Question

Dystrophin is a protein that forms part of a vital protein complex that connects the cytoskeleton of a muscle fiber cell to the extracellular matrix. This connection strengthens and shapes the muscle fibers. Dystrophin is coded by the DMD gene. This is one of the longest human genes known, covering 2,300,000 base pairs (0.08% of the human genome) It is located in chromosome 21. The immature mRNA is 2,100,000 bases long and takes 16 hours to transcribe. It contains 79 exons. The mature mRNA measures 14,000 and codes for a protein with 3,685 amino acids. Abnormal expression of dystrophin leads to severe symptoms like muscle weakness and fatigability, a disease that is called muscular dystrophy. Most patients with muscular dystrophy become wheelchair dependent early in life. Cardiac muscle is also affected which results typically in premature death (~ second or third decade of life). Several mutations in this gene have led to the production of low levels of dystrophin or of a defective, shortened (but partially functional) protein. The table below contains the following nucleotide changes found in the dystrophyn gene when comparing the DNA sequence of a healthy individual (Elijah) and an individual with muscular dystrophy (Liam). Use your knowledge to learn about mutations and determine which change is the most likely cause of

Answer 1

The most likely mutation to cause Liam's disease is Mutation 3.

Since these sequences are of the template strand, the coding sequence is complementary to the template sequence given.

Mutation #4:

Location of mutation: Absent in mature mRNA (As this is an Intronic mutation, it will be spliced out of the mRNA)

Amino Acid NA for Amino Acid NA (Mutation is intronic, no amino acids are coded for by introns)

Type of change NA (No change occurs in the mRNA/protein sequence)

Mutation #5:

Location of mutation: Present in mature mRNA (As mutation is present in an Exon, it will be present in the mRNA)

Amino Acid GLU for Amino Acid ASP (Mutation is exonic and will change the Amino acid)

Type of change Neutral (As both Glutamic Acid (Glu) and Aspartic Acid (Asp) are acidic residues, this is a Neutral mutation as it will not affect the protein structure/function to a large extent)