INVERSIONS DISRUPTING THE FACTOR-VIII GENE ARE A COMMON-CAUSE OF SEVERE HEMOPHILIA-A

被引：676

作者：

LAKICH, D

KAZAZIAN, HH

ANTONARAKIS, SE

GITSCHIER, J

机构：

[1] UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143

[2] UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143

[3] JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21287

[4] JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287

[5] UNIV GENEVA,SCH MED,DEPT GENET,CH-1211 GENEVA 4,SWITZERLAND

来源：

NATURE GENETICS | 1993年 / 5卷 / 03期

关键词：

D O I：

10.1038/ng1193-236

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in approximately 45% of families with severe disease.

引用

页码：236 / 241

页数：6

共 23 条

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