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BIO403: Biotechnology

Unit 7: Genetic Defects and Gene Therapy   One of the great potentials of biotechnology is the ability to create cures for human genetic defects.  Because such a disease is directly caused by a dysfunctional or missing gene, in theory, by injecting patients with a product that replaces or adds the target gene, they will be cured forever.  Gene therapy efforts attack retroviral infections as well, for example, by modifying the host cell’s virus recognition site.  

Unit 7 Time Advisory
This unit should take you approximately 14.5 hours to complete.

☐    Subunit 7.1: 2.0 hours

☐    Subunit 7.2: 3.5 hours

☐    Subunit 7.3: 1.0 hour

☐    Subunit 7.4: 2.0 hours

☐    Subunit 7.5: 3.5 hours

☐    Subunit 7.6: 3.0 hours

Unit7 Learning Outcomes
Upon successful completion of this unit, the student will be able to:

  • Compare and contrast chromosomal and genetic defects.
  • Describe gene therapies for monogenic disorders.
  • Define the scope of genetic screening and counseling.
  • Compare and contrast gene therapy designs for loss-of-function disease and dominant disease.
  • Compare and contrast ex vivo and in vivo gene therapies.
  • Describe prodrug treatment.

7.1 Abnormal Chromosomes   7.1.1 Altered Chromosome Number   - Reading: National Center for Biotechnology Information’s Bookshelf: W.H. Freeman: Griffiths, Gelbart, Miller, et al.’s Modern Genetic Analysis: “Changes in Chromosome Number” Link: National Center for Biotechnology Information’s Bookshelf: W.H. Freeman:Griffiths, Gelbart, Miller, et al.’s Modern Genetic Analysis:  “Changes in Chromosome Number” (HTML)
 
Instructions: Please study the content of the “Aneuploidy” section, including the “Nondisjunction,” “Monosomics (2 - 1),” and “Trisomics (2n + 1)” subsections on this page.
 
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7.1.2 Chromosomal Rearrangement   - Reading: National Center for Biotechnology Information’s Bookshelf: W.H. Freeman: Griffiths, Gelbart, Miller, et al.’s Modern Genetic Analysis: “Chromosomal Rearrangements” Link: National Center for Biotechnology Information’s Bookshelf:  W.H. Freeman:  Griffiths, Gelbart, Miller, et al.’s Modern Genetic Analysis:  “Chromosomal Rearrangements” (HTML)
 
Instructions: Please study this page.
 
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7.1.3 Epigenetic Defects   - Reading: Nature Education’s Scitable: Danielle Simmons’ “Epigenetic Influences and Disease” Link: Nature Education’s Scitable:  Danielle Simmons’ “Epigenetic Influences and Disease” (HTML)
 
Instructions: Please study this page.  Epigenetics is "in addition to" genetics.  Please note that epigenetic changes result in gene expression changes without changing the sequence of the genomic DNA.  Identical twins may be susceptible to different diseases, if their epigenetics are different due to different life style.
 
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7.2 Genetic Disorders   7.2.1 Sickle Cell Anemia   - Reading: Nature Education’s Scitable: Abram Gabriel and Jennifer Przybylski’s “Sickle-Cell Anemia: A Look at Global Haplotype Distribution” Link:  Nature Education’s Scitable:  Abram Gabriel and Jennifer Przybylski’s “Sickle-Cell Anemia: A Look at Global Haplotype Distribution” (HTML)
 
Instructions: Please study the content of this page.  Authors Gabriel and Przybylski work at the Rutgers University.  Please note the advantage, what the deadly sickle-cell anemia provides for heterozygous individuals.
 
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7.2.2 Cystic Fibrosis   - Reading: National Human Genome Research Institute’s “Learning about Cystic Fibrosis” Link: National Human Genome Research Institute’s  “Learning about Cystic Fibrosis” (HTML)
 
Instructions: Please study the content of this page.
 
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7.2.3 Hemophilia   - Reading: National Center for Biotechnology Information’s PubMed: Blackwell Publishing Ltd.'s British Journal of Haematology: Samuel L. Murphy and Katherine A. High’s “Gene Therapy for Haemophilia” Link: National Center for Biotechnology Information’s PubMed: Blackwell Publishing Ltd.'s British Journal of Haematology:  Samuel L. Murphy and Katherine A. High’s “Gene Therapy for Haemophilia” (HTML or PDF)
 
Instructions: Please study the content of this page. You can access the PDF from the top right corner of the page.  The authors work in the Department of Pediatrics at the Children's Hospital of Philadelphia. This is a peer-reviewed publication.
 
