Exploring Biomedical Gene Dosage Compensation in Trisomy 21
This instructional material focuses on teaching gene dosage compensation in the context of addressing the inactivation of one copy of Chromosome 21 in trisomy 21. The activity is designed for courses in Molecular Gene Regulation and Genetics, aiming to enhance students' understanding through hands-on activities and discussions.
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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: 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 Amy Hansen Paul Greenwood Natalie Farny Terence Capellini Fabienne Furt Facilitators : Camille Hardiman Marvin O Neal
Course Context Course: Introduction to Molecular Biology Level: Sophomore Course (200 level) Size: 40-50 students (scalable) Pre-requisites: Introduction to Biology Pre- Target Unit Post- Central Dogma (2 weeks) Molecular Gene Regulation (2 weeks) Epigenetics (2 weeks)
Prior knowledge 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- Target Unit Post- Central Dogma (2 weeks) Molecular Gene Regulation (2 weeks) Epigenetics (2 weeks) Learning Goals 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- Target Unit Post- Central Dogma (2 weeks) Molecular Gene Regulation (2 weeks) Epigenetics (2 weeks) Learning Goals 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
Goal 3: Learning Objectives 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
Goal 3: Learning Objectives 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 Heterochromatin formed, genes silenced http://embryology.med.unsw.edu.au/embryology/images/thumb/3/3f/X_inacti vation_Xist.jpg/400px-X_inactivation_Xist.jpg
What we know: 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 : Quantify gene expression from chromosomes 9 & 21 Wild type Trisomy 21 Trisomy 21 + XIST 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.
The Next Challenge 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. Which graph reflects most accurately this experimental error? Wild type a c Gene expression level Gene expression level b d Gene expression level Gene expression level
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
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
