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Muatations

Emma Lloyd Genetics I English 63 cards

Cards in this deck (63)

  1. 1What are mutations?Heritable changes in the genetic material that are not due to genetic recombination. They are the ultimate source of differences among species.
  2. 2What causes most of the genetic variation among a species?Genetic recombination (genetic material exchange between pairs of homologous chromosomes) and sex (independent assortment of paternal and material chromosomes in meiosis)
  3. 3Where can mutations occur?They are random events so can occur at any position in the genome
  4. 4What is a 'wild-type'?A normal DNA sequence prior to mutation. However, as there is so much genetic variation, it is difficult to define a wild-type. In terms of genetic diseases, wild-type will mean 'not diseased'
  5. 5What are the two broad groups of mutations?Point mutations (minor changes in DNA following only one or a few nucleotides) or rearrangements (extensive chromosomal alterations involving hundreds of base pairs or even whole chromosomes)
  6. 6What ways are mutations classified?Based on origin, cell type, expression, effect of function, molecular change or effect on translation
  7. 7Which different ways can mutations be classified by origin?Spontaneous (occurs without a known mutagen, usually due to DNA replication errors or compounds that are usually in the cell) OR induced (in the presence of a known mutagen)
  8. 8What is a mutagen?A chemical or physical agent that increases the rate of mutagenesis. There are thousands of natural and synthetic chemicals that can cause DNA damage, like ionising radiation and UV
  9. 9How can mutations be classified by cell type?They can be somatic (occurs in non reproductive cells and wont be passed to next generation) or germ-line (occurs in the reproductive cells and will be passed on to next gen)
  10. 10How can mutations be classified by expression?They can be unconditional (expressed at all times) or conditional (expressed only under some conditions like temperature sensitive mutations)
  11. 11How can mutations be classified by effect on function?-Can have a loss of a function (also called knockout or null mutations)
    -Can be hypomorphic which reduces normal function (sometimes called leaky)
    -Hypermorphic which increases normal function)
    -Gain-of-function but expressed at incorrect time or in inappropriate cells
  12. 12How can mutations be classified by molecular change?They can be base substitution like transition (purine to other purine or pyrimidine to other pyrimidine) or transversion (purine to pyrimidine or vice versa). They can also be insertions or deletions.
  13. 13How can mutations be classified by effect on translation?-Point mutations just change one letter and the sequence is translated the same just with that different nucleotide which can sometimes still code for the same a.a
    -Frameshift mutations are insertions or deletions and they mean all the codons following it in the sequence are read wrong
  14. 14What is a missense (nonsynonymous) mutation?It changes the amino acid that is encoded
  15. 15What is a nonsense (termination) mutation?It creates a termination codon. These are opal (TGA), ochre (TAA) or amber (TAG)
  16. 16What is a neutral mutation?Changes the amino acid encoded for into another amino acid BUT it has a similar function
  17. 17What is a silent (synonymous) mutation?Doesn't change the amino acid coded for at all
  18. 18An example of a missense mutation?Phenylketonuria which is a mutation in the phenylalanine hydroxylase gene that turns a C to a T, resulting in Arg to Trp. It is an autosomal recessive trait and sufferers cannot consume phenylalanine
  19. 19What causes sickle cell anemia?An autosomal recessive missense mutation in the beta globin gene that turns A to T resulting in Glu to Val.
  20. 20What causes Pelizaeus-Merzbacher-like disease?An autosomal recessive nonsense mutation in the gap junction protein gamma-2 gene. It turns a C to a T which turns Arg to a stop codon TGA (opal)
  21. 21What causes beta-thalassemia?It is a disorder that reduces the production of hemoglobin and is caused by the deletion of AA which causes a frameshift mutation
  22. 22What is the most common mutation to cause cystic fibrosis?A deletion of 3 bases in the CFTR gene. TTT is deleted so there is no Phe. It is autosomal recessive.
  23. 23What is a reversion mutation?A back mutation in which the sequence is reverted back to the wild-type
  24. 24What is a suppressor mutation?A mutation that cancels out (either partially or totally) the effect of another mutation elsewhere on the genome
  25. 25What are the three main causes of mutation?-Errors in replication
    -Spontaneous damage due to endogenous compounds
    -Damage due to exposure to a mutagen
  26. 26Which different tautomeric forms can bases have?-Imino cytosine to amino adenine
    -Enol thymine to keto guanine
    -Imino adenine to amino cytosine
    -Enol guanine to keto thymine
    (Tautomeric shift during DNA replication can lead to mutation)
  27. 27Which of the four tautomeric versions are the rare forms?The imino and the enol forms. Amino and keto are regular.
  28. 28When are insertion and deletion mutations created?When bases in the template or new strand slip out of alignment during replication. Frequently happens during replication of DNA sequences.
  29. 29Why are insertions and deletions more likely in repetitive sequences?If a sequence, for example, is GTCGTCGTCGTC, this might fold in on itself and the Gs bond to the Cs, causing a whole loop in the DNA strand that won't be present in the sequence
  30. 30How can hydrolysis (oxidative deamination) affect bases?Cytosine can be deaminated to uracil and methylcytosine to thymine. Adenine can be deaminated rarely to hypoxanthine and guanina to xanthine.
