DEVELOPMENT OF A GENOTYPING ASSAY USING MAS TECHNOLOGY

More than three million single nucleotide polymorphisms have been identified in the human genome, but technology that is able to detect the allelic frequency of these SNPs lags behind the ability to identify them. If synthetic oligonucleotide arrays could be combined with enzymatic allele detection strategies, sensitive and accurate genotyping of alleles could be performed at a throughput rate and cost unprecedented in the industry. NimbleGen uses its proprietary Maskless UV light projector to synthesize high-density custom oligonucleotide microarrays. This technology has successfully produced genome scale oligonucleotide arrays for several species, such as drosophila and human. Current arrays are synthesized in the 3'-5' direction due to limitations in synthesis chemistry, which leaves the 3' end of synthesized oligonucleotides covalently linked to the array surface, unavailable to enzymatic extension. NimbleGen will optimize the use of synthetic monomers that will enable 5'-3' oligonucleotide array synthesis. These arrays will then be used to develop an enzymatic based genotyping technique that will detect single nucleotide polymorphisms, as well as small insertions and deletions mutations. This system will have very high throughput, a low cost per SNP, and have accuracy >99 percent.