SCOR IN PEDIATRIC CARDIOVASCULAR DISEASE

（摘自申请人摘要）这个名为“参与心脏发育的基因”的SCOR由六个项目和一个核心实验室组成。本SCOR的主题涉及与心脏发育有关的基因的鉴定、表征和功能。这些项目和核心实验室被纳入他们的工作，并由在解剖学和细胞生物学、生物化学、生物科学、儿科（心脏病学和遗传学）、生理学和生物物理学、预防医学和环境卫生等部门任职的研究人员指导。SCOR项目并不试图解决所有与先天性心脏病相关的基础和临床问题。SCOR项目的主要焦点和基本原理如下：房间隔、室间隔和房室管缺陷存在遗传易感性。参与这些心脏间隔区域形成的基因将从啮齿动物胚胎的时间和空间研究中确定，并将成为本SCOR进一步研究的候选基因。项目1是一项人体研究，将招募并检查患有这三种心脏畸形的先证者及其家庭成员。这些受试者的DNA将用于使用个体和汇总DNA样本中特征的STRP标记对候选遗传区域进行连锁和关联研究。项目2和原位核心实验室将识别在心脏发育过程中受到空间和/或时间调控的基因。项目3将评估与这三种缺陷以及其他先天性畸形相关的差异表达基因在心脏形态发生中的作用。项目4将研究在整个胚胎心脏发育过程中表达的糖酐的作用。项目5将重点研究冠状动脉血管生成和血管生成的时空调控，这是心肌和间隔发育所必需的。项目6将开发载体，以研究早期心脏发育过程中涉及间隔和其他形态区域的基因的空间和时间表达。In Situ Core Laboratory将为项目3、4、5和6定位选定克隆的时空表达模式。这些努力有很大的潜力来确定基因是经常发生的心脏出生缺陷的风险因素，从而有制定预防措施的额外潜力。

(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.