With the completion of the first draft of human genomic sequence, and the identification of over 1.4 million SNPs (single nucleotide polymorphisms) (SNP Consortium, 2001) we have the tools to fully explore the genetic basis of complex human diseases and response to drugs. Complex diseases being studied at Washington University School of Medicine include Alzheimer's disease, Alcohol Dependence, Nicotine Dependence, Diabetes and Psoriasis. The identification of SNP alleles that are associated with risk variants for common diseases will pinpoint the locations of the genetic risk factors for disease and drug response and lead to their identification. The Sequenom MassARRAY system allows one to accurately type large numbers of SNPs in large numbers of samples in a cost-effective manner. Because it relies on MALDI-TOF (Matrix Assisted Laser Desorption/Ionization - Time-of-Flight mass spectrometry), many of the limitations of traditional approaches to SNP analyses are overcome. In this system mass spectrometry is used to identify alleles on the basis of mass. It is therefore not hindered by the nuances caused by allele dropout and mismatched hybridizations. The MassARRAY system is automated and high throughput. It also has a low error rate when compared to other SNP genotyping technologies. Other instruments used for high throughput SNP typing cannot handle the large number of samples that the Sequenom MassArray system can, and genotyping costs are greater. The acquisition of this instrument at Washington University School of Medicine is likely to greatly speed up the identification of genetic risk factors for common diseases and drug response at this institution. At the end of the grant period it will be incorporated into a core genotyping facility within the Division of Human Genetics.
