trinucleotide repeat expansion disorders

Question 1

what are the trinucleotide repeats?

Answer 1

1. they are repeats of 3 nucleotides
2. everyone has them but they stay relatively constant from generation to generation
3. replication errors cause repeat numbers to expand
4. they cause genetic disorders that do not follow mendelian inheritance
5. display genetic anticipation

Question 2

how does the tranmitting parent play a role in the disease?

Answer 2

1. depending on whether the repeats were transmitted from the mother or father

Question 3

what is the correlation between the location of the TNR and how many TNR you need to cause a disease

Answer 3

The order of importance is exon, intron, then uncoded regions. the moreimportant (exon) requires much less TNR to cause disease. For disease in introns and exons there isnt even a permutation zone

Question 4

what is a permutation?

Answer 4

a zone between being normal but below the threshold of the disease. these patients are mildly affected and have distinct clinical syndromes

Question 5

what is the strict definition of anticipation

Answer 5

as TNR’s expandwith each generation, the disease phenotype shows up earlier and with increased severity

Question 6

the protein that is affected by Huntington’s is largly found in___ and thus

Answer 6

largely found in the brain and thus only affects CNS and causes neurodegenerative diseases

Question 7

where does the repeat expansion happen for huntintons and what does that mean for the child?

Answer 7

for huntingtons the repeats expand during spermatogenesis so only a father who has it can transmit a worse form to their child. if a mother has it, they will trnasmit it to their child the smae number they had

Question 8

how do you detect TNR caused a disease

Answer 8

TNR expansions increase the PCR product number. see in the picture, the chid has a longer strand

Question 9

which disorder has the FMR protein and what is its normal function

Answer 9

Fragile X has the FMR protein. it is a translational regulator of mRNAs

Question 10

full mutation is Fragile X is caused by

Answer 10

mutation in FMR causes transcriptional silencing of FMR1 gene and absense of protein

Question 11

Freideich’s ataxia is caused by a defect in what gene?

Answer 11

in the Frataxin gene (FRDA). Causes mRNA to be degraded

Question 12

Why is the heart and spinal cord most affected by Friedreich’s ataxia?

Answer 12

the Frataxin gene ismost abundant in the mitochondria. The mitochondria is most abundant in the heart and spinal cord. Loss of Frataxin causes mitochondrail dysfunction

Question 13

what protein is affected by myotonia dystrophe?

Answer 13

Dytrophia myotonia protein kinase DMPK

Question 14

even though both parents can transmit Myotonia Dystrophy to child, who is most likely to transmit the congenital type?

Answer 14

mother

Question 15

how does RNA mediated toxicity promote Myotonia Dystrophy happening?

Answer 15

they stabilize the hairpin loop formed in the 3’ UTR