Mutations

Question 1

Base substitutions

Answer 1

Transitions and transversions

Question 2

Transitions

Answer 2

Replace a pyrimidine with a pyrimidine or a purine with a purine

Question 3

Transversions

Answer 3

Replaces a pyrimidine with a purine or vice versa

Question 4

Insertions and deletions

Answer 4

Can cause frameshift mutations and I frame insertions and deletions

Question 5

Frameshift mutations

Answer 5

Insertion or deletion of one or two base pairs, alters the reading frame of the gene distal to the site of mutation
Protein sequence can change dramatically

Question 6

Inframe insertions and deletions

Answer 6

Insertion or deletion of just one codon so the codons stay intact

Question 7

Tautomeric shift

Answer 7

Reversible change in the location of a hydrogen atom in a molecule that alters it from one to another isomer
Or movement of H+ atoms from one position in a purine or pyrimidine to another
There are keto/enol and amino/imino
Can generate rare base pairings
When dna with the tautomer is replicated just one of the new strands is affected

Question 8

Expanding nucleotide repeats

Answer 8

Increase In the number of copies of a set of nucleotides over time
Expansion of triplet repeats causes numerous human diseases.
Mechanism of expansion involves DNA replication.
It can be outside of the coding region, if it affects the expression like in the case of fragile X syndrome,
in the course of replication, a hairpin forms, which result in more repeat, being added

Question 9

Why are expanding nucleotide repeats considered a dynamic mutation

Answer 9

it’s known as a dynamic mutation, because the nucleotide repeat copy number can expand or contract dramatically in each germ cell or over generations

Question 10

What are the functional effects of mutations

Answer 10

Forward mutation
Reverse mutation
Missense mutation
Nonsense mutation
Silent mutation
Neutral mutation
Loss of function mutation
Gain of function mutation
Conditional mutation
Lethal mutation
Suppressor mutation

Question 11

Forward mutation

Answer 11

Wild type to mutant type

Question 12

Reverse mutation

Answer 12

Mutant type to wild type

Question 13

Missense mutation

Answer 13

Amino acid to different amino acid
A base substitution can result in a new codon coding for new amino acid

Question 14

Nonsense mutation

Answer 14

Sense codon to nonsense codon
Can end translation prematurely
A base substitution that changes a sense codon to one of the three nonsense codons: UAG, UGA and UAA

Question 15

Silent mutation

Answer 15

Codon to synonymous codon
A base substitution that changes the codon to one still specifying the same amino acid

Question 16

Neutral mutation

Answer 16

Missense mutation in which the amino acid is changed to one of a similar chemical type
Ex. Glycine to alanine

Question 17

Loss of function mutation

Answer 17

Result of mutation that cause the complete or partial loss of normal protein function
Ex. Cystic Fibrosis results from a loss of function mutation in the CF gene

Question 18

Gain of function mutation

Answer 18

Result of mutation that causes the cell to produce a protein or gene product whose function is not normally present
Ex. Legs as antennae

Question 19

Conditional mutation

Answer 19

Mutation that’s expressed only under certain conditions
ex. Temperature sensitive allele

Question 20

Lethal mutation

Answer 20

Causes premature cell death

Question 21

Suppressor mutations

Answer 21

Second site mutation that hides or suppresses the effect of the first mutation
Can be within the same gene (intragenic suppressor)
Not a reverse mutation
Or can be present in a different gene (intergenic suppressor)

Question 22

Reverse mutation

Answer 22

Restores the wild type gene and phenotype

Question 23

Factors that affect mutation rate

Answer 23

Frequency
Probability
Detection

Question 24

What are some causes of DNA damage

Answer 24

Cellular metabolism
UV light exposure
Ionizing radiation
Chemical exposure
Replication errors

Question 25

Mutation rate for bacteria

Answer 25

1-100 per 10 billion cells

Question 26

Eukaryotes mutation rate

Answer 26

1-10 mutations per million gametes

Question 27

APC gene

Answer 27

Mutations in this gene account for over 80% of all colon cancers Within this gene, majority of mutations occur in the mutation cluster region (MCR)

Question 28

Do dna in nucleosomes have less or more mutations

Answer 28

Less May be due to reduced exposure to mutagens

Question 29

Spontaneous mutations

Answer 29

Mutations that occur under normal circumstances Factors as a result of internal factors

Question 30

Induced mutation

Answer 30

Those that occur as a result of exposure to external factors (such as environmental chemicals and radiation)

Question 31

Is most dna damage caused by internal or external factors

Answer 31

Internal generated by metabolic processes inside the cell By Water (through hydrolysis) Oxygen (through oxidation) Alkylating agents (through alkylation)

Question 32

Spontaneous dna damage types

Answer 32

Tautomeric shifts Mispairing due to other structures Incorporated errors and replication errors Deletions and insertions

