Course Description
Examines a variety of genetic and epigenetic mechanisms by which organisms and disease states can exhibit accelerated rates of phenotypic change.
Additional Requirements for Graduate Students:
Students will be expected to produce a presentation and written
report that reflects mastery of the subject material beyond that
required for an undergraduate. The paper will be expected to
integrate primary research literature with an extensive synthesis
and critique of the material. Grading on both the presentation
and the report will be more extensive and detailed than that for
undergraduates, reflecting a higher standard of scholarship and
research.
Athena Title
Epigenetics
Prerequisite
GENE 3200-3200D or GENE 3200H
Semester Course Offered
Not offered on a regular basis.
Grading System
A - F (Traditional)
Course Objectives
The course is primarily lecture-based and deals with in-depth coverage of important examples of epigenetics. The different mechanisms leading to multigenerational and/or somatic cell inheritance of epigenetic changes will be addressed. The influence of environment on epigenetic reprogramming will be discussed. Lecture material and reading will be from recent primary scientific literature.
Topical Outline
Topics might include the following: Genetic instability in cancer. 1) Background on cancer hallmarks and cancer genomes; Incidence of cancers; Contagious cancers. 2) Mechanisms that accelerate mutation rates in cancers: Telomere dysfunction, chromosome instability, Chromothrypsis, Replication fragile sites, Microsatellite instability, Point mutation instability, and Kateigis. 3) DNA repair mechanisms and their role in preventing mutation. 4) V(D)J joining, somatic hypermutation, and adenine deaminase in normal immune function and in cancer. Rapid genetic and phenotypic change in prokaryotes. 1) Background on bacterial genomes, bacterial diseases, horizontal gene transfer, and the rapid acquisition of novel traits in prokaryotes. 2) Genetic exchange in bacteria; mechanisms and consequences: Transduction and site-specific recombination; Transformation (Type IV pili, homologous recombination, and Gene Transfer Agents); Conjugation, plasmids, antibiotic resistance, and Toxin/antitoxin systems. 3) Examples of genetic change related to pathogenicity: Cholera (toxins and secretins), Staphylococcus and pathogenicity islands, Neisseria, and natural competence. 4) Other contributors to genetic instability in prokaryotes: Transposons and Integrative conjugative elements; Integrons; Simple sequence repeats and rapid mutation; Phase variation; Mismatch repair and hypermutability; CRISPR/CAS systems; Phenotypic bistability, epigenetics, stochastic noise, and persistors; Gene amplification; Diversity Generating Retro Elements. Microsatellites in disease and genetic diversity 1) Repeat expansion diseases. 2) Microsatellite instability and developmental plasticity in vertebrates. Prions and amyloid diseases 1) Vertebrate prions: Background, prion diseases (Kuru, Scrapie, vCJD, BSE) and prion structure. 2) Prions of yeast and fungi and the reversible phenotypic variation they induce. 3) Amyloids (Alzheimers, Senile Systemic Amyloidosis) as “protein cancers.” Part 2. Background on epigenetic control of disease and development as mediated by changes in cis-acting chromatin structure (epitype) a. A brief history of epigenetics b. Defining different classes of epitype and epigenetic control c. Mechanisms of small RNAs mediated silencing d. The genetic basis for transgenerational vs. somatic epigenetic inheritance •DNA methylation •Nucleosome positioning •Post translational modification of histones e. Specific examples of disease and aberrant development caused by “epimutation,” or defects in epigenetic control •Cancer •Lupus •Obesity, inflammation, cardiovascular disease, metabolic syndrome, and diabetes. f. Therapeutics targeting of epigenetic controls over cancer and inflammation.
Syllabus