目的：建立理想的STR遗传标记体系，对广西地区血友病A携带者进行快速简便的基因诊断。方法：选取广西地区10个血友病A家系作为研究对象，运用荧光PCR联合毛细管电泳的方法，对家系成员中FⅧ基因内外具有高度遗传性的3个STR位点F8Int13、DXS1073、DXS9901进行等位基因分型，评估该体系用于家系中血友病A携带者的诊断效率，并对待检者进行携带者诊查。结果：10个血友病A家系中，11例肯定女性携带者均含有与相应先证者完全一致的3个STR等位基因（F8Int13、DXS1073、DXS9901）片段长度；在待检的8例女性中，5例检出3个STR等位基因片段与相应家系中先证者完全相同，被诊断为血友病A携带者。结论：联合应用3个STR位点F8Int13、DXS1073、DXS9901进行遗传分析能够快速检出血友病A携带者，给血友病A产前诊断提供可靠的依据。
Abstract
OBJECTIVE: To establish a fast and simple genetic diagnosis technique based on a reliable, short tandem repeat (STR) genetic marker system for the detection of hemophilia A carriers in Guangxi, China. METHODS: Fluorescent PCR and capillary electrophoresis were used for allele genotyping at three intragenic/extragenic STR loci (F8Int13, DXS1073, and DXS9901) of FVIII gene in the members of 10 hemophilia A families in Guangxi, so as to evaluate the diagnostic efficiency of the STR genetic marker system for detection of hemophilia A carriers. Then the STR genetic marker system was used to detect hemophilia A carriers among examinees. RESULTS: In the 10 hemophilia A families, 11 confirmed female carriers had the same allele fragment lengths at the three STR loci (F8Int13, DXS1073, and DXS9901) as the probands. Of the 8 females examined, 5 had allele fragments at the three STR loci (F8Int13, DXS1073, and DXS9901) which were identical to those of the probands, and thus they were diagnosed as hemophilia A carriers. CONCLUSIONS: Genetic analysis at the three STR loci (F8Int13, DXS1073, and DXS9901) can be used to detect hemophilia A carriers rapidly and provide reliable basis for prenatal diagnosis of hemophilia A.
关键词
短串联重复序列 /
血友病A /
基因分型 /
携带者
Key words
Short tandem repeats /
Hemophilia A /
Genotyping /
Carrier
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参考文献
［1］邵宗鸿，杨天楹. 中国血友病患病率与八个地区生存率调查［J］. 中华血液学杂志，1992，13（9）：461-463.
［2］杨仁池，王鸿利. 血友病［M］. 上海：上海科学技术出版社，2007: 1-20.
［3］Fang Y, Wang XF, Dai J, Wang HL. A rapid multifluorescent polymerase chain reaction for genetic counselling in Chinese haemophilia A families［J］. Haemophilia, 2006, 12(1): 62-67.
［4］侯一平，刘雅诚. 法医DNA分型［M］. 北京：科学出版社，2007: 274-284.
［5］朱春江，龙桂芳. 微卫星及在血友病甲基因诊断中的研究进展［J］. 华夏医学，2006，19（3）：595-597.
［6］Liang Y, Zhao Y, Yan M, Fan XP, Xiao B, Liu JZ. Prenatal diagnosis of haemophilia A in China［J］. Prenat Diagn, 2009, 29(7): 664-667.
［7］Lalloz MR, McVey JH, Pattinson JK, Tuddenham EG. Haemophilia A diagnosis by analysis of a hypervariable dinucleotide repeat within the factor VIII gene［J］. Lancet, 1991, 338(8761): 207-211.
［8］Lalloz MR, Schwaab R, McVey JH, Michaelides K, Tuddenham EG. Haemophilia A diagnosis by simultaneous analysis of two variable dinucleotide tandem repeats within the factor VIII gene［J］. Br Haematol, 1994, 86(4): 804-809.
［9］吕宝忠. 多态信息量（PIC）等于杂合度吗？［J］. 遗传，1994，16（4）：31-33.
［10］李彩霞，凌凤俊，涂政，郑秀芬. 犬的三个STR基因座遗传多态性［J］. 动物医学进展，2002，23（5）：80-81.
［11］Lakich D, Kazazian HH Jr, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A［J］. Nat Genet, 1993, 5(3): 236-241.
［12］Bagnall RD, Waseem N, Green PM, Iannelli F. Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A［J］. Blood, 2002, 99(1): 168-174.
［13］丁秋兰，王学锋，王鸿利，孙竞，华宝来，吴竞生,等. 血友病诊断和治疗的专家共识［J］. 临床血液学杂志，2010，23（1）：49-53.
［14］Dai J, Lu Y, Ding Q, Wang H, Xi X, Wang X. The status of carrier and prenatal diagnosis of haemophilia in China ［J］. Haemophilia, 2012 ,18(2): 235-240.
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