Classical genetic analysis is a powerful approach to dissect complex biological processes. Selective removal, addition, or alteration of specific proteins creates mutant phenotypes that give insight into the normal roles of those genes. Analysis of double mutants lets one deduce the order of events and infer interactions between proteins. These methods let one propose mechanisms for processes that may be too complex to study effectively with biochemical or molecular approaches. Genetic studies can also provide definitive functional assignments for predicted genes, regardless of whether those genes exhibit sequence homology or have orthologues in other systems.
We will employ genetic analysis to identify and characterize genes governing mating of yeast, patterning of the Drosophila body and the Arabidopsis flower, and stress response mechanisms in flies and plants. This year, I will also include a third model, the worm C. elegans. We will discuss methods for disrupting gene function randomly, through large-scale mutagenesis screens, and specifically, through homologous recombination or construction of chimeric genes. This latter approach will let us investigate structure/function relationships within proteins. We will evaluate the nature of mutant alleles, considering the effects of dominant vs. recessive mutations and the impact each has on our interpretation of a process. We will use epistasis tests to establish the order of genes in a pathway. We will discuss the tissue and temporal requirement for gene function and consider how these insights from model organisms inform our approaches to understand phenotypes in other organisms. Finally, we will discuss how classical genetics in combination with other approaches can yield novel insights in the era of next-generation sequencing and genome-wide association mapping.
25% assigned homework for each reading, 25% participation in class discussion (ASK QUESTIONS!), 50% final exam
Course web site:
|1||Genetic Analysis in a Single-cell Eukaryote||How mutant phenotypes give insight into a biological process|
|2||Ordering genes in a pathway by double mutant analysis||How to interpret function based on differences in alleles|
|3||Using genetics to characterize the structure and function of a protein||Genetic Analysis in a Metazoan System|
|4||Defining the pathway: Isolation of mutants; phenotypic characterization; mosaic analysis||Arriving at pathway models: dissecting complex phenotypes with allelic series and reverse genetics|
|5||The power of forward mutation screens in the postgenomic era: smart screens can identify novel players in a well-characterized organismal phenotype|