IDENTIFICATION OF GENES CAUSING GINGIVAL FIBROMATOSIS

引起牙龈纤维瘤的基因的鉴定

• 批准号: 6225928
• 负责人: Thomas C Hart
• 金额: $ 26.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6225928
• 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; 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 导致孤立的遗传牙龈纤维瘤病（HGF）。牙龈 纤维瘤病是指涉及扩大的临床状况 牙齿周围的角化牙龈。 条件可能 作为简单的孟德尔特征，作为遗传综合征的一部分或 暴露于某些药理剂后。 基因 负责遗传牙龈纤维瘤病是未知的， 尚不理解潜在的病因。 试图阐明 遗传牙龈纤维瘤病的病因受到遗传的限制 异质性，诊断困难和缺乏统一的科学 假设。 识别HGF的遗传基础将增加 我们对牙龈组织的生长和发展的理解 允许识别同质研究人群。 我们将采用基因映射策略来识别HGF的两个基因。 我们已经确定了两个大家庭，将高度渗透物分离出来， HGF的常染色体显性形式。 我们将HGF基因局部 一个家庭（家庭1）中的2p2l染色体2p2l，已排除 来自该地区第二个家庭的HGF基因（家庭2）， 证明遗传异质性。 我们建议继续遗传 链接研究以将HGF基因在2p21染色体上进行跨科目，也是如此 识别家庭数中HGF基因的染色体位置 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，并帮助识别 HGF基因座的候选基因/EST。 基因策略 识别和突变分析将用于评估和 鉴定基因和负责HGF的特定基因突变 这两个家庭。 这些特定目标的完成将首次确定 负责HGF的基因。 鉴定分子基础 HGF将提供有价值的信息来研究 健康）状况。 了解HGF的遗传原因有含义 用于诊断和治疗孤立的HGF以及综合症和 牙龈纤维瘤病的药理诱导形式。