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UK Hospital To Sequence the Exomes of 10,000 Heart Disease Patients on SOLiD

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By Monica Heger

This article has been updated from a version posted June 23 to include additional information about the project.

The UK's Royal Brompton Hospital said last week that it would begin sequencing the exomes of 10,000 heart disease patients on Life Technologies' SOLiD machine, which the hospital has recently acquired.

Dudley Pennell, director of the joint Royal Brompton/Imperial National Institute of Health Research Cardiovascular Biomedical Research Unit, told In Sequence that the team has already completed the sequencing of 400 exomes and has begun to analyze the results. He declined to give details on the results or capture method, because he said the team plans to publish them soon.

The UK's NIHR funded the purchase of the sequencer, and is funding the first four years of the project through a grant it awarded to a partnership between the hospital and Imperial College London in April 2008 of more than £10 million ($15 million) for respiratory and cardiac biomedical research units. Pennell said the group would apply to the NIHR for additional funding for the remainder of the project.

Although the price of whole-genome sequencing is continuing to drop, Pennell said that the group plans to stick with exome sequencing for the length of the project. "At the moment, the understanding of the function of the non-coding portions of DNA is so poor that we don't believe [the whole genome] is worth chasing," he said.

The exome sequencing project is scheduled to proceed over the next 10 years, but could be done sooner. Pennell said that the team would be publishing results as quickly as possible. "In the last three months, our sequencing has increased in speed by a factor of 10, so by this time next year it may have increased by another factor of 10."

The goal is to determine molecular subtypes of cardiovascular disease in order to eventually be able to tailor treatment. For example, the hearts of cardiomyopathy patients are not all the same, and patients exhibit a range of abnormalities, including enlarged hearts, thick and heavy hearts, or even enlargements of one side of the heart, said Pennell.

While subdividing into physical appearances helps to "pigeonhole" the cause of cardiomyopathy and other forms of heart disease, even among one of those physical categories, "there might be 50 different diseases that cause it," said Pennell. The goal is to "start with the overall categorization and then move to an overall genetic understanding," Pennell said.

The hospital also plans to use the SOLiD to study other diseases. Pennell declined to give details, though, because he said these other projects are still in the very early stages.

Meanwhile, the US National Human Genome Research Institute also recently moved into using whole-exome sequencing in its study of the genetic causes of heart disease (IS 6/8/2010). The NHGRI-led ClinSeq project, which is focused on atherosclerosis, aims to recruit 1,500 patients.

There are also several other large-scale studies using exome sequencing to find the causative mutations and genes in both rare, Mendelian disorders, as well as more complex, common disorders such as heart disease and Alzheimer's (IS 2/9/2010).

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