Single nucleotide substitutions and small unique base insertions or deletions are the most frequent form of DNA polymorphism and disease-causing mutation in the human genome. Therefore, it is important to develop efficient and accurate methods to identify and type these changes in populations. In fact, the ability to evaluate the relevance of specific variations with regard to phenotype will likely hinge on these issues. The goal of this project is to increase the speed and accuracy of automated approaches for identifying and typing DNA variations by improving base-calling software for automated sequences such that DNA polymorphisms and mutations will be automatically identified with greater accuracy and speed. Overall, this project focuses on the use of automated DNA sequencing as an approach that can be applied broadly to identifying and/or typing DNA variations in the human genome for a number of applications including genetic and disequilibrium mapping, DNA diagnostics (genetic and infectious diseases), tissue typing, and forensic testing.
| Subrahmanyan, L; Eberle, M A; Clark, A G et al. (2001) Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus. Am J Hum Genet 69:381-95 |
| Rieder, M J; Taylor, S L; Clark, A G et al. (1999) Sequence variation in the human angiotensin converting enzyme. Nat Genet 22:59-62 |
| Rieder, M J; Taylor, S L; Tobe, V O et al. (1998) Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome. Nucleic Acids Res 26:967-73 |
| Nickerson, D A; Tobe, V O; Taylor, S L (1997) PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res 25:2745-51 |
