High Throughput Genotyping Technology

高通量基因分型技术

• 批准号: 6644605
• 负责人: Thomas D. WILLIS
• 金额: $ 46.35万
• 依托单位: PARALLELE BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644605
• 关键词: IgA nephropathy; automated data processing; biotechnology; clinical research; computer program /software; computer system design /evaluation; data collection methodology /evaluation; functional /structural genomics; genetic polymorphism; genotype; high throughput technology; human genetic material tag; linkage mapping; microarray technology; nucleic acid sequence; technology /technique development

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.

描述（由申请人提供）：开发了分子倒置探针技术，可在单个试管中检测1000个SNP。这项技术有望实现大规模廉价的遗传分析，包括整个基因组的分析。在考虑进行此类研究之前，需要进一步开发平台。必须开发软件工具来处理MIP技术数据，并与LIMS数据库接口，以确保数据和工艺的完整性。在此基础上，将进行试点研究。申请人与耶鲁大学的一个小组合作，该小组拥有来自患有伊加肾病的人群的样本，IgA肾病是一种与6号染色体上的遗传因素有关的衰弱性肾脏疾病。中试规模的研究，将允许MIP技术被应用到一个真实的世界协会的研究。同时，将开发自动化，这将允许芯片处理和测定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光谱复用水平（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的使用并提高操作的紧凑性）来添加附加功能。这些发展将使ParAllele的SNP通量增加到> 500，000 SNP/天，并为新的使能技术提供基础。这个应用程序代表了第二阶段的建议，从资助STTR赠款。在第一阶段，申请人成功地超过了设定的发展里程碑。开发具有>98%准确度和95%识别率的100重测定的目标用具有97%识别率和>99%准确度的1000重测定来满足。我们希望，这一学术/工业伙伴关系的成功将使进一步的发展能够得到所要求的资金。