50 The recent technological development of quick, high-throughput methods for genotyping has projected SNPs into the limelight, over the last few years.51 Added to this is the fact that SNPs are abundant, and occur throughout the human genome, in regulatory, coding, and noncoding regions, with an average frequency of approximately 1 per 1000 bp.48 When it falls within coding regions, the variant may actually result, in an amino acid change, which in turn may be of medical Inhibitors,research,lifescience,medical significance. A major interest among research groups concentrating on SNPs is the

identification of the genetic variation that underlies common, complex traits. It, is no coincidence that these are the ailments for which the pharmaceutical companies are most, interested in developing new drugs and being able to test for the efficacy of their drugs. The SNP Consortium (TSC), which comprises pharmaceutical and bioinformational companies, five academic centers, and a charitable trust, is currently producing Inhibitors,research,lifescience,medical an ordered high-density SNP map of the

human genome. Mapped SNPs are regularly being placed on public domain websites. TSC’s mission was to develop up to 300 000 SNPs distributed evenly throughout the human genome and, at the beginning of 2001, they published a map containing 1.4 million SNPs.53 More recently, a Inhibitors,research,lifescience,medical high-resolution human SNP linkage map with a resolution of 3.9 centimorgans, and an SNP screening set was published.54 Since SNPs constitute the bulk of human genetic variation, they can be used Inhibitors,research,lifescience,medical to track the inheritance of genes in traditional family-based linkage studies. On a larger scale, though, they can be used to track associations to disease, without necessarily finding each functionally important SNP, due to a phenomenon called linkage disequilibrium (LD). LD occurs when combinations of alleles at Inhibitors,research,lifescience,medical different, loci occur more frequently together than would be expected

from random association. LD fades with time (in successive generations), at, a rate depending on the amount, of recombination that, occurs during meiosis between the loci. The closer two SNP loci are together on a chromosome, the more learn more likely they are to be inherited PD184352 (CI-1040) together than those that are further apart. Therefore, SNPs that, are close to or within a particular gene are likely to be inherited together with the gene when they are in LD, and the variation of particular SNPs can act as markers for particular forms of the gene. Combinations of alleles are referred to as haplotypes, and the study of haplotypes has been instrumental in analyzing the link between genetic variation and disease predisposition. A haplotype block can be defined by a set of SNPs on a chromosome and ranges from 3 to 150 kb.