116. Improved Detection of Single Nucleotide Polymorphisms (SNPs)  

Scott L. Taylor, Natali Kolker, and Deborah A. Nickerson  
Department of Molecular Biotechnology, University of Washington, Box 357730, Seattle, WA 98195  
stay@u.washington.edu 

Single nucleotide substitutions and unique base insertions and deletions are the most common form of polymorphism and disease-causing mutation. Based on the natural frequency of these variants, they are likely to be the underlying cause of most phenotypic differences among humans. Because of their functional importance, their frequency, and amenability to automated genotyping, large mapping of single nucleotide polymorphisms (SNPs) are now underway for the human genome. We have developed a computer program known as PolyPhred which together with Phred, Phrap, and Consed automatically identifies single nucleotide substitutions using fluorescence-based sequencing. Over the past year, we have evaluated several approaches to increase the accuracy and selectivity of PolyPhred. We will present information on a binning process that greatly improves SNP identification by PolyPhred and that speeds the analysis of sequence diversity in human genes.