Instructional materials summary – Harvard SI 2014
Title of teachable tidbit: “Biomedical Applications of Gene Dosage Compensation”
General Topic: Molecular Gene Regulation
Two sentence synopsis of tidbit:
Type of activity (or activities):
Designed for what level course and type of students?
Materials required:
Comments on out of class preparation required by students and instructor:
General comments:
Tidbit focuses on teaching gene dosage compensation to students and having them apply this knowledge to address a biomedical issue regarding the inactivation of one copy of Chromosome
21 in trisomy 21.
Brainstorm, index card question/reflection; group (table) activity; clicker question; take home assignment
Introduction to Molecular Biology; Introduction to Genetics; Introduction to Developmental
Biology; Majors; Sophomore (200) level course
Laptop with connection to projector; slide changer; laser pointer; Turningpoint software; this
PPT; index cards, magic markers, large poster-size graph paper; clickers; dry erase boards
Students: Read background content in textbook and watch video on X-inactivation/gene dosage compensation online (see links in outline); Attend class time before this session.
Instructor: Prepare materials for hands-on activity by acquiring all materials above; inform teaching assistants as to their different roles during the activity.
See notes on each slide
List five keywords that would allow others to search for this activity in a database:
Names and institutions of group members:
Contact person for questions:
Molecular Gene Regulation; Gene Dosage Compensation; X chromosome inactivation; trisomy
21; gene expression
S. Tariq Ahmad (stahmad@colby.edu); Paul Greenwood (pggreenw@colby.edu); Terence
Capellini (tcapellini@fas.harvard.edu); Amy Hansen (amyhansen@g.harvard.edu); Natalie Farny
(nfarny@wpi.edu); Fabienne Furt ( fabiennefurt@wpi.edu
)
Facilitators: Camille Hardiman (camille.hardiman@gmail.com) and Marvin O'Neal
(marvin.oneal@stonybrook.edu)
Natalie Farny (nfarny@wpi.edu)

Group 8 (The 21-ists)
HHMI Summer Institute
S. Tariq Ahmad
Amy Hansen
Paul Greenwood
Natalie Farny
Facilitators : Camille Hardiman
Terence Capellini
Fabienne Furt
Marvin O’Neal

Course: Introduction to Molecular Biology
Level: Sophomore Course (200 level)
Size: 40-50 students (scalable)
Pre-requisites: Introduction to Biology
Pre-
Central Dogma
(2 weeks)
Target Unit
Molecular Gene Regulation
(2 weeks)
Post-
Epigenetics
(2 weeks)

Students will have learned:
- Bloom’s taxonomy
- Scientific method
- DNA structure and function
- Chromosomes and cell division
- Central dogma
- Lab methods for measuring gene expression and fluorescence localization

Pre-
Central Dogma
(2 weeks)
Target Unit
Molecular Gene Regulation
(2 weeks)
Post-
Epigenetics
(2 weeks)
1) Students will understand why genes are regulated
2) Students will understand the various levels at which gene regulation can occur
3) Students will understand technological applications of gene regulation to biomedicine

Pre-
Central Dogma
(2 weeks)
Target Unit
Molecular Gene Regulation
(2 weeks)
Post-
Epigenetics
(2 weeks)
1) Students will understand why genes are regulated
2) Students will understand the various levels at which gene regulation can occur
3) Students will understand technological applications of gene regulation to biomedicine

Students should be able to:
3.1. Describe and explain the experimental tools that allow for the artificial control of gene expression
3.2. Identify a situation where manipulation of the expression of a single gene is appropriate to biomedicine (gene therapy)
3.3. Provide examples of dosage compensation in nature and biomedicine
3.4 Propose an experiment and predict the results of the experiment
3.5 Discuss ethical implications of artificially manipulating gene expression

Students should be able to:
3.1. Describe and explain the experimental tools that allow for the artificial control of gene expression
3.2. Identify a situation where manipulation of the expression of a single gene is appropriate to biomedicine (gene therapy)
3.3. Provide examples of dosage compensation in nature and biomedicine
3.4 Propose an experiment and predict the results of the experiment
3.5 Discuss ethical implications of artificially manipulating gene expression

Female cells have double the number of X chromosomes as male cells. Therefore, female cells should express twice the amount of X chromosome genes than male cells. BUT - they DON’T.
Male and female cells express X chromosome genes at the same level. Take 30 seconds and brainstorm several ways that this might be achieved.
XX XY

Mechanisms of X chromosome dosage compensation wormbook.org

Xist gene
X Chromosome
Inactivation
Barr body http://embryology.med.unsw.edu.au/embryology/images/thumb/3/3f/X_inacti vation_Xist.jpg/400px-X_inactivation_Xist.jpg
Heterochromatin formed, genes silenced

Aberrant gene dosage: What’s wrong with this karyotype?

1. Normally occurring X-inactivation via XIST
2. Gene dosage problem – Trisomy 21

Predicting Gene Expression
Aim: Investigate how formation of a Chr21 Barr body affects gene expression
Method:
Samples - 3 different cell types: Technique :
Wild type Trisomy 21 Trisomy 21 + XIST
Quantify gene expression from chromosomes 9 & 21
Predict: The level of gene expression in each cell type, from the two different chromosomes. Draw your predicted gene expression data on the graph provided.

You accidentally have targeted Chromosome 9 with Xist instead of Chromosome 21.
Which graph reflects most accurately this experimental error?

You accidentally have targeted Chromosome 9 with Xist instead of
Chromosome 21. a
Which graph reflects most accurately this experimental error?
Wild type c b d

• Proposed an experiment to apply dosage compensation to biomedical research
• Predicted the results of the proposed experiment
• Provide examples of dosage compensation in nature and for biomedicine

Ethical reflection on the implication of manipulation of gene regulation
Assignment : In one or two paragraphs, identify and discuss two ethical implications raised by this research