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Biomedical Applications of Gene Dosage Compensation

Instructional materials summary – Harvard SI 2014 Title of teachable tidbit: “Biomedical Applications of Gene Dosage Compensation”. Biomedical Applications of Gene Dosage Compensation. Group 8 (The 21- ists ) HHMI Summer Institute. S. Tariq Ahmad Paul Greenwood Terence Capellini

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Biomedical Applications of Gene Dosage Compensation

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

  2. Biomedical Applications of Gene Dosage Compensation Group 8 (The 21-ists) HHMI Summer Institute S. Tariq Ahmad Paul Greenwood Terence Capellini Amy Hansen Natalie FarnyFabienneFurt Facilitators : Camille Hardiman Marvin O’Neal

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

  4. 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 Prior knowledge

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

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

  7. 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 ofartificially manipulating gene expression Goal 3: Learning Objectives

  8. 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 ofartificially manipulating gene expression Goal 3: Learning Objectives

  9. 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

  10. Mechanisms of X chromosome dosage compensation wormbook.org

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

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

  13. What we know: 1. Normally occurring X-inactivation via XIST 2. Gene dosage problem – Trisomy 21

  14. 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.

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

  16. 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

  17. Learning Outcomes of Tidbit • Proposed an experiment to apply dosage compensation to biomedical research • Predictedthe results of the proposed experiment • Provideexamples of dosage compensation in nature and for biomedicine

  18. 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

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