Module 9 - Chromosomal Mutations, Gene Mutations & Repair

Question 1

What is a mutation?

Answer 1

• inherited change in genetic information

Question 2

What is a somatic mutation?

Answer 2

• occurs in somatic cells
• the earlier in development a somatic mutation is, the larger the clone of cells that will carry the mutation

Question 3

What is a germline mutation?

Answer 3

• occurs in germline (gamete) cells or progenitors of these cells
• germline mutations can be passed on to the next generation

Question 4

What is a gene mutation?

Answer 4

• relatively small DNA lesion that affects a single lesion

Question 5

What is a chromosome mutation?

Answer 5

• large-scale DNA alternation that affects the chromosomal structure or the number of chromosomes

Question 6

Chromosome Morphology of Eukaryotes

Answer 6

• a chromosome has 3 basic elements:
• centromere (point of attachment for spindle microtubules)
• telomere (ends of a chromosome that stabilize them and have repetitive sequences)
• origin of replication (multiple ori sites)

Question 7

What is a karyotype?

Answer 7

• a karyotype is a complete set of chromosomes that an organism possesses
• it is usually presented by a metaphase chromosome spread (where chromosomes are condensed and easier to see)
• chromosomes are lined up in order of descending size

Question 8

What are the steps in Chromosome Rearrangements?

Answer 8

1. Duplication:
   - tandem duplication: if a duplicated region is immediately adjacent to the original segment
   - displaced duplication: when a duplicated region is at a distance from the original segment
   - reversed duplication: when a duplicated region is duplicated
2. Deletion: a segment of a chromosome is deleted
3. Inversion: a segment of the chromosome becomes inverted
4. Translocation: chromosome segment moves from one chromosome to another place on the same chromosome, or to a non-homologous chromosome

Question 9

What is aneuploidy?

Answer 9

• change in number of individual chromosomes. This gives rise to:
  1. chromosome loss at mitosis or meiosis
  2. nondisjunction: failure of homologous chromosomes to separate at meiosis OR failure of sister chromatids to separate at mitosis
• nondisjunction leads to gametes or cells with an extra chromosome or none

Question 10

Types of aneuploidy

Answer 10

1. nullisomy - loss of both members of a homologous pair
2. monosomy - loss of a single chromosome
3. Trisomy - gain of a single chromosome
4. Tetrasomy - gain of two homologous chromosomes

• more than one aneuploid mutation can occur in the same individual

Question 11

Aneuploidy in Humans

Answer 11

• 50% of miscarriages are due to chromosome abnormalities; the majority being aneuploidy (embryo isn’t viable)
• down syndrome (some intellectual challenges, poor muscle tone) due to trisomy 21

Question 12

Spontaneous errors in replication

Answer 12

• errors by DNA polymerase during replication can lead to base changes
• wobble base pairing can lead to replication error
• also, strand slippage can occur in replication

Question 13

Spontaneous chemical changes

Answer 13

• e.g. depurination (loss of a purine base from a nucleotide produces an apurinic) due to a spontaneous chemical change
• nucleotide is randomly inserted across from the AP site during replication; can cause permanent mutation

Question 14

Exposure to mutagens (NOT spontaneous)

Answer 14

• base analogs
• alkylating agents
• reactions of oxygen radicals
• intercalating agents
• UV radiation

Question 15

What do intercalating agents do?

Answer 15

• insert themselves between adjacent bases causing distortion of the 3D structure of the DNA

Question 16

What does UV radiation do?

Answer 16

• causes formation of pyrimidine dimers

Question 17

DNA repair

Answer 17

• most repair pathways require two DNA strands; a template strand to specify the correct information and a second strand to be corrected
• DNA is often redundant: many types of DNA damage can be corrected by more than one repair pathway
• DNA repair is extremely important for cell viability and so redundancy is a safeguard mechanism

Question 18

Common DNA repair mechanisms

Answer 18

• mismatch: replication errors, including mispaired bases and strand slippage
• direct: pyrimidine bases; or other specific types of alterations
• base excision: abnormal bases, modified bases, and pyrimidine dimers
• nucleotide excision: DNA damage that distorts the double helix including abnormal bases, modified bases, and pyrimidine dimers
• homology-directed repair: double-stranded breaks
• non-homologous end joining - double-stranded breaks

Question 19

Cancer as a genetic disease

Answer 19

• cancer arises because of abnormal cell division which predominantly occurs as a result of genetic changes. Thus, cancer is a genetic disease
• cancer is a result of a multistep process that requires several mutations

Question 20

Clonal evolution of cancers

Answer 20

• cancer begins when a mutation causes a cell to divide faster than normal
• this cell will proliferate, giving rise to a clone of cells which will all carry the mutation