13a: Trinucleotide Repeats

Question 1

One hypothesis on how trinucleotide repeat expansions occur is related to (X) during which process?

Answer 1

X = Backward slippage of DNA Pol

DNA replication

Question 2

Trinucleotide repeat expansions (increase/decrease/don’t change) in size with each successive generation of patients.

Answer 2

Increase

Question 3

The molecular connection between growing number of trinucleotide repeats and increase in severity of disease phenotype.

Answer 3

Anticipation

Question 4

Often, increase in severity of disease manifests as:

Answer 4

Younger age of onset

Question 5

T/F: All diseases that arise by mechanism of tri-NT repeat expansion exhibit anticipation.

Answer 5

True

Question 6

In Huntington’s Disease, where in gene do the tri-NT repeat expansions occur?

Answer 6

Within exons

Question 7

The expansion in HD results in (increase/decrease) size of (X) tract in (Y) protein.

Answer 7

Increase;
X = glutamine
Y = huntingtin

Question 8

The mutated version of huntingtin protein (breaks down/aggregates).

Answer 8

Aggregates

Question 9

Most characteristic result/symptom of neuronal degeneration of HD.

Answer 9

Increased involuntary muscle movements

Question 10

In Fragile X syndrome, where in gene do the tri-NT repeat expansions occur?

Answer 10

Promoter region

Question 11

Which tri-NT repeat is implicated in Fragile X syndrome? In which gene?

Answer 11

CGG repeat in FMR1 gene

Question 12

In (X), the tri-NT repeat expansion in the promoter region cause (Y) and silencing of the (Z) gene.

Answer 12

X = Fragile X syndrome
Y = methylation of CpG islands
Z = FMR1

Question 13

HD is (dominant/recessive) defect with (gain/loss) of function.

Answer 13

Dominant; gain

Question 14

Fragile X is (dominant/recessive) defect with (gain/loss) of function.

Answer 14

Recessive; loss

Question 15

(Males/females) more vulnerable to Fragile X syndrome.

Answer 15

Males (only 1 X chromosome)

Question 16

Friedreich’s Ataxia involves (X) tri-NT repeat expansion in which region of (Y) gene?

Answer 16

X = GAA
Intron;
Y = FRDA1 (frataxin)

Question 17

Key symptoms of Friedreich’s Ataxia.

Answer 17

Loss of voluntary movement and enlarged hearts

Question 18

Myotonic dystrophy is associated with expansion of (X) tri-NT repeat in (Y) region of (Z) gene.

Answer 18

X = CTG
Y = 3' untranslated region (UTR)
Z = DMPK

Question 19

The 3’ UTR begins just (before/after) stop codon.

Answer 19

After

Question 20

An expansion in 3’ UTR region compromises which characteristic of the (X) molecule?

Answer 20

X = mRNA

Stability

Question 21

Myotonic dystrophy is (dominant/recessive) defect with (gain/loss) of function.

Answer 21

Dominant; gain

Question 22

The 5’ UTR of gene is also known as:

Answer 22

The promoter region

Question 23

T/F: It’s possible to predict the precise age of onset of HD based on number of CAG repeats.

Answer 23

False - only approximation

Question 24

Diseases that result from expansions in (X) regions of gene cannot be amplified by PCR because the expansions are too (Y).

Answer 24

X = non-coding;
Y = large

Question 25

An alternative technique used to detect large-scale tri-NT expansions is (X), where (DNA/mRNA) is processed/analyzed in which ways?

Answer 25

X = Southern blotting
Genomic DNA;

Digested by restriction enzymes and run on a gel

Question 26

Since in (X) technique the DNA appears as smear on the gel, it’s necessary to subsequently use probe that’s labeled with (identical/complementary) sequence.

Answer 26

X = southern blotting;

Complementary

Question 27

T/F: Southern blotting incapable of detecting methylation status of gene.

Answer 27

False

Question 28

To detect methylation status of gene, the (DNA/mRNA) must be digested by enzyme that specifically:

Answer 28

DNA;

Digests unmethylated regions

Question 29

The pre-mutation allele of Fragile X has which phenotype, if any?

Answer 29

Development of Fragile X associated tremor/ataxia (FXTAS)