良性家族性婴儿惊厥疾病基因的位点异质性研究

Research on benign familial infantile convulsion (BFIC) disease locus heterogene ity

目的 研究 5个良性家族性婴儿惊厥 (benign familial infantile convulsion,BFIC)家系的疾病基因与BFIC位点的连锁关系以及是否存在疾病基因位点异质性。方法 选择 D19S2 45、D19S2 50、D16S3 13 1、D16S3 13 3、D2 S3 99、D2 S2 3 3 0等 6个 STR作为 DNA标记 ,应用聚合酶链反应 (PCR)、变性聚丙烯酰胺凝胶电泳 (PAGE)和银染技术 ,采用 L INKAGE软件包中的 ML INK程序及遗传分析程序 HOMOGM对 5个 BFIC家系进行连锁分析和位点异质性检测。结果 连锁分析结果显示 ,在 AD模式下 ,标记位点 D19S2 50处 ,家系 2、3、5在重组率为 0 .0 0 0 ,外显率为 90 %时 ,获得最大两点 L OD值总和为 2 .151;标记位点 D16S3 13 1处 ,家系 2、5在重组率为 0 .0 85,外显率为 70 %、60 %时 ,获得最大两点 L OD值分别为 1.0 56、1.155,提示这两个位点与疾病基因可能存在连锁关系。在其它位点处未获得提示连锁关系的信息。异质性检测显示 ,BFIC家系之间存在位点异质性。结论 BFIC致病基因可能与 D19S2 50或 D16S3 13 1存在连锁关系 ,BFIC存在位点异质性。

Objective To test the relationship between the ge n e for BFIC in five BFIC pedigrees and BFIC loci,and certain the locus heterogene ity among these pedigrees.Methods Six short tandem repeat loci including D19S245,D19S250,D16S3131,D16S3133,D2S399 and D2S2330 were chosen as DN A markers for linkage analysis.Several technical measures including PCR,PAGE and sliver straining were used.Linkage analysis and heterogeneity detection were pe rformed respectively by MLINK program from LINKAGE package and genetic analysis program HOMOGM.Results One maximu m two-point LOD score of 2.151 for D19S250 was obtained at recombination rate o f 0.000 under autosomal dominant model with 90% penetrance.For D16S3131,two maxi mum two-point LOD score of 1.056 and 1.155 were obtained at recombination rate of 0.085 under autosomal dominant model with 70% and 60% pene trance. This suggested that the gene for BFIC pedigrees maybe linked to D16S3131 or D19S250. At other D NA markers,no information that suggested linkage was produced. The results of he terogeneity detection showed that there was locus heterogeneity among BFIC pedig rees.Conclusion The gene for BFIC may be linked to D16S3131 or D19S250. There is heterogeneity in BFIC.