A major goal of current human genome-wide studies is to identify the genetic 
basis of complex disorders. However, the availability of an unbiased, reliable, 
cost efficient and comprehensive methodology to analyze the entire genome for 
complex disease association is still largely lacking or problematic. Therefore, 
we have developed a practical and efficient strategy for whole genome 
association studies of complex diseases by charting the human genome at 100 kb 
intervals using a collection of 27,039 microsatellites and the DNA pooling 
method in three successive genomic screens of independent case-control 
populations. The final step in our methodology consists of fine mapping of the 
candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) 
analysis. This approach was validated upon application to rheumatoid arthritis, 
a destructive joint disease affecting up to 1% of the population. A total of 47 
candidate regions were identified. The top seven loci, withstanding the most 
stringent statistical tests, were dissected down to individual genes and/or SNPs 
on four chromosomes, including the previously known 6p21.3-encoded Major 
Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based 
genome-wide association analysis complemented by end stage SNP typing provides a 
new tool for genetic dissection of multifactorial pathologies including common 
diseases.