I-c.   Insertion of a Retrotransposable Element

The insertion of an L1 fragment within the IVS-II of the beta-globin gene results in a beta°-thal. This condition was observed in the mother and daughter of a Czech family who exhibited the clinical picture of beta-thal trait with microcytic anemia and elevated Hb A2. Restriction endonuclease analyses indicated a previously undescribed chromosomal rearrangement involving an insertion of 6-7 kb DNA into beta-IVS-II. Restriction mapping of the insertion was identical to an L1.2 transposon and showed the reverse orientation of the L1 element with respect to the beta-globin gene. Sequence analysis of the 3' end of the insertion (~600 bp) displayed 97% homology to the 5' terminal region of the L1.2 including 100% homology to the unique G/C rich promoter consensus sequence which initiates L1 transcription. The insertion breakpoint is located at the 3' end of beta-IVS-II within the "recombination region" previously identified to be a part of an ancestral L1 element. The parental target DNA sequence forms a 34 bp hairpin loop as well as a short palindrome and is homologous to a conserved transposonal heptanucleotide (ACGAAAA). The affected gene expresses full length beta-globin transcripts at the level corresponding to about 15% of total beta-globin mRNA. The L1 insertion within beta-IVS-II represents a new form of beta-thal.

1. Divoky, V., Mrug, M., Brabec, V., Indrak, K., Huisman, T.H.J., and Prchal, J.T.: Blood, 88:148a (Suppl. 1), 1996.

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.