1. 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

2. Instructor: Dr. Michael Scheid
Rm. 236 Farqharson Building
Website: scheid.blog.yorku.ca
Office hours:
Tuesday/Thursday 10:15-11:00 am

3. 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.

4. 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.

5. 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:

6. • 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.

7. Overview of Gene Expression
Mechanisms to control gene expression
Spatial/temporal consideration

8. Overview of Gene Expression
RNA Polymerase II
Transcription factors and cis-acting regulatory sequences

9. Overview of Gene Expression
Epigenetic regulation

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14. 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

15. DNA Methylation Determine the biological role of methylation
Disrupt genes involved – DNMT (DNA methyltransferase)

16. Li E, et al. Cell, 1992, 69:
“Homolgous knockout of DNA methyltransferase in mice leads to embryonic lethality.”

17. DNA Methylation Determine the biological role of methylation
Disrupt genes involved – methyl-binding-domain proteins (eg MeCP2)

18. 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.”  

19. Rett Syndrome Occurrence: 1 in 10,000
Neuron, November 2007, Pages

20. Rett Syndrome In humans, MeCP2 is mutated in 1 in 10,000 females
Causes severe neurological disorders
Rett Syndrome

21. Rett Syndrome

22. 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

28. Inappropriate Silencing of Genes
Fragile-X Syndrome

29. 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

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33. Skewed X-Chromosome inactivation in a family with Fragile X

34. 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.”