Question

1.) In a small number of patients whose families appear to have all the classical characteristics of FAP, a mutation cannot be found in the APC cDNA. What are two possible reasons for why mutations may not be found in some patients whose families appear to have FAP?

2.) Using the diagrams of APC domains and interactions provided in the case study, hypothesize the most likely effect of this mutation on APC ability to perform its function within the protein complex. Would you expect Sam’s APC mutation to change the ability of the APC protein to bind to β-catenin for example?

View Conse Results ▼ Conserved domains on [i182397gblAAA03586.1] APC [Homo sa sapiens] Graphical summary □ Zoom to residue level hide extra options « / Show site features Horizontal zoom Update graph 500 1000 1500 2000 2843 Query seq. protein binding surface protein binding surface Specific hits Superfanilies Multi-donains RMARM AR SuP ARM su bindi asic Figure 2. Diagram of one of APC's cellular functions. APC binds to β-catenin in the cytoplasm Binding to APC mediates the degradation of β-catenin, keeping overall β.catenin levels low APC β-catenr β catenin cell nucleus If not bound to APC and degraded, β-catenin accumulates and can ent the nucleus and bind Binding to TCF triggers the transcription of genes that promote 3-catenin T-cell factor (TCF) TCF wwwww cell division mR

Answer 1

Answer:

(1) The two possible reasons are:

a. APC cDNA only includes exons by definition since it was reverse transcribed from mRNA. The causative mutation may be in an intron, affecting a splice site or an enhancer site. The mutation could also be in the promoter and affect APC expression. Intron and promoter mutations would not be found in the cDNA.

b. Mutations outside of the APC gene could cause FAP mutations (meaning the mutations of other genes), but all lead up to the same outcome.

(2) A non sense mutation has resulted in a truncated non-functional protein. So, Sam's APC mutation would decrease the APC protein's ability to bind to $\beta$ -catenin.