甲型血友病：芬兰所有可获得家系中的遗传预测与连锁研究。

Hemophilia A: genetic prediction and linkage studies in all available families in Finland.

作者信息

Lehesjoki A E, Sistonen P, Rasi V, de la Chapelle A

机构信息

Department of Medical Genetics, University of Helsinki, Finland.

出版信息

Clin Genet. 1991 Mar;39(3):199-209. doi: 10.1111/j.1399-0004.1991.tb03012.x.

DOI:10.1111/j.1399-0004.1991.tb03012.x

PMID:2036741

Abstract

RFLP studies were done in 82 (75%) of all known hemophilia A families in the Finnish population (approximately 5 million). Two intragenic RFLPs (Bc1I/F8A, XbaI/p482.6) and two extragenic markers (TaqI/St14, Bg1II/DX13) were used. Among 263 females at risk, carriership could be evaluated with an intragenic marker in 47% and with an extragenic marker in 26%. In 27% of the females, carriership could be neither excluded nor confirmed; 68% of these females were relatives of an isolated patient. Eight recombinations between the factor VIII gene (F8C) and DXS52 (lod 25.02 at theta max 0.06), eight recombinations between F8C and DXS15 (lod 21.91 at theta max 0.05), and two recombinations between DXS52 and DXS15 (lod 33.56 at theta max 0.01) were found. Using multipoint linkage analysis, the most likely order of loci supported by the data was: F8C-DXS15-DXS52-DXS134. RFLP segregation analysis provides a highly useful method of carrier detection and prenatal diagnosis of hemophilia A, but its limitations must be carefully taken into account.

摘要

对芬兰人群（约500万）中所有已知的甲型血友病家族中的82个（75%）进行了限制性片段长度多态性（RFLP）研究。使用了两种基因内RFLP（Bc1I/F8A、XbaI/p482.6）和两种基因外标记（TaqI/St14、Bg1II/DX13）。在263名有风险的女性中，47%的女性携带者状态可通过基因内标记评估，26%的女性携带者状态可通过基因外标记评估。27%的女性携带者状态既不能排除也不能确定；这些女性中有68%是孤立患者的亲属。在凝血因子VIII基因（F8C）和DXS52之间发现了8次重组（在θ最大值为0.06时lod值为25.02），在F8C和DXS15之间发现了8次重组（在θ最大值为0.05时lod值为21.91），在DXS52和DXS15之间发现了2次重组（在θ最大值为0.01时lod值为33.56）。使用多点连锁分析，数据支持的最可能的基因座顺序为：F8C-DXS15-DXS52-DXS134。RFLP分离分析为甲型血友病携带者检测和产前诊断提供了一种非常有用的方法，但必须仔细考虑其局限性。