Question

	Muscular Dystrophy (BMD), and an individual with Duchene’s Muscular Dystrophy (DMD). DNA Sequence (1141-1200 bp) WT#1 cagaatgaa gcagagcca gagtttgct tcgagactt gacacggaa ctcaaagaa cttaac WT#2 aagaatgaa gctgagcca gagttcgct tcgagactt gacacagaa ctgaaagaa cttaac WT#3 aagaatgaa gcagagcca gagtttgct tcgagaatt gagacagaa ctcaaagaa cttaac BMD aagaatgaa gctgagcca gagtttgct tcgagactt gagacagaa ctcaaagaa cttaac DMD aagaacgaa gcagagcca gagattgct tagagaatt gacacggaa ctcaaagaa cttaac DNA Sequence (1201-1260bp) WT#1 actcagtgg gatcacatg tgccaacag gtatagaca atctctttc actgtcgct agcctc WT#2 acgcagtgg gatcatatg tgccaacag gtatagaca atctccttc actgtggct agcctc WT#3 acgcagtgg gatcacatg tgccaacag gtatagaca atctccttc actgtcgct tgcttc BMD accagtggg accacatgt gccaacagg tatagacaa tctctttca ctgtggctt gcttca DMD actcagtgg gaccatatg tgccaacag gtatagaca atctctttc actgtggct agcctc

6.What type(s) of mutations are there between the BMD strand and the WT strands. What effects, if any, do you think these mutations have on the function of the dystrophin protein. Explain your reasoning. (Assume that the observed mutations ONLY affect the polypeptide sequence in this exon.)

Answer 1

The DNA sequences were subjected to ClustalW alignment. The results are as follows:

The site marked with "1" indicates a "deletion" of nucleotide. This deletion leads to frameshift mutation, i.e. the complete reading frame for the DNA transcription (DNA -> mRNA) is altered. This results in extensive changes in the resultant polypeptide sequence:

Here, the area marked inside the red box in BMD shows completely changed polypeptide sequence as compared to the three WT samples. Also, the WT sequences exhibit a "Stop" (*) after the 30th amino acid. However, the BMD protein sequence does not encounter any "Stop" due to the frameshift mutation.

The mutation marked with "2" (first figure) indicates a substitution mutation (change from T to C).

The BMD mutations result in a completely different protein sequence, and subsequently a completely different protein structure. This may result in a non-functional protein, or even a lethal protein, which may promote disease progression.