Lecture 16

Question 1

CF (Cistic Fibrosis) is an Autosomal ______ desease. One of the causes, the delta F508 mutation, is a class___ mutation characterized by defective ______ because of a ______ deletion.

Answer 1

CF is an Autosomal RECESSIVE disease. The delta F508 mutation is a Class II mutation characterized by defective PROCESSING because of a 3BP deletion.

Question 2

DMD (Duchenne Muscular Dystrophy) is an X-linked ______ disease characterized by high levels of _____, indicating muscle cell degeneration.

Answer 2

DMD is an X-linked RECESSIVE disease characterized by high levels of CPK (creatine phosphokinase.)

Question 3

70% of DMD cases are attributed to LARGE _____ and 30% of cases are attributed to _____ mutations. Missense mutations in the dystrophin gene are unlikely to cause a disease phentoype because the protein is a large structural protein; changing 1 AA is unlikely to cause issue in such a large protein with no enzymatic activity.

Answer 3

70% of cases are attributed to large DELETIONS and 30% of cases are attributed to NONSENSE mutations.

Question 4

The reason DMD is much more severe than Becker Muscular Dystrophy (BMD) (also X-linked recessive) is because DMD deletions are ______ shift deletions, where as BMD deletions are in-_____, and BMD never occurs from ______ mutations, as seen in 30% of DMD cases.

Answer 4

DMD deletions are FRAME-SHIFT deletions, whereas BMD deletions are in-FRAME, and BMD never occurs from NONSENSE mutations.

Question 5

How does aminoglycoside (i.e. Streptomycin) therapy work to treat DMD arising from a nonsense mutation?

Answer 5

At high doses, aminoglycoside can cause Eukaryotic ribosomes to misread a nonsense mutation (premature stop codon) as a sense codon, then it could restore some functionality to the protein (it wont be degraded by nonsense mediated decay.)

Question 6

1/3 of DMD and BMD affected males suffer from __ ____ mutations.

What does this suggest about the susceptibility of the DMD gene to new mutations, and what might be the cause for this susceptibility?

Answer 6

De Novo

This suggests the DMD gene is highly susceptible to new mutations, likely because it is LARGELY comprised of Repetitive sequences in its introns –> predisposition to deletion.

Question 7

How was the DMD gene isolated?

Answer 7

By studying 4 affected girls exhibiting an X:autosome translocation (Xp21 gene.)

Question 8

There are 4 classes of mutations associated with Cistic Fibrosis:

Class I –> the protein is completely _____ bc of a spice site mutation that prevents _____ (protein precursor) from being made.

Class IV–> defective _____ due to alteration of the Cl- channel (issue with G551D).

Class II –> Defective processing leading to ______ (issue with delta-F508)

Class III –> Defective _____.

Answer 8

Absent

mRNA

Conductance

Misfolding

Regulation