SNP discovery with the Finch™-Server

     Todd M. Smith and Sandra G. Porter
     Geospiza, Inc. 3939 NW Leary Way, Seattle WA 98107, USA

Single nucleotide polymorphisms (SNPs) are a major source of genetic and thus, phenotypic variation within species. The genomic community has, accordingly, focused efforts on locating SNPs as part of the goal to further understanding of human disease and behavior. In this project we tested the ability of the Finch-Server to act as a tool in SNP discovery. The human genome project has provided a resource for finding SNPs by sequencing DNA from different individuals. Phrap, the assembly algorithm used in the Finch server, was not designed with the idea of finding genetic variation. However, the discrepancy values calculated by phrap, combined with the graphical reports produced by Finch-Assembly Manager, make it simple to identify sequence variation by scanning the output an assembly.

Trace files, obtained from public databases, were assembled using the Finch Chromatogram and Assembly Managers. The Assembly Manager stores assembly information output in a relational database management system, allowing the identification of high quality discrepancies. In this analysis, potential polymorphisms were identified and assigned to sets using different cut-off scores for the discrepancy values. The hypothesis that these discrepancies might be SNPs was tested by comparing these positions with known SNPs in public databases. PolyBayes was also used to determine the probability that these sequence variants might be SNPs.

 Genome Sequencing and Analysis Conference, 2001