Limits...
Short tandem repeats in human exons: a target for disease mutations.

Madsen BE, Villesen P, Wiuf C - BMC Genomics (2008)

Bottom Line: 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.These results are preserved when we limit the analysis to STRs outside known longer tandem repeats.Based on our findings we conclude that STRs represent hypermutable regions in the human genome that are linked to human disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark. eskerod@birc.au.dk

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.

Show MeSH
Distribution of indel lengths in exons. Left: insertions of different lengths inside STRs (red bars) and outside STRs (black bars). Right: deletions of different lengths inside and outside STRs. A majority of all insertions have a length different from 3, 6 or 9 bp; both inside and outside STRs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2543027&req=5

Figure 4: Distribution of indel lengths in exons. Left: insertions of different lengths inside STRs (red bars) and outside STRs (black bars). Right: deletions of different lengths inside and outside STRs. A majority of all insertions have a length different from 3, 6 or 9 bp; both inside and outside STRs.

Mentions: The majority of indels found in exons have lengths different from the codon size (3, 6 or 9 bp), both inside and outside STRs (Figure 4). To test whether the increased frequency of indels is confined to long tandem repeat-like regions, we limited our analysis to STRs (≤25 bp) not overlapping with known tandem repeats. We found that the higher frequency of indels in STRs is preserved (Additional file 1: Figure S1) in the set of STRs with length ≤25 bp.


Short tandem repeats in human exons: a target for disease mutations.

Madsen BE, Villesen P, Wiuf C - BMC Genomics (2008)

Distribution of indel lengths in exons. Left: insertions of different lengths inside STRs (red bars) and outside STRs (black bars). Right: deletions of different lengths inside and outside STRs. A majority of all insertions have a length different from 3, 6 or 9 bp; both inside and outside STRs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2543027&req=5

Figure 4: Distribution of indel lengths in exons. Left: insertions of different lengths inside STRs (red bars) and outside STRs (black bars). Right: deletions of different lengths inside and outside STRs. A majority of all insertions have a length different from 3, 6 or 9 bp; both inside and outside STRs.
Mentions: The majority of indels found in exons have lengths different from the codon size (3, 6 or 9 bp), both inside and outside STRs (Figure 4). To test whether the increased frequency of indels is confined to long tandem repeat-like regions, we limited our analysis to STRs (≤25 bp) not overlapping with known tandem repeats. We found that the higher frequency of indels in STRs is preserved (Additional file 1: Figure S1) in the set of STRs with length ≤25 bp.

Bottom Line: 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.These results are preserved when we limit the analysis to STRs outside known longer tandem repeats.Based on our findings we conclude that STRs represent hypermutable regions in the human genome that are linked to human disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark. eskerod@birc.au.dk

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.

Show MeSH