Rare SNP associations are more likely to be detected by resequencing of relevant regions in hundreds or thousands of individuals (by convention, resequencing, sometimes now called “medical sequencing,” determines an individual’s DNA sequence, vs. sequencing of an organism’s genome). Botstein and Risch (30) encouraged systematic study of nsSNPs in common diseases. Multiple rare pathogenic variants have been discovered by resequencing genes influencing lipid metabolism (31) and hypertension (32), and also genes in which GWAS had already detected common-SNP associations.(33-35) It is anticipated that advances in resequencing technologies will make it feasible to search systematically for rare variant effects in parts of the genome (e.g., linkage regions, all exons, all promoters) and eventually genomewide.
