The $1000 Genome

Our esteemed colleague, Dr. Joel Studebaker writes today about The $1000 Genome



The $1000 genome, referring to the cost of sequencing all 3.2 billion bases in a human’s DNA, has long been the goal of new developments in sequencing technology. The cost per base pair for sequencing has been dropping rapidly, almost following a Moore’s Law for genetics. Many believe that the $1000 price will make it attractive to sequence the genomes of many people and that, with many more genome sequences available, analysts will be able to gain new insights into how sequence variations influence health and disease. A recent announcement from a laboratory at Stanford appears to have brought the cost for a human sequence below $50,000.



Since the human genome effort started, the hope has been that comparison of the genomes of patients with particular medical conditions to those of suitable control groups would provide several benefits to pharmaceutical therapy.



1. Genetic variations that occur in DNA coding for proteins or in DNA that regulates production of proteins will point to new targets for therapy.



2. The variations will identify subgroups of patients who would benefit from a drug that would not show a statistically significant effect in a more general population. As in the case of Herceptin, diagnostic tests would be necessary to find the members of these subgroups.



3. The variations will identify patients whose genetic makeup make them more susceptible to adverse side effects that might lead to discontinuation of development if those patients were part of a clinical trial population. The hypersensitivity reaction of patients with a particular HLA type to abacavir is an example. Again, diagnostic tests would identify these patients.



Points 2 and 3 are clearly aspects of personalized medicine, which is a double edged sword for the pharmaceutical industry in that it may lead to more narrowly defined markets as well as to approval of drugs that might not be approved otherwise.



These three considerations were among the reasons for the effort to identify the genetic variations known as single nucleotide polymorphisms (SNPs) in laboratories sponsored by the SNP consortium and in the more recent HapMap (Haplotype Map) project. Despite the availability of over three million SNPS that provide good coverage of the genome, correlation of SNP genotypes with disease conditions has not yet had a wide impact on pharmaceutical development. After several years of SNP studies, the view has emerged that many rare genetic variations may contribute to susceptibility to disease (or efficacy of therapy or to increased risk of adverse reactions). If that view is correct, complete DNA sequences represent a more efficient way than SNP assays to find multiple rare variations that have predictive value.