Naylor J A, Buck D, Green P, Williamson H, Bentley D, Giannelli F
Division of Medical and Molecular Genetics, United Medical School of Guy's Hospital, London, UK.
Hum Mol Genet. 1995 Jul;4(7):1217-24. doi: 10.1093/hmg/4.7.1217.
A region of intron 22 of the factor VIII gene, which contains factor VIII-associated gene A (F8A), is repeated twice more nearer the Xq telomere. It has been proposed that intrachromosomal homologous recombination occurs between the intron 22 repeat and either of the two extragenic copies, resulting in the recurrent inversions that cause almost half of all cases of severe haemophilia A. We have precisely defined the repeated region as 9.5 kb of DNA which we have termed int22h (intron 22 homologous region). The junctions of the inversions examined were shown to represent precise exchanges between the int22h repeats, thus providing conclusive evidence for homologous recombination. The three copies of int22h were compared along 8 kb of their length, using chemical mismatch analysis, and found to be 99.9% similar. The presence of such long, almost identical inverted repeats near the Xq telomere could account for the high frequency at which the inversions occur.
因子 VIII 基因内含子 22 的一个区域包含因子 VIII 相关基因 A（F8A），该区域在更靠近 Xq 端粒的位置又重复了两次。有人提出，染色体内部的同源重组发生在内含子 22 重复序列与两个基因外拷贝中的任意一个之间，导致反复出现的倒位，几乎造成了所有严重甲型血友病病例的一半。我们已将重复区域精确界定为 9.5 kb 的 DNA，我们将其称为 int22h（内含子 22 同源区域）。所检测倒位的连接点显示为 int22h 重复序列之间的精确交换，从而为同源重组提供了确凿证据。使用化学错配分析对 int22h 的三个拷贝沿其 8 kb 的长度进行了比较，发现它们的相似度为 99.9%。在 Xq 端粒附近存在如此长且几乎相同的反向重复序列，可以解释倒位发生的高频率。
