Phylogenetic analysis of the friedreich ataxia GAA trinucleotide repeat

Friedreich ataxia is an autosomal recessive neurodegenerative disorder asso ciated with a GAA repeat expansion in the first intron of the gene (FRDA) e ncoding a novel, highly conserved, 210 amino acid protein known as frataxin . Normal variation in repeat size was determined by analysis of more than 6 00 DNA samples from seven human populations. This analysis showed that the most frequent allele had nine GAA repeats, and no alleles with fewer than f ive GAA repeats were found. The European and Syrian populations had the hig hest percentage of alleles with 10 or more GAA repeats, while the Papua New Guinea population did not have any alleles carrying more than 10 GAA repea ts. The distributions of repeat sizes in the European, Syrian: and African American populations were significantly different from those in the Asian a nd Papua New Guinea populations (p < 0.001). The GAA repeat size was also d etermined in five nonhuman primates. Samples from 10 chimpanzees, 3 orangut ans, 1 gorilla, 1 rhesus macaque, 1 mangabey, and 1 tamarin were analyzed. Among those primates belonging to the Pongidae family, the chimpanzees were found to carry three or four GAA repeats, the orangutans had four or five GAA repeats, and the gorilla carried three GAA repeats. In primates belongi ng to the Cercopithecidae family, three GAA repeats were found in the manga bey and two in the rhesus macaque. However, an AluY subfamily member insert ed in the poly(A) tract preceding the GAA repeat region in the rhesus macaq ue, making the amplified sequence approximately 300 bp longer. The GAA repe at was also found in the tamarin, suggesting that it arose at least 40 mill ion years ago and remained relatively small throughout the majority of prim ate evolution, with a punctuated expansion in the human genome.