Class 12 - No known homologies May function in development...

Info iconThis preview shows pages 1–18. Sign up to view the full content.

View Full Document Right Arrow Icon
Huntingtons disease
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 2
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Disease characteristics Dominant Autosomal disorder (i.e. every affected has at least 1 parent affected) Progressive dementia usually in early 50s Relatively rare but in some partially inbred communities (i.e.Lake Maricaibo Venezuela) affects many Traced to European founder ~1800s
Background image of page 4
Symptoms Chorea - involuntary movements Rigidity - usually late with tremor Early dystonia - unusal posture Eye, gait, refex, speech, dysphagia Cognition, memory, attention, language, vision, psychiatric, mood, delusions
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Population distribution 4-8/100,000 frequency - complete penetrance Phenotype same in homo- and heterozygotes Shows “anticipation” Tends to have great severity in succeeding generations No new mutations found
Background image of page 6
Gene Mapping • Venezuelan families gathered – Entire villages affected – Easy to gather 3 generation pedigrees • Mapped to chromosome 4p16 • Took 10 years to map and 10 more to clone gene Fnally in 1993
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
350kDa lethal CNS protein Alternatively spliced
Background image of page 8
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 10
Background image of page 11

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 12
Background image of page 13

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 14
Background image of page 15

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 16
Background image of page 17

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 18
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: No known homologies May function in development and maintenance of basal ganglia Appears to be a GOF mutant Gene/Protein Normally has stretch of CAG repeats of 10-35 Expands to 36-121 in patients Paternal allele seems most affected Sporadic cases appear in some families with repeats of 29 or more Pathogenesis Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo Cell 90:549-558, 8 August 1997 Eberhard Scherzinger,1 Rudi Lurz,1 Mark Turmaine,3 Laura Mangiarini,2 Birgit Hollenbach,1 Renate Hasenbank,1 Gillian P Bates,2 Stephen W Davies,3 Hans Lehrach,1 and Erich E Wanker1 EM of aggregates Birefringence Transgenic aggregates EM of NIIs Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington s Disease Cell, 101:57-66, 31 March 2000 Ai Yamamoto,1 Jos J. Lucas,1 and Ren Hen1 Expression phenotype Mouse phenotype Phenotype reversal...
View Full Document

Page1 / 18

Class 12 - No known homologies May function in development...

This preview shows document pages 1 - 18. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online