Impact of Advances in DNA Sequencing Technology on Genetic Diagnostic Testing

Dr. Ellen Jorgensen of Genspace, one of the witnesses at the U.S. Patent and Trademark Office's first hearing regarding the advisability of permitting "second opinions" for patented genetic diagnostic tests without patent infringement liability, advocated "at-home" or "do-it-yourself" DNA testing as a solution (see "USPTO Holds First Hearing on 'Second Opinion' Genetic Testing").  This proposal raises a significant number of questions, particularly with regard to the potential for harm to the public due to errors that might arise from such "at-home" genetic diagnostic testing or whether precautions in interpreting results would be taken concerning the emotional consequences of finding a genetic mutation in an individual's BRCA genes.

However, the saliency of any technical objections to the idea must be considered to be significantly reduced by an announcement from Oxford Nanopore Technologies at the Advances in Genome Biology and Technology Conference at Marco Island, FL last week:  a disposable gene sequencing machine the size of a standard USB thumb drive and capable of providing a complete genomic sequence for about $900.  Terming the business model for the device "pay-as-you-go" sequencing, the chief technology officer of the company, Clive G. Brown stated that the new device eliminates the need for expensive ($50,000 - $750,000) machines currently in use for gene sequencing, and touted the use of the device for bedside genetic testing, biological field work, and food safety (e.g., for identifying pathogens in situ in real time).

The basis of the device is so-called "nanopore" sequencing (explained in greater detail for the interested in "The $1,000 Genome: The revolution in DNA sequencing and the new era of personalized medicine" by Kevin Davies).  Briefly, the technology employs alpha-hemolysin, a bacterial membrane "pore" protein, stabilized with cyclodextrin, to measure changes in electrical current as each base moves through the pore after exonuclease cleavage.  The devices take advantage of parallel processing on a chip and computer analysis of the data to create the linear sequence.  Initially each chip will contain 2,000 pores with machines using chips having 8,000 pored being developed for release in 2013.  While the sequencing capacity ("tens of thousands bases per read") is higher than with competing machines, so is its error rate (4%).  This level of error would preclude use of the device for genetic diagnostic sequencing, for example.

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