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UVA-Led Research Team Partners with OGT on 10,000-Sample Type 1 Diabetes Study

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By Justin Petrone

A team headed by researchers at the University of Virginia will work with Oxford Gene Technology on a large study of type 1 diabetes, an OGT official told BioArray News this week.

Led by Stephen Rich, director of UVA's Center for Public Health Genomics, the project will use array comparative genomic hybridization to investigate the relationship between genome structural variation and susceptibility to the disease. According to the US Centers for Disease Control and Prevention, about 13,000 people are diagnosed with type 1 diabetes in the US every year.

To achieve the study's goals, OGT will in coming months screen 10,000 patient samples using custom arrays manufactured by Agilent Technologies with the aim of identifying copy number variants associated with type 1 diabetes. The ultimate goal of the project is to allow researchers to better predict disease susceptibility and find potential therapeutic targets.

In addition to UVA's CPHG, other collaborators in the study include Matt Hurles' group at the Wellcome Trust Sanger Institute, John Todd's lab at the University of Cambridge, and Vincent Plagnol's lab at University College London. The team was last year awarded a three-year, $6.4 million grant from the National Institute of Diabetes, Digestive and Kidney Diseases to investigate the role of CNVs in type 1 diabetes. The study is slated to end on Aug. 31, 2012.

Financial terms of the agreement with OGT were not disclosed.

According to Gareth Thomson, director of genomic services at OGT, the deal with the UVA-led research consortium is a big win for the Oxford, UK-based firm, which has invested resources to build out and gain recognition for its Genefficiency service business. "As one of the largest single-project contracts secured by OGT, this study represents a significant milestone in the commercial history of the company," Thomson told BioArray News this week.

OGT last year processed 22,000 samples in 20 weeks as part of a Wellcome Trust Case Control Consortium CNV study (BAN 6/2/2009). To support that study, OGT used Agilent’s instrumentation, including the Velocity 11 Bravo, a robotics platform that automates most of the steps in the labeling process. Additionally, OGT developed a custom laboratory information management system for use in the WTCCC project.

Rich said in a statement this week that his team decided to use OGT's Genefficiency service in part because he was familiar with the firm's role in the WTCCC CNV study and array CGH sample processing system.

Rich also spoke about the study during a workshop hosted by OGT at the American Society of Human Genetics annual meeting, held in Washington, DC, earlier this month. In his talk, Rich said that the rationale for the study is that type 1 diabetes is determined by genetic and environmental factors and that "not all of the genetic risk has been accounted for, even after looking at all the genome-wide results" obtained from previous association studies. His team believes there may be rare variants as well as structural variants that contribute to disease risk.

The study design calls for looking at 10,000 samples from affected sibling pair families, where both siblings have the disease, as well as trios and case-control samples. Analyzing sibling pair families will not only help the researchers detect structural variants, but determine "whether they are transmitted in a familial pattern, and also whether the affected sib pairs are concordant for the particular variant," Rich said.

Thomson said that OGT has already completed a pilot study for the project using catalog Agilent arrays on several hundred samples. "We have completed an initial pilot study, which has been used to test the overall quality of the samples and also the bulk reagent batches that will be used for the main study," he said.

Rich said the pilot study taught the team "a great deal about sample preparation and the best way to optimize" study results. Now OGT is ramping up to characterize the 10,000 samples using an array designed for the study. Specifically, the researchers will use a custom Agilent G3 array containing eight 60,000-probe subarrays per slide.

Sanger's Hurles has led the design of the array, which Rich said contains about 1,500 clusterable but untaggable CNVs, 2,000 unclusterable CNVs, novel insertion sequences, and structural variants selected from 1000 Genomes Project data. Each CNV is represented by about 10 probes on the array. Rich said that the array design should be completed in about a month.

Thomson said that once the custom-designed array for the main study has been manufactured, OGT will undertake an initial 1,000-sample run in January to "help the team understand how the custom array is performing under test conditions and decide if any further modifications are required," he said. "Obviously, when you make a custom array, you are worried about things not going well," Rich noted.

Should the custom design work out, Thomson said OGT expects to complete the processing of samples for the type 1 diabetes project by next May. OGT will be responsible for processing all samples, Thomson said. The firm has also been "closely involved in all of the planning stages required to manage such a large study" and has "offered support on experimental design and sample preparation as well as managing reagent batch control and logistics," Thomson added.


Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.

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