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  • Web Media: Khanacademy’s “Sex-Linked Traits” Link: Khanacademy’s “Sex-Linked Traits” (Adobe Flash)
     
    Also available in:

    YouTube
     
    Instructions: Please watch the video (15 minutes) for a step by step tutorial on the inheritance of sex-linked traits.  You may need to review Punnett squares (see subunit 1.2 of this course) and to follow this video several times.
     
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7.2.4 Phenylketonuria   - Reading: National Center for Biotechnology Information’s “Phenylketonuria” Link: National Center for Biotechnology Information’s  “Phenylketonuria” (HTML)
 
Instructions: Please study the content of this page.  Please note that phenylalanine is an essential amino acid, thus it can not be omitted entirely from the diet.
 
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7.2.5 Duchenne muscular dystrophy   - Reading: National Center for Biotechnology Information’s “Duchenne Muscular Dystrophy” Link: National Center for Biotechnology Information’s  “Duchenne Muscular Dystrophy” (HTML or PDF)
 
Instructions: Please study the table on this page.  Please note that Duchenne muscular dystrophies are X-linked, thus the disease is more common in males.
 
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7.2.6 Repeat extensions   - Reading: Nature Education’s Scitable: Heidi Chial’s “Huntington’s Disease: The Discovery of the Huntingtin Gene” Link: Nature Education’s Scitable:  Heidi Chial’s “Huntington’s Disease: The Discovery of the Huntingtin Gene” (HTML)
 
Instructions: Please study this page.  More than 40 CAG nucleotide repeat in the HTT gene is linked to the onset of Huntington’s disease.
 
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  • Reading: National Center for Biotechnology Information’s “Fragile X Syndrome Link: National Center for Biotechnology Information’s  “Fragile X Syndrome” (HTML or PDF)
     
    Instructions: Please study the content of this page.  Fragile X syndrome is the most common inherited mental retardation.  It is an X-linked condition.  Please note that the chromosome becomes fragile only during a staining procedure; it is not fragile in the cell.  More than 200 CGG nucleotide repeat in the fragile X gene causes the disease.
     
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  • Assessment: The Saylor Foundation: "BIO403 Unit 7.2 Assessment" Link: The Saylor Foundation: "BIO403 Unit 7.2 Assessment" (HTML)
     
    Instructions: You will find links to five pedigrees within the "Family Pedigree" assessment on this page. These are multiple choice assessments with one correct answer. You are asked to determine if the highlighted trait in the pedigree follows dominant, or recessive or sex-linked inheritance. Clicking on an answer will bring you to another page. If your answer is correct, then it is acknowledged with a short explanation. Please read the explanation carefully. If you clicked on the wrong answer, then the click will bring you to a tutorial page. Please study the tutorial page carefully. You will be prompted to return to the assessment and complete it again. Please note that family pedigrees are indispensable in medical counseling.

7.3 Genetic Screening and Counseling   - Reading: Nature Education’s Scitable: Karen E. Norrgard’s “Genetic Counseling: Genetic Testing, Family History and Psychosocial Evaluation” Link:  Nature Education’s Scitable:  Karen E. Norrgard’s “Genetic Counseling: Genetic Testing, Family History and Psychosocial Evaluation” (HTML)
 
Instructions: Please study the three case studies on this page.
 
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  • Web Media: Khanacademy’s “Hardy-Weinberg Principle” Link: Khanacademy’s “Hardy-Weinberg Principle” (Adobe Flash)
     
    Also available in:

    YouTube
     
    Instructions: Please watch the video (15 minutes) for a step by step tutorial on calculating probabilities of the expected traits of the offspring.  You may need to review Punnett squares (see subunit 1.2 of this course) and to follow this video several times.
     
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  • Reading: Nature Education’s Scitable: Karen Norrgard’s “Diagnosing Down Syndrome, Cystic Fibrosis, Tay-Sachs Disease and Other Genetic Disorders” Link: Nature Education’s Scitable:  Karen Norrgard’s “Diagnosing Down Syndrome, Cystic Fibrosis, Tay-Sachs Disease and Other Genetic Disorders” (HTML)
     
    Instructions: Please study the content of this page.  Dr. Norrgard reviews genetic screening in the newborn, during pregnancy and before implantation.
     
