GENETIC BASIS OF PEANUT ALLERGY

该应用程序旨在为医学博士Scott H. Sicherer提供一个指导的、以患者为导向的研究项目，这将促进他作为一名独立的内科科学家的发展。Sicherer博士完成了他的儿科住院医师和首席住院医师，他在过敏和免疫学方面获得了奖学金，自1997年7月以来他一直是Mount Sinai School of Medicine的儿科助理教授。在他的奖学金培训的后期和作为教师，他集中了他的研究工作在食物过敏的临床表现，特别是花生过敏。他收集了大量花生过敏患者的临床数据，包括表明花生过敏遗传影响的初步数据。该奖项将使他有机会获得遗传学交叉训练，同时进行多学科，以患者为导向的研究项目，以解剖花生过敏的遗传基础。对花生过敏影响了0.6%的普通人群，是大多数严重的，危及生命的食物过敏反应的原因，敏感性很少长大。由于花生在美国人的饮食中无处不在，易感人群的致敏是规律，过敏人群的意外摄入是常见的。尽管过敏很严重，但人们对这种或任何其他食物过敏的遗传基础知之甚少。这一提议将验证花生过敏是一种复杂遗传疾病的假设。将采用几种方法来检验这一假设：1)花生过敏的遗传性将通过比较单卵双胞胎和异卵双胞胎过敏的一致性来确定；2)由于HLA II类分子是花生过敏的一个有吸引力的决定因素，因此将进行血清分型和基因型频率比较，以证明受影响先证家族的相关性；3)对有两个患病兄弟姐妹的家庭进行全基因组搜索，使用高多态性标记系统地覆盖整个基因组，并分析与花生过敏主要基因位点的联系。Sicherer博士将在受保护的研究时间、普通临床研究中心和机构核心设施以及专用实验室空间中获得支持。他的导师会认真负责地指导他的研究和负责任的研究行为，西奈山优秀的研究和学术环境也会促进他的发展。

This application is designed to provide Scott H. Sicherer, MD with a program of mentored, patient-oriented research that will facilitate his development as an independent physician scientist. Dr. Sicherer completed his residency and chief residency in pediatrics, his fellowship in allergy and immunology and he has been Assistant Professor of Pediatrics at Mount Sinai School of Medicine since July, 1997. During the latter portion of his fellowship training and as faculty, he has concentrated his research efforts on the clinical manifestations of food allergy, particularly peanut allergy. He has amassed clinical data on a large group of peanut-allergic patients including preliminary data to indicate a genetic influence on peanut allergy. This award would allow him the unique opportunity to acquire cross- training in genetics while pursuing a multidisciplinary, patient- oriented research project to dissect the genetic basis of peanut allergy. Allergy to peanut affects 0.6 percent of the general population, is responsible for the majority of severe, life-threatening food allergic reactions, and sensitivity is rarely outgrown. Because peanut is ubiquitous in the American diet, sensitization among susceptible individuals is the rule and accidental ingestions among allergic individuals is common. Despite the seriousness of the allergy, little is known about the genetic basis of this or any other food allergy. This proposal will test the hypothesis that peanut allergy is a complex genetic disease. Several approaches will be taken to test the hypothesis: 1) The heritability of peanut allergy will be determined by comparing the concordance rate of the allergy in mono- and dizygotic twin pairs; 2) Since HLA class II molecules are an attractive candidate as one determinant for peanut allergy, serotyping will be performed and genotype frequencies compared for evidence of association in families with affected probands; and 3) a genome- wide search will be performed on families with two affected siblings using highly polymorphic markers that systematically cover the entire genome and the data analyzed for linkage to major loci contributing to peanut allergy. Dr. Sicherer will be supported in his endeavors with protected research time, access to the General Clinical Research Center and institutional core facilities, and dedicated laboratory space. His development will be fostered by the serious committment of his mentors to guide him in the proposed studies and in the responsible conduct of research, and by the outstanding research and intellectual environment at Mount Sinai.