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08.20.08: Genetics of Human Disease: Hemoglobinopathies
 

08.20.08: Genetics of Human Disease: Hemoglobinopathies

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Slideshow is from the University of Michigan Medical School's M1 Patients and Populations: Medical Genetics Sequence. ...

Slideshow is from the University of Michigan Medical School's M1 Patients and Populations: Medical Genetics Sequence.

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    08.20.08: Genetics of Human Disease: Hemoglobinopathies 08.20.08: Genetics of Human Disease: Hemoglobinopathies Presentation Transcript

    • Author(s): David Ginsburg, 2009License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Noncommercial–Share Alike 3.0 License:http://creativecommons.org/licenses/by-nc-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
    • Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (USC 17 § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (USC 17 § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (USC 17 § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
    • M1 Patients and Populations: Genetics of Human Disease: Hemoglobinopathies David Ginsburg, MDFall 2008
    • Learning Objectives•  Understand how the basic anatomy of a gene has a direct bearing on the occurrence of genetic disease.•  Know the normal and abnormal expression patterns of the hemoglobin genes.•  Understand the mutations that cause quantitative abnormalities in globin. –  Unequal crossing over, and every other possible type of mutation•  Recognize mutations that cause qualitative abnormalities in globin.•  Understand the molecular basis of sickle cell anemia.
    • kb 0 10 20 30 40 50 60 ε Gγ Aγ ψβ1 δ β LCR CHROMOSOME 11 ζ ψζ ψα2 ψα1 α2 α1 θ1 CHROMOSOME 16 Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 5.2
    • Source Undetermined
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.4
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.5
    • Zephyris (wikimedia)
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.3
    • Regents of The University of MichiganReview of Medical Physiology 22E; Figure 27.19
    • Quantitative Abnormalities of Hemoglobin•  α Thalassemia –  deficiency of α globin chains•  β Thalassemia –  deficiency of β globin chains•  HPFH –  Hereditary persistence of fetal hemoglobin
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.14
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.16
    • Source Undetermined
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.15
    • Normal peripheral blood smearHgb H disease Source Undetermined ( All Images)
    • Map of gene frequencies ofthalassemias and endemic malaria removed Miller LH. Nature, 383:480, 1996.
    • Gelehrter, Collins and Ginsburg:Principles of Medical Genetics 2E;Figure 6.16
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.19
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.20
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.21
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.22
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.18
    • Normal peripheral blood smearβ-Thalassemia (homozygous) Source Undetermined ( All Images)
    • Image of boy withThalassemia removed
    • Gelehrter, Collins and Ginsburg: Principles of MedicalGenetics 2E; Figure 6.24
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.25 Source Undetermined
    • Image of amino acid residue variations in beta thalassemia hemoglobin removedOriginal Image From Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.6
    • Qualitative Abnormalities of Hemoglobin•  Silent Variants•  Unstable hemoglobins –  Heinz body hemolytic anemia•  Methemoglobinemia•  High affinity hemoglobins –  polycythemia (↑hematocrit and hemoglobin)•  Low affinity hemoglobins –  mild anemia (↓hematocrit and hemoglobin)•  Hemoglobin S•  Hemoglobin C
    • Regents of The University of MichiganGelehrter, Collins and Ginsburg: Principles of MedicalGenetics 2E; Figure 6.7
    • SC SS AA AC sickle Nl trait Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.9
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 6.8
    • Oxygenated and Deoxygenated Sickle Red Blood Cell Bunn & Forget. Hemoglobin: Molecular, Genetic and Clinical Aspects. 1986.
    • Hemoglobin SS DiseaseSource Undetermined Source Undetermined
    • Complications of Sickle Cell Anemia•  autosplenectomy•  hyposthenuria•  Infections –  encapsulated organisms-- pneumococcus –  salmonella, staph•  Painful crises•  Bone infarcts, aseptic necrosis•  Stroke•  Acute chest syndrome•  Hand-foot syndrome•  Chronic organ damage
    • Source Undetermined
    • Regents of The University of MichiganReview of Medical Physiology 22E; Figure 27.19
    • Source UndeterminedHb S only occurs on 4 haplotypes…only occurred 4 times in history
    • Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E; Figure 4.2Hb S is a balanced polymorphism * homozygotes (1 in 500) are selected against * heterozygotes (1 in 12) are selected for
    • Sickle Cell Anemia: Treatment•  IV fluids•  Analgesia•  Infection –  penicillin prophylaxis –  vaccines•  Oxygen•  Transfusion•  Erythropoietin•  Hydroxyurea•  Bone Marrow Transplantation
    • Learning Objectives•  Understand how the basic anatomy of a gene has a direct bearing on the occurrence of genetic disease.•  Know the normal and abnormal expression patterns of the hemoglobin genes.•  Understand the mutations that cause quantitative abnormalities in globin. –  Unequal crossing over, and every other possible type of mutation•  Recognize mutations that cause qualitative abnormalities in globin.•  Understand the molecular basis of sickle cell anemia.
    • Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 5: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 5.2 Slide 6: Source Undetermined Slide 7: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.4 Slide 8: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.5 Slide 9: Zephyris (wikimedia) Slide 10: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.3 Slide 11: Regents of The University of Michigan; Review of Medical Physiology 22E, Figure 27.19 Slide 13: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.14 Slide 14: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.16 Slide 15: Source Undetermined Slide 16: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.15 Slide 17: Source Undetermined ( All Images) Slide 18: Miller LH. Nature, 383:480, 1996. Slide 19: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.16 Slide 20: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.19 Slide 21: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.20 Slide 22: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.21 Slide 23: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.22 Slide 24: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.18 Slide 25: Source Undetermined ( All Images) Slide 27: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.24 Slide 28: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.25; Source Undetermined Slide 29: Original Image From Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.6 Slide 31: Regents of The University of Michigan; Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.7 Slide 32: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.9 Slide 33: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 6.8 Slide 34: Bunn & Forget. Hemoglobin: Molecular, Genetic and Clinical Aspects. 1986. Slide 35: Soure Undetermined; Source Undetermined
    • Slide 37: Source UndeterminedSlide 38: Regents of The University of Michigan; Review of Medical Physiology 22E, Figure 27.19Slide 39: Source UndeterminedSlide 40: Gelehrter, Collins and Ginsburg: Principles of Medical Genetics 2E, Figure 4.2