Analysis of CAG/CTG triplet repeats in the human genome: Implication in transcription factor gene regulation
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Instability and polymorphism at several CAG/CTG trinucleotide repeat loci have been associated with human genetic disorders. In an attempt to identify novel sites that may be possible loci for expansion of CAG/CTG repeats, we searched all human sequences in the EMBL nucleotide sequence database for (CAG)5 and (CTG)5 repeats. We have identified 121 human DNA sequences of known and unknown functions that contain stretches of five or more CAG or CTG repeats. Many repeat stretches were interrupted by variant triplets, a significant number of which differ from the repeat triplet only by a single base, suggesting that these evolved from the parent triplet by point mutations. A large number of human transcription factor genes were found to contain CAG repeats within their coding sequences. Analysis of the EMBL transcription factors database showed that many transcription factor genes of other eukaryotes, including genes involved inDrosophila embryo development, possess these repeats. Interestingly, CAG repeats are absent from prokaryotic transcription factors. Different sequence entries for the human TATA box binding protein showed a polymorphism in the length of the CAG repeat in this gene, suggesting that loci other than those already known to be associated with genetic diseases may be possible sites for repeat instability related disorders. On the basis of our findings in this database analysis, we propose a role for CAG repeats as cisacting regulatory elements involved in fine-tuning gene expression.
KeywordsTriplet repeats sequence analysis transcription factor genes TBP
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- Fu Y H, Pizzuti A, Fenwick R G Jr, King J, Rajnarayan S, Dunne P W, Dubell J, Nasser G A, Ashizawa T, Jong P D, Wieringa B, Korneluk R, Perryman M B, Epstein H F and Caskey C T 1992 An unstable triplet repeat in a gene related to myotonic muscular dystrophy;Science 255 1256–1258PubMedCrossRefGoogle Scholar
- Kimura M 1983The neutral theory of molecular evolution (Cambridge: Cambridge Univ. Press)Google Scholar
- Koide R, Ikeuchi T, Onodera O, Tanaka A H, Igarashi S, Endo K, Takahashi H, Kondo R, Ashikawa A, Hayashi T, Saito M, Tomoda A, Miike T, Naito H, Ikuta F and Tsuji S 1994 Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA);Nature Genet. 6 9–12PubMedCrossRefGoogle Scholar
- Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemeiya C, Jansen G, Neville C, Narang M. Barcelo J, O’Hoy K, Leblund S, Earle-Macdonald J, deJong P J, Wieringa B and Komeluk R G 1992 Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene;Science 255 1253–1255PubMedCrossRefGoogle Scholar
- Tripathi J and Brahmachari S K 1991 Distribution of simple repetitive (TG/CA)n and (CT/AG)n sequences in human and rodent genomes;J. Biomol. Struc. Dyn. 9 387–397Google Scholar