Research Project
9041400
? DESCRIPTION (provided by applicant): DNA, and particularly high molecular weight (HMW) DNA, is known to become fragmented over time, even under optimal storage or shipping conditions. This is a consequence of inexorable chemical, physical, and enzymatic processes that occur even under even the most stringent DNA preservation regimes. These facts are of renewed and growing concern because in the US alone it is estimated that there are more than half a billion human samples (tissue or DNA) in storage, while the global market for human biospecimens and related services is predicted to grow to $2.25B in 2015. Large-scale genome analysis with high-quality, HMW DNA is imperative to the understanding of human biology and its impact on human health, since only HMW DNA retains vital information about linkage and phase. Such information is critical to clinical genomics for the understanding and treatment of genetic diseases and cancers. In addition to medicine, there are clear societal benefits from long-term DNA preservation in forensics, agriculture, environmental studies, renewable energy, species preservation, and many other areas. Current DNA stability solutions offer protection against fragmentation, but none can prevent it altogether. Furthermore, with current methods one is forced to choose between effective but costly (e.g. cold storage) or affordable but imperfect (e.g. FTA cards) approaches. Dovetail Genomics is proposing research that will ultimately yield a simple, inexpensive, and powerfully preservative kit for the stabilization of DN for long-term storage or long-range transport. Crucially, the proposed method preserves long-range DNA information in spite of the presence of fragmentary DNA damage. This feature is completely unique in the domain of DNA preservation. The kit may be used alone or in concert with existing methods for DNA stabilization, e.g., cold storage or drying approaches. It will be agnostic to the source of DNA so can be flexibly mated to a variety of DNA collection methods from diverse sample sources (e.g. blood, saliva, or cheek swabs). Finally, its use will require minimal, standard laboratory equipment and very little hands on time. These features culminate in a product that will simply and cost-effectively extend the range of retrievable genomic information from preserved samples from thousands of nucleotides to millions, with a similar improvement to the longevity of such samples in storage. Better retention of long-range genomic information for DNA in transit removes substantial barriers to worldwide studies of human genetic diversity and its impacts on human health. Similarly, the protection of long-range information in storage ensures high quality genomes for long-term human health studies and valuable retrospective repositories for as of yet unimagined studies of human populations and shifts in their genomic underpinnings over time. Both of these goals are cornerstones of the nascent but expanding DNA economy and are barriers to the broader adoption of genomic analysis. We will demonstrate the retention of long-range genomic information with our method and the sufficiency of that information for the reconstruction of high quality human genomes.
