Lecture 12

Question 1

what percent of genetic diseases are due to missense mutations?

Answer 1

50%

Question 2

what percent of genetic diseases are due to nonsense mutations?

Answer 2

12%

Question 3

what percent of genetic diseases are due to addition/deletion mutations?

Answer 3

25%

Question 4

what percent of genetic diseases are due to RNA splicing mutations?

Answer 4

10%

Question 5

what is the difference between and exact reversion and an equivalent reversion?

Answer 5

exact results in the exact same codon as the original protein, equivalent results in a different codon that still codes for the original protein (GAG vs GAA for Glu)

Question 6

what is the difference between an intragenic mutation and an extragenic mutation?

Answer 6

• an intragenic mutation is a suppressor mutation that occurs on the same gene as the original mutation.
• an extragenic mutation is a suppressor mutation that occurs elsewhere in the genome but has an effect that alleviates the primary mutation.

Question 7

what is a suppressor mutation?

Answer 7

it is a secondary mutation that alleviates or reverts the phenotypic effect of a primary mutation

Question 8

what are most phenotypic reversions are usually due to?

Answer 8

genetic suppression at a different site within the same gene or another gene altogether.
- rarely every an exact reversion

Question 9

what are four routes for acquiring spontaneous mutations?

Answer 9

1 - polymerase errors on normal templates that escape fidelity checks
2 - misreplication at repetitive sites due to to strand slippage
3 - misreplication at damaged template sites
4 - transposable genetic elements

Question 10

what are the four forms of fidelity checks?

Answer 10

1) high polymerase selectivity
2) polymerase proofreading
3) post-replication mismatch repair
4) repair and error-avoidance mechanisms

Question 11

how is the parental strand of DNA distinguished from a newly replicated daughter strand?

Answer 11

parental stand is fully methylated while the daughter strand is hemi-methylated

Question 12

what are the steps for mismatch repair?

Answer 12

• MutS binds to mismatched DNA, recruits MutL
• MutL activates endonuclease MutH
• MutH binds hemimethylated GATC (dam) site and nicks daughter strand
• helicase and an exonuclease start at this nick and remove surrounding sequence including mismatch
• DNA Polymerase fills the gap

Question 13

what is the overall error rate of DNA Synthesis?

Answer 13

10 to the negative 10

Question 14

what is the error rate of polymerase selectivity?

Answer 14

10 to the negative 5

Question 15

what is the error rate of proofreading and post-replication mismatch repair, respectively?

Answer 15

10 to the negative 2 for both

Question 16

what occurs in Lynch Syndrome?

Answer 16

• mutation in the genes coding for mismatch repair

Question 17

what is another name for lynch syndrome?

Answer 17

HNPCC (hereditary non-polyposis colon cancer)

Question 18

what is the most mutagenic DNA lesion produced by oxygen radicals?

Answer 18

8-oxoguanine

Question 19

what does 8-oxoguanine bind to and why?

Answer 19

• adenine instead of cytosine
• imadizole part of the purine gets oxidized, removing a bond from the nitrogen closest to the carboxyl group. This nitrogen gains a hydrogen which allows it to now hydrogen bond.

Question 20

what makes transposable genetic elements mutagenic?

Answer 20

• if a transposon jumps and inserts within a gene it will deactivate that gene.

Question 21

What is DNA breathing?

Answer 21

The continuous unannealing and reannealing of DNA strands from each other. Can result in slippage.

Question 22

What can cytosine be mutated into and how?

Answer 22

-it can be deaminated into uracil