental reading may be provided. Term paper required (see below).
Prerequisites: Biochem 442 or Genetics 372 or equivalent, or instructor permission. For students who feel that their background in basic molecular biology and genetics requires updating, we recommend any basic textbook in molecular genetics or medical genetics. A particularly good text is: “Principles of Medical Genetics”, 2nd Edition, TD Gelherter, FS Collins and D Ginsburg, Williams & Wilkins, 1998 (about $40), although it is getting out dated (third edition is due in 2008). A more recent textbook would be Strachan and Read’s “Human Molecular Genetics” (2003).
Class assignments and grading
Come to class, participate in discussion, write a term paper.
You will be asked to choose a particular disease that has both a genetic and an environmental component to it, and write a brief paper (10-15 pages, double spaced) describing what is known about the etiology of the disease. In the paper, you should cover: 1. the fundamental biology of the disease, including which genes are involved 2. identify candidate genes that might act as susceptibility genes, and discuss their function 3. review the basic epidemiology of the disease that has led to discoveries that genetic factors are involved 4. identify and discuss any environmental factors that have been implicated in the etiology of the disease; environmental factors are defined in their broadest terms, and include diet, viruses and other microbiological factors, occupation, lifestyle factors, etc. 5. identify and discuss at least one “ELSI” problem – real or potential- that has surfaced in your study of the disease. 6. Include all appropriate references
The course will include 3 exams (multiple choice / short answer) over materials covered in class and assigned readings that will count for 75% of your grade (25% for each of 3 exams). The remaining 25% of your grade will be based on your class term paper. An average numeric score of 80 will be approximately equal to a grade point score of 3.0, a score of 90 will be a 3.5 and average scores of 95 and above will be 4.0.