INVESTIGATION OF THE FACTOR-VIII INTRON-22 REPEATED REGION (INT22H) AND THE ASSOCIATED INVERSION JUNCTIONS

A region of intron 22 of the factor VIII gene, which contains factor V III-associated gene A (F8A), is repeated twice more nearer the Xq telo mere, It has been proposed that intrachromosomal homologous recombinat ion occurs between the intron 22 repeat and either of the two extragen ic copies, resulting in the recurrent inversions that cause almost hal f 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 2 2 homologous region), The junctions of the inversions examined were sh own to represent precise exchanges between the int22h repeats, thus pr oviding conclusive evidence for homologous recombination, The three co pies of int22h were compared along 8 kb of their length, using chemica l mismatch analysis, and found to be 99.9% similar, The presence of su ch long, almost identical inverted repeats near the Xq telomere could account for the high frequency at which the inversions occur.