Lecture 32 - Molecular basis of DMD Flashcards Preview

Molecule to Malady > Lecture 32 - Molecular basis of DMD > Flashcards

Flashcards in Lecture 32 - Molecular basis of DMD Deck (25):
1

The sacrolemma is the muscle ___

membrane

2

_____links the sacroglycan complex/dystroglycan complex to the actin filaments

Drostrophin links the sacroglycan complex/dystroglycan complex to the actin filaments

3

The dystrophin gene is on the _ chromosome 21

x chromosome - very large genes 1% of x chromosome

4

mutations associated with ______cause DMD and BMD (becker muscular dystrophy)

mutations associated with dystrophin cause DMD and BMD (becker muscular dystrophy)

5

What is the most common human MD?

Duchenne muscular dystrophy

6

Isoforms exist as a result of an...

alternative promotor usage and splicing of pre-mRNA

7

There are _ long isoforms of the dystrophin gene

4

skeletal, cardiac, smooth, brain

8

What are the 4 domains of Dystrophin?

1) N-terminal "actin binding" domain

2) Middle "rod" domain

3) a cysteine-rich domain (constant in all isoforms)

4) A C-terminal end allowing assembly of the DAPC

9

The most important bits are the ___ of the protein

ends

10

The _____ ___determines whether you have a truncated (abnormal) protein, DMD, BMD

The reading frame determines whether you have a truncated (abnormal) protein, DMD, BMD

11

silent mutations..

have no change in protein product

12

nonsense mutations causes a...

premature stop codon

13

15% of all gene mutations in DMD are ______

nonsense

14

deletions account for __ of DMD cases (out of frame)

60%

15

BMD will typically feature _-___ deletions

In-frame deletions

16

_______ is a link of the internal cytoskeletion to the ECM

Dystrophin

17

The ____links the actin cytoskeleton to the ECM

The CAPC links the actin cytoskeleton to the ECM

18

Dytrophin has also been proposed to play a role in __ homeostasis

Dytrophin has also been proposed to play a role in Ca homeostasis

19

True or False

In mdx mice and DMD patients, resting IC calcium levels are elevated in muscles

True

Activates inflammatory responses

20

What are the consequences of membrane instability?

Calcium influx
apoptosis, necrosis
Inflammation Fibrosis

disrupted muscle architecture

clinical muscle weakness

21

Deletions (65%) and duplications (5%) for DMD are detected by...

Deletions (65%) and duplications (5%) for DMD are detected by multiplex ligation dependent probe amplification analysis (MLPA)

22

True or False

All people with DMD can be detected with MLPA

False

some patients have small duplications/deletions or point mutations - not detected by MLPA

23

MLPA looks at ___ exons

all exons- unlike old PCR

24

What are the characteristic findings in DMD (histology)

Variable fibre size

Hypercontracted (opaque) muscle fibres

Immature muscle fibre internal architecture

absent dystrophin

increased fibrosis and inflammatory cells within muscle

25

Western blotting quantifies...

the amount of a protein in a specific tissue (determines size of protein) - useful for dystrophin