Trinucleotide Repeat Disorders (Huntingtons)

Question 1

What are the two types of TRE’s

Answer 1

Expansions in Open Reading Frames
(9 CAG/polyQ disorders, 9 polyAla)

Expansions in noncoding regions

Question 2

What diseases are caused by expanded glutamine tracts (polyQ)?

Answer 2

Huntingtons disease
Kennedy disease (Spinobulbar muscular atrophy)
Haw-River Syndrome (Dentatorubral-pallidoluysian atrophy)
Spinocerebellar ataxia type 1,2,3,6,7,17

Question 3

How are polyglutamine (polyQ) repeat disorders inherited?

Answer 3

All are autosomal dominant (except Kennedys)
More commonly paternal allele expansion

Question 4

How is polyQ pathogenic and dominant?

Answer 4

Mis-folding leading to aggregation
Causes Neuronal intranuclear inclusions (NII)
Longer the repeat, the more NIIs in culture and models