Minh Duc Cao, Edward Tasker, Kai Willadsen, Michael Imelfort, Sailaja Vishwanathan, Sridevi Sureshkumar, Sureshkumar Balasubramanian, Mikael Boden. Inferring short tandem repeat variation from paired-end short reads. Nucleic acids research, 42(3):e16. 2014.
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Abstract:
The advances of high-throughput sequencing offer an unprecedented opportunity to study genetic variation. This is challenged by the difficulty of resolving variant calls in repetitive DNA regions. We present a Bayesian method to estimate repeat-length variation from paired-end sequence read data. The method makes variant calls based on deviations in sequence fragment sizes, allowing the analysis of repeats at lengths of relevance to a range of phenotypes. We demonstrate the method's ability to detect and quantify changes in repeat lengths from short read genomic sequence data across genotypes. We use the method to estimate repeat variation among 12 strains of Arabidopsis thaliana and demonstrate experimentally that our method compares favourably against existing methods. Using this method, we have identified all repeats across the genome, which are likely to be polymorphic. In addition, our predicted polymorphic repeats also included the only known repeat expansion in A. thaliana, suggesting an ability to discover potential unstable repeats.