A method for the preservation of long-range genomic information during DNA storage and transport.

一种在 DNA 存储和运输过程中保存远程基因组信息的方法。

• 批准号: 9041400
• 负责人: Marco Blanchette
• 金额: $ 22.47万
• 依托单位: DOVETAIL GENOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9041400
• 关键词: Adoption; Aging; Agriculture; Area; Biological Preservation; Blood; Cheek structure; Chemicals; Chromatin; Clinical; Clinical Research; Collection; Communities; Companions; Cryopreservation; DNA; DNA Damage; DNA Fragmentation; DNA Maintenance; Data; Disease; Ensure; Forensic Medicine; Future; Generations; Genetic Variation; Genome; Genomics; Goals; Hand; Health; Hereditary Disease; Human; Human Biology; Human Genetics; Human Genome; Information Retrieval; Libraries; Longevity; Malignant Neoplasms; Maps; Marketing; Measures; Mediating; Medicine; Methods; Molecular Weight; Nucleotides; Outcome; Partner in relationship; Phase; Process; Proxy; Reading; Research; Saliva; Sampling; Services; Shipping; Ships; Source; Swab; Technology; Temperature; Time; Tissue Sample; Tissues; aged; commercial application; cost; crosslink; genome analysis; human genomics; human population study; laboratory equipment; physical process; prevent; protective effect; public health relevance; reconstitution; reconstruction; repository; scaffold

 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.

 描述(由申请人提供)：DNA，特别是高分子量(HMW)DNA，已知会随着时间的推移而碎裂，即使在最佳的储存或运输条件下也是如此。这是不可阻挡的化学、物理和酶过程的结果，即使在最严格的DNA保存制度下也会发生这些过程。这些事实再次引起人们越来越多的关注，因为据估计，仅在美国就有超过5亿份人类样本(组织或DNA)储存，而全球人类生物检疫和相关服务市场预计将在2015年增长到22.5亿美元。大规模的高质量HMW DNA基因组分析对于理解人类生物学及其对人类健康的影响是必不可少的，因为只有HMW DNA保留了关于连锁和阶段的重要信息。这些信息对于了解和治疗遗传性疾病和癌症的临床基因组学至关重要。除了医学，在法医学、农业、环境研究、可再生能源、物种保护和许多其他领域，长期保存DNA还有明显的社会好处。目前的DNA稳定性解决方案提供了防止碎片的保护，但没有一个能完全防止它。此外，在目前的方法下，人们被迫在有效但昂贵的方法(例如冷藏)或负担得起但不完美的方法(例如FTA卡)之间进行选择。燕尾基因组公司正在进行一项研究，最终将产生一种简单、廉价和强大的防腐剂试剂盒，用于稳定糖尿病肾病的长期储存或长距离运输。最重要的是，尽管存在片断的DNA损伤，该方法仍能保存远程DNA信息。这一特征在DNA保存领域是完全独一无二的。该试剂盒可以单独使用，也可以与现有的DNA稳定方法一起使用，例如冷藏或干燥方法。它将与DNA的来源无关，因此可以灵活地与来自不同样本来源(例如血液、唾液或面颊拭子)的各种DNA收集方法相匹配。最后，它的使用将需要最少的标准实验室设备和非常少的动手时间。这些特征最终将产生一种产品，它将简单且具有成本效益地将可从保存的样本中检索的基因组信息的范围从数千个核苷酸扩展到数百万个核苷酸，并类似地改善此类样本在存储中的寿命。在运输过程中更好地保留DNA的远程基因组信息，消除了在世界范围内研究人类遗传多样性及其对人类健康的影响的重大障碍。同样，对储存中的远程信息的保护确保了高质量的基因组用于长期的人类健康研究，并为迄今为止尚未想象的人类群体及其基因组基础随着时间的变化而进行的研究提供了宝贵的回溯性储存库。这两个目标都是新生但不断扩大的“DNA经济”的基石，也是更广泛采用基因组分析的障碍。我们将用我们的方法证明远程基因组信息的保留，以及这些信息对于高质量人类基因组重建的充分性。