Lecture 9: Repeat Expansions II Flashcards
What are features of dystrophia myotonica?
Impaired muscle relaxation
Muscle wasting
Cataracts
Are DM1 and DM2 caused by repeat expansions in the same or different genes?
Different
What gene and what repeats are expanded in DM1?
CTG repeats in the 3’ UTR of DMPk gene
What is the normal repeat length of CTG repeats in DMPK genes?
5-37
What is the permutation repeat length of CTG repeat sin DMPK genes?
37-50
What is the pathogenic repeat length of CTG repeat sin DMPK genes?
50-1000
What is the congenital form repeat length of CTG repeat sin DMPK genes?
Over 1000
What gene and what repeats are expanded in DM2?
CCTG repeats in intron 1 of ZNF9
What is the normal repeat length of CCTG in ZNF9/CNBP gene?
Less than 30
What is the permutation repeat length of CCTG in ZNF9/CNBP gene?
31-74
What is the pathogenic repeat length of CCTG in ZNF9/CNBP gene?
75-11000
How does disease associated by RNA gain of function work in a sentence?
By sequestration of splicing proteins
What do repeat conniving RNA form?
Imperfect hairpins
How do hairpin cause RNA gain of function?
Hairpins are bound to specific proteins and may stop the protein acting as it should.
What gene and repeat is the cause of amyotrophic lateral sclerosis?
GGGGCC first intron of C9orf72
What are the 3 mechanisms that explain how expansions cause?
Loss of function-haploinsufficiency
RNA toxicity- RNA with many repeats forming hairpin
Toxic RAN peptides
What three DNA processes can contribute to repeat expansion in proliferating cells?
DNA replication
DNA repair
DNA recombination
What DNA processes contribute to repeat expansion in non-proliferating cells?
DNA repair
DNA recombination
