Mutation

Name seven examples of human trinucleotide repeat disorders.

1. Fragile X syndrome, 2. friedreich ataxia, 3. huntington disease, 4. jacobsen disease, 5. myotonic dystrophy (type I), 6. spinal and bulbar muscular atrophy, 7. spinocerebellar ataxia

Name the 6 ways chemical mutagens may act on DNA.

1. Nucleotide base analogs; 2. Deaminating agents; 3. Alkylating agents; 4. Oxidizing agents; 5. Hydroxylating agents; 6. Intercalating agents

Nitrogenous bases adopt one of two chemical forms:

1. Pair normally in the standard base-pairing form; 2. Base undergoes a tautomeric shift and pairs with a different base

A thymine dimer has ___ covalent bonds joining the ___ and ___ carbons of thymines that are adjacent in the same DNA strand.

2; 5; 6

The formation of pyrimidine dimers distorts the DNA by pulling the dimerized nucleotide bases (further apart/closer together) and disrupting _______ bond formation with their complementary nucleotides on the opposite strand.

Closer together; hydrogen

Null mutation results in what kind of gene function?

Complete loss of gene function

A non-conservative missense mutation causes a nucleotide sequence change that corresponds to a (similar/completely differently-functioning) amino acid.

Completely differently-functioning

A 5' or 3' splice site that is not normally used except when a mutation either inactivates an authentic splice site or creates a new splice site at the cryptic site location; This is a type of splicing mutation

Cryptic splice site

Both of the pyrimidine dimers can also involve the pyrimidine, __________, rather than thymine, but it is less commonly included.

Cytosine

Which nucleotide base is frequently a source of mutation by deamination?

Cytosine

Tautomeric shifts (occur spontaneously/are induced).

Occur spontaneously

UV irradiation alters DNA nucleotides by inciting the formation of additional bonds that form aberrant structures called ________.

Photoproducts

Nonsense, silence, and missense are point mutations that describe the effect of the mutation on the _______.

Polypeptide

Which kinds of mutations are naturally occurring and arise in cells without being induced by exposure of DNA to a physical, chemical, or biological agent capable of creating DNA damage?

Spontaneous mutations

Mutations altering the number of DNA repeats occur by a process called ______ ______.

Strand slippage

DNA nucleotide bases are organic chemical structures that can occasionally convert, in what are called ______ _____, to alternative structures called ________.

Tautomeric shifts; tautomers

DNA nucleotide structures that have the same composition and general arrangement, but a slight difference in bonding and placement of hydrogen

Tautomers

What are the two types of point mutations?

Transition and transversion

Replacement of one base with a different base of the same chemical category (i.e. purine to purine or pyrimidine to pyrimidine)

Transition mutation (point mutation)

Replacement of one base with a different base of other chemical category (i.e. purine to pyrimidine or pyrimidine to purine)

Transversion (point mutation)

The wild-type alleles of the genes in question normally contain a variable number of DNA trinucleotide repeats, however in this instance of this disorder (on rare occasions), these genes undergo mutation through strand slippage events that cause the number of trinucleotide repeats to increase.

Trinucleotide repeat disorder

True or false: We have thousands of trinucleotide repeats in our genome. This variation has no effect on phenotype, unless the threshold is passed.

True

In this kind of mutation, the wild-type DNA sequence is restored to encode its original message by a second mutation at the same site or within the same codon.

True reversion

Cytosine is mutated into _______ when it is deaminated b/c the amino group mutates to O

Uracil (not a problem in DNA b/c DNA knowns uracil does not belong in its structure, allowing it to reverse/fix the problem)

"Wild-type" is a set of genes or characteristics of the strain that is (used in lab/present in reality).

Used in lab (there are no real human wild-types)

Mutation --> ______ --> (acted on by _________ ______) --> New species

Variation; natural selection

What is the problem with photoproducts formed by UV light?

When DNA repairs this, the repair process is not as good as normal DNA replication so the rate of mutation is increased

Which kind of oxidative reactions lead to a mutation?

When compounds that contain reactive forms of oxygen (often identified as oxygen radicals) react with DNA bases

If 1 or 2 (or multiples of 2 that are NOT multiples of 3) base pairs are inserted or deleted, there (will/will not) be a frameshift and everything downstream will be different than in the original, and it is likely that there will be a premature stop codon.

Will

If you insert or delete a 3 (or multiple of 3) base pair sequence, there (will/will not) be a frameshift.

