High Throughput Genotyping Technology

描述（由申请人提供）：分子倒置探针技术已经开发出来，可以在单管中调用1000个snp。这项技术有望实现大规模廉价的遗传分析，包括全基因组分析。在进行此类研究之前，需要进行进一步的平台开发。必须开发软件工具来处理MIP技术数据，并与LIMS数据库接口，以确保数据和过程的完整性。在此基础上，将进行试点规模的研究。这些申请者与耶鲁大学的一个研究小组合作，该小组从患有IgA肾病的人群中提取样本，IgA肾病是一种使人衰弱的肾脏疾病，与6号染色体上的遗传因素有关。描述了一项中试规模的研究，该研究将允许MIP技术应用于现实世界的关联研究。同时，自动化将被开发，这将允许芯片处理和分析流体处理的高通量操作。SGTC的研究人员将在开发这项任务所需的硬件方面发挥核心作用。最后，将通过增加用于芯片检测的频谱复用水平（这将降低成本并提高数据质量）和增加SNP复用水平（这将减少DNA的使用并增加操作的紧凑性）来添加额外的功能。这些发展将使parallel的SNP吞吐量提高到50万SNP /天，并为新的使能技术提供基础。此申请是继STTR资助后的第二阶段提案。在第一阶段，申请人成功地超过了设定的开发里程碑。开发100plex检测，准确率为>98%，准确率为95%，而1000plex检测，准确率为97%，准确率为>99%。我们希望这种学术/工业伙伴关系的成功将使进一步的发展得到所需水平的资助。

DESCRIPTION (provided by applicant): The Molecular Inversion Probe technology has been developed to allow 1000 SNPs to be called in a single tube. This technology holds the promise of enabling large scale inexpensive genetic analysis including the analysis of whole genomes. Before such studies can be contemplated, further platform development is required. Software tools must be developed to process MIP technology data and interface with a LIMS database to ensure data and process integrity. With this in place, a pilot scale study will be conducted. The applicants have formed a collaboration with a group at Yale University who have samples from a population that is afflicted with IgA nephropathy, a debilitating kidney disorder which has been linked to genetic factors on Chromosome 6. A pilot scale study is described that would allow the MIP technology to be applied to a real world association study. Concurrently, automation will be developed that will allow high throughput operations of both the chip processing and assay fluid handling. Researchers at the SGTC will play a central role in developing the hardware necessary for this task. Finally, additional functionality will be added by increasing the level of spectral multiplexing for the chip detection (which will decrease the cost and increase the data quality) and increasing the level of SNP multiplexing (which will decrease the usage of DNA and increase the compactness of the operation). These developments will increase the SNP throughput at ParAllele to >500,000 SNPs/day and provide the basis for a new enabling technology. This application represents a Phase II proposal that follows on from a funded STTR grant. During Phase I, the applicants successfully exceeded the development milestones that were set. The targets of developing a 100plex assay with >98% accuracy and 95% call rate were met with a 1000plex assay with 97% call rate and >99% accuracy. We hope that the demonstrated success of this academic/industrial partnership will enable further development to be funded at the level requested.