Case Study: Four new mutations in the gene CFTR have been associated with a high
ID: 161508 • Letter: C
Question
Case Study: Four new mutations in the gene CFTR have been associated with a higher risk of developing cystic fibrosis. Three of the mutations are single base changes that map in the transcribed region of the gene, whereas the fourth mutation is a small deletion of 7 base-pairs that maps in the upstream non-transcribed region of the gene.
The sequence below represents the part of the sequence of the sense strand of CFTR (also called coding or non-template strand). Various features of this sequence are indicated on the sequence as well (+1, AUG, introns, stop codon, polyA signal, location of mutations). Below the DNA sequence, there is an explanation of some of these features:
CTGAGAAGC ….. Transcribed sequence (in red type).-----------> (The capital letters are written in Red color).
AATTAAGAT ….. Un-transcribed sequence (in black type).----------> (The capital letters are written in black color)
GCCAACTTC ….. Intron sequence
AATC The green boxes mark the identified mutations -----------> (The background of these capital letters is green)
ATG The magenta boxes mark the start and stop codon and polyA signal ----------> (The background of these capital letters is red).
Answer the following questions:
a) In a short paragraph below, please describe how you think that each mutation identified in this case might affect the function of the CFTR gene. Hint: first examine if the mutation might affect the encoded protein or the regulation of expression of the gene. Describe the hypothetical mechanism of how each of these mutations might impair the function of the CFTR gene.
b) Based on your previous analysis, which mutation do you think is most likely to cause the disease?
c) If you decided to develop a genetic test for this disease, which human tissue would you use as a sample?
Explanation / Answer
a. Mutation in CFTR gene leads to an absent or defective production of cystic fibrosis transmembrane regulator protein. Out of the four mutations, three mutations are single base changes which mean one base pair is replaced by a different base pair. This can or cannot cause a change in the amino acid which the affected base pair codes for. And if it causes a change the damage to the protein may be minimal. The fourth mutation is a deletion mutation of 7 base pairs where 7 base pairs are taken out of the gene sequence. This may change the entire line of amino acids down the entire gene.
b. According to the data, the fourth mutation i.e. deletion mutation is most likely to cause the disease as it deletes 7 base pairs thereby changing the nature of the protein.
c. Cystic fibrosis can be confirmed by performing diagnostic genetic testing of human sweat.