DNA Mutations, Damage, and Repair Mechanisms - Genetics

Mutations can cause a huge variety of effects, including proteins that don't work (loss-of-function) and proteins that are too active (gain-of-function). Not all mutations are loss-of-function. Mutations can be inherited or from environmental factors, and many times a mutation will mean nothing at all for the organism.

A nonsense mutation will cause the protein to never be completed because of a premature stop codon, hence the protein "never makes sense," ie nonsense. Missense will make a protein with the incorrect amino acid sequence. A point mutation can cause a nonsense mutation, but is not the best answer, as it is vague. The other two mutations also theoretically can cause a nonsense mutation, but nonsense is most specific answer.

Point mutations occur when one nucleic base is swapped for a different nucleic base.

DNA helicase is responsible for breaking bonds between base pairs in the DNA thus unwinding it for replication.

It is an insertion because a nucleic acid was added to the sequence.

Epigenetic deals with which genes are expressed and which are repressed. Genes are turned on or off via methylation or acetylation of the histone wrapping the DNA. Single nucleotide polymorphism is an inherited single nucleotide change at a specific position of the genome, contributing to risk factors or being a modifier to a disease. Copy number variation are the repeats of sequence in the genome and the number of repeats vary for each individual. Non-coding RNA refers to RNA that is not translated into a protein.

Sub-metacentric is when the the centromere is off to one side. Metacentric is when the centromere is in the middle. Acrocentric is when the centromere is at one end. Lop-centric is not a real thing.

Isochromosome is when one arm is deleted and the other arm is copied to make the second arm a copy of the first. Translocation is an even exchange of information between non-homologous chromosomes. Inversion is when a piece of a chromosome switches direction or is reversed. Ring chromosome is when the telomeres are the end of a chromosome are cleaved off and the remaining chromosomal ends join forming a ring.

BAX is pro- apoptotic along with BID. BAK, BAD. Bcl-2, Bcl-XI, Mcl-1 are all anti-apoptotic. This is important in the mitochondrial death pathways.

Nucleotide excision repairs refers to short sequences of DNA being removed and repaired with the undamaged strand. It is usually removing bulky adducts on DNA, mostly thymine dimers which are caused by UV radiation. DNA mismatch repair is fixing a single mismatched DNA. Homologous recombination repair is fixing a double stranded break and using the sister chromosome as a template. These are mostly autosomal recessive disorders. Genomic instability simply refers to the high number of mutation which leads to instabilities in the genome.

Nucleotide excision repair corrects DNA that turns into pyrimidine dimers. These are usually caused by ultraviolet radiation and result in sizable DNA adducts.

A transition mutation represents a purine-to-purine mutation or a pyrimidine-to-pyrimidine mutation. This could be a change of A to T, or vice versa. It could also be a change of C to G, or vice versa. Remember, a transition mutation does not insert or delete any bases. It simply changes a base.

The most deleterious mutation would be a frameshift mutation. This would attained by inserting or deleting multiples of 1 or 2 bases in any important coding regions (exons, splice site, translation start site). Inserting or deleting multiples of 3 bases would not cause a frameshift mutation. A mutation in 3' UTR or intron would essentially have minimal effects. A mutation in the wobble position would most likely not change the amino acid.

The correct answer here is 21. Remember that we can begin by excluding the option that is 25 because there are only 23 pairs of chromosomes in a human being. If you chose any of the other options, remember that down syndrome is also called trisomy 21. This is a syndrome where the 21st pair of chromosomes has a third mutation on it.

The correct answer here is apoptosis. All other options are things that can occur to a cell that has been damaged, however, the only option where a cell will abruptly commit suicide is apoptosis. The other options, such as cancerous cells or dormancy do occur.

Recall that a frameshift mutation occurs when part of one or more codons in lost in such a way that the entire sequence of codons "shifts," making the transcribed mRNA translate as a different pattern of amino acids during protein synthesis. This is a big problem, since it means that a sequence of DNA coding for a specific protein now likely codes for a completely, fundamentally different one.

The correct answer is:

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

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

Compare to the original DNA, and note where one base pair was removed:

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

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

The codons on a piece of mRNA transcribed from the top strand of the non-mutated form would read:

UAC GGA CCU AUC GAU

However, mRNA transcribed from the mutated DNA would read:

UAC GAC CUA UCG AT\[ \] (we don't know the last codon, since the next base pair is not given)

This is a serious issue. The non-mutated form codes for these first four amino acids...

tyr gly pro ile

...while the mutated form codes for these first four amino acids:

tyr asp leu ser

Clearly, frameshift mutations can be very dangerous.

A frameshift mutation results in a change of the codon reading frame and results from the addition or deletion of a set of nucleotides that is not a multiple of three. If a mutation occurs that is a multiple of three, the reading frame is unchanged and a simple addition or deletion has occurred.

Template: 5'-AGC-CTT-AGC-3'

Frameshift mutant: 5'-AGC-GCT-TAG-C-3'

Point mutant: 5'-TGC-CTT-AGC-3'

Point mutant: 5'-AGC-CTT-AGG-3'

Deletion: 5'-CTT-AGC-3'

Insertion: 5'-TTT-AGC-CTT-AGC-3'

Note that all except the frameshift mutation contain sets of three nucleotides to create triplets. The frameshift leaves a singular, un-grouped cytosine.

Mutations can cause a huge variety of effects, including proteins that don't work (loss-of-function) and proteins that are too active (gain-of-function). Not all mutations are loss-of-function. Mutations can be inherited or from environmental factors, and many times a mutation will mean nothing at all for the organism.

A nonsense mutation will cause the protein to never be completed because of a premature stop codon, hence the protein "never makes sense," ie nonsense. Missense will make a protein with the incorrect amino acid sequence. A point mutation can cause a nonsense mutation, but is not the best answer, as it is vague. The other two mutations also theoretically can cause a nonsense mutation, but nonsense is most specific answer.