Following are a list of mutations in the chromosomal DNA that carries the CFTR g
ID: 177974 • Letter: F
Question
Following are a list of mutations in the chromosomal DNA that carries the CFTR gene. Provide a specific explanation of which of the ones are likely to produce a defective copy of the CFTR protein. This explanation must include the details of the faulty molecular events, proteins and DNA segements involved.
Mutations:
a) the most common CFTR mutation is a deletion of just three DNA nucleotides in exon 3 which leads to the deletion of an amino acid (phenylalanine) at position 508 of the protein sequence.
ii) mutation in the 5' splice site in gene intron 16 resulting in the substitution of G with an A.
iii) Single base change A--> C as shown below:
iv) Mutation in exon 5 that leads to change replacement of arginine with histidine at position 711 in the protein.
-25 WT 3' 5,-------- TATA TGA -25 Mutant 3 ---------------------------------------T 5'---------TCTA-----------------------A---------------------------------TGA--------3Explanation / Answer
Mutations:
a) the most common CFTR mutation is a deletion of just three DNA nucleotides in exon 3 which leads to the deletion of an amino acid (phenylalanine) at position 508 of the protein sequence:
ANS: When this sort of a mutation happens, the protein is degraded very quickly. Also, the protein fails to reach the cell membrane as it does not fold normally.
ii) mutation in the 5' splice site in gene intron 16 resulting in the substitution of G with an A.
ANS: Since there will be a mutation in the 5' splice site, it will thus result in an incorrect splicing of the gene, thus resulting in reduction of the formed protein due to the incorrect splicing.
iii) Single base change A--> C :
ANS: A single base change from A-->C in the above image implies that there has been a change in the TATA box which lies upstream to the the nucleotide +1, is one of the core promoter segments. Also, TATA box also serves as the specific binding site for some transcriptional factors. Impairment or mutation in any one of the two core promoter segments would hamper the transcription of the protein.
iv) Mutation in exon 5 that leads to change replacement of arginine with histidine at position 711 in the protein.
ANS: Also known as missense mutations where one amino acid is replaced by another one. Such mutations affect the domain domain interactions although the exact outcome of the disease can only be predicted when these are in combination with some other disease.