Sequencing and disease variation detection tools and techniques

Next-generation sequencing technology provides greater sequencing capacity to identify disease-causing variations. Currently there are many alignment tools and variation detection techniques, multiple SNP data sets used to filter out benign polymorphisms with the intent of enriching for disease-causing variations, and many tools and websites for annotating variations and performing pathogenicity prediction of variations. There is no consensus or standard with regards to which tools and corresponding parameter settings for each tool is appropriate for the different application of next-generation sequencing technologies for disease-causing variation identification. We have implemented an annotation pipeline that can easily use the output from different alignment tools (BLAT, BWA, BFAST, Bowtie) typically used to align sequence from next-generation sequencing and Sanger sequencing experiments. The Automated Sequence Analysis Pipeline (ASAP) reports variations using the HGVS standardized nomenclature[1] to facilitate comparison across tools and publications. To date, we have annotated the sequence from 13 exomes in an effort to identify disease-causing mutations.