Question 33

Spontaneous chemical changes

Answer 33

Deputination Deamination Methylated cytosine

Question 34

Chemically induced mutations

Answer 34

Base analogs Alkylating agents Deamination chemicals Hydroxylamine Oxidative radicals Intercalating agents

Question 35

Tautomeric shifts

Answer 35

Position of the protons (H atoms) in the bases change Occurs in each of the 4 bases Hard to detect and differentiate from other mechanisms Type of spontaneous dna damage

Question 36

Mispairing due to other structures

Answer 36

- Type of spontaneous dna damage - arise through wobble - flexibility in the dna helical structure Shifts in the helix can allow for different bases to bond Or by protonated forms of certain bases Addition of hydrogen can allow for non-conventional bonds - this can lead to an incorporated and then replicated error

Question 37

Incorporated errors

Answer 37

Type of spontaneous DNA damage Occur when a base substitution causes a mispaired base to incorporate into a newly synthesized strand Leads to replicated error when dna is replicated

Question 38

Replicated error

Answer 38

Type of spontaneous dna damage Occurs when original incorporated dna error strand is replicated Creates a permanent mutation bc the base pairings are correct following mutation but they’re not what they’re supposed to be so the difference goes undetected, no way for repair systems to detect error

Question 39

Insertions or deletions

Answer 39

Type of spontaneous dna damage Can arise during replication or crossing over Can be result of strand slippage, if template strand loops out can result in deletion in newly synthesized strand If new strand forms loop, can result in addition of nucleotide/insertion Insertions and deletions can also arise from unequal crossing over during meiosis - if homologous chromosomes misalign during meiosis, one strand contains insertion and other one has deletion

Question 40

Depurination

Answer 40

A type of spontaneous chemical change Loss of a purine base from a nucleotide Caused by breakage of a covalent bond btw purine base and 1’ carbon atom of the deoxyribose sugar Apurinic site cannot provide a template for a complementary base on the newly synthesized strand A nucleotide with incorrect base (most often A) is incorporated into newly synthesized strand At next round of replication, this incorrectly invorporated base will be used as a template, leading to permanent mutation

Question 41

Deamination

Answer 41

Type of spontaneous chemical change Loss of an amino group, typically from cytosine Gives rise to uracil, which will pair with adenine during replication In next cycle A will pair with T and end result is a C—> T transition

Question 42

Methylated cytosine

Answer 42

Type of spontaneous chemical changes If cytosine is methylated then it will convert to thymine End result is C—> T transition Over time, genomes will become increasingly AT rich and GC poor

Question 43

Mutagen

Answer 43

Any environmental agent that increases the mutation rate above the spontaneous rate

Question 44

Base analogs

Answer 44

Chemicals with structures similar to any of the standard 4 nucleotides

Question 45

5-bromiuracil (5BU)

Answer 45

is an analog of thymine (pairs with adenine, but occasionally with guanine) thus, A—>G transition

Question 46

2-amino purine

Answer 46

a base analog of adenine, can mispair with cytosine resulting in T—>C transition

Question 47

Alkylating agents

Answer 47

Type of chemically induced mutation Mutagens that react with DNA bases and add methyl (CH3) or ethyl groups Ex. Ethyl methyl sulfonate (EMS) and Mustard gas are alkylating agents Adds an ethyl group to guanine, which can base pair with thymine G—>A transition

Question 48

Deaminating Chemicals

Answer 48

Type of chemically induced mutation Nitrous acid: Can change cytosine to thiamine Can change adenine to hypoxanthine, which am an base pair with citosine (A to G transition) Can change guanine into xanthine , which can base pair with thymine (G to A transition)

Question 49

Hydroxylamine

Answer 49

Chemically induced mutation Very specific base modifying mutagen Adds hydroxyl group to cytosine creating hydroxylaminocytosine Increases occurrence of rare tautomer that pairs with adenine Only affects cytosine C to T transition

Question 50

Oxidative radical

Answer 50

Chemically induced Molecular mechanism of mutations Reactive forms of oxygen Ex. (H2O2) Produced through normal aerobic metabolism Can also be produced by chemicals and radiation Can affect different bases

Question 51

Intercalating agents

Answer 51

Chemically induced Molecular mechanism of mutation Ex. Ethidium bromide, acridine orange, dioxin and proflavin Sandwich themselves (intercalate) btw adjacent base pairs Distorts dna helix Causes insertions and deletions —> Frameshift mutations

Question 52

Radiation

Answer 52

X-rays produce ionizing radiation Dislodge electrons from the atoms they encounter Stable atom —> free radicals, reactive ions Break phosphodiester bonds leading to double stranded breaks

Question 53

UV radiation

Answer 53

UV radiation is less intense than ionizing radiation Pyrimidine bases absorb UV light Induced chemical bonds btw two adjacent pyrimidine molecules in the same strand of DNA (stop signal) Thymidine diners most frequent