SNP genotyping is routinely used in the investigation of human disease. The transition from research application to clinical utility, however, has been a stumbling block for many technologies. The future role for SNP genotyping in the development of diagnostics is reviewed in this article.
The instructions that allow our bodies to develop and be maintained are shared by our species, but they are also unique to us as individuals. Typically our health is determined by this individuality in combination with our environment, and although our molecular cards are shuffled and dealt before we are born, only time reveals this hand as we progress through life.
So-called complex diseases typically result from the interaction of the body and environment, and this has made their understanding at the molecular level extremely challenging. Further still, the molecular basis of such disorders may involve variations at many places within our molecular instructions, and this has added another level of difficulty for those tasked with understanding diseases in order to develop therapeutics.
It was with considerable excitement that the profile of single nucleotide polymorphisms was raised as the genome sequencing projects progressed. SNPs, it seems, offer a promising means for investigation.
It was proposed that a set of SNPs evenly spread across the human genome could be used to screen two populations (typically populations with and without a disorder) and that some SNPs would associate more with the disease group, thus implicating the SNP, or a DNA sequence close by, in the disease state. A massive technological effort followed and whole genome scans, using tens of thousands of SNPs, were made a reality with the advent of array-based technologies.
Complementary technologies were developed to allow smaller numbers of SNPs to be screened against populations to build confidence that SNPs identified by array-based screens were indeed influential. For those on smaller budgets, this approach allowed educated guessing games where small numbers of SNPs, suspected to be involved in a disease, were screened economically in large populations. Initial efforts were frustrating, but progress has been made.
The successes are perhaps not on the scale that many had hoped for as the contribution to a disease state from any individual variant site has typically been demonstrated to be small. SNPs also offer a lot of potential for use in the field of personalized medicine, where therapeutics are tailored to an individual’s metabolism. In this field, correlation between variation in the genes of drug-metabolizing enzymes and drug metabolism is sought so that the patient can be prescribed a therapeutic agent based on his/her genetic profile. The reality of so-called theranostics is upon us.