Genetic Mechanisms in Pediatric Heart Disease

描述（由申请人提供）： 基因异常现在已经被证明是负责的一些类型的先天性心脏病的发病机制。因此，拟议的费城儿童医院（CHOP）SCCOR计划是基于以下工作假设：有关基因异常和基因表达相关模式的基本发现可以应用于统一的方法，既了解心脏畸形的复杂基础，也为翻译方向提供治疗见解。与先天性心脏病遗传基础相关重大发现的强有力的先前合作将促进该SCCOR的活动，其中包括结束SCOR计划的十年生产力，继续临床和细胞培养/DNA核心，以及继续核心主任。这些核心也是国家和国际合作的资源。在过去十年中，主要人员之间的合作产生了150多份出版物。SCCOR将设在CHOP的心脏中心，该中心最近根据JCAHO评估被儿童杂志评为全国心脏护理第一名。该计划的目标可以总结如下：项目1（基础）将研究用于先天性心脏病手术的新型异种移植生物材料，强调影响生物相容性的细胞和分子机制。项目2（临床）将继续SCOR关于流出道畸形的工作，其目标是使用基于家族的遗传关联研究以及基于基因相互作用和复杂关联的指导，评估心脏病患者心脏发育中涉及的特定基因的贡献和相对风险。项目3（临床）的目的是将与先天性心脏缺陷相关的基因异常的发现与心脏结局联系起来。项目4（临床）将研究临床细胞遗传学发现，揭示与端粒下区域基因缺失相关的心脏畸形发生机制的新关系。项目5（临床）将研究染色体易位断点基因异常与先天性心脏病的新关联。这些项目将得到六个核心的支持：行政;临床技能发展;临床;细胞培养和DNA分析;心脏形态学，基因表达和组织学;生物信息学和数据分析。

DESCRIPTION (provided by applicant): Gene abnormalities have now been demonstrated to be responsible for the pathogenesis of a number of types of congenital heart disease. Thus, the proposed Children's Hospital of Philadelphia (CHOP) SCCOR program is based on the following working hypothesis: Basic discoveries concerning gene abnormalities and related patterns of gene expression can be applied to a unifying approach for both understanding the complex basis for cardiac dysmorphogenesis as well as providing therapeutic insights for translational directions. Strong prior collaborations with major discoveries concerning the genetic basis of congenital heart disease will facilitate the activities of this SCCOR, and these include ten years of productivity in the concluding SCOR programs, with continuing Clinical and Cell Culture/DNA Cores, and continuing Core Directors. These Cores have also been resources for both national and international collaborations. Previous collaborations among the Key Personnel have produced more than 150 publications over the past decade. The SCCOR will be based in CHOP's Cardiac Center, which was recently ranked first in the nation for cardiac care by Child magazine based on JCAHO evaluations. The objectives of the program may be summarized as follows: Project 1 (basic) will investigate novel heterograft biomaterials for use in congenital heart surgery, emphasizing cellular and molecular mechanisms that affect biocompatibility. Project 2 (clinical) will continue its work from the SCOR on outflow tract malformations and its objective is to assess the contribution and relative risk of specific genes involved in cardiac development in cardiac patients using family-based genetic association studies, and directions based on gene interactions and complex associations. The Project 3 (clinical) objectives relate discoveries of gene abnormalities associated with congenital heart defects to cardiac outcomes. Project 4 (clinical) will investigate clinical cytogenetics discoveries revealing new relationships to mechanisms of cardiac dysmorphogenesis that are associated with gene deletions in the subtelomere regions. Project 5 (clinical) will investigate the novel association of chromosomal translocation break point gene abnormalities with congenital heart disease. The Projects will be supported by six cores: Administrative; Clinical Skills Development; Clinical; Cell Culture and DNA Analysis; Cardiac Morphology, Gene Expression, and Histology; and Bioinformatics and Data Analysis.