High Throughput Genotyping Technology

描述(申请人提供)：分子反转探针技术已经被开发出来，允许在一个试管中调用1000个SNPs。这项技术有望实现大规模、廉价的基因分析，包括全基因组分析。在考虑这样的研究之前，需要进一步的平台开发。必须开发软件工具来处理MIP技术数据并与LIMS数据库接口，以确保数据和流程的完整性。有了这一点，将进行一项规模试验研究。申请者与耶鲁大学的一个小组合作，该小组的样本来自患有IgA肾病的人群，IgA肾病是一种与6号染色体上的遗传因素有关的衰弱肾脏疾病。报道称，一项中试规模的研究将使MIP技术应用于现实世界的关联研究。同时，将开发自动化，允许芯片处理和化验液处理的高通量操作。国家技术委员会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，将通过增加芯片检测的光谱多路复用级(这将降低成本并提高数据质量)和增加SNP多路复用级(这将减少DNA的使用并增加操作的紧凑性)来增加额外的功能。这些进展将把ParAllele的SNP生产能力提高到每天500,000个SNP，并为新的使能技术奠定基础。这项申请代表了一项第二阶段的提案，该提案是在一笔资助的STTR赠款的基础上提出的。在第一阶段，申请者成功地超过了设定的发展里程碑。100plex的准确率和呼叫率分别为98%和95%，1000plex的呼叫率和呼叫率分别为97%和99%。我们希望，这一学术/工业伙伴关系取得的成功将使进一步发展的资金能够达到所要求的水平。

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.