EARLY ONSET PERIODONTITIS GENE MAPPING

以往的研究表明，人类白细胞抗原区域的遗传变异 染色体6p可能影响早发性牙周炎的易感性 (EOP)。隔离分析的结果支持风险的可能性 EOP的发生可能是由单个主基因引起的。我们进行了连锁分析 来评估假设在人类白细胞抗原区域内的一个基因显著地 增加了EOP的风险。50个家庭，有两个或两个以上亲近的家庭 受EOP影响的亲属在弗吉尼亚州、美国和智利被确定。 从血液中提取DNA，并定位一个高度多态的标记 在人类白细胞抗原区域(肿瘤坏死因子β基因附近)是 用聚合酶链式反应进行分型。连锁分析是 使用疾病传播的主导模式执行，该模式是最 之前的研究有力地支持了这一观点。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 假设易感基因在10 cM以内(约10 约占人类基因组0.5%的百万个碱基。其他内容 计划对疾病基因传播的替代模式进行分析。 假设EOP实际上可能由几个 具有非常相似的临床表现的病因不同的疾病 我们的数据仍然不支持人类白细胞抗原区域的参与。然而， 我们的数据在统计学上不排除(LOD&lt；02.0)疾病假说 基因座异质性包括高达一半的家庭 含有一种位于人类白细胞抗原区域的基因，该基因使人对 EOP。这是由于即使是我们相对较大的 家系收集和基因定位的固有困难 具有复杂和不同病因的疾病。其他内容 统计分析、家庭招募和侧翼DNA分型 标记员计划以尊重的态度更果断地解决这些问题 人类基因组中的人类白细胞抗原区域和其他候选位置。

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.