BSCI266 – Advanced Molecular Genetics
Instructor: Katherine Friedman, Ph.D.
Course Overview
This course will use articles from both textbooks and the primary literature to familiarize
you with the historical foundations of modern genetics and with the use of genetic
methodology and reasoning in the dissection of complex biological systems. Genetics as
an experimental approach will be emphasized. To do this, we will draw from examples of
major genetic model organisms (peas, bacteria, yeast, flies, worms, and mice),
emphasizing both the similarities and the particular strengths and weaknesses of each
model organism. The following is a broad outline of the subject material of the course:
Part I: Historical Overview
Laws of segregation
Linkage and chromosome theory of inheritance
Genetic maps and crossing-over
Advanced mapping techniques (yeast and Neurospora)
Mechanisms of Recombination
Contribution of microbial genetics to molecular biology
Part II: Genetic Approaches to the Dissection of Complex Systems
Genetic screens
Conditional alleles
Epistasis
Genetic interactions
Multicopy suppressors
Allele-specific suppression
Synthetic genetic interactions
Part III: The Genomic Era
Genome sequencing projects
Genome organization
Analyzing gene function at the genomic level
Gene knockout arrays
Transcriptional arrays
Analyzing DNA/protein interactions
Genome-wide genetic screens
Course Goals
There are three fundamental goals of this course. The first goal is to learn how genetic
methodology is applied to complex problems in biology. The second goal is to learn the
fundamentals of model organism genetics – what are the contributions and detractions of
the different major genetic model organisms? And the third goal is to learn to read and
critically evaluate the primary scientific literature and to communicate effectively about
the ideas found in that literature.
Class Format
Class will be highly interactive in the Socratic style. Although background material will
be presented in a lecture format, much of the learning will take place during group
discussions and through individual contributions. Reading will be assigned for each class
period. These readings will either be available for download from Blackboard or will be
distributed as photocopies in class. There will be occasional textbook reading
assignments. These will be primarily drawn from Genetics: Genes to Genomes by Lee
Hartwell. I hope that most of you have either the first or second edition of this textbook-page numbers will be given for both editions. If you do not have this book, please let me
know and we will make appropriate arrangements.
Completion of the reading assignments BEFORE class will be absolutely critical. We
will spend most of the class period discussing the papers both in small group and whole
class formats. Because part of your grade in the course is based on participation, it is vital
that you read, re-read, and critically evaluate the paper in preparation for class. You may
find it useful to form a study group for this purpose. For the first several papers, I will
hand out a list of questions to consider when you read the paper. Because part of the
purpose of this course is to develop your critical thinking skills, I will gradually “wean”
you of this study guide and you will be on your own to identify the most critical
questions and issues. Don’t be concerned if reading the papers is difficult at the outset.
Because this is new to many of you, we will spend time in class talking about strategies
for critically reading the primary literature. Also, do not hesitate to see me in my office
hours if you need additional guidance. We are partners in this endeavor, and the goal is to
make this class as rich a learning experience as possible.
Course Syllabus
Aug. 26
Aug. 31
Sept. 2
Sept. 7
Sept. 9
Sept. 14
Sept. 16
Sept. 21
Sept. 23
Sept. 28
Sept. 30
Oct. 5
Oct. 7
Oct. 12
Oct. 14
Oct. 19
Oct. 21
Oct. 26
Oct. 28
Nov. 2
Nov. 4
Nov. 9
Nov. 11
Nov. 16
Nov. 18
Nov. 23
Nov. 25
Nov. 30
Dec. 2
Dec. 7
Dec. 9
Dec. 16
Introduction and historical significance
Gregor Mendel; Experiments in Plant Hybridization
Sex-limited inheritance in Drosophila and the first genetic map
The Chromosome Theory of Inheritance
Correlation between cytogenetic and genetic crossing-over
Correlation between cytogenetic and genetic crossing-over (cont.)
Genetic analysis in yeast and mechanisms of recombination (lecture)
Tetrad analysis in Arabidopsis
Exam 1
Overview of genetic interactions (lecture)
Mutant screens (yeast)
Mutant screens (Drosophila P-element)
Temperature-sensitive mutants
Epistasis analysis
Overexpression suppression
FALL BREAK
Allele-specific suppression
Synthetic lethality
Studying protein-protein interaction: 2 hybrid, co-IP
RNAi
RNAi
Exam 2
Genome sequencing projects
Genome-wide RNAi
Functional profiling (yeast)
THANKSGIVING BREAK
THANKSGIVING BREAK
Synthetic lethality (genome-wide)
Expression profiling (microarray, SAGE, etc)
Chromatin immunoprecipitation
Wrap-up (final paper due)
FINAL EXAM 9:00 AM