Diseases

Question 1

What are the 5 key pathways resulting in disease?

Answer 1

3' processing 
Splice site mutation
Aberrant miRNA
Aberrant splicing factors 
Premature stop codons

Question 2

Give 2 diseases caused by missplicing?

Answer 2

B-thalassemia
Spinal muscular atrophy
Frontotemporal dementia with Parkinsonism

Question 3

What is the mutation in SMA?

Answer 3

Defective SMN protein splice site results in loss of protein

Question 4

What is the cause of Frontotemporal dementia?

Answer 4

Missplicing C17 tau exon 10 creates pro-aggregatory form

Question 5

Which disease is caused by premature stop codon/NMD?

Answer 5

Ataxia telangiectesia

Question 6

How many ataxia cases are caused by nmd?

Answer 6

88% in ATM gene

Question 7

Which splicing factor is implicated in retinis pigmentosa?

Answer 7

PRP31

Question 8

What causes occulopharangeal muscular dystrophy?

Answer 8

Aberrant 3’ PABP causing muscle fibre inclusions and progressive degeneration

Question 9

What can be observed in rod and cone cells in retinis pigmentosa?

Answer 9

Globular inclusions

Question 10

How can SMA be treated?

Answer 10

Antisense oligo restores ESE to restore splicing

Question 11

BROADLY How can aberrant splicing be treated?

Answer 11

Restore wt function in mutant
Supplement wt product
KO mutant

Question 12

How can Small Mwt compounds be used to treat RNA diseases?

Answer 12

Controlling transcription or translation

Question 13

2 diseases treated with antisense oligos?

Answer 13

B-thalassemia

SMA

Question 14

What causes B-thalassemia?

Answer 14

Blocking of splice site causes intron inclusion