Department of Biology Faculty of Science and Engineering Course outline Human Molecular Genetics SCBIOL 4285 30 W2015 Prerequisite SCBIOL 3130 2 Instructor Dr Michael Scheid Rm 236 ID: 321384
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YORK UNIVERSITY
Department of Biology
Faculty of Science and Engineering
Course outline
Human Molecular Genetics
(SC/BIOL
4285 3.0)
W2015
Prerequisite:
SC/BIOL 3130Slide2
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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 amSlide3
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STUDENT EVALUATION:
There will be
ONE Midterm exam, worth 30%
of your grade:
Midterm – February 13You will submit a RESEARCH PAPER, worth 20% of your grade:Paper – due March 27The FINAL EXAM will be worth 50% of your grade.Slide4
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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.Slide5
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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.htmSlide6
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• 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.Slide7
Overview of Gene ExpressionMechanisms to control gene expressionSpatial/temporal considerationSlide8
Overview of Gene ExpressionRNA Polymerase IITranscription factors and cis-acting regulatory sequencesSlide9
Overview of Gene ExpressionLigand-inducible transcription factorsexamplesSlide10
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Overview of Gene ExpressionEpigenetic regulationSlide14
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Paula Quintero-Ronderos and GladisMontoya-OrtizAutoimmune Diseases Volume 2012, Article ID 593720, 16 pagesSlide19
DNA MethylationHost defense vs. Gene regulationParent of origin: imprintingBiallelic vs monoallelic expressionInappropriate DNA methylation can cause problemseg. CancerBeckwith-Wiedemann syndromeSlide20
DNA MethylationDetermine the biological role of methylationDisrupt genes involved – DNMT (DNA methyltransferase)Slide21
Li E, et al. Cell, 1992, 69:915-26.“Homolgous knockout of DNA methyltransferase in mice leads to embryonic lethality.” Slide22
DNA MethylationDetermine the biological role of methylationDisrupt genes involved – methyl-binding-domain proteins (eg MeCP2)Slide23
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.” Slide24
Rett SyndromeOccurrence: 1 in 10,000Neuron, November 2007, Pages 422-437 Slide25
Rett SyndromeIn humans, MeCP2 is mutated in 1 in 10,000 femalesCauses severe neurological disordersRett SyndromeSlide26
Rett SyndromeSlide27
Rett Syndrome80% of females with Rett syndrome have mutations in MeCP2Example of a strong single-gene disorderResult of inappropriate loss of gene silencingSlide28Slide29Slide30Slide31Slide32Slide33
Inappropriate Silencing of GenesFragile-X SyndromeSlide34
Fragile-X SyndromeLength
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 affectedSlide35
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Skewed X-Chromosome inactivation in a family with Fragile XSlide39
Southern Blot Analysis“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.”
Blood sample
Digest genomic DNA with EcoRI and EagI
Electrophoresis and transfer to membrane
Hybridize with FMR1 specific probe