Instructional materials summary – Harvard SI 2014Title of teachable tidbit: “Biomedical Applications of Gene Dosage Compensation”

General Topic: Molecular Gene Regulation

Two sentence synopsis of tidbit: 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.

Type of activity (or activities): Brainstorm, index card question/reflection; group (table) activity; clicker question; take home assignment

Designed for what level course and type of students?

Introduction to Molecular Biology; Introduction to Genetics; Introduction to Developmental Biology; Majors; Sophomore (200) level course

Materials required: 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

Comments on out of class preparation required by students and instructor:

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.

General comments: See notes on each slide

List five keywords that would allow others to search for this activity in a database:

Molecular Gene Regulation; Gene Dosage Compensation; X chromosome inactivation; trisomy 21; gene expression

Names and institutions of group members:

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)

Contact person for questions: Natalie Farny (nfarny@wpi.edu)

Biomedical Applications of Gene Dosage Compensation

Group 8 (The 21-ists)HHMI Summer Institute

S. Tariq Ahmad Paul Greenwood Terence CapelliniAmy Hansen Natalie Farny Fabienne Furt

Facilitators : Camille Hardiman Marvin O’Neal

Course ContextCourse: Introduction to Molecular BiologyLevel: Sophomore Course (200 level)Size: 40-50 students (scalable)Pre-requisites: Introduction to Biology

Molecular Gene Regulation(2 weeks)

Pre- Post-

Central Dogma(2 weeks)

Epigenetics(2 weeks)

Target Unit

Prior knowledge

- Bloom’s taxonomy- Scientific method- DNA structure and function- Chromosomes and cell division- Central dogma- Lab methods for measuring gene expression

and fluorescence localization

Students will have learned:

Learning Goals1) 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

Molecular Gene Regulation(2 weeks)

Pre- Post-

Central Dogma(2 weeks)

Epigenetics(2 weeks)

Target Unit

Learning Goals1) 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

Molecular Gene Regulation(2 weeks)

Pre- Post-

Central Dogma(2 weeks)

Epigenetics(2 weeks)

Target Unit

Goal 3: Learning Objectives

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 andbiomedicine

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:

Goal 3: Learning Objectives

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 andbiomedicine

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:

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.

XX XY

Male and female cells express X chromosome genes at the same level. Take 30 seconds and brainstorm several ways that this might be achieved.

Mechanisms of X chromosome dosage compensation

wormbook.org

X Chromosome Inactivation

http://embryology.med.unsw.edu.au/embryology/images/thumb/3/3f/X_inactivation_Xist.jpg/400px-X_inactivation_Xist.jpg

Heterochromatin formed, genes silenced

Xist gene

Barr body

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

What we know:

1. Normally occurring X-inactivation via XIST

2. Gene dosage problem – Trisomy 21

Predicting Gene ExpressionAim: Investigate how formation of a Chr21 Barr body affects gene expression

Method: Samples - 3 different cell types:

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.

Quantify gene expression from chromosomes 9 & 21

Wild type Trisomy 21 Trisomy 21 + XIST

Technique :

The Next Challenge

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

Gen

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pres

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leve

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ene

expr

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Gen

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Wild type

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

Learning Outcomes of Tidbit

• 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

In one or two paragraphs, identify and discuss two ethical implications raised by this research

Ethical reflection on the implication of manipulation of gene regulation

Assignment :