High resolution DNA copy/LOH measurements on WGG arrays

WGG 阵列上的高分辨率 DNA 拷贝/LOH 测量

• 批准号: 6934807
• 负责人: KEVIN L GUNDERSON
• 金额: $ 58.4万
• 依托单位: ILLUMINA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934807
• 关键词: chromosome disorders; computer program /software; computer system design /evaluation; gene deletion mutation; genotype; human genetic material tag; human tissue; laser capture microdissection; loss of heterozygosity; neoplasm /cancer genetics; technology /technique development

DESCRIPTION (provided by applicant): Anomalies of the genome, such as congenital chromosomal imbalances, can be present from birth or can arise during cell division and lead to formation of cancer. Progression of cancer can be followed by monitoring changes in the genome. For instance, allelic deletions of tumor suppressor genes and amplifications of oncogenes are well known events in carcinogenesis. The primary goal of this project is to develop a high resolution array-based approach to detecting and monitoring changes in tumor samples. A secondary goal is to detect microdeletions and amplifications in congenital chromosomal disorders. The proposed work will focus on developing DNA copy and loss of heterozygosity (LOH) measurements using our novel whole genome genotyping (WGG) platform. The WGG technology was developed, in part, through phase I funding. Under phase I, we developed a whole genome amplification protocol and an arraybased primer extension assay that enabled direct readout of the genome - both copy number and genotypes. This development obviates the need for the original proposed complexity reduction step (reduced representation). The number of genotypes that can be read out from a single sample is limited only by the number of probes on the array. The proposed work will use a WGG array that is currently under development to perform genotyping and copy number analysis at the same time, at an average resolution of approximately 30 kb across the genome. This revolutionary assay system will allow regions of genomic alteration to be precisely defined accurately and robustly, and has the potential to be used directly in clinical applications. Once fully developed, the assay will be employed to characterize biological tumor/normal sample pairs as well as congenital chromosomal imbalances.

描述（由申请人提供）：基因组的异常，例如先天性染色体失衡，可以从出生中出现，也可以在细胞分裂期间出现并导致癌症的形成。癌症的进展可以通过监测基因组的变化。例如，肿瘤抑制基因的等位基因缺失和癌基因的扩增是癌变中众所周知的事件。该项目的主要目标是开发一种基于高分辨率阵列的方法来检测和监测肿瘤样品的变化。第二个目标是检测先天性染色体疾病的微缺失和扩增。拟议的工作将着重于开发DNA复制和使用我们新型的整个基因组基因分型（WGG）平台的杂合性（LOH）测量的丢失。 WGG技术是通过I阶段资金开发的。在第一阶段，我们开发了整个基因组扩增方案和一个基于阵列的引物扩展测定法，该测定能够直接读取基因组 - 拷贝数和基因型。这种发展避免了对原始提出的复杂性降低步骤（减少表示）的需求。可以从单个样本中读取的基因型数量仅受阵列上的探针数量的限制。拟议的工作将使用目前正在开发的WGG阵列同时进行基因分型和拷贝数分析，平均分辨率在整个基因组上约为30 kb。该革命性测定系统将使基因组改变区域得到准确，稳健的定义，并有可能直接用于临床应用中。一旦完全开发，该测定法将用于表征生物肿瘤/正常样品对以及先天性染色体失衡。