Faculty of Science and Engineering Human Molecular Genetics
YORK UNIVERSITY Department of Biology Faculty of Science and Engineering Course outline Human Molecular Genetics (SC/BIOL ) W2016 Prerequisite: SC/BIOL 3130 Instructor:Dr. Michael Scheid
Rm. 236 Farqharson Building Website: scheid.blog.yorku.ca Office hours: Tuesday/Thursday 10:15-11:00 am STUDENT EVALUATION: There will be ONE Midterm exam, worth 30% of your grade: Midterm February 12 You will submit a RESEARCH PAPER, worth 20% of your grade: Paper due April 1 The FINAL EXAM will be worth 50% of your grade. Please note : There will be NO MAKE-UP of the midterm exams. For medical issues please have your physician fill out the Attending Physician Statement. This form is available from the Registrars website. Academic Integrity: Senate Policy on Academic Dishonesty
Students are expected to be familiar with and follow York Universitys Policies regarding academic integrity. Please consult the website below for more details: ACADEMIC MISCONDUCT WILL NOT BE TOLERATED.
Cheating is the attempt to gain an improper advantage in an academic evaluation. Forms of cheating include: Obtaining a copy of an examination before it is officially available or learning an examination question before it is officially available; Copying another persons answer to an examination question; Consulting an unauthorized source during an examination; Obtaining assistance by means of documentary, electronic or other aids which are not approved by the instructor; Changing a score or a record of an examination result; Submitting the work one has done for one class or project to a second class, or as a second project, without the prior informed consent of the relevant instructors; Submitting work prepared in collaboration with another or other member(s) of a class, when collaborative work on a project has not been authorized by the instructor; Submitting work prepared in whole or in part by another person and representing that work as ones own; Offering for sale essays or other assignments, in whole or in part, with the expectation that these works will be submitted by a student for appraisal; Preparing work in whole or in part, with the expectation that this work will be submitted by a student for appraisal. Overview of Gene Expression
Mechanisms to control gene expression Spatial/temporal consideration Overview of Gene Expression
RNA Polymerase II Transcription factors and cis-acting regulatory sequences Overview of Gene Expression
Epigenetic regulation 10_18.jpg 10_18.jpg 10_19.jpg 10_19.jpg 10_19_2.jpg 10_19_2.jpg DNA Methylation Host defense vs. Gene regulation
Parent of origin: imprinting Biallelic vs monoallelic expression Inappropriate DNA methylation can cause problems eg. Cancer Beckwith-Wiedemann syndrome DNA Methylation Determine the biological role of methylation
Disrupt genes involved DNMT (DNA methyltransferase) Li E, et al. Cell, 1992, 69: Homolgous knockout of DNA methyltransferase in mice leads to embryonic lethality. DNA Methylation Determine the biological role of methylation
Disrupt genes involved methyl-binding-domain proteins (eg MeCP2) Tate, P., Skarnes, W. & Bird, A. Nature Genet. 12, 205-208 (1996).
The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse. Rett Syndrome Occurrence: 1 in 10,000
Neuron, November 2007, Pages Rett Syndrome In humans, MeCP2 is mutated in 1 in 10,000 females
Causes severe neurological disorders Rett Syndrome Rett Syndrome Rett Syndrome 80% of females with Rett syndrome have mutations in MeCP2 Example of a strong single-gene disorder Result of inappropriate loss of gene silencing Inappropriate Silencing of Genes
Fragile-X Syndrome Completely methylated
Fragile-X Syndrome Length Methylation Females Males Stable 6 to ~45 Unmethylated Not affected Gray zone ~45 to ~55 Premutation ~55 to ~200 Usually not affected Full mutation >200 Completely methylated ~50% affected All affected 11_05.jpg 11_05.jpg 11_05_2.jpg 11_05_2.jpg Skewed X-Chromosome inactivation in a family with Fragile X Southern Blot Analysis
Blood sample Digest genomic DNA with EcoRI and EagI Electrophoresis and transfer to membrane Hybridize with FMR1 specific probe A normal female will show an unmethylated 2.8-kb band and a 5.2-kb methylated band that correspond to the normal FMR1 gene present in the active and inactive X chromosome, respectively.