Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochemistry > Trinucleotide Repeat Disease > Flashcards

Trinucleotide Repeat Disease Flashcards

1
Q

Fragile X syndrome

A

premutation has its own phenotype

premutation doesn’t give fragile x syndrom but has fragile x associated tremor ataxia syndrome

the larger the repeat, the earlier the onset

Macroorchidism & mental retardation

Inherted through mother

Constriction of long arm of X chrom & breakage in repeat region.

Mutation in 5’ UTR of FMR-1 gene.

Deactivated promotor= no RNA transcript

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Fragile X syndrome

A

Fragile X syndrome- 200-2000 repeats; hypermethylation of DNA

FXTAS- premutation, 55-200 in older men. gait ataxia, intention termor, cognitive impairment

premutation related disorders-

  • primary ovarian insufficiency- females w/ emotional problems & perserverative thinking
  • children w/ ADHD or autism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Fragile X Syndrome

A

FMRP binds to RNA molecs & regulates translation which is very critical @ synapse

Neurons have increased number of long immature looking spines

Stimulation of postsynaptic mGluR results in increased protein & internalization of AMPA R= long term depression.

FMRP puts break on protein syn & dampens this response.

Fragile X neurons, protein syn, AMPA internalization & long term depression= exaggerated w/o FMRP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Type I diseases vs. Type II diseases

A

Type I disease

  • CAG as repeating trint unit
  • Gln as aa
  • exceed 35 Gln as repeats
  • affects brain

Type Ii disease

  • variety of nt
  • no aa
  • massive repeats
  • affects numerous parts of body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Disease Severities

A

Red= normal

orange= premutation

yellow= full mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Hungtington’s disease

A

30-55 yo symptom onset

  • twitching
  • chorea- writhing/dance movements
  • dementia- forgetfulness
  • can’t control their movement
  • fatal

Repeats of CAG in coding region

10-29 in normal

more than 30= male gametogenesis issues

36-40 = affected but incomplete penetrance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Hungtington’s disease

A

Embryogenesis= both normal & mutant same f; essential for gastrulation & dev of nervous sys

Adulthood= wild type controls neuron activity while mutant causes toxicity & interfers w/ normal f!

Polyglutamine (polyQs) enhance protein-protein interaction but when expanding their region= protein aggregate!

PolyQs also stop acetylation from sequestering acetyl transferases. This means DNA cannot be recognized by TFs & genes= silent.

Mutant HD unable to keep repressor-silencing TF (REST/NRSF) in cytoplasm so many important neuronal genes are transcriptionally silenced like BDNF.

BDNF supposed to travel along MT. Mutant HD binds on HAP1/ BDNF vesicle too tightly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Hungtington’s Disease

A

BDNF used for promoting neuronal survival, synaptic plasticity & stimulating cholesterol syn via Trk-B

HD mutant decreases BDNF & cholesterol syn!

Lose gray matter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Dystrophia Myotonica

A

Expansion of CTG or CCTG repeat in 3’ UTR of 2 genes

more than 1000 repeats

Type I & II

Progressive m. wasting/weakness in 20s & 30s

Myotonia

slow relaxation of certain m.

cataracts

cardiac conduction defects

men- hormonal changes

babies- mental retardation & death

Type 1= CTG repeat in 3’ UTR of DMPK gene

Type 2= CCTG in 3’ UTR, CNBP gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

DM1 vs. DM2

A

DM1

  • premutation 35-49 CTG
  • no symptoms
  • full penetrance alles
  • 50 CTG= w/ disease

DM2

  • 11-26 CCTG
  • no premutation alles
  • full penetrance abnormal alleles
  • 75-11,000 repeats= w/ disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Dystrophia myotonica

A
  • CUG-BP1 splicing in fetus (insuline R, cardiac troponin T, chlorine channel in m. etc.)
  • CUG-BP1 expression diminishes during dev
  • MBNL protein responsible for splicing RNA transcripts in adults
  • MBNL high affinity for CUG repeats, exapnded CUG reduces MBNL
  • MBNL promotes decay of CUG-BP1 mRNA= more is made b/c of diminished MBNL!
  • CUG-BP1 alternative splicing: insulin from embryo so insulin resistance & loss of Cl- channel so myotonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Friedreich Ataxia

A

AR

Onset 8-15 yo but before 20

Gait ataxia

Become wheelchair bound & early death.

Loss of large myelinated axons in peripheral n.

Frataxin gene

GAA trint in 1st intron

Normal- 50 repeats

disease- 200 to >1000

decrease syn of frataxin protein

Larger the repeats more of a reduction in frataxin expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Freidreich’s Ataxia

A

Frataxin inovlved in mitochondiral iron homeostasi (Fe-S center, heme & mitochondira Fe storage)

Reduce Fe export

Increase Fe uptake, decrease iron release & mitochondiral Fe loading

Free radical generation increases

Cell death of neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly

Biochemistry (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions