POLYMORPHISM OF TAP GENES IN GRAVES' DISEASE

格雷夫斯病中 Tap 基因的多态性

• 批准号: 6107268
• 负责人: MILDRED H. OFOSU
• 金额: $ 4.6万
• 依托单位: DELAWARE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107268
• 关键词: African American; DNA; Graves disease; alleles; antigen presentation; clinical research; disease /disorder proneness /risk; gene expression; genetic polymorphism; histocompatibility antigens; histocompatibility typing; human genetic material tag; human population genetics; human subject; immunogenetics; major histocompatibility complex; nucleic acid sequence; polymerase chain reaction; serology /serodiagnosis; single strand conformation polymorphism

The overall objectives are to detect genetic polymorphisms at the DNA level in African-American unrelated volunteer controls, in patients with Graves' Disease and their family members: to expand scientific knowledge regarding Graves' disease and the distribution of genes within the major histocompatibility complex in this ethnic group; and to motivate minority graduate and undergraduate students to pursue biomedical research careers. The specific aims are to determine polymorphism in TAP1 and TAP2 genes within African-American volunteer controls and within Graves' disease patients; to sequence alleles of TAP1 and TAP2 associated with Graves' disease patients; to train students in basic and sophisticated molecular genetic techniques by using hands-on laboratory equipment, by participating in workshops and seminars, and by presenting research results at scientific local and national meetings. The hypothesis is that genetic polymorphisms that are unique to this ethnic group are present in the TAP region genes. HLA associations with Graves' disease have been reported for both Class I and Class II antigens. This study will add to the pool of knowledge on whether it is Class 1 and define the boundaries of the region within the major histocompatibility complex that determines susceptibility to Graves' Disease. There are new alleles to be detected. Transporters associated with antigen processing (TAP) genes are polymorphic and function to transport antigenic peptides to be loaded in HLA class I molecules. TAP1 and TAP2 are involved in restricted antigen processing. Class I antigens may be important in the development of class II associated disease. methods to be used are basic and sophisticated molecular genetic techniques of molecular biology; i.e., PCR based single strand conformational polymorphism (SSCP) method. PCR products will be subjected to SSCP analysis to correlate SSCP patterns with allelic sequence variation. Serological test will be done to determine if there are antibodies to microsomal antigen and to thyroglobulin. Much information will be obtained to greatly add to the pool of knowledge about TAP polymorphism, specifically in African-American volunteer controls and in patients with Graves' disease

总体目标是检测DNA中的遗传多态性， 非裔美国无关志愿者对照组中， Graves病及其家族成员：扩大科学知识 关于格雷夫斯病和基因分布的主要 组织相容性复合体;并激励少数民族 研究生和本科生追求生物医学研究事业。 具体目的是确定TAP 1和TAP 2基因的多态性 在非裔美国志愿者对照组和格雷夫斯病组中， 对与Graves病相关的TAP 1和TAP 2等位基因进行测序， 疾病患者;培养学生在基础和复杂的分子 基因技术，通过使用实验室设备， 参加讲习班和研讨会，并提出研究报告， 在地方和国家科学会议上取得成果。 前提是 这一族群特有的遗传多态性存在于 TAP区域基因。 HLA与Graves病的相关性一直是 报告了I类和II类抗原。 这项研究将增加 知识库对它是否是1类和定义的界限 主要组织相容性复合体中决定 对格雷夫斯病的易感性。 有新的等位基因有待检测。 与抗原加工相关的转运蛋白（TAP）基因是 多态性和转运抗原肽的功能， HLA I类分子。 TAP 1和TAP 2参与限制性抗原 处理. I类抗原可能是重要的发展中的类 II相关疾病 要使用的方法是基本的和复杂的 分子生物学的分子遗传技术;即，基于PCR的单个 链构象多态性（SSCP）方法。 PCR产品将 进行SSCP分析，以将SSCP模式与等位基因 序列变异 将进行血清学测试，以确定是否有 是微粒体抗原和甲状腺球蛋白的抗体。 多 将获得信息，以大大增加知识库， TAP多态性，特别是在非洲裔美国志愿者对照组和 Graves病患者