caa a22 4500 397573758 CHVBK 20180308164849.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1945 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1945 Two Chimaeric Transcription Units Result from an Inversion Breaking Intron 1 of the Factor VIII Gene and a Region Reportedly Affected by Reciprocal Translocations in T-cell Leukaemia [Elektronische Daten] [Astrid Brinke, Luigina Tagliavacca, Jennifer Naylor, Peter Green, Paul Giangrande, Francesco Giannelli] Analysis of mRNA in two haemophilic monozygotic twins offers novel information on the organisation of expressed sequences distal to the coagulation factor VIII gene. These patients show an inversion that, in contrast to the common inversions responsible for 1/5 of all haemophilia A, affects the first rather than intron 22 of the gene. This displaces the most telomeric of the factor VIII exons (exon 1) by ∼100 kb towards the telomere, and close to the region of the C6.1A gene. This novel inversion creates two hybrid transcription units: one formed by the promoter and first exon of the factor VIII gene followed by a widely expressed sequence; the other by the promoter and coding region of the C6.1A gene plus most of the factor VIII gene (part of intron 1 and exons 2-26). Investigation of this transcription unit reveals that the C6.1A gene has an unsuspected intron in the region coding for the previously described 3′-untranslated tail of the message. Furthermore, exons located beyond the known C6.1A sequence and present in normal transcripts precede exons 2-26 of the factor VIII gene in the hybrid mRNA of the haemophilic twins. The factor VIII sequences in this hybrid mRNA are not expected to be expressed because they lack the first exon, encoding the prepeptide, and follow a translation stop in the C6.1A gene. Leukaemia-related translocations in the C6.1A region suggest that this region may be somewhat unstable. © 1993 Oxford University Press Brinke Astrid Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut Tagliavacca Luigina Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut Naylor Jennifer Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut Green Peter Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut Giangrande Paul Oxford Haemophilia Centre, Churchill Hospital, Oxford, UK aut Giannelli Francesco Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1945-1951 0964-6906 5:12<1945 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1945 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1945 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brinke Astrid Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Tagliavacca Luigina Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Naylor Jennifer Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Green Peter Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Giangrande Paul Oxford Haemophilia Centre, Churchill Hospital, Oxford, UK aut NATIONALLICENCE 700 1- Giannelli Francesco Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1945-1951 0964-6906 5:12<1945 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford