Mutations and Repair (Lec 14)

Question 1

The following type of mutation arises in tissues other than those that produce gametes and is restricted to the individual

Answer 1

somatic mutation

Question 2

The following type of mutation arises in tissues that produce gametes and can be passed to offspring

Answer 2

germ-line mutation

Question 3

In regards to Dr. Biddle’s analysis of DNA from blood (germline) and the atrial septum (somatic) from 4 babies with hypoplastic left heart syndrome, how many somatic and gremlin mutations were found?

Answer 3

somatic: 5-11 mutations in coding sequences/splice sites
germline: 2000-3000 variants in coding sequences/splice sites

Question 4

A base substitution where purine replace by purine or pyrimidine replaced by pyrimidine is called what?

Answer 4

transition

Question 5

A base substitution where a purine is replaced by pyrimidine or vice versa is called what?

Answer 5

transversion

Question 6

True or false?

Insertion and deletions can be considered frameshift mutations

Answer 6

true

Question 7

What are the possible base changes of a purine to purine transition?

Answer 7

A - G or G - A

Question 8

What are the possible base changes of a pyrimidine to pyrimidine transition?

Answer 8

T - C or C - T

Question 9

What are the possible base changes of a purine to pyrimidine transversion?

Answer 9

A - C
A - T
G - C
G - T

Question 10

What are the possible base changes of a pyrimidine to purine transversion?

Answer 10

C - A
C - G
T - A
T - G

Question 11

Define forward mutation

Answer 11

mutation that alters the wild-type phenotype

Question 12

Define reverse mutation

Answer 12

mutation that changes the mutant phenotype back into the wild-type

Question 13

The following type of mutation can be described as a base substitution that results in a different amino acid

Answer 13

missense

Question 14

The following type of mutation can be described as a mutation that changes a sense codon into a termination codon

Answer 14

nonsense

Question 15

Define silent mutation

Answer 15

mutation changes the codon but not the amino acid

Question 16

Define neutral mutation

Answer 16

missense mutation that alters the amino acid sequence but does not change the function of the protein

Question 17

This type of mutation causes the complete or partial absence of a normal protein function and is usually recessive

Answer 17

loss of function mutation

Question 18

This type of mutation produces an entirely new trait or causes it to appear in an inappropriate tissue or at an inappropriate time

Answer 18

gain of function mutation

Question 19

Define suppressor mutation

Answer 19

genetic change that hides or suppresses the effect of another mutation

Question 20

What is the difference between the two subclasses of suppressor mutations: intragenic and intergenic?

Answer 20

intragenic: occurs in same gene as that containing the mutation being suppressed
intergenic: occurs in gene other than the one bearing the original mutation

Question 21

The following syndrome is characterized by coloboma of the eye, heart defects , atresia of the choanae, retardation, genital and or urinary abnormalities, and ear abnormalities and deafness and occurs about 1 in 10,000 births

Answer 21

CHARGE

hint: first letter of each symptom spells charge

Question 22

Is the mutation that causes CHARGE syndrome dominant or recessive?

Answer 22

dominant

Question 23

UAG codon signals for what?

Answer 23

stop

Question 24

True or false?

A base substitution can change many codons, while an insertion or deletion alters a single codon

Answer 24

false; a base substitution alters a single codon, while an insertion or deletion alters the reading frame and may change many codons

Question 25

How does a trinucleotide repeat mutation occur?

Answer 25

In the course of replication, a hairpin can form on the newly synthesized strand causing part of the template strand to be replicated twice and increasing the number of repeats on the newly synthesized strand, the two strands of the new DNA separate and the strand with the extra copies serves as a template for replication. The resulting DNA contains five additional copies of the repeat (CAG)

note: leads to fragile site in DNA

Question 26

Some common diseases associated with trinucleotide repeats are fragile-x syndrome and Huntington’s disease. What are their repeated sequences?

Answer 26

Fragile-X syndrome: CGG

Huntington’s Disease: CAG

Question 27

What is the result of DNA mispairing?

Answer 27

an altered nucleotide that does not correct in the next round of replication

Question 28

In regards to causes of gene mutations; spontaneous replication errors can be responsible. One of these spontaneous replication errors is called strand slippage. What does it entail?

Answer 28

newly synthesized strand forms a loop resulting in insertion or deletion

Question 29

In regards to causes of gene mutations; spontaneous replication errors can be responsible. One of these spontaneous replication errors is called unequal crossing-over. What does it entail?

