YORK UNIVERSITY
Department of Biology
Faculty of Science and
Engineering
Course outline
Human Molecular Genetics
(SC/BIOL 4285 3.0)
W2016
Prerequisite:
SC/BIOL 3130
1
Instructor: Dr. Michael Scheid
Rm. 236 Farqharson Building
Website: scheid.blog.yorku.ca
E-mail: mscheid@yorku.ca
Office hours:
Tuesday/Thursday 10:15-11:00 am
2
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.
3
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.
4
Academic Integrity: Senate Policy on Academic Dishonesty
Students are expected to be familiar with and follow
York University’s Policies regarding academic integrity.
Please consult the website below for more details:
http://www.yorku.ca/academicintegrity/students.htm
5
• 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 person’s 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 one’s 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.
6
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_19.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, 69:915-26.
“Homolgous knockout of DNA
methyltransferase in mice leads to
embryonic lethality.”
DNA Methylation
• Determine the biological role of
methylation
• Disrupt genes involved – methyl-bindingdomain 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 422-437
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
Fragile-X Syndrome
Length
Methylation
Females
Males
Stable
6 to ~45
Unmethylated
Not affected
Not affected
Gray zone
~45 to ~55
Unmethylated
Not affected
Not affected
Premutation
~55 to ~200
Unmethylated
Usually not
affected
Usually not
affected
Full mutation
>200
Completely
methylated
~50%
affected
All affected
11_05.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.”