Question

1. You are a scientist studying a rare heritable disease, Pitt-Hopkins syndrome. This disease is caused by mutations in the basic helix-loop-helix transcription factor, TCF4. You sequence the TCF4 gene in your patients and identify several sequence variants.

a) The TCF4 coding region and sites of mutations for several patients are shown here (lines between codons indicate the open reading frame). For each patient, identify the impact of the mutation on the coding sequence (1 mark each) and the likely impact on the resultant protein (1 mark each).

2. b) How would each of these mutations affect the ability of TCF4 to influence transcription (1 mark each)?

3. c) A partial sequence for the start of the TCF4 mRNA is shown below highlighting the 3 possible reading frames. Based on this information, please identify the version of this sequence that represents the most likely open reading frame (1 mark), including the location of the translational start site (1 mark) and a justification for your answer (1 mark)

Reading frame 1: A/UGU/ACC/AUG/GUG/CGU/AGG/GUC/GAU/UGG/CGC/AGA/AAG/UGU/GUU/AGA/G

Reading frame 2: AU/GUA/CCA/UGG/UGC/GUA/GGG/UCG/AUU/GGC/GCA/GAA/AGU/UAG/GAG

Reading frame 3: AUG/UAC/CAU/GGU/GCG/UAG/GGU/CGA/UUG/GCG/CAG/AAA/GUU/AGU/UAG/AG

I was hoping to double check my answers for this question to see if I got the same answers.

Answer 1

c. The reading frame 3 is correct one as it indicates intiation codon AUG, other two reading frames does not have intiation codons so translation cant get started, so no protein can be formed from ist two reading frames.

For part a and b there is no sequence given, so can not be answered.