The primary technology for the detection of rare SNPs is sequencing, which may target regions of interest, or may examine the whole genome. ‘Next-generation’ sequencing technologies, which process millions of sequence reads in parallel, provide monumental increases in speed and volume of generated data free of the cloning biases and arduous sample preparation characteristic of capillary sequencing43. Detection of associations with low frequency and rare variants will be facilitated by the comprehensive catalogue of variants with MAF ≥ 1% being generated by the 1,000 Genomes Project (http://www.1000genomes.org/page.php), which will also identify many variants at lower allele frequencies. The pilot effort of that program has already identified more than 11 million new SNPs in initially low-depth coverage of 172 individuals44.
