With the unravelling of the Human Genome sequence and the identification of many DNA sites where individuals differ via the International HapMap 3 we now have the raw information required to find disease predisposing (or protective) genetic variants for complex traits 4. Phase II of HapMap provides information on the location of nearly four million common SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) across the genome in four populations of different ethnic origin (Caucasians of Northern & Western European origin; Japanese from Tokyo; Han Chinese from Beijing; and Yoruba from Nigeria). More importantly, within each population, HapMap provides information about the allelic association between SNPs located near each other, also termed ‘LINKAGE DISEQUILIBRIUM (LD)’. LD is the population-genomic feature used in genetic association studies to find the location of a disease-predisposing genetic variant. Knowing the LD structure, either in a candidate region or across the genome, helps the investigator to select a subset of SNPs that capture the majority of all common genetic variation because they predict the allelic status of other nearby SNPs (and thus also any common disease-predisposing variants) without having to genotype these variants themselves. How to select such ‘tagSNPs’ will be discussed in the next paper in this series.
