EARLY ONSET PERIODONTITIS GENE MAPPING

早发性牙周炎基因图谱

• 批准号: 2572401
• 负责人: S R DIEHL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2572401
• 关键词: clinical research; disease /disorder proneness /risk; family genetics; gene expression; genetic mapping; genetic markers; genetic polymorphism; human genetic material tag; human subject; linkage mapping; major histocompatibility complex; periodontitis; polymerase chain reaction; statistics /biometry

Previous studies suggested that genetic variation in the HLA region of chromosome 6p may influence susceptibility to early onset periodontitis (EOP). Results of segregation analyses support the possibility that risk of EOP may be due to a single major gene. We conducted linkage analyses to evaluate the hypothesis that a gene within the HLA region significantly contributes to risk of EOP. Fifty families, with two or more close relatives affected by EOP, were ascertained in Virginia, USA and Chile. DNA was extracted from blood and a highly polymorphic marker located within the HLA region (near the Tumor Necrosis Factor Beta locus) was typed using the polymerase chain reaction. Linkage analyses were performed using a dominant model of disease transmission which is most strongly supported by previous studies. For the dominant model, assuming that EOP is a homogeneous disorder, our results statistically exclude the hypothesis that a susceptibility gene lies within 10cM (approximately 10 million bases of approximately 0.5% of the human genome. Additional analyses are planned for alternative modes of disease gene transmission. Under the assumption that EOP may actually consist of several etiologically distinct diseases having very similar clinical presentations our data still provide no support for HLA region involvement. However, our data do not statistically exclude (LOD <02.0) hypotheses of disease locus heterogeneity including models where up to half of our families contain a gene located in the HLA region which confers susceptibility to EOP. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome.

先前的研究表明 HLA 区域的遗传变异 6p 染色体的变化可能影响早发的易感性 牙周炎（EOP）。分离分析的结果支持 EOP 的风险可能是由单一主要基因引起的。 我们 进行连锁分析以评估基因的假设 HLA 区域内的基因显着增加 EOP 的风险。 五十个家庭，有两个或两个以上近亲受 EOP 影响， 已在弗吉尼亚州、美国和智利得到证实。 DNA 提取自 血液和位于 HLA 区域内的高度多态性标记 （靠近肿瘤坏死因子β基因座）使用 聚合酶链式反应。 使用以下方法进行连锁分析： 疾病传播的主导模式是最强烈的 得到先前研究的支持。 对于主导模型，假设 EOP 是一种同质性疾病，我们的结果在统计上排除了 假设易感基因位于 10cM 以内（大约 1000 万个碱基，约占人类基因组的 0.5%。 计划对疾病基因的替代模式进行更多分析 传播。 假设 EOP 实际上可能包括 几种病因不同的疾病具有非常相似的临床症状 演示文稿我们的数据仍然不支持 HLA 区域 参与。 然而，我们的数据并没有在统计上排除（LOD <02.0) 疾病位点异质性假设，包括模型 多达一半的家庭含有位于 HLA 的基因 该区域对 EOP 具有易感性。 这是由于 即使是我们相对较多的家庭，权力也有限， 绘制疾病基因图谱的固有困难 病因复杂且异质。 附加统计 分析、招募家庭以及侧翼 DNA 标记分型 计划更彻底地解决这些问题 HLA 区域和人类基因组中的其他候选位置。