Mutation & Disease

Question 1

Define mutation

Answer 1

permanent, heritable change in DNA

Question 2

Are mutations pathologic?

Answer 2

not necessarily

Question 3

What is pathologic mutation

Answer 3

change in DNA taht has effect on the encoded protein or on gene expression that results in disease

Question 4

What are examples of mutations

Answer 4

base substitution
insertions
deletions

Question 5

mutations can be ____ or _____ line

Answer 5

somatic or germ line

Question 6

will mutations be passed onto the next generation?

Answer 6

not unless they occur in the germline

Question 7

What should you always keep in mind regarding mutations and how it affects protein

Answer 7

what affect the change in DNA sequence will have on gene function - look at protein folding, transcription, will function be completely lost, etc.

Question 8

it’s not always loss of function, you can have what

Answer 8

gain of function of a protein

Question 9

what is wild-type allele

Answer 9

most common allele for a gene within the population

Question 10

what is a polymorphism

Answer 10

allele that is less common than the wt allele but occurs at frequency of less than 1%
they are still relatively “common”

Question 11

What is a variant

Answer 11

change in DNA sequence that may or mayt notbe polymorphic and may or may not be pathogenic

Question 12

what is a rare varient

Answer 12

found at frequency of less than 1%

Question 13

How often do mutations occur per gene?

Answer 13

1.65 x 10^-7 per gene per cell division (1 in 10 billion)

Question 14

There is one replication error per how many divisions?

Answer 14

1.66 diploid cell divisions

Question 15

How many novel mutations are there per zygote?

Answer 15

138

Question 16

How many novel mutationsin haploid sperm?

Answer 16

128

Question 17

How many novel mutations in haploid egg?

Answer 17

10

Question 18

What is mutagenesis

Answer 18

the process by which mutations occur

Question 19

what are spontaneous mutations?

Answer 19

occur in affected person for the first time
not from parent
occur continuously

Question 20

What are mutagens

Answer 20

they increase the rate of mutagenesis

Question 21

describe dna repair

Answer 21

reduce mutation rate by 100 fold

Question 22

What is a synonymous substitution?

Answer 22

silent mutation, same amino acid

Question 23

What is a non-synonymous mutation?

Answer 23

aa will change - can have missense, nonsense, splice site, promoter

Question 24

what is a conservative mutation

Answer 24

aa change to another aa of similar type (so like glutamic acid to aspartic acid)

Question 25

what is non-conservative mutation?

Answer 25

aa changes to another type of aa so like glutamic acid to valine

Question 26

synonymous and non-synonymous are both what class of mutations

Answer 26

substitution

Question 27

what do promoter mutations do

Answer 27

alter gene expression

Question 28

what do splice site mutations do?

Answer 28

aberrant splicing - exon skipping or intron retention

Question 29

describe the three types of deletions

Answer 29

multiple of 3 - codon not multiple of 3 large deltion

Question 30

describe the affects of codon deletion

Answer 30

in-frame deletoin of one or more aa - may affect protein function or stability

Question 31

what is a deletion, not a multiple of three clled?

Answer 31

frameshift

Question 32

what are the results of a frameshift mutation?

