Genomics Core
Single nucleotide polymorphism (SNP) discovery and genotyping are key features of several projects in this proposal. The Genomics Core has extensive experience in both of these activities and will serve the consortium by performing DNA sequencing for SNP discovery and SNP genotyping for the projects. Approximately 75 candidate genes will be evaluated to identify SNPs for the human cohort projects. The resources of the HapMap Consortium will be used to select haplotype-tag SNPs for those genes with good coverage (1kb average SNP density by October 2005). DNA sequencing will be performed for polymorphism discovery for those genes with insufficient HapMap coverage. Common SNPs discovered in the candidate genes will be used to construct haplotype maps of these genes to identify the haplotype tag SNPs (htSNPs) for association studies. The htSNPs will be genotyped for association studies of longevity phenotypes using a variety of scale-appropriate high-throughput genotyping platforms (e.g. FP-TDI, TaqMan, SNPstream).
In addition, ancestry informative markers (AIMs) will be validated and genotyped on all 12,100 samples in the human cohort studies to assess any stratification and/or cryptic substructure in the study populations.
Targeted sequence scanning of regions found associated with longevity phenotypes will also be performed to identify potential functional variants.
SNP identification, validation and genotyping will also be performed for the animal model studies in the Consortium (Miller, Bartke).
The Genomics Core will perform ~100,000 sequencing reactions and obtain ~1.83 million genotypes for the consortium. In addition, the Genomics Core will provide both genotyping and sequencing service to projects selected for support under the “opportunities fund” program. The Genomics Core will also serve as a resource for the consortium regarding quality control and new genomic technologies, evaluating and implementing new technologies as they become available. This will be done with the aid of a Genomics Core Advisory Committee composed of experts in the field of human genetics and genomic technologies.