EARLY ONSET PERIODONTITIS GENE MAPPING

以前的研究表明，HLA区域的遗传变异 染色体6p的突变可能影响早发性 牙周炎（EOP）。分离分析的结果支持 EOP的风险可能是由于单一的主要基因。 我们 进行了连锁分析，以评估一个基因的假设， HLA区域内的突变显著增加了EOP的风险。 50个有两名或以上近亲受老年痴呆症影响的家庭， 在美国弗吉尼亚州和智利被证实。 提取dna 血液和位于HLA区域内的高度多态性标记 (near肿瘤坏死因子β基因座）使用 聚合酶链反应 连锁分析使用 疾病传播的主要模式， 支持以前的研究。 对于主导模型，假设 EOP是一种同质性疾病，我们的结果在统计学上排除了 假设易感基因位于10 cM（约 约占人类基因组的0.5%的1000万个碱基。 计划对疾病基因的替代模式进行额外分析 传输 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 我们的数据仍然不支持HLA区域 参与。 然而，我们的数据在统计上并不排除（LOD <02.0）疾病位点异质性的假设，包括模型 我们有一半的家庭都有一个位于HLA的基因 该区域赋予EOP易感性。 这是由于 即使是我们相对庞大的家庭， 为那些具有遗传缺陷的疾病绘制基因图谱的固有困难， 病因复杂多样。 附加统计 分析、家族招募和侧翼DNA标记分型 计划更有说服力地解决这些问题， HLA区域和人类基因组中的其他候选位置。

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.