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Open Access Highly Accessed Research article

Short Tandem Repeats in Human Exons: A Target for Disease Mutations

Bo Eskerod Madsen, Palle Villesen and Carsten Wiuf*

  • * Corresponding author: Carsten Wiuf wiuf@birc.au.dk

  • † Equal contributors

Author Affiliations

Bioinformatics Research Center (BiRC), University of Aarhus, DK-8000 Aarhus C, Denmark

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BMC Genomics 2008, 9:410  doi:10.1186/1471-2164-9-410

Published: 12 September 2008

Abstract

Background

In recent years it has been demonstrated that structural variations, such as indels (insertions and deletions), are common throughout the genome, but the implications of structural variations are still not clearly understood. Long tandem repeats (e.g. microsatellites or simple repeats) are known to be hypermutable (indel-rich), but are rare in exons and only occasionally associated with diseases. Here we focus on short (imperfect) tandem repeats (STRs) which fall below the radar of conventional tandem repeat detection, and investigate whether STRs are targets for disease-related mutations in human exons. In particular, we test whether they share the hypermutability of the longer tandem repeats and whether disease-related genes have a higher STR content than non-disease-related genes.

Results

We show that validated human indels are extremely common in STR regions compared to non-STR regions. In contrast to longer tandem repeats, our definition of STRs found them to be present in exons of most known human genes (92%), 99% of all STR sequences in exons are shorter than 33 base pairs and 62% of all STR sequences are imperfect repeats. We also demonstrate that STRs are significantly overrepresented in disease-related genes in both human and mouse. These results are preserved when we limit the analysis to STRs outside known longer tandem repeats.

Conclusion

Based on our findings we conclude that STRs represent hypermutable regions in the human genome that are linked to human disease. In addition, STRs constitute an obvious target when screening for rare mutations, because of the relatively low amount of STRs in exons (1,973,844 bp) and the limited length of STR regions.