Hypoxia Responses: How Different Cells and Tumors React to Oxygen Shortage

We used the LOKI software to generate multipoint identity-by-descent matrices for a microsatellite map (with 31 markers) and two single-nucleotide polymorphism (SNP) maps to examine information content across chromosome 7 in the Collaborative Study on the Genetics of Alcoholism dataset. Despite the lower information provided by a single SNP, SNP maps overall had higher and more uniform information content across the chromosome. The Affymetrix map (578 SNPs) and the Illumina map (271 SNPs) provided almost identical information. However, increased information has a computational cost: SNP maps require 100 times as many iterations as microsatellites to produce stable estimates. Background Traditionally, the mainstay of linkage has been use of highly polymorphic microsatellite markers. The ultimate goal would be completely polymorphic markers – each parent would have two uniquely occurring alleles. A highly polymorphic microsatellite provides a great deal of segregation information at a particular locus. At the other extreme, single-nucleotide polymorphisms (SNPs) usually have only two alleles (more alleles are possible but uncommon) and alone provide much less information for segregation. Because SNP typing is less expensive, and available at a finer density than microsatellites, the use of dense SNPs in the place of microsatellites for linkage analysis is being investigated using data from the Collaborative Study of the Genetics of Alcoholism (COGA). Because segregation is at the heart of any linkage analysis, we examined IBD (identity by descent) matrices to compare the information content of SNPs versus microsatellites for linkage. We used the LOKI software [1,2] to create the matrices after a set of preliminary tests to determine the appropriate number of iterations. However, due to time and computational constraints, we have restricted our attention to chromosome 7. Although the matrices are created irrespective of phenotype, published results from the COGA project have shown linkage with multiple phenotypes on this chromosome [3]. Other members of our group used the matrices to replicate some of these findings [4].