Mutations and Repair (Lec 14) Flashcards
The following type of mutation arises in tissues other than those that produce gametes and is restricted to the individual
somatic mutation
The following type of mutation arises in tissues that produce gametes and can be passed to offspring
germ-line mutation
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?
somatic: 5-11 mutations in coding sequences/splice sites
germline: 2000-3000 variants in coding sequences/splice sites
A base substitution where purine replace by purine or pyrimidine replaced by pyrimidine is called what?
transition
A base substitution where a purine is replaced by pyrimidine or vice versa is called what?
transversion
True or false?
Insertion and deletions can be considered frameshift mutations
true
What are the possible base changes of a purine to purine transition?
A - G or G - A
What are the possible base changes of a pyrimidine to pyrimidine transition?
T - C or C - T
What are the possible base changes of a purine to pyrimidine transversion?
A - C
A - T
G - C
G - T
What are the possible base changes of a pyrimidine to purine transversion?
C - A
C - G
T - A
T - G
Define forward mutation
mutation that alters the wild-type phenotype
Define reverse mutation
mutation that changes the mutant phenotype back into the wild-type
The following type of mutation can be described as a base substitution that results in a different amino acid
missense
The following type of mutation can be described as a mutation that changes a sense codon into a termination codon
nonsense
Define silent mutation
mutation changes the codon but not the amino acid
Define neutral mutation
missense mutation that alters the amino acid sequence but does not change the function of the protein
This type of mutation causes the complete or partial absence of a normal protein function and is usually recessive
loss of function mutation
This type of mutation produces an entirely new trait or causes it to appear in an inappropriate tissue or at an inappropriate time
gain of function mutation
Define suppressor mutation
genetic change that hides or suppresses the effect of another mutation
What is the difference between the two subclasses of suppressor mutations: intragenic and intergenic?
intragenic: occurs in same gene as that containing the mutation being suppressed
intergenic: occurs in gene other than the one bearing the original mutation
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
CHARGE
hint: first letter of each symptom spells charge
Is the mutation that causes CHARGE syndrome dominant or recessive?
dominant
UAG codon signals for what?
stop
True or false?
A base substitution can change many codons, while an insertion or deletion alters a single codon
false; a base substitution alters a single codon, while an insertion or deletion alters the reading frame and may change many codons
How does a trinucleotide repeat mutation occur?
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
Some common diseases associated with trinucleotide repeats are fragile-x syndrome and Huntington’s disease. What are their repeated sequences?
Fragile-X syndrome: CGG
Huntington’s Disease: CAG
What is the result of DNA mispairing?
an altered nucleotide that does not correct in the next round of replication
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?
newly synthesized strand forms a loop resulting in insertion or deletion
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?
If homologous chromosomes misalign during crossing over, one crossover product contains an insertion and the other has a deletion
What are the two types of spontaneous chemical changes that lead to genetic mutation?
depurination: loss of purine
deamination: loss of amino group
True or false?
converting Cytosine to Uracil is an example of deamination
true
Would converting methlcytosine to thymine be an example of deamination or depurination?
deamination
In regards to causes of gene mutations, Mutagens and Base analogues can be considered what?
chemically induced mutations
What is a base analogue?
chemical with structure similar to normal bases
ex: Analogue of thymine (5-bromouracil) normally pairs with A but may mispair with G
The following is a chemically induced mutation that works by donating an alkyl group. Examples are EMS and Mustard gas
alkylating agents
True or false?
Nitrous acid works to cause chemically induced mutations by deamination
true
What are chemicals that induce mutation by an oxidation reaction?
superoxide radicals such as hydrogen peroxide
Proflavin, arcidine orange, and EtBr are all examples of what
intercalating agents
Base analogs are mutagenic because of what characteristic?
they are similar in structure to the normal bases
__ greatly increased mutation rates in all organisms
radiation
How does a pyrimidine dimer affect replication?
two thymine bases block replication
How does the SOS system work in bacteria?
allows bacteria cells to bypass the replication block with a mutation-prone pathway
True or false?
If a thymine dimer is repaired, it often leads to errors such as mutations
true
How does the Ames test detect mutagens?
any chemical that significantly increased the number of colonies appearing on the treatment plate is mutagenic and therefore probably also carcinogenic
How does mismatch repair work?
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
Describe the direct repair of pyrimidine alkylation by methyl transferase
a specific methyl transferase simply removes the unwanted methyl group, restoring the normal guanine structure
Mismatch repair in bacteria distinguishes between old and new strands of DNA on the basis of what?
methyl groups on the old strand
How does base-excision repair work?
specialized enzymes excise modified bases and upon replication, the original sequence is restored
How does nucleotide-excision repair work?
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
What type of damage do homologs recombination and non homologous end joining repair?
double-strand breaks
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
bloom syndrom
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
xeroderma pigmentosum
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
Cockayne syndrome and Trichothiodystrophy
Hereditary nonpolyposis colon cancer is responsible for about ___% of colon cancers and arises from mutations in proteins that carry out ____ ___ processes
15; mismatch repair