Will not

Fragile X syndrome is (autosomal/x-linked) (dominant/recessive).

X-linked recessive

Does the result of deamination change if the cytosine has been methylated?

Yes; deamination of methylated cytosine creates thymine and generates a base-pair mismatch btwn the newly formed thymine on one strand and the previous complementary guanine on the other strand.

The loss of an amino (NH2) group from a nucleotide base, is a form of ________ chemical modification that can lead to mutation.

spontaneous

What is the average mutation rate?

10^-5 - 10^-7

When a mutation occurs, a gene changes from one _____ ____ to another.

Allelic form

In this kind of mutation, the wild-type DNA sequence is restored to encode its original message by a mutation in a different gene, that does not revert the original mutation, but causes the w-t phenotype to reappear

Second-site reversion

A mutation that changes the nucleotide sequence, but the new nucleotide sequence corresponds to the same amino acid as the original, so it does not really have an effect on the polypeptide

Silent mutation

A conservative missense mutation causes a nucleotide sequence change that corresponds to a (similar/completely differently-functioning) amino acid.

Similar

A mutation altering the normal splicing pattern of a pre-mRNA

Splicing mutation

Mutations altering the number of DNA repeats occur by a process called _____ _______.

Strand slippage

What are the two prominent kinds of pyrimidine dimers caused by UV irradiation?

Thymine dimer and 6-4 photoproduct

Trinucleotide repeats can expand or ______ because there is a very (low/high) level of variation in a species.

contract; high

Mutations in your ______ will be passed on to your offspring

gametes

In addition to producing the wrong amino acids in a portion of the polypeptide, frameshift mutations also commonly generate _______ _____ codons that result in a truncated polypeptide.

premature stop

Repeating DNA sequences are often ______ of mutation due to strand slippage.

Hotspots

What are the three ways that we can classify mutations?

How they affect DNA, how they affect encoded polypeptides, and their genetics (dominant, recessive, etc.)

Hydroxylation is the addition of a hydroxyl (OH) group to a recipient compound by a donor called a ___________ agent. (chemical mutagen)

Hydroxylating

What agents add bulky side groups such as methyl (CH3) and ethyl (CH3-CH2) groups to nucleotide bases to change base-pairing properties? What is the most commonly used chemical? (chemical mutagen)

Alkylating agents; EMS

**Nearly all lost purines are replaced before the next DNA replication cycle, but a few are not. What is an unrepaired lesion of this type called? What does this mean?

Apurinic site, meaning a nucleotide that lacks a purine base

Huntington's disease is caused by the expansion of a trinucleotide repeat. This disorder is (autosomal/x-linked) (dominant/recessive).

Autosomal dominant

In terms of a trinucleotide repeat disorder, once you pass a certain threshold you (can/cannot) revert back to a lesser number of repeats.

Cannot (Once you pass a certain threshold, you inexorably expand and the further you go past the threshold, the more severe your phenotype is)

A chemical compound that has a structure similar to the one of DNA nucleotides and therefore can work its way into DNA, where it pairs with a nucleotide. (chemical mutagen)

Base analog

Gain-of-function mutation, also called ___________ or ___________. What kind of gene function does this type of mutation result in?

Hypermorphic; neomorphic; Increased or novel gene function (Dominant)

Mutations occur due to alteration in the ____ of an organism.

DNA

Transition and transversion mutations describe the effect the mutations have on the ____.

DNA

What are the names of large compounds that can find their way between base pairs and distort the duplex? These compounds can also attach to nucleotide bases to form bulky adducts that contribute to DNA distortion.

DNA Intercalating agents

What kind of repair is used to undo the deamination of cytosine to uracil?

DNA mismatch repair

An agent that is capable of removing amino groups (NH2) from any nucleotide. (chemical mutagen)

Deaminating agent

Expansion of fragile X repeat leads to (increased/decreased) expression of the FMR-1 gene

Decreased

Loss-of-function mutation results in what kind of gene function? Is this dominant or recessive?

Decreased gene function; generally recessive, unless haploinsufficient

Indel

Deletion or insertion of a small region of DNA

The loss of one of the purines, adenine or guanine, from a nucleotide by breakage of the covalent bond at the 1' carbon of deoxyribose that links the sugar to the nitrogenous base

Depurination

Gain/loss of function and null mutations classify mutation according to what?

Genetics

Fragile X is visualized as the constriction at the (distal/proximal) end of the X chromosome.

