Mutations S1M1

  1. What is a mutation?
    Any change in the base sequence of DNA
  2. What’s so special about abnormal DNA mutations
    Mutations are heritable. Once the mutation arises, it stays and is passed on.
  3. What can a mutation do
    It can lead to a faulty or missing protein.
  4. Are mutations important only for inherited diseases?
    No, mutations in somatic cells can do a lot of damage as well.
  5. Two types of Single-base substitution (“pointmutation”)
    • Transition - Pyr for a Pyr (T-C; A-G)
    • Transversion Pyr for a Pur or vice a vsImage Upload 1
  6. Somatic mutations are important for
    Aging and Cancer
  7. Germline mutations
    In gametes or the precursors of gametes. Can lead to genetic diseases
  8. Duplication is most common when
    During crossing over in MeiosisImage Upload 2
  9. How many hydrogen bonds are between the base pairs
    Only two
  10. What is the weakest bond between bases in DNA
    A Purine base, and a deoxyribose
  11. 90% of disease causing mutations are found in what
    The coding sequence of the gene
  12. What is a somatic cell
    Any cell but those in the germline
  13. What is neoplasia
    An abnormal growth
  14. Each child is born with about
    • 100 new mutations.
    • − Most of these mutations are harmless.
    • − A few are slightly unfavorable. They contribute to polygenic diseases.
    • − Rarely, a single mutation is bad enough to cause a disease.
    • − Favorable mutations are very rare
  15. Why are most serious genetic diseases rare?
    Those carrying the genes usually die or can't reproduce
  16. Is purifying selection more effective for recessive or for dominant disease mutations?
    • Recessive can be passed without ever manifesting itself
    • Dominant always express themselves, but remain low causing disease. This is when natural selection kicks in, therefore dominant
  17. Causes of mutations can be
    • Spontaneous tautomeric shifts
    • Ionizing radiation (X-rays, radioactivity)
    • UV radiation (sunlight)
    • Chemicals
  18. Spontaneous tautomeric shifts
    A change in a bases in nucleic acid, shift between keto and enol forms or between amino and imino formsImage Upload 3
  19. The risk of new mutations depends on parental
    • Age,
    • Increased maternal age is a risk factor for aberrations in chromosome number.
    • Advanced paternal age is a risk factor for point mutations.
  20. Nucleotide excision repair
    • Image Upload 4
    • This is for lesions that are large enough to distort the geometry of the DNA double helix
    • The removed gap is filled by DNA polymerase and DNA ligase
  21. Two defects of nucleotide excision repair
    • Xeroderma pigmentosu
    • Cockayne syndrome
  22. Xeroderma pigmentosu
    • − Defect of genome-wide nucleotide excision repair
    • − Sunburn, skin cancer
    • − Autosomal recessive
    • − 7 different types
    • Image Upload 5
  23. Cockayne syndrome
    • − Defect of transcription-coupled nucleotide excision
    • repair
    • − Poor growth, neurological problems, early senility
    • − Autosomal recessive
    • − 2 different types
    • Image Upload 6
    • Happens most in quickly dividing cells
    • − Defect of post-replication mismatch repair
    • − ≥50% risk of colon cancer
    • − Also increased risk of other cancers
    • − Autosomal dominant inheritance
  25. Post-replication mismatch repair happens how
    When mismatched DNA is found it is removed (while still attached to the original strand) and then repaired by DNA polymerase and ligase
  26. Why does a defect of post-replication mismatch repair cause cancer
    All cells have a heterozygous defect in a mismatch repair protein. When a somatic mutation disrupts the single intact copy of the gene, the cell becomes a mutator. Some of these mutator cells become cancerous.
    • Caused by a mutation in a signaling protein required for the repair of DNA double-strand breaks.
    • Abnormalities:
    • Cerebellar ataxia (loss of body movement) starting in early childhood
    • Dilation of small blood vessels
    • Sensitivity to ionizing radiation
  28. Radiation ionizing has what effect on the body
    • 1. Can knock off electrons off orbitals
    • 2. Can hit DNA directly
    • 3. Makes hydroxyl radicals
  29. What is the only base with a methyl group
  30. Free radicals are present in the body where
    Wherever oxydation takes place
  31. What can a Thymine base be replaced with
  32. Nitrite is partially
    Mutagenic and is used as a preservative in meat
  33. Depurinated means
    A base is deleted
  34. AP endonuclease, Polymerase B
    • AP endonuclease, polymerase beta remove wrong material
    • Polymerase Beta replaces with correct nucleotide
    • Ligase fills the small gap leftover
  35. Why is the advantage of having Thymine instead of Uricil in the DNA
    The deamination of uricil to cytosine is not detected and therefore won't be repaired
  36. Methylcytosine has high mutation rate why
    • Its deamnination produces thymine that won't be detected to be repaired by incision repair
    • This is what makes CG sequences a hot spot for mutations
  37. Base excision repair
    Image Upload 7
  38. Nucleotide Excision repair
    Is one of the most important repair systems!!
  39. Deamination
    Removal of an amine. Because base pair excision can't recognize this it is considered a hot spot for mutationsImage Upload 8
  40. What are intercalating agents
    Aromatic structures that place themselves between base pairs pushing them apart. These can contribute to small insertions and deletions
Card Set
Mutations S1M1