Gene Discovery in Venous Thrombosis:  Progress and Promise

As a result of rapid technological progress in single-nucleotide polymorphism (SNP) genotyping and the availability of appropriate large-scale epidemiological studies and clinical trials, an increasing number of genome-wide association and gene-centric genotyping studies of complex multigenic diseases, such as venous thrombosis and atherosclerosis, are appearing in the literature.^1- 2 Genome-wide association studies take advantage of the fact that SNPs occur in approximately one per thousand base pairs and are common in the population (frequency ≥1%). Thus, tools such as the recently available 1 million–SNP chip make it possible to study common genetic variance in coding and noncoding regions across the genome. In contrast, gene-centric genotyping usually focuses on genes likely to be informative and uses specific SNPs that mark functional changes in coding, are in nearby regulatory regions, or are representative of other SNPs residing on local haplotypes. “Tag-SNPs” representative of human haplotypes can be identified from the human HapMap.³