SBIR-STTR Award

The objective of this proposal is to develop an innovative, high- throughput, reliable and accurate method of SNP-haplotyping. To date, there are no high-throughput, reliable SNP-haplotyping methods available. The specific aims of this proposal are designed to develop a novel, allele-specific oligonucleotide hybridization approach for haplotype determination using either a microarray or a 384 well microtiter-plate format. These formats will allow the high-throughput determination of haplotypes containing 2 SNPs (microtiter-plate format) or multiple SNPs (microarray format) for both chromosomes of an individual. Plus/minus, automatable scoring of hybridization patterns will determine the haplotypes for both chromosomes. The ability to accurately haplotype SNP loci in a high-throughput fashion has important applications for; 1) saturation genotyping studies using haplotypes to narrow candidate genomic regions defined by previous linkage studies carried out with individual SNPs or other markers, 2) linkage disequilibriurn and association studies of genes located in candidate genomic regions or candidate genes identified by other methods, 3) analyzing large numbers of samples for haplotypes previously determined to be associated with the susceptibility of a particular disease, 4) diagnostic tests and kits for haplotypes associated with disease susceptibility, pharmacogenetic and immunologic profiling. PROPOSED COMMERCIAL APPLICATION: A high-throughput, accurate and reliable SNP-haplotyping technology will support population analyses for linkage disequilibrium and association studies. Such studies will allow the genetic dissection of complex traits such as diabetes, coronary artery disease and asthma. This has significant commercial application for the understanding and diagnosis of many common diseases, the development of diagnostic/prognostic test kits and the discovery of novel therapeutic treatments.

Thesaurus Terms:
genetic polymorphism, genotype, haploidy, high throughput technology, method development, nucleic acid hybridization genetic marker, linkage disequilibrium, oligonucleotide clinical research, human genetic material tag

Objectives are refining a novel, high-throughput method for haplotype analysis of single nucleotide polymorphisms (SNPs) and developing assays for specific haplotypes of significant scientific/clinical and commercial relevance. Presently, no simple, reliable, accurate methods exist for high-throughput SNP haplotyping. Applications are; 1) screening large numbers of samples for haplotypes associated with susceptibility to a particular disease; 2) diagnostic tests for haplotypes associated with disease susceptibility, pharmacogenetic and immunologic profiling; 3) saturation genotyping using haplotypes to narrow candidate genomic regions defined by linkage studies based on individual SNPs; and 4) linkage disequilibrium and association studies of genes located in candidate genomic regions or candidate genes identified by other methods. Phase I activities converted a plate-based 2-SNP haplotyping assay to a multi-SNP bead-based assay yielding dramatic throughput and reproducibility improvements while decreasing cost, labor and time, and demonstrated utility in haplotyping the E-selectin gene. Phase II aims are: 1) To reduce assay development effort and assay cost; 2) To develop rapid, easy kits for haplotyping several cytokines of functional and clinical significance, including both individual and multiplexed assays 3) To develop assays for haplotypes of potential clinical/scientific/commercial value, identified in the scientific literature and/or HAPMap database for genes presumed to have value.

Thesaurus Terms:
genetic polymorphism, genotype, haploidy, high throughput technology, method development, nucleic acid hybridization, single nucleotide polymorphism genetic marker, linkage disequilibrium, oligonucleotide