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Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships, Workshop Summary
IMPACT OF GENOMICS
Genome-wide scanning is a relatively new genetic technology for finding biomarkers associated with disease. It is a method of scanning the entire genome in the search for single nucleotide polymorphisms (SNPs) that are correlated with disease. While the vast majority of SNPs are innocuous, SNPs associated with disease are identifiable in combination with other data, including epidemiology studies that compare large groups of individuals with the disease against other groups without the disease. When SNPs associated with disease are found on particular regions of the chromosome, these SNPs subsequently can be used to pinpoint disease-specific loci to the disease-related gene.
An outgrowth of the Human Genome Project and the International HapMap Project, genome-wide scanning has a myriad of applications, including the identification of targets for drug development. Dr. Allen Roses, senior vice president of GlaxoSmithKline, Inc., focused his presentation on genomics’ impact for development of biomarkers for nervous system disorders. He pointed out that genotypes associated with disease eventually may be used to predict which patient groups are more susceptible to disease, which are more likely to experience adverse effects of drugs, or which are more likely to benefit from drug therapy and at what doses (among other applications).
Genome-wide scanning already has been applied successfully to at least one nervous system disorder, Alzheimer’s disease (Martin et al., 2000), and is soon expected to yield results for schizophrenia, according to Roses. It is now well established that the gene APOE is a susceptibility gene for Alzheimer’s disease (Roses, 1996). Drawing from this pioneering work, Roses first focused on the value and efficiency of genome-wide scanning as a method to validate and confirm genetic loci first found by previous methods that were more labor intensive (Lai et al., 1998). Genome-wide scanning, said Roses, has an equally important role in disconfirming other loci identified by earlier methods. Narrowing the search for the most important loci is essential before undertaking the laborious process of finer mapping and positional cloning to find, within the loci, specific genes that are defective. Genome-wide scanning also can be used, on its own, without being hypothesis-driven about which chromosomal regions to search. In other words, it can be used in a hypothesis-free manner to examine new regions of the genome not explored in earlier studies. Those studies were often small, family-based