Lecture 2 - DNA Mutations And repair

Question 1

What are mutations?

Answer 1

Changes in DNA that may or may not affect the phenotype (looks, how gene is expressed)

Question 2

What can random changes in an organisms DNA be caused by?

Answer 2

• It can be inherited (passed down from parent to offspring)
• Can be caused by carcinogens (cancer causing agents in the environment)

Question 3

What are replication dependent or independent mutations

Answer 3

• Replication-dependent mutations - Errors that can occur during DNA replication
• Replication-independent mutations - Errors that also occur independently of DNA replication

Question 4

Spontaneous mutations vs induced

Answer 4

Spontaneous - Mutations that occur as a result of natural changes in DNA

Induced - Changes caused by environmental chemicals and radiation
- Mutagen chemicals that increase the rate of mutations above the spontaneous

Question 5

Environmental agents (mutagens)

Answer 5

• Physical - radiation
  – heat
  – UV
  – Ionizing
• Chemicals
  – Natural toxins
  – Synthetic substances
  —> Laboratory substances
  —> Pollutants
  —> Chemoterapeutics

Question 6

How many mutations does our DNA undergo during our lifetime and why?

Answer 6

• 30 New mutations
• Because of mistakes during DNA copying or cell division, but more often because of damage from the environment

Question 7

What are hotspots? And are all sites equally susceptible to mutations?

Answer 7

• Hotspots are sites that gain more mutations than expected
• No, different sites are not equally susceptible to mutations

Question 8

How does gender affect mutations?

Answer 8

• Male/female ration is ~6
• Higher mutability in human and mammalian males

Question 9

What are Somatic mutations, where do they occur and how?

Answer 9

• Somatic mutations - Not inherited, don’t play a role in evolution
• Localized within cells of an organism (arise in Somatic cells)
• Passed on to other cells through mitosis
• Mosaicism: tumors, antibody diversity, etc..
• Higher in dividing cells

Question 10

What are germ-line(Generative) mutations?

Answer 10

• Germ-line mutations - Inherited and thus are important in evolution
• Occur in cells that produce gametes
• Passed on to future generations

Question 11

What kind of mutations are there?

Answer 11

There are two kinds:

1. Chromosomal mutations
2. Gene mutations

Question 12

Mutation sizes and what they mean

Answer 12

1. Large mutations - Genome mutations -> Change of chromosome number
2. Medium mutations - Chromosome mutations -> Change of chromosome structure
3. Small mutations - Gene mutations -> Ranging from change to a single nucleotide to a whole gene (not visible)
   – Affecting the length of DNA:
   —> Deletion (single base or shorter-longer sequences)
   —> Insertion (single base or shorter-longer sequences- repetitive more insertions than deletions)
   – No effect on the length of DNA (nucleotide substitution)

Question 13

Neutral, Beneficial and Harmful mutations

Answer 13

• (Most) Neutral - During evolution later might be harmful or beneficial
• (Some) Beneficial:
  – Harmful one mutates back to wild
  – Getting beneficial function
  —> Diversity of antibody
  —> CCR5^32 - HIV resistance (^ = delta)
  —> Sickle cell anemia - malaria resistance
• (Some) Harmful - Causing diseases (all monogenic inherited diseases)

Question 14

What are gain-of-function mutations and what do they do?

Answer 14

• They are mutations that change the gene production such that it gains a new and abnormal function
• Produce an entirely new trait
• Causes a trait to appear in inappropriate tissues or at inappropriate times in development
• Frequently dominant

Question 15

What are loss-of-function mutations and what do they do?

Answer 15

• Gene product having less or no function
• Complete or partial loss of normal function
• Structure of protein so altered it no longer works correctly
• Can occur in a regulatory region that affects transcription, translation or splicing of the protein
• Frequently recessive

Question 16

Back mutation or reversion and lethal mutations.

Answer 16

• Back mutation or reversion: A point mutation that restores the original sequence and hence the original phenotype
• Lethal mutations: Mutations that lead to the death of the organisms which carry the mutations

Question 17

Phenotypes in back mutation or reversion and lethal mutation

Answer 17

• Most often recessive
  – Exception, Haploid sufficiency - when the reduced dosage of a normal gene product is not enough for a normal phenotype
• Dominant negative mutations
  – In humans have been implicated in cancer (e.g. Mutations in genes p53, ATM)

Question 18

Suppressor mutations

Answer 18

• Suppresses the effect of other mutation
• Occurs at the site different from the site of the original mutation
• An organism with a suppressor mutation is a double mutant but exhibits the phenotype of un mutated wild type

Question 19

What are chromosomal mutations? What is a normal chromosome amount for humans? Example of a mutation

Answer 19

• Abnormal changes in the structure of all or part of a chromosome, OR in the number of chromosomes an organism has
• Normal humans have 46 chromosomes -> 23 pairs
• E.g. Down syndrome that has 47 chromosomes

Question 20

What do we do and see during karyotyping?

Answer 20

• We take a sample of blood cells
• Chromosomes get separated out, viewed with a microscope and photographed
• The photograph gets rearranged to show the paired chromosomes
• Size, shape and banding pattern are used to pair the chromosomes

Question 21

What are the different types of DNA damage?

Answer 21

1. Mismatches - arise from occasional incorporation of incorrect nucleotides
2. Abnormal bases - Arise from spontaneous deamination, chemical alkylation, or exposure to free radicals
3. Pyrimidine dimers - Form when DNA is exposed to UV light
4. Backbone lesions - occur from exposure to Ionizing radiation and free radicals