The complex pathology of trinucleotide repeats

doi:10.1016/S0955-0674(97)80009-9

Current Opinion in Cell Biology

Volume 9, Issue 3, June 1997, Pages 364-372

https://doi.org/10.1016/S0955-0674(97)80009-9 Get rights and content

Abstract

The expansion of trinucleotide repeat sequences has now been shown to be the underlying cause of at least ten human disorders. Unifying features among these diseases include the unstable behavior of the triplet repeat during germline transmission when the length of the repeat exceeds a critical value. However, the trinucleotide repeat disorders can be divided into two distinct groups. Type I disorders involve the expansion of CAG repeats, which encode an expanded polyglutamine, inserted into the open-reading frame of a gene that is usually quite broadly expressed. Recently, mouse models for type I disorders have been developed and the basis of pathology is under study, both in these models and through biochemical and cell biological approaches. The type II disorders involve repeat expansions in noncoding regions of genes. The mechanisms by which these repeat expansions lead to pathology may be quite diverse.

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¹: Present address: Sequana Therapeutics, 11099 North Torrey Pines Road, La Jolla, CA 92037, USA

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The complex pathology of trinucleotide repeats

Abstract

Science

Nat Genet

J Med Genet

Science

Nature

Cell

Cell

Nucleic Acids Res

Nat Genet

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes

Cell

Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy

Nature

Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

Nat Genet

Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p

Nat Genet

CAG expansions in a novel gene for Machado—Joseph disease at chromosome 14q32.1

Nat Genet

Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1

Nat Genet

Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats

Nat Genet

Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2

Nat Genet

Identification of the spinocerebellar ataxis type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT

Nat Genet

Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel

Nat Genet

Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript-encoding a protein kinase family member

Cell

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome

Cell

Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion

Science

Fragile X syndrome: a unique mutation in man

Annu Rev Genet Dev

Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia

Can J Neurol Sci

Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues

Nat Genet

DRPLA gene (atrophin-1) sequence and mRNA expression in human brain

Brain Res Mol Brain Res

Influence of sex of the transmitting parent as well as of parental allele size on the CTG expansion in myotonic dystrophy (DM)

Am J Hum Genet

Single sperm analysis of the trinucleotide repeats in the Huntington's disease gene: quantification of the mutation frequency spectrum

Hum Mol Genet

Length of uninterrupted CGG repeats determines instability in the FMR1 gene

Nat Genet

Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation

Nat Genet

Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice

Nat Genet