Key result
The prevalence of GAA repeats correlates with the evolutionary age of Alu subfamilies, and the length of GAA repeats is determined by the relative length of the flanking A stretch.
The study proposes a mechanism for the origin of GAA repeats from Alu elements and how flanking sequences modulate repeat instability, relevant to Friedreich's ataxia.
No immediate clinical implications for Friedreich's ataxia; leaves open evolutionary mechanisms of GAA repeat instability.
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.
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Chauhan et al. (2002) studied Friedreich's ataxia. GAA repeats and Alu elements was evaluated on Origin, polymorphism, and stability of GAA repeats. The prevalence of GAA repeats correlates with the evolutionary age of Alu subfamilies, and the length of GAA repeats is determined by the relative length of the flanking A stretch.
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