Answer 32

likely to result in premature termination with loss of function or xpression

Question 33

what are two types of large deletions

Answer 33

partial gene deletion | whole gene deltion

Question 34

what is the result of partial gene deletion

Answer 34

may result in premature terminatino with loss of function or expression

Question 35

what is the restulf of whole gene deletion

Answer 35

loss of expression

Question 36

what are the four types of insertion mutations

Answer 36

codon not multiple of 3 large insertion expansion of trinucleotide repeat

Question 37

what are the null mutations

Answer 37

``` nonsense frameshift deletion frameshift insertion partial gene or whole gene deletion sometimes splice site ```

Question 38

what is the affect of codon insertion

Answer 38

in-frame insertion of one or more aa - may alter protein function or stability

Question 39

what is the affect of not multiple of 3 insertion

Answer 39

premature termination with loss of function or expression

Question 40

what is the affect of large insertion , partial gene duplication

Answer 40

may result in premature termination or loss of function,

Question 41

what are the two type of large insertions

Answer 41

partial gene duplication | whole gene duplication

Question 42

what is the affect of large insertion, whole gene duplication

Answer 42

may have affect due to increased gene dosage

Question 43

what type of mutation is expansion of trinucleotide repeat

Answer 43

dynamic mutation

Question 44

splicing always goes from splice donor to what

Answer 44

splice acceptor

Question 45

whathappens if splice acceptor is mutated

Answer 45

the intron stays in messenger RNA

Question 46

what is it called when the splice acceptor does not function

Answer 46

intron retention

Question 47

what will intron retention do to protein

Answer 47

make it biger

Question 48

what ahppens if splice donor looks for next splice acceptor when the one next to it doesn't function

Answer 48

exon skipping

Question 49

what does exon skipping do to protein

Answer 49

deletions, make it shorter

Question 50

if exon skipping and intron retention are not multiples of 3 what happens

Answer 50

frameshift - a null mutation

Question 51

if splie acceptor or splice donor is mutated which are the two possibilities that could happen for each

Answer 51

exon skipping or intron retention

Question 52

what is activation of crytpic splice site

Answer 52

creating splice acceptor or splice donor

Question 53

activation of cryptic splice acceptor site in intron what does what to the gene

Answer 53

extended exon 2

Question 54

activation of cryptic splice donor in exon 2 does what to gene

Answer 54

shortened exon 2

Question 55

GT acts as what

Answer 55

splice donor

Question 56

AG acts as what

Answer 56

splice acceptor

Question 57

splice site mutations almost always do what to protein function

Answer 57

completely destroy

Question 58

what does Indels stand for

Answer 58

insertion/deletion mutations

Question 59

what is at danger to ahve slippage

Answer 59

repetitive sequenes

Question 60

what is at danger to have slippage

Answer 60

repetitive sequenes

Question 61

what does backward slippage cause

Answer 61

insertions

Question 62

forward slippage causes what

Answer 62

deletion

Question 63

an indel that is not a multiple of 3 will result in what

Answer 63

frameshift

Question 64

a dyanmic mutation due to expansion of trinucleotide repeat has what affect on protein?

Answer 64

altered gene expression or altered protein stability/function

Question 65

If there's a (-) or a (+) for designation what does it mean

Answer 65

it's a splice mutation

Question 66

What is incidence

Answer 66

the rate at which new cases (disease) occur

Question 67

what is prevalence

Answer 67

the proportion of the population affected (usually less than incidence)

Question 68

what is frequencey

Answer 68

usually synonymous with incidence

Question 69

almost all enzyme and transporter defects lead to what mode of inheritance

Answer 69

recessive

Question 70

almost all structural protein and transcription factor defects lead to what mode of inheritance

Answer 70

dominant

Question 71

majority of mutations caused by transcription factors are what

Answer 71

AD

Question 72

majority of modifier or protein function have what mode of inheritance?

Answer 72

1/2 AD 1/2 AR

Question 73

majority of receptors have what mode of inheritance?

Answer 73

1/2 AD 1/2 AR

Question 74

What is phenotypic heterogenity

Answer 74

variations in a trait, or in the cinical presentation of a disease

Question 75

what is genetic heterogenity

Answer 75

may cause phenotypic heterogenity

Question 76

what is allelic heterogeneity**

Answer 76

variety of mutations (alleles) occurring within the same gene (locus Eg: some residual function alleles result in a mild phenotype, or partial phenotype

Question 77

what is locus heterogeinity**

Answer 77

different genes are involved mutations w/in a variety of genes (loci) may cause the same disease/trait multiple inheritance patterns may occur

Question 78

most diseases have what kind of heterogeneity

Answer 78

all 2 types: cliniical, allelic, locus

Question 79

What is the most likely affect on gene of a large deletion or insertion?

Answer 79

most likely to abolish function completely

Question 80

What is the most likely affect on a gene of duplication of whole gene?

Answer 80

increase product by 50% - normally no change phenotypically unless dosage-sensitive product

Question 81

What is the most likely affect on a gene with mutation: change in promoter or regulatory sequence

Answer 81

reduces or increases level of transcription | product has normal structure and function

Question 82

What is the most likely affect on a gene with mutation: change in intron

Answer 82

usually no affect. possibly change in splicing

Question 83

What is the most likely affect on a gene with mutation: change in 5' or 3' untranslated region of mRNA

Answer 83

usually no affect. possibly affect stability or translation efficienty of mRNA

Question 84

What is the most likely affect on a gene with mutation: splicing mutation

Answer 84

most likely complete loss of function

Question 85

What is the most likely affect on a gene with mutation: frameshfit mutation

Answer 85

most likely complete loss of function

Question 86

What is the most likely affect on gene with mutation: nonsense mutation

Answer 86

most likely complete loss of function

Question 87

What is the most likely affect on gene with mutation: missense mutation

Answer 87

Variable Loss or gain of function No affect

Question 88

What is the most likely affect on gene with mutation: synonymous substitution

Answer 88

most likely no affect