GENETIC CORE

The Genetics Core is responsible for providing support for the projects to identify new longevity genes (projects 1 &2), to delineate genotypes of interest in the individual longitudinal projects (Projects 3 &4), and to validate the genetic data in an independent non-Jewish population and our new recruits (Projects 3&4). This Core will isolate, purify, send for assay or store genomic DNA obtained from peripheral blood samples from all subjects collected as part of this program. Whole genome SNP analysis will be performed on the purified DMAs of 250 centenarians and 250 unrelated younger control, using the Affimetrix 500K mapping set (Project 1). As part of Project 1 we will determine the frequency of significant SNPs in 750 longevity genes and 750 buffered-killing'genes, from the genomic DNA in the offspring of centenarians and more centenarians and control by partnering with Illumina Corporation. For this study, we will grid the subjects DNA samples of and send to Illumina Services for genotyping a total of 1536 custom SNPs in their GoldenGate array. Among the SNPs are these find significant in Project 1 and 2, and for CETP, APOC3, ADIPOQ and 2 APOE for subjects in projects 3 and 4. Pyrosequencing will be used to perform high throughout screening of DNAs from large numbers of study subjects with limited numbers of SNPs in the GH/IGF pathway identified in Projects 2 (years 3-5). The genetic information obtained by this Core will be communicated to the Statistical and Bioinformatics Core, where it will become available to all investigators. Dr. Morrow is currently the Faculty Advisor of the DNA Processing Core, which has been functioning to store cell lines and isolate DNA from blood samples for the last ten years. Similarly, she also oversees the DNA Sequencing and Genotyping Core, in which Mr. David Reynolds is the Director. Both of these Cores are housed in the Department of Molecular Genetics at AECOM. Thus, the Genetics Core proposed here, in effect, combines two well-established functioning core services at our institution with extensive experience in technologies required for performing the studies outlined in this section and in achieving the goals of this application.