title: Repeat-encoded poly-Q tracts show statistical commonalities across species.
abstract: BACKGROUND
  Among repetitive genomic sequence, the class of tri-nucleotide repeats has received much attention due to their association with human diseases. Tri-nucleotide repeat diseases are caused by excessive sequence length variability; diseases such as Huntington's disease and Fragile X syndrome are tied to an increase in the number of repeat units in a tract. Motivated by the recent discovery of a tri-nucleotide repeat associated genetic defect in Arabidopsis thaliana, this study takes a cross-species approach to investigating these repeat tracts, with the goal of using commonalities between species to identify potential disease-related properties.
  
  
  RESULTS
  We find that statistical enrichment in regulatory function associations for coding region repeats - previously observed in human - is consistent across multiple organisms. By distinguishing between homo-amino acid tracts that are encoded by tri-nucleotide repeats, and those encoded by varying codons, we show that amino acid repeats - not tri-nucleotide repeats - fully explain these regulatory associations. Using this same separation between repeat- and non-repeat-encoded homo-amino acid tracts, we show that poly-glutamine tracts are disproportionately encoded by tri-nucleotide repeats, and those tracts that are encoded by tri-nucleotide repeats are also significantly longer; these results are consistent across multiple species.
  
  
  CONCLUSIONS
  These findings establish similarities in tri-nucleotide repeats across species at the level of protein functionality and protein sequence. The tendency of tri-nucleotide repeats to encode longer poly-glutamine tracts indicates a link with the poly-glutamine repeat diseases. The cross-species nature of this tendency suggests that unknown repeat diseases are yet to be uncovered in other species. Future discoveries of new non-human repeat associated defects may provide the breadth of information needed to unravel the mechanisms that underpin this class of human disease.
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane QLD 4072, Australia.
authors: Kai
authors: K
authors: Willadsen
authors: Minh Duc
authors: MD
authors: Cao
authors: Janet
authors: J
authors: Wiles
authors: Sureshkumar
authors: S
authors: Balasubramanian
authors: Mikael
authors: M
authors: Bodén
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D005787:Gene Frequency; D005796:Genes; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D016366:Open Reading Frames; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D018911:Trinucleotide Repeats
chemical_list: D010455:Peptides; D011506:Proteins; C097188:polyglutamine
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