IDENTIFICATION OF GENES CAUSING GINGIVAL FIBROMATOSIS

引起牙龈纤维瘤的基因的鉴定

• 批准号: 2897221
• 负责人: Thomas C Hart
• 金额: $ 0.05万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897221
• 关键词: autosomal dominant trait; chromosomes; clinical research; cytogenetics; family genetics; fluorescent in situ hybridization; gene mutation; genetic disorder; genetic markers; genetic susceptibility; genotype; gingiva hyperplasia; human genetic material tag; human subject; linkage mapping; nucleic acid sequence; polymerase chain reaction; sequence tagged sites; single strand conformation polymorphism

In this study we propose to identify and characterize two genes that cause isolated hereditary gingival fibromatosis (HGF). Gingival fibromatosis refers to a clinical condition that involves enlargement of the keratinized gingiva surrounding the teeth. The condition may occur as a simple Mendelian trait, as part of a genetic syndrome, or following exposure to certain pharmacological agents. The genes responsible for hereditary gingival fibromatosis are unknown, and the underlying etiology is not understood. Attempts to elucidate the etiology of hereditary gingival fibromatosis are limited by genetic heterogeneity, diagnostic difficulties and a lack of unifying scientific hypotheses. Identification of the genetic basis for HGF will increase our understanding of the growth and development of gingival tissues and permit identification of homogeneous study populations. We will employ gene mapping strategies to identify two genes for HGF. We have identified two large families segregating a highly penetrant, autosomal dominant form of HGF. We have localized an HGF gene to chromosome 2p2l in one family (Family number 1), and have excluded an HGF gene from this region in a second family (Family number 2), demonstrating genetic heterogeneity. We propose to continue genetic linkage studies to sublocalize the HGF gene on chromosome 2p21, and also to identify the chromosomal location for the HGF gene in Family number 2. Molecular and cytogenetic studies will be performed to resolve physical and genetic maps of the candidate regions, and to help identify candidate genes/ESTs for the HGF loci. Strategies for gene identification and mutational analysis will be utilized to evaluate and identify genes and the specific gene mutations responsible for HGF in these two families. Completion of these specific aims will for the first time, identify genes responsible for HGF. Identification of the molecular basis for HGF will provide valuable information to study the biologic basis of the condition. Understanding the genetic causes for HGF has implications for diagnosis and treatment of isolated HGF, as well as syndromic and pharmacologically induced forms of gingival fibromatosis.

在这项研究中，我们建议识别和表征两个基因 导致孤立性遗传性牙龈纤维瘤病(HGF)。牙周炎 纤维瘤病指的是一种临床症状，包括肿大。 牙齿周围的角化牙龈。这种情况可能 作为简单的孟德尔特征出现，作为遗传综合征的一部分，或者 在接触到某些药理物质之后。基因 遗传性牙龈纤维瘤病的病因尚不清楚， 潜在的病因尚不清楚。试图澄清 遗传性牙龈纤维瘤病的病因受遗传因素的限制 异质性、诊断困难和缺乏统一的科学 假设。对肝细胞生长因子遗传基础的鉴定将增加 我们对牙龈组织生长发育的认识和认识 允许对同类研究群体进行鉴定。 我们将使用基因作图策略来识别HGF的两个基因。 我们发现两个大家族隔离了一个高渗透率的人， 常染色体显性遗传型HGF。我们已经定位了一个HGF基因 染色体2p2l位于一个家系(家系编号1)，并排除了一个 来自第二个家族(家族2)该区域的HGF基因， 表现出遗传异质性。我们建议继续遗传 染色体2p21上HGF基因亚区块化的连锁研究 家系中肝细胞生长因子基因的染色体定位 2.将进行分子和细胞遗传学研究以解决 候选区域的物理和遗传图谱，并帮助识别 HGF基因座的候选基因/EST。基因战略 将利用鉴定和突变分析来评估和 确定与肝细胞生长因子相关的基因和特定的基因突变 这两个家庭。 完成这些具体目标将首次确定 导致肝细胞生长因子的基因。分子基础的鉴定 HGF将为研究糖尿病的生物学基础提供有价值的信息。 条件。了解HGF的遗传原因具有重要意义 诊断和治疗孤立性肝细胞生长因子，以及综合征和 药物性牙周纤维瘤病。