Sequencing of Newborn Blood Spot DNA to Improve and Expand Newborn Screening

新生儿血斑 DNA 测序可改善和扩大新生儿筛查

• 批准号: 8915730
• 负责人: Pui-Yan KWOK
• 金额: $ 115.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8915730
• 关键词: Address; Biochemical; Biological Assay; Blood; Child; Clinical Data; Constitutional; DNA; Data; Disease; Excision; Genes; Genome; Health Benefit; Health Policy; Incidental Findings; Laws; Legal; Link; Metabolic; Metabolic Diseases; Methods; Mutation; Neonatal; Neonatal Screening; Newborn Infant; Parents; Participant; Policies; Public Health; Recommendation; Risk; Scanning; Science Policy; Sensitivity and Specificity; Severe Combined Immunodeficiency; Spottings; T-Cell Receptor; Technology; Testing; base; congenital immunodeficiency; cost; cost effective; drug metabolism; exome sequencing; falls; genetic variant; genome analysis; improved; interest; preference; programs; screening; tool

DESCRIPTION (provided by applicant): Newborn screening (NBS) is an essential public health program in all 50 states. The falling cost of whole genome/ exome sequencing provides an opportunity to ask whether whole genome analysis (WGA) might serve as a method of cost-effective newborn screening for any and every condition. We will address certain critical questions raised by the application of this technology to NBS. We will use Whole Exome Sequencing (WES) as a cost-effective method of WGA in 1620 newborn blood spots that are linked to the clinical data of the newborns. We will then test WES as a NBS Tool for metabolic and immunological disorders. These data will be used to 1) compare the sensitivity and specificity of mutation data with biochemical testing, 2) identify gene variants that predict which children with certain metabolic disorders are at greater risk for metabolic decompensation, 3) identify mutations in genes responsible for those primary immunodeficiencies that are not detected by the current T-Cell receptor excision circle assay used for severe combined immunodeficiency screening, and 4) scan 9 genes for variants that are clinically important for drug metabolism and would be typical "secondary findings" if WES were to be used as a NBS method. We will also develop a participant protection framework for conducting WGA during the neonatal period, determine the views, perspectives, and value preferences of key stakeholders about using WGA for NBS, collaborate with the UC Hastings Consortium on Law, Science and Health Policy, to identify the legal and constitutional issues for using WGA, and for incorporating PGx into NBS programs, and develop and disseminate policy recommendations for expanded NBS programs based on WGA.

描述（由申请人提供）：新生儿筛查 (NBS) 是所有 50 个州的一项重要公共卫生计划。全基因组/外显子组测序成本的下降提供了一个机会来询问全基因组分析（WGA）是否可以作为一种针对任何情况的具有成本效益的新生儿筛查方法。我们将解决将该技术应用于 NBS 时提出的某些关键问题。我们将使用全外显子组测序 (WES) 作为一种经济高效的 WGA 方法，对 1620 个与新生儿临床数据相关的新生儿血点进行分析。然后我们将测试 WES 作为代谢和免疫疾病的 NBS 工具。这些数据将用于 1) 将突变数据的敏感性和特异性与生化测试进行比较，2) 识别预测哪些基因变异 患有某些代谢紊乱的儿童出现代谢失代偿的风险更大，3) 识别导致原发性免疫缺陷的基因突变，而目前用于严重联合免疫缺陷筛查的 T 细胞受体切除环测定法无法检测到这些突变，以及 4) 扫描 9对于临床上对药物代谢很重要的变异基因，如果将 WES 用作 NBS 方法，这些变异基因将是典型的“次要发现”。我们还将制定新生儿期进行 WGA 的参与者保护框架，确定关键利益相关者对 NBS 使用 WGA 的观点、观点和价值偏好，与加州大学黑斯廷斯法律、科学和卫生政策联盟合作，以确定使用 WGA 以及合并的法律和宪法问题 将 PGx 纳入 NBS 计划，并根据 WGA 为扩大的 NBS 计划制定和传播政策建议。