EARLY ONSET PERIODONTITIS GENE MAPPING

早发性牙周炎基因图谱

• 批准号: 5201864
• 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/5201864
• 关键词: 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.

以前的研究表明，在HLA区域的遗传变异， 染色体6p可能影响早发性牙周炎的易感性 （EOP）。分离分析的结果支持风险 EOP的发生可能是由一个主基因决定的。 我们进行了关联分析 为了评估HLA区域内的基因显著地 增加了EOP的风险。 50个家庭，有两个或两个以上的密切 受EOP影响的亲属，在美国弗吉尼亚州和智利被确定。 从血液中提取DNA， 在HLA区域内（靠近肿瘤坏死因子β基因座）， 用聚合酶链反应分型。 连锁分析是 使用占主导地位的疾病传播模式进行， 得到了以往研究的有力支持。 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（约10 约占人类基因组的0.5%。 额外 计划对疾病基因传播的其他模式进行分析。 假设EOP实际上可能由多个 具有非常相似临床表现的病因不同的疾病 我们的数据仍然没有提供HLA区域参与的支持。 然而，在这方面， 我们的数据在统计学上没有排除（LOD <02.0）疾病的假设 基因座异质性包括我们一半的家庭 含有位于HLA区域的基因，该基因赋予对以下疾病的易感性 EOP。 这是由于即使我们相对较大的 家庭的收集和基因定位的固有困难， 具有复杂和异质病因的疾病。 额外 统计分析、家族招募和侧翼DNA分型 计划采用标记，以便更明确地解决这些问题， HLA区域和人类基因组中的其他候选位置。