Origin and Instability of GAA Repeats: Insights from Alu Elements

Expansion of GAA repeats in the intron of the frataxin gene is involved in the autosomal recessive Friedreich's ataxia (FRDA). The GAA repeats arise from a stretch of adenine residues of an Alu element. These repeats have a size ranging from 7-38 in the normal population, and expand to thousand...

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Bibliographic Details
Published inJournal of biomolecular structure & dynamics Vol. 20; no. 2; pp. 253 - 263
Main Authors Chauhan, Chitra, Dash, Debasis, Grover, Deepak, Rajamani, Jaya, Mukerji, Mitali
Format Journal Article
LanguageEnglish
Published England Taylor & Francis Group 01.10.2002
Subjects
3' Flanking Region
Adenine - chemistry
Algorithms
Alleles
Alu Elements - genetics
Chromosomes, Human, Pair 22
Databases, Genetic
Evolution, Molecular
Frataxin
Friedreich Ataxia - epidemiology
Friedreich Ataxia - genetics
Gene Frequency
Genes, Recessive
Genome, Human
Humans
Introns
Iron-Binding Proteins - genetics
Models, Genetic
Mutation
Polymorphism, Genetic
Prevalence
Trinucleotide Repeat Expansion - genetics
Trinucleotide Repeats - genetics
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Summary:Expansion of GAA repeats in the intron of the frataxin gene is involved in the autosomal recessive Friedreich's ataxia (FRDA). The GAA repeats arise from a stretch of adenine residues of an Alu element. These repeats have a size ranging from 7-38 in the normal population, and expand to thousands in the affected individuals. The mechanism of origin of GAA repeats, their polymorphism and stability are not well understood. In this study, we have carried out an extensive analysis of GAA repeats at several loci in the humans. This analysis indicates the association of a majority of GAA repeats with the 3′ end of an "A" stretch present in the Alu repeats. Further, the prevalence of GAA repeats correlates with the evolutionary age of Alu subfamilies as well as with their relative frequency in the genome. Our study on GAA repeat polymorphism at some loci in the normal population reveals that the length of the GAA repeats is determined by the relative length of the flanking A stretch. Based on these observations, a possible mechanism for origin of GAA repeats and modulatory effects of flanking sequences on repeat instability mediated by DNA triplex is proposed.
Bibliography:ObjectType-Article-2
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ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2002.10506841