Multiple choices for SNPs

摘要

Researchers face a myriad of SNP genotyping choices. Even before the completion of the human genome draft sequence, analysis of single nucleotide polymorphisms (SNPs, pronounced "snips") was heralded as the next wave for the genomics field. Knowing all the locations of single-base variations, which occur roughly once every 1000 nucleotides throughout the genome, was supposed to hold the key to curing diseases and tailoring drug therapies for individuals. Since 1999, two large consortia of private and public research entities have deposited >1.8 million SNPs into a free database. Loads of data have been generated, but where's the payoff? "It's not yet been proven that SNPs can be used in all the ways people forecasted that they would," says Jim Lazar of Marligen Biosciences. Although Lazar says that research linking particular SNPs to particular medical conditions is lagging, he adds that it's only a matter of time before reality catches up to the hype. Researchers have already found that a handful of diseases, such as sickle cell anemia, stem from a single-base change, though they caution that most disease etiologies may not be that straightforward. As Hemanth Shenoi of Promega points out, "Life is too complicated to think that everything is a single SNP." Instead, combinations of SNPs may be important. To determine which SNPs are clinically relevant, researchers compare SNPs present in sick and healthy subjects. Sequencing is the gold standard for discovering new SNPs. However, if a researcher wants to find out which known SNPs are different between two individuals, sequencing is not typically the method of choice, according to John Butler of the National Institute of Standards and Technology. For most genotyping applications, the huge amount of data generated by sequencing is not needed to determine a one-base change. Scientists interested in SNP genotyping typically turn to methods that allow them to easily differentiate alleles, or SNP variants, without sorting through an alphabet soup of data. And there's a dizzying number of products on the market to help scientists with the task. Table 1, which is meant to be representative rather than comprehensive, lists several SNP genotyping assays and instruments. Experts say the market is crowded, and it's either growing or cooling off, depending on whom you ask. One company selling its technology to another is common, as is company turnover.