GENETIC BASIS OF PEANUT ALLERGY

此应用程序旨在提供Scott H. Sicherer，医学博士与指导，以病人为导向的研究计划，这将有助于他作为一个独立的医生科学家的发展。Sicherer博士完成了他的儿科住院医师和首席住院医师，他在过敏和免疫学的奖学金，他一直在西奈山医学院儿科助理教授自1997年7月。 在他的奖学金培训和教师的后一部分，他集中了他的研究工作的食物过敏，特别是花生过敏的临床表现。 他收集了大量花生过敏患者的临床数据，包括初步数据，表明花生过敏的遗传影响。 这一奖项将使他获得独特的机会，获得交叉培训的遗传学，同时追求一个多学科的，以病人为导向的研究项目，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，敏感性很少会消失。 由于花生在美国人的饮食中无处不在，易感个体中的致敏是规律，过敏个体中的意外摄入是常见的。 尽管过敏的严重性，很少有人知道这种或任何其他食物过敏的遗传基础。 这项提议将检验花生过敏是一种复杂的遗传疾病的假设。 将采用几种方法来检验这一假设：1）通过比较单卵和双卵双胞胎中过敏的一致率来确定花生过敏的遗传性; 2）由于HLA II类分子是花生过敏的一个决定因素，因此将进行血清分型，并比较基因型频率与受影响先证者的家族相关性证据;以及3）将使用系统地覆盖整个基因组的高度多态性标记对具有两个受影响兄弟姐妹的家庭进行全基因组搜索，并分析与导致花生过敏的主要位点的连锁的数据。Sicherer博士将在他的努力与保护研究时间，获得一般临床研究中心和机构的核心设施，以及专用的实验室空间的支持。他的发展将促进他的导师的认真承诺，以指导他在拟议的研究和研究的负责任的行为，并在西奈山杰出的研究和智力环境。

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.