Distal

What can happen when DNA polymerase encounters a trinucleotide repeat?

Either the daughter or parent strand can slip back

What is the primary way through which spontaneous mutations arise?

Errors during DNA replication and through spontaneous changes in the chemical structure of nucleotide bases

With each succeeding generation, the expression of trinucleotide repeats (expands/contracts) further and further.

Expands

Mutation that converts a wild-type allele to a mutant allele (often identified simply as a mutation)

Forward mutation

Which trinucleotide repeat disorder is the most common form of genetically inherited mental retardation?

Fragile X

Resulting from a ________ mutation, the mutant polypeptide contains an altered amino acid sequence from the point of mutation to the end of the polypeptide.

Frameshift

The insertion or deletion of one or more base pairs in the coding sequence of a gene that leads to addition or deletion of mRNA nucleotides.

Frameshift mutation

What are the names of these compounds and what do they cause?: H2O2, OH-, O2-

Free radicals; base pairing changes

In which two ways do mutations arise?

Induced and spontaneous

What kind of mutations are produced by interaction between DNA and a physical, chemical, or biological agent that generates damage resulting in mutation?

Induced mutations

What kinds of mutations do intercalating agents cause?

Insertion/deletion agents

In this kind of mutation, the wild-type DNA sequence is restored to encode its original message by a second mutation elsewhere in the same gene. (Does not produce exactly the same protein as the original, but it is still functional)

Intragenic reversion

What are hot spots in the genome?

Loci that tend to be much more easily mutated than others

Most mutations are _____ of function and almost all of these mutations are (dominant/recessive), which means that the heterozygote displays the _______ phenotype.

Loss; recessive; dominant

As gene expands and there is a full-force trinucleotide repeat mutation, the gene becomes ________ and it is no longer expressed.

Methylated

Is deamination of regular cytosine or methylated cytosine more difficult for the cell to detect?

Methylated cytosine

What is the most common form of DNA replication error?

Mispairing of DNA nucleotides due to the presence of tautomers

A mutation that changes the nucleotide sequence, therefore changing the corresponding amino acid. What are the two categories of this mutation?

Missense; conservative and non-conservative

There are way (more/less) ways to make a gene lose function than to make a gene function better.

More

Depurination is one of the (least/most) frequent spontaneous chemical changes affecting DNA.

Most (Occurs about 10,000 times per day in a typical human cell)

The agents generating mutation-inducing DNA damage are called ______.

Mutagens

A change from one hereditary state to another

Mutation

_______ is the engine that drives evolution

Mutation

_______ _______ is the result of gene mutations that have occurred over time.

Natural variation

In most instances, deamination produces (severe/no) mutagenic effect; but deamination of 5-methylcytosine is an exception leading to...

No; G-C to A-T base-pair substitution

Which two types of mutations are the most likely to have a substantial effect on protein function?

Nonsense and frameshift

A mutation that causes the nucleotide sequence to correspond to a stop codon, prematurely terminating translation.

Nonsense mutation

Mutations that alter consensus sequence nucleotides and interfere with efficient transcription initiation

Promoter mutations

What are three types of regulatory mutations that are commonly recognized?

Promoter mutations, splicing mutations, and cryptic splice sites

UV light causes adjacent (purines/pyrimidines) in DNA to covalently bond. This type of photoproduct is called a _________ _____.

Pyrimidines; pyrimidine dimer

Mutations that occur in non-coding regions of genes, such as promoters, introns, and regions coding 5'UTR and 3'UTR segments of RNA that have the effect of reducing or increasing the amount of wild-type gene transcript and the amount of w-t polypeptide without affecting the transcript and polypeptide sequences

Regulatory mutations

_____ ______ confirms that mutations are pre-existing.

Replica plating

Mutation that converts a mutation to a wild-type or near wild-type state

Reverse mutation (more commonly referred to as a reversion)

In trinucleotide repeat disorder, expansion of the numbers of repeats (beyond/within) the wild-type range results in a (hereditary/non-hereditary) disorder by blocking the production of (mutant/wild-type) mRNA and (reducing/increasing) the production of the wild-type protein.

beyond; hereditary; wild-type; reducing (eliminating)

Chemical mutagens are classified according to their ______ of ______ on ___.

mode; action; DNA

A 6-4 photoproduct joins adjacent _______ by formation of a bond between the ___ carbon of one thymine and the ___ carbon of the other thymine.

thymines; 6; 4