SCOR IN PEDIATRIC CARDIOVASCULAR DISEASE

小儿心血管疾病中的 SCOR

• 批准号: 6343648
• 负责人: RONALD M LAUER
• 金额: $ 94.47万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343648
• 关键词: congenital heart disorder; developmental genetics; histogenesis

(Adapted from the Applicant's Abstract) This SCOR entitled "Genes Involved in Cardiac Development" consists of six projects and one Core Laboratory. The themes of this SCOR relate to the identification, characterization and function of genes that relate to cardiac development. These projects and the core laboratory are integrated in their efforts and directed by investigators who have appointments in the Departments of Anatomy and Cell Biology, Biochemistry, Biological Sciences, Pediatrics (Cardiology and Genetics), Physiology and Biophysics and Preventive Medicine and Environmental Health. The SCOR program does not try to address all of the basic and clinical issues related to congenital heart disease. The major focus and rationale for the SCOR Program is as follows: There exists a genetic susceptibility to atrial septal, ventricular septal and AV canal defects. The genes that are involved in the formation of these septal areas of the heart will be identified from temporal and spatial studies of rodent embryos and will become candidates for further investigation in this SCOR. Project 1, a human study, will recruit and examine probands with these three cardiac malformations and their family members. The DNA from these subjects will be used to carry out linkage and association studies of candidate genetic regions using STRP markers characterized in individual as well as pooled DNA samples. Project 2 along with the In Situ Core Laboratory will identify genes that are spatially and/or temporally regulated during heart development. Project 3 will evaluate the role of differentially expressed genes in cardiac morphogenesis that relate to the three defects as well as other congenital malformations. Project 4 will study the role of dystroglycan which is expressed throughout the embryonic heart during development. Project 5 will focus on the spatial-temporal regulation of coronary vasculogenesis and angiogenesis which is necessary for myocardial and septal development. Project 6 will develop vectors to allow investigation of spatial and temporal expression of genes involved in septal and other morphologic areas during early cardiac development. In Situ Core Laboratory will localize temporal and spatial patterns of expressions of selected clones for Projects 3, 4, 5, and 6. These efforts have great potential to identify genes that are risk factors for the development of frequently occurring cardiac birth defects and thus have the additional potential of developing preventive measures.

(摘自申请者的摘要)这份题为“心脏发育相关基因”的研究报告由六个项目和一个核心实验室组成。这一SCOR的主题涉及与心脏发育相关的基因的识别、特征和功能。这些项目和核心实验室整合在一起，由在解剖学和细胞生物学、生物化学、生物科学、儿科(心脏病和遗传学)、生理学和生物物理学、预防医学和环境健康系任命的调查人员指导。SCOR计划并不试图解决与先天性心脏病相关的所有基本和临床问题。SCOR计划的主要关注点和基本原理如下：房间隔、室间隔和房室管缺陷存在遗传易感性。参与心脏这些隔区形成的基因将通过对啮齿动物胚胎的时间和空间研究来确定，并将成为本次SCOR进一步研究的候选基因。项目1是一项人体研究，将招募和检查患有这三种心脏畸形的先证者及其家庭成员。来自这些受试者的DNA将被用来利用以个体和混合DNA样本为特征的STRP标记对候选遗传区域进行连锁和关联研究。项目2将与原位核心实验室一起识别在心脏发育过程中受空间和/或时间调控的基因。项目3将评估差异表达基因在心脏形态发生中的作用，这些基因与这三种缺陷以及其他先天性畸形有关。项目4将研究在胚胎心脏发育过程中表达的营养不良多糖的作用。项目5将集中于冠状动脉血管生成和血管生成的时空调节，这是心肌和间隔发育所必需的。项目6将开发载体，以允许研究心脏发育早期间隔和其他形态区域涉及的基因的空间和时间表达。原位核心实验室将为项目3、4、5和6定位选定克隆的表达的时间和空间模式。这些努力具有巨大的潜力，可以识别导致频繁发生的心脏出生缺陷的危险因素的基因，从而具有开发预防措施的额外潜力。