Slavko is experiencing confusion and memory loss. A DNA sample is taken from Sla

Question

Slavko is experiencing confusion and memory loss. A DNA sample is taken from Slavko and the coding strand for a polypeptide, part of the GABAA receptor is sequenced. Slavko’s GABAA receptor sequence is found to be slightly different from 99.9% of the population. Below are the results:

Common GABAA receptor sequence:

5’ AGG CCT GAC TGT ATC AAT CTG ATC AAT GCG GGG ACG 3’

Slavko’s GABAA receptor DNA sequence:

5’ AGG CCT GAT TGT ATC AAT CTG ATC AAT GCG GGA ACG 3’

a)    Transcribe both of these DNA strands into mRNA.  

b)    Translate both of the mRNA strands using the codon table.

c)    What impact would this altered DNA sequence have upon the polypeptide produced; do you expect any changes in the polypeptide? Why/why not?

d)    GABA normally interacts with the polypeptide at a site where there are Asp-Cys-Ile in sequence. Will GABA bind well to Slavko’s GABAA receptor? What might you conclude about the effect of Slavko’s mutation on the function of the GABAA receptor? In your view, could this mutation potentially explain Slavko’s symptoms? Why/why not?

Explanation / Answer

Please find the answers below:

Answer a: The transcripts from both DNA strands can be found as below:

Normal DNA: 3' GCA GGG GCG TAA CTA GTC TAA CTA TGT CAG TCC GGA 5'

Transcript: 5' CGU CCC CGC AUU GAU CAG AUU GAU ACA GUC AGG CCU 3'

Slavko DNA: 3' GCA AGG GCG TAA CTA GTC TAA CTA TGT TAG TCC GGA 5'

Transcript: 5' CGU UCC CGC AUU GAU CAG AUU GUT ACA AUC AGG CCU 5'

Answer b : The tranlsational products can be found as below:

Normal product: Arg- Pro-Arg-Ile-Asp-Glu-Ile-Thr-Val-Arg-Pro

Slavko product: Arg-Ser-Arg-Ile-Asp-Glu-Ile-Thr-Val-Ile-Arg-Pro

Answer c: As it can be clearly seen from the transcripts and translation peptides, the Slavko's polypeptide contains a mutation at position 2 and 9 which results in change in the type of amino acid coded, hence the damage.

Answer d: Since the GABAA normally interacts with the receptor at sequence Asp-Cys-Ile, and Slavko's receptor peptide sequence lacks it, the receptor would fail to bind to GABAA and hence neurotransmission would be impaired. This substitution mutation thus caused the pathological condition in Slavko.

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