Journal ArticleDOI
Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2
Stefan M. Pulst,Alex Nechiporuk,Alex Nechiporuk,Tamilla Nechiporuk,Tamilla Nechiporuk,Suzana Gispert,Xiao Ning Chen,Iscia Lopes-Cendes,Susan Pearlman,Sidney Starkman,Guillermo Orozco-Diaz,Astrid Lunkes,Pieter DeJong,Guy A. Rouleau,Georg Auburger,Julie R. Korenberg,Carla P. Figueroa,Carla P. Figueroa,Soodabeh Sahba,Soodabeh Sahba +19 more
TLDR
A CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2, which is a member of a novel gene family and not highly polymorphic in normal individuals is identified.Abstract:
The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1. A 1.1-megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2. In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals. In SCA2 patients, the repeat was perfect and expanded to 36-52 repeats. The most common disease allele contained (CAG)37, one of the shortest expansions seen in a CAG expansion syndrome. The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.read more
Citations
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Journal ArticleDOI
Huntington's disease.
TL;DR: Effective intervention by clinicians is possible in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.
Journal ArticleDOI
Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α(1A)-voltage-dependent calcium channel
Olga Zhuchenko,Jennifer Bailey,Penelope E. Bonnen,T. Ashizawa,T. Ashizawa,David W. Stockton,Christopher I. Amos,William B. Dobyns,S. H. Subramony,Huda Y. Zoghbi,Cheng Chi Lee +10 more
TL;DR: It is concluded that a small polyglutamine expansion in the human α1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.
Journal ArticleDOI
A census of human RNA-binding proteins.
TL;DR: This work presents a census of 1,542 manually curated RBPs that are analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression, a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
Journal ArticleDOI
Trinucleotide Repeat Disorders
Harry T. Orr,Huda Y. Zoghbi +1 more
TL;DR: It is exciting that within a span of 15 years, pathogenesis studies of this class of disorders are beginning to reveal pathways that are potential therapeutic targets.
Journal ArticleDOI
Glutamine Repeats and Neurodegeneration
Huda Y. Zoghbi,Harry T. Orr +1 more
TL;DR: A model for pathogenesis that illuminates the unifying features of these polyglutamine disorders is concluded, and may prove relevant to other neurodegenerative disorders as well.
References
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Journal ArticleDOI
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
Marcy E. MacDonald,Christine Ambrose,Mabel P. Duyao,Richard H. Myers,Carol Lin,Lakshmi Srinidhi,Glenn Barnes,Sherryl A.M. Taylor,Marianne James,Nicolet Groot,Heather MacFarlane,Barbara Jenkins,Mary Anne Anderson,Nancy S. Wexler,James F. Gusella,Gillian P. Bates,Sarah Baxendale,Holger Hummerich,Susan F. Kirby,Mike North,S. Youngman,Richard Mott,Günther Zehetner,Zdenek Sedlacek,Annemarie Poustka,Anna-Maria Frischauf,Hans Lehrach,Alan Buckler,Deanna M. Church,Lynn Doucette-Stamm,Michael Conlon O'Donovan,Laura Riba-Ramirez,Manish A. Shah,Vincent P. Stanton,Scott A. Strobel,Karen M. Draths,Jennifer L. Wales,Peter B. Dervan,David E. Housman,Michael R. Altherr,Rita Shiang,Leslie M. Thompson,Thomas J. Fielder,John J. Wasmuth,Danilo A. Tagle,John Valdes,Lawrence W. Elmer,Marc W. Allard,Lucio H. Castilla,Manju Swaroop,Kris Blanchard,Francis S. Collins,Russell G. Snell,Tracey Holloway,Kathleen Gillespie,Nicole A. Datson,Duncan Shaw,Peter S. Harper +57 more
TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.
Journal Article
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more
TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Journal ArticleDOI
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.
TL;DR: It is concluded that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of X-LINKED spinal and bulbar muscular atrophy.
Journal ArticleDOI
Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member
J. David Brook,Mila E. McCurrach,H G Harley,Alan Buckler,Deanna M. Church,Hiroyuki Aburatani,Kent W. Hunter,Vincent P. Stanton,Jean Paul Thirion,Thomas J. Hudson,Robert L. Sohn,Boris V. Zemelman,Russell G. Snell,S A Rundle,Steve Crow,June Davies,Peggy Shelbourne,Jessica L. Buxton,Clare Jones,Vesa Juvonen,Keith J. Johnson,Peter S. Harper,D.J. Shaw,David E. Housman +23 more
TL;DR: Using positional cloning strategies, this work has identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients and PCR analysis of the interval containing this repeat indicates that unaffected individuals have been 5 and 27 copies.
Journal ArticleDOI
CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1
Yoshiya Kawaguchi,Toshihiro Okamoto,Masafumi Taniwaki,Megumi Aizawa,Miho Inoue,Sadao Katayama,Hideshi Kawakami,Shigenobu Nakamura,Masaki Nishimura,Ichiro Akiguchi,Jun Kimura,Shuh Narumiya,Akira Kakizuka +12 more
TL;DR: Southern blot analyses and genomic cloning demonstrates the existence of related genes, raising the possibility that similar abnormalities in related genes may give rise to diseases similar to Machado-Joseph disease.
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