INDUSTRY NEWS
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John Sninsky |
“What you’re seeing now is the fruition of the investment that Celera made five years ago to do genome scans with a fundamentally different approach than is presently being taken,” said John Sninsky, PhD, vice president of discovery research at Celera. “We reasoned that a good objective for investing in finding out where the genes were was to find out whether single nucleotide polymorphisms (SNPs) in genes in which we know their positions are associated with various diseases.”
Celera announced the presentation of data supporting a constellation of seven SNPs that predicts the risk of cirrhosis in patients with chronic hepatitis C (CHC). It is believed that these SNPs offer a better predictor than present clinical risk factors for the disease. Using a combination of SNPs as a prognostic tool suggests that the information will be applicable to a larger fraction of individuals infected with the hepatitis C virus (HCV), will likely prove more robust across risk groups tested, and have more compelling use for patient management than current methodologies.
The seven SNPs were identified and validated through multiple research studies that were conducted during a three-year period. The studies involved approximately 1500 individuals infected with CHC, whose samples were tested for the presence of approximately 25,000 SNPs as part of a Celera functional genome scan. SNPs that were identified as being associated with risk for cirrhosis through initial association studies and survived replication by testing with additional samples were used to develop a training algorithm to select the optimal constellation of seven SNPs. These seven SNPs were finally tested in another set of samples to confirm their performance in predicting risk for cirrhosis.
Celera also announced the publication of findings describing two novel genetic markers associated with an increased risk for myocardial infarction (MI). Neither of the two gene variants has previously been associated with MI.
The retrospective research study evaluated DNA samples from more than 2000 individuals to compare patterns of genetic variation in people with a history of early-onset MI with those with no history of MI. The study identified genetic markers in two genes that are associated with increased risk for early-onset heart attack: VAMP8, which is involved in platelet aggregation, and HNRPUL1, which encodes a ribonuclear protein.
The study’s key finding was that variants of the VAMP8 and HNRPUL1 genes were associated with early-onset MI and had the same risk variants in all three studies. These genetic markers were identified through a genomewide study of an initial 11,647 SNPs in 7136 genes, focusing on SNPs that could influence gene function in order to increase the likelihood of identifying disease-causing gene variants. These SNPs were then tested for association with early-onset MI in three case-control studies with a total of 821 cases and 1200 controls.
Sninsky explained that Celera’s efforts required an investment in determining a larger number of SNPs because the human genome project sequenced only a small number of individuals. Even though it knew the sequence of genes, the company did not know how much sequence variation actually occurred in those genes. By launching a genome initiative to go beyond the human genome, Celera resequenced approximately 24,000 genes in 40 individuals. The company followed by developing a high-throughput platform to be able to take assays for those SNPs and rapidly determine the sequence changes in large groups of highly characterized samples. Celera then obtained large, multiple sample sets for disease indications with unmet diagnostic needs.
“We decided rather than simply doing science and then asking if that had a health implication, we started by identifying what the unmet diagnostic needs were and then focused our scientific studies there,” said Sninsky.
