瘢痕疙瘩候选基因与染色体2q23微卫星扫描及连锁分析的多家系研究

目的：从与瘢痕疙瘩发病可能存在密切关系的基因出发，分析中国汉族瘢痕疙瘩家系致病基因与染色体2q23区域是否存在连锁关系，以定位易感基因位点。方法：采用微卫星扫描及连锁分析方法，选取3个中国汉族瘢痕疙瘩家系中69名成员的外周静脉血标本，根据文献选择位于2q23区域11个微卫星标记，应用多重聚合酶链式反应（mPCR）扩增产物片断，测定PCR产物片段，获得每个样本的基因分型。运用连锁分析软件LINKAGE的MLINK程序计算每个标记位点的LOD值，根据两点间LOD值判断是否存在连锁关系。结果：在重组率θ=0～0．5时，这些微卫星标记的两点LOD值绝大部分都小于1，排除连锁关系存在。结论：中国汉族瘢痕疙瘩家系易感基因位点不在染色体2q23区域。说明瘢痕疙瘩易感基因位点存在异质性。

瘢痕疙瘩候选基因与染色体7p11微卫星扫描及连锁分析的多家系研究

目的:从与瘢痕疙瘩发病可能存在密切关系的基因出发,分析中国汉族瘢痕疙瘩家系致病基因与染色体7p11区域是否存在连锁关系,以定位易感基因位点。方法:采用微卫星扫描及连锁分析方法,选取3个中国汉族瘢痕疙瘩家系中69名成员的外周静脉血标本,根据文献选择位于7p11区域4个微卫星标记,应用多重聚合酶链式反应(mPCR)扩增产物片断,测定PCR产物片段,获得每个样本的基因分型。运用连锁分析软件LINKAGE的MLINK程序计算每个标记位点的LOD值,根据两点间LOD值判断是否存在连锁关系。结果:在重组率θ=0～0.5时,这些微卫星标记的两点LOD值绝大部分都小于1,排除连锁关系存在。结论:中国汉族瘢痕疙瘩家系易感基因位点不在染色体7p11区域。说明瘢痕疙瘩易感基因位点存在异质性。

Confirmation of susceptibility gene loci on chromosome 1 in Northern China Han families with type 2 diabetes

Objective To confirm previous effort to identify type 2 diabetes susceptibility genes in a Northern Chinese population by conducting a new genome scan with both an increased number of type 2 diabetes families and a new set of microsatellite markers within the previously localized regions.Methods A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, we obtained size information for all loci , and then a further study was done by both parametric and non-parametric linkage analysis to investigate the P values and Z values of these loci.Results We surveyed 34 microsatellite markers which distributed within 5 regions along chromosome 1, and a total of 12?000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci. All P values of the 8 loci were lower than 0.05, and the highest Z value was 2.17. A very interesting finding is that all 5 markers at the p- terminal 1p36.3-1p36.23 region, spanning a long range of 16.9?cM, were identified to have a low P value of less than 0.05, which suggests that this region may contain multiple susceptibility genes. Regions 4 and 5 also confirmed the previous findings, and we narrowed these two regions to a 2.7?cM and 2.5?cM regions, respectively.Conclusions We further confirmed the results gained in the previous genome-wide scan using an increased number of NIDDM families and a new set of microsatellite markers lying within the initially localized regions. The fact that all 5 loci at the p- terminal region displayed a low P value of less than 0.05 suggests that more than 1 susceptibility gene may reside in this region.

Na-K-2Cl转运蛋白基因5′端GT重复序列多态性与新疆哈萨克民族原发性高血压的相关性

目的：探讨研究Na-K-2C1转运蛋白（NKCC2，SLC12A1，BSC-1）基因GT重复序列多态性与新疆哈萨克族人原发性高血压（EH）的关系。方法：以人群为基础进行病例-对照研究，随机选取新疆牧区30～55岁的哈萨克族牧民303例（EH患者152例，正常对照151例），采用经典的饱和酚／氯仿抽提法提取白细胞基因组DNA，运用荧光标记多聚酶链式反应（PCR）技术、毛细管电泳和Genetic Profiler自动分析软件进行微卫星基因组扫描分析技术，根据片断大小分离等位基因。检测EH患者与正常对照者的NKCC2基因GT重复序列多态性。结果：在所有研究人群中NKCC2基因重复序列存在14种等位基因（A1～A14），扩增长度为210～238bp，其频率介于0．002～0．281，以扩增长度为224bp的A9等位基因最为常见，其次为A5和A8，分布符合Hardy-Weinberg遗传平衡定律，GT重复多态杂合率为0．812，多态信息量为0．803。EH人群NKCC2基因GT重复多态分布与正常人群差异无统计学意义（χ^2=16．885，P〉0．05）。结论：NKCC2基因5’端GT重复多态性标记与新疆哈萨克民族EH可能不相关。