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Correcting Sickle-Cell Anemia

Correcting Sickle-Cell Anemia . Group B4 Jessica Hambrick Yichen Wang Tyler Fernandez Shawn Haley. Introduction. Hemoglobin : Oxygen-carrying protein Makes up Mammalian red blood cells Tetramer: contains 4 polypeptides (Freeman 2011). http://www.wikipedia.org/. (Freeman 2011).

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Correcting Sickle-Cell Anemia

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  1. Correcting Sickle-Cell Anemia Group B4 Jessica Hambrick Yichen Wang Tyler Fernandez Shawn Haley

  2. Introduction • Hemoglobin: Oxygen-carrying protein • Makes up Mammalian red blood cells • Tetramer: contains 4 polypeptides (Freeman 2011) http://www.wikipedia.org/ (Freeman 2011)

  3. Sickle-cell anemia • Autosomal recessive trait • Primary structure of hemoglobin differs • If oxygen concentrations in the blood low, hemoglobin CRYSTALLIZES • Causes sickle-shape • Cells stuck in capillaries, block flow downstream • Cells starved for oxygen (Freeman 2011) http://familydoctor.org

  4. Transcription of Genes • Transcription: RNA is made from DNA template • Transcription factor: protein that regulates transcription • Regulation of gene transcription: means by which gene expression is controlled to produce different proteins (Latchman 2011)

  5. Data/Results • Fetal hemoglobin (HbF) vs. adult hemoglobin (HbA) • Tested mice with human genes affected with Sickle-cell anemia • Fetal hemoglobin in adults: lessons severity of symptoms (Xuet al. 2011)

  6. Data/Results BCL11A • A “transcriptional repressor” • Involved in “switching” of fetal hemoglobin to adult hemoglobin • Silences fetal hemoglobin in adult cells • The experiment involved inactivating it (Xuet al. 2011)

  7. Data/ Results • In mice genetically engineering with human Sickle-cell hemoglobin… • Inactivated BCL11A • Hemoglobin switching failed in fetal liver • Lots of fetal hemoglobin, but levels declined after birth (Xuet al. 2011)

  8. Data/Results • Can fetal hemoglobin be reactivated? • YES! • Silencing of fetal hemoglobin reversible • Loss of BCL11A enhances effects in fetal hemoglobin inducers • Sickle-cell phenotypes corrected in adults (Xuet al. 2011)

  9. (Xuet al. 2011)

  10. Discussion • Inactivation of a transcription factor can prevent expression of a gene: • Transcription factor = BCL11A • Gene expressed= fetal hemoglobin • HUGE STEP in finding therapy for hemoglobin disorders such as Sickle-Cell (Xuet al. 2011)

  11. Conclusion • Sickle-cell anemia can be treated by the inactivation of a transcription factor!

  12. Literature Cited Freeman, Scott. Biological Science. 4th ed. San Francisco, CA: Benjamin Cummings, 2011. Print. Latchman, D. S. “Transcriptional Gene Regulation in Eukaryotes.” Nov. 2011. eLS. Web. 11 Nov. 2012. Xu, Jian, et al. “Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing.” Science 334 (2011): 993-996. Medline.Web. 11 Nov. 2012.

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