MOLECULAR GENETIC STUDIES OF EARLY ONSET PERIODONTITIS

一段时间以来，人们已经认识到， 疾病（EOP）在家庭中聚集。 近期遗传流行病学 研究表明，这种聚集可能至少部分是由于 对个体的行为有重大影响的一个或多个基因的作用 易患EOP。 几年来，我们的团队一直 进行老年痴呆症的家庭研究。 我们的研究和我们的 合作者已经确定了大量的个人受到影响， 我们招募了许多这样的人， EOP受影响和未受影响的大家庭成员， 参与我们的研究。 这些调查导致我们 建立大量永生化细胞系和DNA 受EOP影响的个人及其家人的样本。 本提案旨在通过以下方式利用这一宝贵资源： 进行分子遗传学研究， 特定的基因和生物化学和生理过程 这是EOP风险的基础。 我们的具体目标是：i.）应用链接 分析技术，以EOP影响的家庭使用高度信息化 微卫星重复多态性，以定位 主要效应的易感基因，和ii.）进行联动， 利用RFLP和PCR进行基因分型的DNA多态性关联研究 在所选择的候选基因附近的基因座的方法， 免疫系统例如，HLA、TCR、IG、细胞因子等）和趋化 受体。

It has been recognized for some time that early onset periodontal diseases (EOP) aggregate in families. Recent genetic epidemiological studies indicate that this aggregation may be due to at least in part to the action of a gene or genes that have a major influence on individuals' susceptibility to developing EOP. For several years our group has been conducting family studies of EOP. Our studies and those of our collaborators have identified a large number of individuals affected by this disorder and we have recruited many of these individuals and both EOP affected and unaffected members of their extended families into participation in our study. These investigations have led to our establishment of a large collection of immortalized cell lines and DNA samples from EOP affected individuals and their families. This proposal is designed to capitalize on this valuable resource by conducting molecular genetic studies with the goal of identifying some of the specific genes and the biochemical and physiological processes that underlie risk of EOP. Our specific aims are: i.) to apply linkage analysis techniques to EOP affected families using highly informative microsatellite repeat polymorphisms, in order to map the location of susceptibility genes of major effect, and ii.) to conduct linkage and association studies using DNA polymorphisms genotyped by RFLP and PCR methods for loci in the vicinity of selected candidate genes of the immune system e.g., HLA, TCR, IG, cytokines, etc.) and chemotactic receptors.