The Role of IgLONS in Cardiac Development and Disease

描述（由申请人提供）： 博士Grossfeld是一位训练有素的儿科心脏病专家，致力于研究先天性心脏病的遗传基础。 该拨款提案的目的是获得支持，使Grossfeld博士能够在拟议的资助期结束时成为独立调查员。 拟议的研究将在圣地亚哥加州大学儿科系Anthony Wynshaw-Boris博士的实验室进行。 在此期间，Grossfeld博士将接受必要的培训，以整合人类和动物遗传模型系统方法，研究导致左心发育不良综合征（HLHS）的基因。 Wynshaw-Boris博士为促进和发展类似的研究兴趣提供了一个非常成功的理想环境。 该项目的长期目标是研究OBCAM和Neurotrimin（IgLON基因亚家族的两个成员）在心脏发育和先天性心脏缺陷（包括HLHS）产生中的作用。HLHS是最严重的先天性心脏病之一，占先天性心脏病婴儿死亡人数的20%。迄今为止，还没有关于HLHS致病基因的报道。 本项目的具体目标是：具体目标1）：胎儿和成人心脏中OBCAM和Neurotrimin表达的表征;具体目标2）：利用小鼠和鸡遗传模型系统改变OBCAM和Neurotrimin的表达，以及具体目标3）：Jacobsen中发生的孤立性心脏缺陷患者中OBCAM和Neurotrimin点突变和微缺失的突变分析综合征，并与Jacobsen综合征患者OBCAM和Neurotrimin单核苷酸多态性。

DESCRIPTION (provided by applicant): Dr. Grossfeld is a highly trained, board-certified pediatric cardiologist who is devoted to studying the genetic basis of congenital heart disease. The purpose of this grant proposal is to obtain support to enable Dr. Grossfeld to become an independent investigator by the end of the proposed funding period. The proposed research will be performed in the laboratory of Dr. Anthony Wynshaw-Boris in the Department of Pediatrics at the University of California, San Diego. During this time, Dr. Grossfeld will receive the necessary training for incorporating human and animal genetic model system approaches for studying genes causing hypoplastic left heart syndrome (HLHS). UCSD and specifically, Dr. Wynshaw-Boris, provide an ideal environment that has been extraordinarily successful for promoting and developing similar research interests. The long-term goal of this project is to study the role of OBCAM and Neurotrimin, two members of the IgLON subfamily of genes, in cardiac development and in the generation of congenital heart defects, including HLHS. HLHS is one of the most severe congenital heart defects, accounting for 20% of all deaths in infants with congenital heart disease. To date, no causative gene for HLHS has been reported. The specific aims of this project are: Specific Aim 1): Characterization of the expression of OBCAM and Neurotrimin in fetal and adult heart; Specific Aim 2): Alteration in the expression of OBCAM and Neurotrimin utilizing mouse and chicken genetic model systems, and Specific Aim 3): Mutation analysis for point mutations and microdeletions in OBCAM and Neurotrimin in patients with isolated heart defects that occur in Jacobsen syndrome, and for single nucleotide polymorphisms in OBCAM and Neurotrimin in patients with Jacobsen syndrome.