The following is a list of mutations that have been...

The following is a list of mutations that have been discovered in a gene that has more than 60 exons and encodes a very large protein of 2532 amino acids. Indicate whether or not each mutation could cause a detectable change in the size or the amount of mRNA and/or a detectable change in the size or the amount of the protein product. (Detectable changes in size or amount must be greater than $1 \%$ of normal values. What kind of change would you predict? a. Lys576Val (changes amino acid 576 from lysine into valine) b. Lys576Arg c. AAG576AAA (changes codon 576 from AAG to AAA) d. AAG576UAG e. Met 1 Arg (at least two possible scenarios exist for this mutation) f. promoter mutation g. one base pair insertion into codon 1841 h. deletion of codon 779 i. IVS18DS, G-A, +1 (this mutation changes the first nucleotide in the eighteenth intron of the gene, causing exon 18 to be spliced to exon $20,$ thus skipping exon 19 ) j. deletion of the poly-A addition site k. G-to-A substitution in the $5^{\prime}$ UTR l. insertion of 1000 base pairs into the sixth intron (this particular insertion does not alter splicing)

The following is a list of mutations that have been discovered in a gene that has more than 60 exons and encodes a very large protein of 2532 amino acids. Indicate whether or not each mutation could cause a detectable change in the size or the amount of mRNA and/or a detectable change in the size or the amount of the protein product. (Detectable changes in size or amount must be greater than $1 \%$ of normal values. What kind of change would you predict?
a. Lys576Val (changes amino acid 576 from lysine into valine)
b. Lys576Arg
c. AAG576AAA (changes codon 576 from AAG to AAA)
d. AAG576UAG
e. Met 1 Arg (at least two possible scenarios exist for this mutation)
f. promoter mutation
g. one base pair insertion into codon 1841
h. deletion of codon 779
i. IVS18DS, G-A, +1 (this mutation changes the first nucleotide in the eighteenth intron of the gene, causing exon 18 to be spliced to exon $20,$ thus skipping exon 19 )
j. deletion of the poly-A addition site
k. G-to-A substitution in the $5^{\prime}$ UTR
l. insertion of 1000 base pairs into the sixth intron (this particular insertion does not alter splicing)

Key Concepts

Intronic Insertion (Non-disruptive)

An insertion within an intron that does not affect the splicing process is generally removed during mRNA processing and has no effect on the size or amount of the final mRNA transcript or the protein product.

5' UTR Mutation

Mutations in the 5' untranslated region (UTR) do not change the coding sequence of the protein, but they can influence mRNA stability or translational efficiency. These mutations affect how much protein is produced rather than altering the protein's size.

Polyadenylation Site Mutation

A mutation in the polyadenylation signal can disrupt the normal addition of the poly-A tail to mRNA transcripts. This disruption can lead to improperly processed mRNA that is prone to degradation, thus affecting the overall amount of mRNA and, consequently, the protein product levels.

Splice Site Mutation

Splice site mutations occur at the exon-intron boundaries and can disrupt the proper splicing of pre-mRNA. Depending on the mutation, this may result in exon skipping or inclusion of intronic sequences in the final mRNA, leading to changes in mRNA size or stability and producing a protein product with altered size or an entirely altered amino acid sequence.

Translation Initiation Mutation

Mutations affecting the translation initiation site, such as those altering the start codon, can prevent correct initiation of translation. This may lead to the use of an alternative start site or complete loss of translation, which in turn can result in an abnormal protein or a reduction in protein levels while typically leaving the mRNA size unchanged.

Frameshift Mutation

A frameshift mutation results from the insertion or deletion of nucleotides that are not in multiples of three, thereby disrupting the reading frame of the mRNA. This type of mutation often leads to a completely different and usually nonfunctional protein, and it may also affect mRNA stability, leading to altered mRNA levels.

Silent Mutation

A silent mutation is a change in the nucleotide sequence that does not alter the amino acid sequence of the protein due to the redundancy of the genetic code. Such mutations typically do not affect mRNA size or quantity, nor do they change the protein’s size, though subtle effects on mRNA stability or translation efficiency are sometimes possible.

Nonsense Mutation

A nonsense mutation is a point mutation in which a codon is changed into a stop codon, leading to premature termination of translation. This mutation can result in a truncated protein that is significantly shorter than the normal protein, and it may also trigger nonsense-mediated mRNA decay, reducing the amount of detectable mRNA.

Missense Mutation

A missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. This kind of mutation usually has no effect on the size or amount of mRNA and typically results in a protein that is the same length as the wild?type, though its function or activity could be altered.

Promoter Mutation

Promoter mutations occur in the regulatory region of a gene and can influence the binding of transcription factors or RNA polymerase. These mutations generally affect the amount of mRNA produced without changing the transcript’s size, ultimately resulting in altered levels of the protein product.

Transcript

00:01 Alright, so we're gonna examine quite a few different possible mutations and if they would affect the detect if they would cause a detectable change in the size or amount of mrna or a detectable change in the size or amount of protein product.

00:15 So let's go ahead and start for a what if the lysine 576 codon the was changed into a valine.

00:27 Well for the mrna because we are changing one amino acid into another that's not gonna affect the length of the mrna at all.

00:40 So not no size difference and it's also not going to change the size of the protein this might cause a change in function, but because this protein is pretty pretty big this is unlikely to cause a change so i'm just gonna indicate if we have a check mark that means that everything's gonna work out pretty much the same but with both protein and mrna so this first one will be mrna and then the second one will be protein.

01:09 So we're good on both camps what about b? well, we would change the 576 amino acid from lysine to an arginine well, that is the same story same amount of base pairs same amount of amino acids same amount of length in the mrna and the protein now we're not seeing if there is a function change you would need to do some sort of testing to know so codon 576 is supposed to be a ag.

01:47 So i have the codon chart over here a ag would be lysine.

01:51 That would be changed to a aa interestingly enough that would also be a lysine so this not only would not change the amount of mrna or the size or the amount of or size of the protein and it also would end up be being a silent mutation which is just a cool little extra.

02:08 So for d we would have the 576 codon a ag become a uag.

02:16 So a a g we know is lysine.

02:20 So what about you a g? okay.

02:23 Well, that's a stop codon so would this change the mrna length? no, why would it remain the same length in mrna? well mrna transcription is not guided by what the actual codons are that are being transcribed that has a promoter region and an ending region for transcription.

02:55 You don't just transcribe the very first codon to the last codon you have some overlap overlap called the untranslated reason on the 5 prime and 3 prime end so the mrna would remain the same length now the thing that would change would be the protein size slash length if this is a 2532 amino acid long protein and at 576 we hit a stop codon.

03:24 There's gonna be no more translation, which means that it's going to be a very small short protein it's definitely gonna lose function...

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