Figueiredo M S, Bowen D J, Silva Júnior W A, Zago M A
Department of Clinical Medicine, School of Medicine of Riberão Preto, University of São Paulo, Brazil.
Br J Haematol. 1994 Aug;87(4):789-96. doi: 10.1111/j.1365-2141.1994.tb06739.x.
Analysis of factor IX gene polymorphisms is considered the best approach for prenatal diagnosis and carrier detection of haemophilia B when the identification of the gene mutation is not possible. Studies involving factor IX gene polymorphisms in Black populations are scarce and essentially restricted to the North-American Black population whose composition is substantially different from that of the Brazilian and presumably other Black populations of South America. In this paper we report the analysis of eight factor IX gene polymorphisms in Brazilian Blacks: 5' BamHI, DdeI, intron 2 BamHI, XmnI, TaqI, TaqI, MspI, MnlI and HhaI. Characterization of the VNTR-like DdeI polymorphism revealed six different alleles: B, AB, A2B, A2B2, A3B and A5B, the last being described here for the first time. The 5' BamHI, DdeI, MspI and HhaI polymorphisms showed the highest heterozygosities (0.40-0.50) and are in linkage equilibrium with one another. 19 complete haplotypes could be identified in this population. Based on the results we propose a systematic strategy for carrier detection and prenatal diagnosis of haemophilia B in this population. The combined analysis of four polymorphisms (5' BamHI, HhaI, MspI and DdeI) provided an informative genetic marker in 85% of the females. The use of all eight polymorphisms allows information in 95% of females. Additionally, differences in gene frequencies and haplotype distribution suggest dissimilarities in factor IX gene polymorphisms between the Brazilian and the North-American Black populations.
当无法鉴定基因突变时，分析因子IX基因多态性被认为是进行B型血友病产前诊断和携带者检测的最佳方法。涉及黑人人群中因子IX基因多态性的研究很少，基本上仅限于北美黑人人群，其组成与巴西黑人以及南美洲其他黑人人群有很大不同。在本文中，我们报告了对巴西黑人中8种因子IX基因多态性的分析：5'BamHI、DdeI、内含子2 BamHI、XmnI、TaqI、TaqI、MspI、MnlI和HhaI。类VNTR DdeI多态性的特征揭示了6种不同的等位基因：B、AB、A2B、A2B2、A3B和A5B，最后一种在此首次描述。5'BamHI、DdeI、MspI和HhaI多态性显示出最高的杂合度（0.40 - 0.50），并且彼此处于连锁平衡状态。在该人群中可鉴定出19种完整单倍型。基于这些结果，我们提出了一种针对该人群B型血友病携带者检测和产前诊断的系统策略。对4种多态性（5'BamHI、HhaI、MspI和DdeI）的联合分析在85%的女性中提供了一个信息丰富的遗传标记。使用所有8种多态性可在95%的女性中获得信息。此外，基因频率和单倍型分布的差异表明巴西黑人和北美黑人人群在因子IX基因多态性方面存在差异。
