1号染色体上高血压病易感基因的定位研究(大家系同胞对分析)

Scanning susceptibility gene for essential hypertension on chromosome 1: sib pair linkage analysis in a large pedigree

目的 定位和筛查高血压病 (EH)的易感基因位点。方法 应用染色体多点扫描策略和扩增片段长度多态性分析技术 ,在 1号染色体上选择 11个短串联重复序列 (shorttandemrepeat,STR) ,对一个典型的EH大家系进行同胞对连锁分析。结果 D1S165 6位点的统计量t值为 1.68,具有显著统计学意义 (t>1.64 )。统计每一位点在同胞组中共享最多的等位片段所占比例 ,观察到D1S165 6位点的 15 4bp等位片段与EH患者伴随频率最高 ,占 5 8.4 %。进一步以此片段作为特定因子进行传递不平衡分析 ,传递 15 4bp等位基因的频率显著高于期望值 (χ2td=6.0 0 ,P <0 .0 5 ) ,表明15 4bp片段在传递过程中存在显著连锁不平衡。结论 1号染色体上的一个遗传标记 (D1S165 6)与EH连锁 ,提示该位点的附近可能存在EH的易感基因 ,这一结果为EH易感基因的进一步定位提供了重要的资料。

Objective To localize and screen susceptibility gene of essential hypertension (EH). Me thods The joint strategies of full chromosome multipoint scan and Amp FLP analysis were adopted. The 11 STR sequences on the chromosome 1 were amplified by PCR, then amplified fragments were isolated and visualized by polyacryamine gel electrophoresis and silver staining. 100 blood samples from a large pedigree were used for linkage analysis (IBD method and TDT analysis). Results The t value (statistic for Suarez) for D1S1656 was 1.68 and reached significant level ( t >1.64), which implied a significant linkage to EH. Then 154 bp allele at D1S1656 locus was observed to coexist with EH more frequently than other alleles. Furthermore, when we studied the same fragments using the TDT method to test for linkage disequilibrium between a specific allele (the 154 bp allele) and EH, from the large EH kindreds, the 154 bp allele was transmitted significantly more frequently than expected (χ 2 td =6.00, P <0.05), which further confirmed the marker, D1S1656, was linked to EH.Conclusion These results suggested that one of the markers on chromosome 1, D1S1656, showed significant evidence of linkage to EH and some susceptibility genes of EH probably lacate in this region, which provided important clue for further study on gene localization of EH.