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7.4 Gene Therapies   7.4.1 Loss-of-Function Disease and Dominant Disease   - Reading: Nature Education’s Scitable: Heidi Chial’s “Gene-Based Therapeutic Approaches” Link: Nature Education’s Scitable:  Heidi Chial’s “Gene-Based Therapeutic Approaches” (HTML)
 
Instructions: Please learn content from the “Putting the Human Genome to Work: Using Genes to Treat Disease” section to the end of this page.
 
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7.4.2 Ex Vivo and In Vivo Gene Therapy   - Reading: National Center for Biotechnology Information’s Bookshelf: Strachan and Read's "Human Molecular Genetics": "Chapter 22: Gene Therapy and Other Molecular Genetic-Based Therapeutic Approaches" Link: National Center for Biotechnology Information’s Bookshelf: Strachan and Read's "Human Molecular Genetics:” "Chapter 22: Gene Therapy and Other Molecular Genetic-Based Therapeutic Approaches" (HTML)
 
Instructions: Please scroll down to and read section 22.2: “The Technology of Classical Gene Therapy.”
 
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7.4.3 Aggressive Gene Therapy: Prodrug Treatment   - Reading: American Society for Clinical Investigation's The Journal of Clinical Investigation: Caroline J. Springer and Ion Niculescu-Duvaz’s “Prodrug-Activating Systems in Suicide Gene Therapy” Link: American Society for Clinical Investigation's The Journal of Clinical Investigation: Caroline J. Springer and Ion Niculescu-Duvaz’s  “Prodrug-Activating Systems in Suicide Gene Therapy” (HTML or PDF)
 
Instructions: Please study the introduction, “Parameters that influence the success of GDEPT systems,” and “Future perspectives” sections.  You can access the PDF under “article tools” on the left-hand side of the page.  The authors work in the Cancer Research Campaign Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, UK.
 
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7.5 Gene Therapy Design   7.5.1 Adenovirus Vectors   - Reading: John W. Kimball’s Biology Pages: “Gene Therapy II” Link: John W. Kimball’s Biology Pages: “Gene Therapy II” (HTML)
 
Instructions: Please study this page.
 
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7.5.2 Retrovirus Vectors   - Reading: Genetherapynet.com’s “Retroviral Vectors” Link: Genetherapynet.com’s “Retroviral Vectors” (HTML or PDF)
 
Instructions: Please study this page. You can access the PDF by clicking on the Adobe icon at the top of the page.
 
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7.5.3 Particle Bombardment   - Reading: Davidson College: Megan McDonald’s “Gene Guns” Link: Davidson College: Megan McDonald’s “Gene Guns” (HTML)
 
Instructions: Please study this page.
 
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7.5.4 Liposomes and Lipofection   - Reading: University of Pennsylvania’s Diamond Lab: “Gene Therapy” Link: University of Pennsylvania’s Diamond Lab:  “Gene Therapy” (HTML)
 
Instructions: Please study this page.
 
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7.5.5 Antisense Therapy   - Reading: Thomas Jefferson University’s “Laboratory of Nucleic Acid Therapeutics” Link: Thomas Jefferson University’s “Laboratory of Nucleic Acid Therapeutics” (HTML)
 
Instructions: Please read this page.
 
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7.6 Current Gene Therapy Models   7.6.1 SCID (Severe Combined Immunodeficiency)   - Reading: John W. Kimball’s Biology Pages: “Gene Therapy I” Link: John W. Kimball’s Biology Pages: “Gene Therapy I” (HTML)
 
Instructions: Please study this page.
 
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7.6.2 Duchenne Muscular Dystrophy   - Reading: Gene Therapy Review: Christophe Pichavant’s “Gene Therapy for Duchenne Muscular Dystrophy” Link: Gene Therapy Review:  Christophe Pichavant’s  “Gene Therapy for Duchenne Muscular Dystrophy” (HTML)

 Instructions: Please study the entire article.  
    
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7.6.3 HIV (Human Immunodeficiency Virus)   - Reading: PLOS Pathogens: Wilen et al’s “Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases” Link: PLOS Pathogens:  Wilen et al’s “Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases” (HTML or PDF)
 
Instructions: Please study the “Abstract,” “Author Summary,” and “Introduction” sections.  You can download the PDF from the top right corner of the page.  This is a peer-reviewed publication.
 
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