Project 3: One of the major difficulties of characterizing structural variation in a large number of individuals has been the lack of an accurate, cost-effective, high-throughput genotyping method. This project focuses on developing methods for genotyping structural variation and assessing their genetic characteristics in the four major HapMap populations. Our strategy is to develop specific high-throughput assays according to the type of structural variation. During the course of this project, we propose to: 1) develop a robust assay to genotype -400 simple insertion/deletion events within 480 HapMap samples using a fluorescent oligonucleotide-extension microbead assay; 2) assess the utility of the oligonucleotide array comparative genomic hybridization by genotyping 300 structural variants within segmental duplications and calibrating these results against corresponding sequence; 3) develop PCR breakpoint assays to genotype 200 complex/inversion rearrangements and 4) assess linkage disequilibrium of structural variation and flanking SNPs. The results of this analysis will provide an assessment of heritability and allele frequency spectrum data for a large subset of structural variation. In addition, these data will allow integration of structural variation data in the HapMap and provide a set of experimentally validated genotyping assays for future disease association studies.
Showing the most recent 10 out of 41 publications
