中国汉族一个家系家族性颅内动脉瘤的候选基因位点连锁分析

Linkage analysis of candidate gene/loci of familial intracranial aneurysm pedigrees in a Chinese Han family

目的对一个汉族家族性颅内动脉瘤(FIA)家系进行遗传连锁定位及基因突变分析。方法纳入19名家系成员,其中2例经DSA确诊为颅内动脉瘤。应用16个短串联重复序列微卫星标记物和3个单核苷酸多态性(SNP)标记物对19名成员进行了18个与FIA发病相关的候选基因/位点的参数连锁分析,并对其中的1个SNP标记物rs1333040进行直接测序,筛查是否存在突变。结果①ANIB1-8等候选基因位点与该家系不连锁,连锁值(LOD)均<1。②曾报道过的13q14.12-21.1上rs7983420和rs17054625之间的7-cM区域、17cen上的TNFRSF13B候选基因位点与该家系不连锁。③9p21上的rs1333040-T等位基因多态性与该FIA家系发病无关。结论排除ANIB1-8、7-cM、TNFRSF13B候选基因/位点与该家系的关系。

Objective To conduct genetic linkage localization and mutational analysis of familial in- tracranial aneurysm （FIA） pedigrees in a Chinese Han family. Methods A total of 19 members in the pedigrees were included in the study, and 2 of them were diagnosed as intracranial aneurysm . Nineteen of the members conducted 19 parametric linkage analyses which were associated with candidate genes/loci on the onset of FIA using the microsatellite markers of 16 short tandem repeat sequences and 3 single nucleo- tide polymorphism （SNP） markers, and one SNP marker rs1333040 was sequenced directly and whether existing mutation or not was screened. Results @The candidate genes/loci of ANIB1, ANIB2, ANIB3, ANIB4, ANIB5, ANIB6, ANIB7, and ANIB8 did not have linkage to the pedigrees. @The previously re- ported a 7-cM region between rs7983420 and rs17054625 on 13q14. 12-21. 1, TNFRSF13B candidate gene/loci on 17cen did not have linkage to the pedigrees. （~）The rs1333040-T allele polymorphism on 9p21 was not associated with the onset in the FIA pedigrees. Conclusion Excluding the relationship between the above candidate genes/loci and the pedigrees, this pedigrees may have new causative genes/loci.