  31. 31What is base loss?Hydrolysis happens on the sugar-base bond which separates them resulting in an abasic site/AP (apurinic/apyrimidinic) sites.
  32. 32Are purines or pyrimidines more unstable?Purines are more unstable so there are 10,000 depurinations per cell per day and only 500 depyrimidations per cell epr day
  33. 33What generates reactive oxygen species?Aerobic metabolism
  34. 34What reactive oxygen species are there?-Singlet oxygens
    -Hydrogen peroxide
    -Superoxide anion radicals
    -Hydrogen radicals
  35. 35How can reactive oxygen species interact with DNA?They can attack the DNA in many ways including strand breaks and base modifications. Reactive oxygen species can have 20,000 hits per cell per day
  36. 36What happens when adenine is methylated?3-methyladenine is formed which blocks DNA replication. 600 of these residues are generated per cell per day
  37. 37What do UV-C and UV-B induce?They induce the formation of pyrimidine dimers where two adjacent pyrimidine bases on the same strand becoming covalently linked. Thymine dimers are the most common. They block transcription and DNA replication.
  38. 38What is the relationship between skin cancer and pyrimidine dimers?If the pyrmidine dimers are not repaired they result in C to T and CC to TT transitions which are the most common type of mutations found in malignant melanoma cancer cells
  39. 39Why does radiation affect DNA?It damages DNA as x-rays, radon and nuclear fallout can generate reactive oxygen species which can create localised damage
  40. 40How do oxidising agents induce DNA damage?Things like nitrous acid work via oxidative deamination of adenine, cytosine, guanine
  41. 41What do intercalating agents do?They cause base insertions or deletions (indels) resulting in frameshift mutations, hence, DNA damage
  42. 42What can base analogue 5-bromouracil (5-BU) do?5-BU can switch between two chemical states, one state which pairs with adenine and one which pairs with guanine. If it changes state after incorporation into DNA this will lead to mutation.
  43. 43What is oxidative damage?Aerobic metabolism generates reactive oxygen species (ROS) like singlet oxygen, hydrogen peroxide, sueproxide anion radicals and hydrogen radicals.
  44. 44What do ROS do?Attack DNA in many ways including strand breaks and base modifications. There are 20,000 hits per cell per day.
  45. 45What does methylation do?Methylation of adenine to form 3-methyladenine blocks DNA replication. 600 3-methyladenine residues are generated per cell per day
  46. 46What does UV-C and UV-B do?UV light that form pyrmidine dimers where two adjacent pyrimidine bases on the same strand are covalently linked. Thymine dimers are the most common.
  47. 47What are the most common mutations in skin cancer?C to T and CC to TT transitions from pyrimidine dimers that go unrepaired
  48. 48What does radiation do?x-rays, radon and nuclear fallout can generate ROS species. They can create localised damage with multiple hits including double strand breaks.
  49. 49What does nitrous acid do?It is an oxidising agent that works via oxidative deamination of adenine, cytosine and guanine
  50. 50What are intercalating agents?They cause base insertions or deletions (indels) resulting in frameshifts
  51. 51What are base analogues?Base analogues, eg, 5-bromouracil (5-BU) can be incorporated into DNA during replication. It can switch between two states, one of which pairs with adenine and the other with guanine. If it changes state after incorporation into the DNA it will lead to mutation.
  52. 52What are base adducts?Mutagens that add chemical groups to DNA bases like alkyl groups. An example is aflatoxins that are produces by moults in foodstuffs and lead to base loss and formation of AP site.
  53. 53What are polyaromatic hydrocarbons (PAHs) and where are they found?it is found in soot, exhaust gas, cigarette smoke and charred food. It causes G to T mutations.
  54. 54What are the two basic mechanisms for DNA repair?Reversal of damage (DNA is repaired without new DNA synthesis) or excision repair (the damaged base or a stretch of DNA is removed and new DNA is then synthesises to replace the damaged DNA)
  55. 55Example of reversal of damage?Repairing damage of pyrimidine dimers caused by UV light is an example. Photolyases use the energy of light to split pyrimidine dimers, a process called photoreactivation.
  56. 56What repairs abasic sites (AP sites)?The AP enconuclease system
  57. 57How does nucleotide excision repair work?1. DNA damage recognition xomplexes recuit the TFIIH complex.
    2. The XPB and XPD helicases unwind DNA around lesion
    3. XFP and XFD excise the damaged DNA
    4. DNA polymerase fills gap
    5. new DNA strand is ligated in place
  58. 58What illnesses are caused by issues with the nucleotide excision repair system?Xeroderma pigmentosum (XP) and cockayne syndrome (premature aging, dwarfism, deaf).
  59. 59How many mutations are there generally per generation and do men or women have a higher rate of mutation?90 mutations per generation and men are more prone to mutations
  60. 60What are 'driver' mutations?Mutations which are found within the 350-2000 cancer genes within the human genome
  61. 61What are passenger mutations?They do not confer growth advantage and were acquired before or after the cell became a cancer cell
  62. 62What is a de novo mutation?A mutation that occurs for the first time in an individual due to a mutation. This wont be present in family members before this individual
  63. 63What causes Rett Syndrome?A de novo germline mutations within a mutational hotspot

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Genetics I Flashcards on Muatations, created by Emma Lloyd on 29/04/2018.
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Emma Lloyd
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