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: 9351187
• 负责人: Pui-Yan KWOK
• 金额: $ 126.8万
• 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 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9351187
• 关键词: Address; Biochemical; Biological Assay; Blood; Child; Clinical; Clinical Data; Constitutional; DNA; Data; Disease; Ethics; Excision; Genes; Health Benefit; Health Policy; Immune System Diseases; 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; whole genome

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个州的重要公共卫生计划。整个基因组/外显子组测序的成本下降提供了一个机会，可以询问整个基因组分析（WGA）是否可以作为任何条件的具有成本效益的新生儿筛查方法。我们将解决通过将该技术应用于NB提出的某些关键问题。在1620个新生儿血点中，我们将使用整个外显子组测序（WES）作为WGA的一种成本效益方法，与新生儿的临床数据相关。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）确定基因变异，以预测哪个 患有某些代谢疾病的儿童发生代谢代谢的危险更大，3）确定对那些因当前T细胞受体切除圈未检测到的原发性免疫缺陷的基因突变，这些突变未检测到，用于严重组合的免疫缺陷筛选，以及4）对于临床上的临床上重要的A scan 9的基因，如果是典型的，是典型的，是典型的，是典型的。 方法。我们还将开发一个参与者保护框架，用于在新生儿期间进行WGA，确定关键利益相关者关于将WGA用于NB的观点，观点和价值偏好，与UC Hastings与法律，科学和健康政策合作，以确定使用WGA的法律和宪法问题，并纳入使用WGA，并合作使用WGA，并与之合作。 PGX进入NBS计划，并为基于WGA扩展的NBS计划制定和传播政策建议。