GENETIC BASIS OF PEANUT ALLERGY

此应用程序旨在为斯科特·H·西切尔医学博士提供一项有指导的、以患者为导向的研究计划，以促进他作为一名独立内科科学家的发展。西切尔博士完成了他的儿科住院医师和首席住院医师资格，他获得了过敏和免疫学方面的研究员资格，自1997年7月以来一直担任西奈山医学院儿科助理教授。在研究员培训的后半部分和教职期间，他将研究重点放在食物过敏的临床表现上，特别是花生过敏。他收集了一大批花生过敏患者的临床数据，包括初步数据，表明基因对花生过敏有影响。这一奖项将使他有独特的机会获得遗传学方面的交叉培训，同时进行一项多学科、以患者为导向的研究项目，以剖析花生过敏的遗传基础。花生过敏影响0.6%的普通人群，是大多数严重的、威胁生命的食物过敏反应的罪魁祸首，敏感性很少超过。由于花生在美国人的饮食中无处不在，易感人群中的过敏反应是常见的，过敏人群中意外摄入花生的情况也很常见。尽管过敏的严重性，但人们对这种或任何其他食物过敏的遗传基础知之甚少。这项提议将检验花生过敏是一种复杂遗传病的假设。将采取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和双卵双胞胎过敏的符合率来确定；2)由于人类白细胞抗原II类分子是花生过敏的一个有吸引力的候选因素，将进行血清分型并比较基因频率，以寻找与受影响的先证者家系相关的证据；以及3)将使用系统覆盖整个基因组的高度多态标记和分析的与导致花生过敏的主要基因座的连锁的数据，对有两个受影响的兄弟姐妹的家庭进行全基因组搜索。西切尔博士的努力将得到支持，他的研究时间受到保护，可以进入普通临床研究中心和机构核心设施，以及专用的实验室空间。他的发展将通过他的导师们的认真承诺来促进，他们将指导他进行拟议的研究和负责任的研究，以及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.