Repeat-encoded poly-Q tracts show statistical commonalities across species

Willadsen, Kai, Minh Duc Cao, Wiles, Janet, Balasubramanian, Sureshkumar and Boden, Mikael (2013) Repeat-encoded poly-Q tracts show statistical commonalities across species. Bmc Genomics, 14 1: 76.1-76.10. doi:10.1186/1471-2164-14-76

Author Willadsen, Kai
Minh Duc Cao
Wiles, Janet
Balasubramanian, Sureshkumar
Boden, Mikael
Title Repeat-encoded poly-Q tracts show statistical commonalities across species
Journal name Bmc Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2013-02-01
Year available 2013
Sub-type Article (original research)
DOI 10.1186/1471-2164-14-76
Open Access Status DOI
Volume 14
Issue 1
Start page 76.1
End page 76.10
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted 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.

Conclusion: 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.
Keyword Intrinsically Unstructured Proteins
Tandem Repeats
Evolutionary Rate
Human Genome
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID ID 1004112
Institutional Status UQ

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