Faculty of Science and Engineering Human Molecular Genetics
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Transcript of Faculty of Science and Engineering Human Molecular Genetics
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.