Answer 29

If homologous chromosomes misalign during crossing over, one crossover product contains an insertion and the other has a deletion

Question 30

What are the two types of spontaneous chemical changes that lead to genetic mutation?

Answer 30

depurination: loss of purine
deamination: loss of amino group

Question 31

True or false?

converting Cytosine to Uracil is an example of deamination

Answer 31

true

Question 32

Would converting methlcytosine to thymine be an example of deamination or depurination?

Answer 32

deamination

Question 33

In regards to causes of gene mutations, Mutagens and Base analogues can be considered what?

Answer 33

chemically induced mutations

Question 34

What is a base analogue?

Answer 34

chemical with structure similar to normal bases

ex: Analogue of thymine (5-bromouracil) normally pairs with A but may mispair with G

Question 35

The following is a chemically induced mutation that works by donating an alkyl group. Examples are EMS and Mustard gas

Answer 35

alkylating agents

Question 36

True or false?

Nitrous acid works to cause chemically induced mutations by deamination

Answer 36

true

Question 37

What are chemicals that induce mutation by an oxidation reaction?

Answer 37

superoxide radicals such as hydrogen peroxide

Question 38

Proflavin, arcidine orange, and EtBr are all examples of what

Answer 38

intercalating agents

Question 39

Base analogs are mutagenic because of what characteristic?

Answer 39

they are similar in structure to the normal bases

Question 40

__ greatly increased mutation rates in all organisms

Answer 40

radiation

Question 41

How does a pyrimidine dimer affect replication?

Answer 41

two thymine bases block replication

Question 42

How does the SOS system work in bacteria?

Answer 42

allows bacteria cells to bypass the replication block with a mutation-prone pathway

Question 43

True or false?

If a thymine dimer is repaired, it often leads to errors such as mutations

Answer 43

true

Question 44

How does the Ames test detect mutagens?

Answer 44

any chemical that significantly increased the number of colonies appearing on the treatment plate is mutagenic and therefore probably also carcinogenic

Question 45

How does mismatch repair work?

Answer 45

methylation at GATC sequences allows old and newly synthesized nucleotide strands to be differentiated; the mismatch repair complex brings the mismatched bases close to the methylated GATC sequence, and the new strand is identified; Exonucleases remove nucleotides on the new strand between the GATC sequence and the mismatch; DNA polymerase then replaces the nucleotides, correcting the mismatch, and DNA ligase seals the nick in the sugar-phosphate backbone

Question 46

Describe the direct repair of pyrimidine alkylation by methyl transferase

Answer 46

a specific methyl transferase simply removes the unwanted methyl group, restoring the normal guanine structure

Question 47

Mismatch repair in bacteria distinguishes between old and new strands of DNA on the basis of what?

Answer 47

methyl groups on the old strand

Question 48

How does base-excision repair work?

Answer 48

specialized enzymes excise modified bases and upon replication, the original sequence is restored

Question 49

How does nucleotide-excision repair work?

Answer 49

removes bulky DNA lesions, like pyrimidine dimers that distort the double helix. The distortion is cut out and polymerase and ligase restore the original sequence

Question 50

What type of damage do homologs recombination and non homologous end joining repair?

Answer 50

double-strand breaks

Question 51

The following symptoms describe what syndrome:
mutations in the gene encoding DNA helicase RecQ protein-like-3 resulting in flaws in sister chromatid exchange, autosomal recessive disorder characterized by proportionate pre and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo-and hyper pigmented skin; predisposition to malignancy and chromosomal instability

Answer 51

bloom syndrom

Question 52

Name the disease:
autosomal recessive; abnormal skin pigmentation and acute sensitivity to sunlight; strong predisposition to skin cancer; sunlight exposure produces pyrimidine dimers in skin cell DNA which can’t be repaired; cells in most individuals with this disease are defective in nucleotide-excision repair, 1 in 250,000 incidence

Answer 52

xeroderma pigmentosum

Question 53

Name the disease(s):
No increased risk of cancer; multiple developmental and neurological problems; result from mutations in some of the same genes that cause xeroderma pigmentosum; incidence 1 in 250,000 US; 1 in 40,000 Japan

Answer 53

Cockayne syndrome and Trichothiodystrophy

Question 54

Hereditary nonpolyposis colon cancer is responsible for about ___% of colon cancers and arises from mutations in proteins that carry out ____ ___ processes

Answer 54

15; mismatch repair