INVESTIGATION OF THE FACTOR-VIII INTRON-22 REPEATED REGION (INT22H) AND THE ASSOCIATED INVERSION JUNCTIONS
INVESTIGATION OF THE FACTOR-VIII INTRON-22 REPEATED REGION (INT22H) AND THE ASSOCIATED INVERSION JUNCTIONS
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DOI：
10.1093/hmg/4.7.1217
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发表时间：
1995-07-01
影响因子：
3.5
通讯作者：
GIANNELLI, F
中科院分区：
文献类型：
--
作者：
NAYLOR, JA;BUCK, D;GIANNELLI, F
第VIII因子基因内含子22的一个区域在XQ端粒附近重复两次，该区域含有第VIII因子相关基因A(F8A)。有人提出，内含子22重复与两个外源拷贝中的任何一个之间发生了染色体内同源重组，导致了几乎一半的严重血友病A病例的反复反转。我们准确地将该重复区域定义为9.5kb的DNA，我们称之为INT22h(内含子22同源区域)，所检测的倒置的连接代表了INT22h重复之间的精确交换，从而为同源重组提供了确凿的证据。用化学错配分析比较了Int22h的三个拷贝沿其8kb的长度，发现99.9%的相似，XQ端粒附近如此长、几乎相同的反向重复序列的存在可能解释了倒置发生的高频率。
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.