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

Madsen, Bo Eskerod; Villesen, Palle; Wiuf, Carsten
January 2008
BMC Genomics;2008, Vol. 9, Special section p1
Academic Journal
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.


Related Articles

  • Missense Mutation in Exon 2 of SLC36A1 Responsible for Champagne Dilution in Horses. Cook, Deborah; Brooks, Samantha; Bellone, Rebecca; Bailey, Ernest // PLoS Genetics;Sep2008, Vol. 4 Issue 9, p1 

    Champagne coat color in horses is controlled by a single, autosomal-dominant gene (CH). The phenotype produced by this gene is valued by many horse breeders, but can be difficult to distinguish from the effect produced by the Cream coat color dilution gene (CR). Three sires and their families...

  • Patterns of somatic mutation in human cancer genomes. Greenman, Christopher; Stephens, Philip; Smith, Raffaella; Dalgliesh, Gillian L.; Hunter, Christopher; Bignell, Graham; Davies, Helen; Teague, Jon; Butler, Adam; Stevens, Claire; Edkins, Sarah; O’Meara, Sarah; Vastrik, Imre; Schmidt, Esther E.; Avis, Tim; Barthorpe, Syd; Bhamra, Gurpreet; Buck, Gemma; Choudhury, Bhudipa; Clements, Jody // Nature;3/8/2007, Vol. 446 Issue 7132, p153 

    Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than...

  • Evidence for Nonindependent Evolution of Adjacent Microsatellites in the Human Genome. Varela, Miguel A.; Amos, William // Journal of Molecular Evolution;Feb2009, Vol. 68 Issue 2, p160 

    Microsatellites are short tandem repeats that evolve predominantly through a stepwise mutation model. Despite intensive study, many aspects of their evolution remain unresolved, particularly the question of how compound microsatellites containing two different motifs evolve. Previous work...

  • Microsatellite Mutation Models: Insights From a Comparison of Humans and Chimpanzees. Sainudiin, Raazesh; Durrett, Richard T.; Aquadro, Charles F.; Nielsen, Rasmus // Genetics;Sep2004, Vol. 168 Issue 1, p383 

    Using genomic data from homologous microsatellite loci of pure AC repeats in humans and chimpanzees, several models of microsatellite evolution are tested and compared using likelihood-ratio tests and the Akaike information criterion. A proportional-rate, linear-biased, one-phase model emerges...

  • Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 (NF1) gene. Song Han; Cooper, David N.; Upadhyaya, Meena // Human Genetics;Nov2001, Vol. 109 Issue 5, p487 

    The identification of mutations in the NF1 gene causing type 1 neurofibromatosis (NF1) has presented a considerable challenge because of the large size of the gene, the lack of significant mutational clustering, the diversity of the underlying pathological lesions and the presence of NF1...

  • A novel intronic mutation of the TAZ (G4.5) gene in a patient with Barth syndrome: creation of a 5' splice donor site with variant GC consensus and elongation of the upstream exon. Sakamoto, Osamu; Ohura, Toshihiro; Katsushima, Yuriko; Fujiwara, Ikuma; Ogawa, Eishin; Miyabayashi, Shigeaki; Iinuma, Kazuie // Human Genetics;Nov2001, Vol. 109 Issue 5, p559 

    Mutation analysis of the TAZ (G4.5) gene was performed on a patient with Barth syndrome. The reverse transcription/polymerase chain reaction procedure showed aberrant splicing and elongation of exon 3 because of the insertion of 106 bases (IVS3+1 to +106) between exons 3 and 4. The genomic DNA...

  • Novel mechanism of conjoined gene formation in the human genome. Kim, Ryong; Kim, Aeri; Choi, Sang-Haeng; Kim, Dae-Soo; Nam, Seong-Hyeuk; Kim, Dae-Won; Kim, Dong-Wook; Kang, Aram; Kim, Min-Young; Park, Kun-Hyang; Yoon, Byoung-Ha; Lee, Kang; Park, Hong-Seog // Functional & Integrative Genomics;Mar2012, Vol. 12 Issue 1, p45 

    Recently, conjoined genes (CGs) have emerged as important genetic factors necessary for understanding the human genome. However, their formation mechanism and precise structures have remained mysterious. Based on a detailed structural analysis of 57 human CG transcript variants (CGTVs,...

  • Mutation Rate Variation at Human Dinucleotide Microsatellites. Hongyan Xu; Chakraborty, Ranajit; Yun-Xin Fu // Genetics;May2005, Vol. 170 Issue 1, p305 

    Mutation is the ultimate source of genetic variation, and mutation rate is thus an important parameter governing the extent of genetic variation. Microsatellites are highly informative genetic markers that have been widely used in genetic studies. While previous studies showed that the mutation...

  • Non-LTR retrotransposons and microsatellites Partners in genomic variation. Grandi, Fiorella C.; Wenfeng An // Mobile Genetic Elements (2159-2543);Jul/Aug2013, Vol. 3 Issue 4, p1 

    The human genome is laden with both non-LTR (longterminal repeat) retrotransposons and microsatellite repeats. Both types of sequences are able to, either actively or passively, mutagenize the genomes of human individuals and are therefore poised to dynamically alter the human genomic landscape...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics