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.
Several evolutionarily conserved proteins constitute a universal mitotic trigger that is precisely controlled during the orderly cell divisions of embryogenesis. As development progresses, the mechanisms controlling this trigger change. Early divisions are executed by maternally synthesized gene products, and in Xenopus they are timed by the accumulation and periodic degradation of cyclin, a trigger component. Later, the zygotic genome assumes control, and in Drosophila, zygotic transcription is required for production of another trigger protein, the product of string. After this transition to zygotic control, pulses of string transcription define the timing of highly patterned embryonic cell divisions and cyclin accumulation is not rate limiting.
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