3 credits, Winter Term 2011

Professors: Dr. Hoyun Lee and Dr. James Knockleby
email: hlee@hrsrh.on.ca; jknockleby@hrsrh.on.ca

Course Summary: Advanced Genetics will focus on the fundamental concepts of molecular biology, including the regulation of DNA replication, transcription, translation and recombination. Additionally, students will review model organism genetics. As the class progresses further, students will be exposed to cutting-edge technologies that have been the engines of ‘big science’ including: genome and proteome projects, synthetic genetics and array-based gene analysis. PREREQ BIOL 3017. (lec3) cr 3.

Recommended Texts

one of the following:

Molecular Biology of the Gene, 6th ed. (2008) Watson, et al. Cold Spring Harbor Lab Press, ISBN 080539592X

Molecular Biology of the Cell, 5th ed. (2007) Alberts, et al. Garland Science Press, ISBN 0815341059

Lectures
          
Broad themes

I. Maintenance of the Genome   (3 weeks)
II. Expression of the Genome     (2.5 weeks)
III. Experimental Genetics        (3 weeks)
IV. The 'omics era: Recent Trends in Genomics and Proteomics (3 weeks)

I . Maintenance of the Genome

(A) Central Dogma of Molecular Biology
(B) Molecular Structure of Genes and Chromosomes
1.Molecular Definition of a Gene
2.Chromosomal Organization of Genes and Non-Coding DNA
3.Structural Organization of Eukaryotic Chromosomes
4.Morphology and Functional Elements of Eukaryotic Chromosomes

(C) DNA Replication and Recombination
1. The regulation of DNA replication in the context of maintaining genome stability
2. The mechanism of initiation and chain elongation
3. chromosome segregation
4. General and Site Specific recombination

(D) Mutations and Genomic instability
1. Proofreading repair and mismatch repair
2. Incomplete and excess replication
3. Repair of induced damage
4. Repair by recombination
5. Gene amplification and genome instability
6. Generation of aneuploidy and genome instability
7. Fate of cells with damage

(E) Defects in cell-cycle checkpoints and genome instability       
1. Checkpoint control is to keep genome integrity
2. Pronounced cell cycle checkpoint control mechanisms (G1, G1/S, S, damage-induced, G2/M, and M checkpoints)
3. Inactivation of checkpoints by virus oncoproteins

II. Expression of the Genome
  
(A) Transcription of protein coding genes
1. Eukaryotic Gene control and RNA Polymerases
2. Regulatory Sequences in Protein Coding genes
3. Activators and Repressors of Transcription
4. RNA Polymerase II Transcription
5. Molecular mechanisms of Transcription Activation and Repression
6. Regulation of Transcription Factor Activity
7. Pol I and Pol III Transcription systems
 
(B) Post-transcriptional gene control
1. Processing of pre-mRNA
2. Regulation of pre-mRNA Processing
3. Transport Across Nuclear Envelope
4. Cytoplasmic Mechanisms of Post-transcriptional control
5. Processing of rRNA and tRNA

Study Week: February 21 to 25

III. Experimental Genetics

(A) Introduction: Molecular Genetic Techniques
1.Genetic Analysis of Mutations to Identify and Study Genes
2.DNA Cloning by Recombinant DNA Methods
3.Characterizing and Using Cloned DNA Fragments
4.Genomics: Genome Wide Analysis of Gene Structure and Expression
5.Inactivating the Function of Specific Genes in Eukaryotes
6.Identifying and Locating Human Disease Genes
 
(B) Model Genetic Organisms (Based off of “Art and Design” articles)
1. Bacteria and phage
2. Budding yeast (Saccharomyces cerevisiae)
3. Drosophila melanogaster
4. C. elegans
5. mouse
6. Homo sapiens
7. Systematic discovery of nonobvious human disease models through orthologous phenotypes

(C) Cancer genetics
1. What is Cancer – Cancer as a genetic disease
2. What are oncogenes and tumor suppressor genes
3. Naturally occurring genetic mutations in the human population
4. Animal models for Cancer
5. Clincal relevance to cancer genetics

IV. The 'omics era: Recent Trends in Genomics and Proteomics

(A) Genomic sequencing projects – the promise (un)fulfilled?
1. Genome projects in general
2. Yeast genome: life with 6000 gene
3. Human genome: where are the cures?

(B) BLAST – The genomic Google™
1. bioinformatics as GPS for the genome
2. Databases – NCBI and ExPASy
3. Species databases

(C)Forward Genetics in the post-genomic era
1. RNAi
2. directed mutagenesis/knockout collections
3. chemical genetics – Shokat analogue sensitive alleles
(D) Synthetic genetics
1.Genetic buffering
2.Synthetic Genetic Analysis (SGA) in budding yeast
3. Cancer synthetic genetics
(E)  Genomics to Proteomics
1. ESTs and cDNAs assist in determining expressed proteins
2. The genome offers clues to open reading frames, but...
3. Mass spectrometry allows for large scale identification of proteins in complex mixture
4. Human proteomics – Cancer proteomics
5. Yeast as post-proteomic creature – the interactome (TAP tag and 2 hybrid screens of proteome)

Literature Reviews

Reviews of a paper from the current primary literature will be due approximately every three weeks, coinciding with the end of each of the four main topics (I-IV). These reviews will be linked to the material covered. These mini-reviews should be clearly written in the format of a scientific review for publication and explain the basic science of the paper, including the main goals and hypotheses being tested, and any novel technique or technology that was central to the research (see Nature News and Reviews for example). A list of manuscripts suitable for the assignment will be provided near the beginning of the term, and electronic copies will be made available.

The format will be two-page single spaced, Times New Roman 12pt font with 2cm margins. The general outline will be:

½ page outlining a brief summary, including important findings and significance to field
½ page description of your opinions on the interest and novelty of the study
½ page identifying potential shortcomings or problems associated with study
½ page indicating anticipated future directions based off of data from study

Review due dates are at the beginning of each of the four main topics: February 1st, March 1st , March 22, and April 5th (end of the term).