disease that result from expansion of trinucleotide repeats tianyang wang

Disease That Result from ExpansiDisease That Result from Expansion of Trinucleotide Repeatson of Trinucleotide RepeatsTianyang WangTianyang Wang

•Genes transmit from Genes transmit from generation to generationgeneration to generation

•Rarely changesRarely changes

Is it virtually this Is it virtually this case?case?

Dynamic mutation, 1991Dynamic mutation, 1991

Small number, stableLarge number, unstable

Gene changes dramatictlyGene changes dramatictlyAffect genes containing a repeating trinAffect genes containing a repeating trinucleotideucleotide

Critical number——onset disorders

• Huntington’s diseaseHuntington’s disease• Fragile X syndromFragile X syndrom• Myotonic dystrophyMyotonic dystrophy

Diseases attributed to expansion of trinucleotide repeat

• Genetic AtaxiaGenetic Ataxia

DominantDominant– Spinocerebellar Ataxia (SCA) 1,2,3…..Spinocerebellar Ataxia (SCA) 1,2,3…..

RecessiveRecessive– Friedreich AtaxiaFriedreich Ataxia– Ataxia With Vitamin E Deficiency (AVED)Ataxia With Vitamin E Deficiency (AVED)– Ataxia TelangiectasiaAtaxia Telangiectasia– Ataxia With Retained ReflexesAtaxia With Retained Reflexes

SCASCA

Atrophied cerebellum

Fragile X syndromeFragile X syndrome

Categories of DiseaseCategories of Disease• Type ⅠType Ⅰ

• Type ⅡType Ⅱ

Neurodegenerative disordersNeurodegenerative disorders

Variety of trinucleotide repeats within Variety of trinucleotide repeats within noncoding portionnoncoding portion

CAG repeats within coding portion or exonCAG repeats within coding portion or exon

Categories of DiseaseCategories of Disease

Huntington’s Disease (HD)Huntington’s Disease (HD)

•Type Ⅰ diseaseType Ⅰ disease•Affects about 1:10,000Affects about 1:10,000


Involuntary, uncoordinated Involuntary, uncoordinated movementsmovements

Change in personalityChange in personalityGradual intellectual declineGradual intellectual decline

•SymptomsSymptoms

ventriculi lateralis

Expanded ventriculi lateralis and atrophied caput nuclei caudati


Not losing a function, but acquiring an additional function

•DominantDominant genetic disorder genetic disorder

Gain-of-function mutation


Autosomal 4CAG Repeat

Polyglutamine tract(huntingtin)Normal huntingtin —— 6~35 repeatsAbnormal huntingtin —— more than 35 repeats

•Gene Identified In 1993Gene Identified In 1993


Why dose only huntingtin Why dose only huntingtin containing more than 35 containing more than 35 glutamine residues causglutamine residues cause the HD?e the HD?

Huntington’s Disease (HD)Huntington’s Disease (HD)Abnormal foldingAbnormal folding

Binds to other mutant huntingtinBinds other proteinTranscription factors, such

as TBP & CBP

Never fiber tangle of Alzheimer’s victim


•Genetic anticipationGenetic anticipation

Disease passed from generation to generation, its severity increases and/or it strikes at an increasingly early age.


There is no efficient drug that There is no efficient drug that can cure the HD by now.can cure the HD by now.

But people are trying their best to defeat it!!!

World Congress on Huntington's Disease: 11th–13th September 2005International Huntington Association Meeting: 13th–14th September 2005

ReferenceReference• Dr David Amor, Novel Mechanisms of Dr David Amor, Novel Mechanisms of

genetic disease, genetic disease, Murdoch Children Research Murdoch Children Research InstituteInstitute• 楊永正楊永正 ,, 基因體計畫基因體計畫 (( 續續 )) ,, 陽明生物資訊所陽明生物資訊所 , , Jan. Jan.

3, 20053, 2005• www.hda.org.ukwww.hda.org.uk ,The Huntington’s Dis ,The Huntington’s Dis

ease Associationease Association

http://www.hda.org.uk/

disease that result from expansion of trinucleotide repeats tianyang wang

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