Lecture 22

Question 1

do most mutations occur in somatic cells or gamete cells?

Answer 1

somatic cells

Question 2

when are mutations inherited?

Answer 2

if mutations are in gametes

Question 3

what percent of offspring carry the mutation if a gamete is mutated?

Answer 3

50%

Question 4

why do only 50% of F1 generation carry mutation from germ-line mutant?

Answer 4

mutation occurs randomly so only 1 homologous chromosome will get mutation, so only F1s that inherit that chromosome will have mutation

Question 5

chromosome mutation VS insertional mutation VS point mutation

Answer 5

chromosome mutation: gain/loss of all or part of a chromosome

insertional mutation: insertion of large region of DNA

point mutation: changes in 1 nt

Question 6

2 categories of point mutations

Answer 6

1. base substitution
2. indel

Question 7

2 types of base subtitutions

Answer 7

1. TRANSITION
2. TRANSVERSION

Question 8

what is a transition base substitution?

Answer 8

purine –> purine
pyrimidine –> pyrimidine

Question 9

what is a transversion base substitution?

Answer 9

pyrimidine –> purine
purine –> pyrimidine

Question 10

which bases are purine?

Answer 10

A and G

Question 11

which bases are pyrimidine?

Answer 11

C and T

Question 12

4 types of point mutations in ORF

Answer 12

1. Synonymous/Silent Mutation
2. Nonsynonymous/Missense Mutation
3. Nonsense Mutation
4. Frameshift Mutation

Question 13

what happens in a Synonymous/Silent Mutation?

Answer 13

nt sequence changes but aa sequence does not change

Question 14

what happens in a Nonsynonymous/Missense Mutation?

Answer 14

nt sequence changes and changes aa sequence

Question 15

2 types of Nonsynonymous/Missense Mutations and what they mean

Answer 15

1. conservative –> mutant encodes chemically similar aa
2. non-conservative –> mutant encodes chemically different

Question 16

what happens in a Nonsense Mutation?

Answer 16

change sequence of codon that codes for an aa into a stop codon

Question 17

what does the effect of a Nonsense Mutation rely on?

Answer 17

depends on the distance from 3’ end of ORF

Question 18

what does a Nonsense Mutation lead to?

Answer 18

triggers nonsense-mediated decay which degrades mRNA

Question 19

what causes a Frameshift Mutation? and what does it lead to?

Answer 19

caused by an insertion or deletion, leading to a change in the translation reading frame for codons downstream of the mutation

Question 20

3 effects of point mutations on gene function

Answer 20

1. WT function
2. LOF
3. GOF

Question 21

2 types of LOF and what they mean

Answer 21

1. HYDROMORPHIC: weak/partial function
2. NULL: non-functional or not produced

Question 22

3 types of GOF and what they mean

Answer 22

1. HYPERMORPHIC: protein is hyperactive
2. ECTOPIC: more protein made or made in wrong time/place
3. NEOMORPHIC: protein gains new function

Question 23

where in the genome can point mutations be found?

Answer 23

in coding AND non-coding regions

Question 24

example of gene that has LOF after mutation

Answer 24

p53

Question 25

example of gene that has GOF after mutation

Answer 25

RAS

Question 26

what happens to RAS function with GOF?

Answer 26

becomes constitutively active

Question 27

what is the mutation that occurs to make RAS constitutively active?

Answer 27

G --> T Gly --> Val

Question 28

how does mutation cause RAS to become constitutively active?

Answer 28

blocks conversion from GTP to GDP so RAS is stuck in active form and cells receive growth signal

Question 29

mutations in non-coding regions affect: (5)

Answer 29

1. transcription 2. splicing 3. stability 4. translation 5. function

Question 30

2 ways point mutations can affect mRNA splicing

Answer 30

1. make new splice site in wrong place 2. remove splice site so there is no splicing

Question 31

outcome of PBRM1 mutation on cancer patients

Answer 31

PBRM1 mutation causes worse cancer prognosis

Question 32

describe what happens with a BAP1 mutation

Answer 32

GGT --> GGG, still Glycine exon 11 spliced out and causes framshift that makes a stop codon mRNA and protein are degraded (LOF) therefore, mutation is silent in coding region but visible in translation

Question 33

what do Northern and Western blots look like if there's a MISSENSE MUTATION?

Answer 33

aa is just swapped, so northern and western blots look the same as WT

Question 34

what do Northern and Western blots look like if there's a NONSENSE MUTATION?

Answer 34

makes early stop codon, so northern looks same as WT but western shows smaller protein OR mRNA degradation via NMD

Question 35

what do Northern and Western blots look like if there's a FRAMESHIFT MUTATION?

Answer 35

can make smaller protein, so northern looks the same as WT but western shows smaller protein OR mRNA degradation via NMD

Question 36

what do Northern and Western blots look like if there's a REGULATORY REGION MUTATION?

Answer 36

northern and western both show no band

Question 37

2 origins of spontaneous mutations

Answer 37

1. errors in DNA replication 2. chemical changes to DNA

Question 38

2 ways that errors in DNA replication can occur

Answer 38

1. base mispairing 2. strand slippage

Question 39

what is the DNA pol error rate?

Answer 39

300 mutations per mitosis

Question 40

are most DNA pol errors harmful?

Answer 40

no, >99% are fixed by DNA repair mechanisms

Question 41

2 types of chemical changes in DNA that lead to mutation?

Answer 41

1. depurination 2. deamination

Question 42

what happens to DNA if there are no proofreading mechanisms?

Answer 42

any mismatch = mutation

Question 43

3 types of errors in base pairing

Answer 43

1. tautomeric base pair 2. ionized base pair 3. wobble base pair

Question 44

what is a tautomer?

Answer 44

isomaer of a base with diff positions of atoms and their bonds, the forms are in eqb

Question 45

what happens when a thymine base pairs with an enol form of guanine?

Answer 45

error in replication causes T-G mismatch when the DNA is replication, one product will be normal C-G pairing and the mutant product will be A-T pairing

Question 46

when does a mismatch become permanent?

Answer 46

once replicated