MOLECULAR ANALYSIS OF THE T17 IMMUNOGLOBULIN CH MULTIGENE DELETION (DEL A1-GP-G2-G4-E)

In the human, the order of the immunoglobulin heavy chain constant reg ion (Ig CH) genes is the following: 5'-M-D-G3-G1-EP1-A1-GP-G2-G4-E-A2- 3'. Extensive multigene deletions have been described in the Ig CH loc us, some of these encompassing up to 160 kb. To date six different mul tigene deletion haplotypes have been identified, designated I to VI ac cording to the chronological order of their being found: deletion I (d el G1-EP1-A1-GP-G2-G4), II (del. EP1-A1-GP), LU (del A1-GP-G2-G4-E), I V (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G 2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly (17 cases out of 1 8) in the Mediterranean area. So far, deletions I and LI have been fou nd in Tunisia, deletions III, IV and V in Italy, and deletion VI in Sw eden. In this paper, we show that a Tunisian, T17, previously reported as being homozygous for a deletion of type IV, is, in fact, homozygou s for a deletion that encompasses A1-GP-G2-G4-E. Therefore T17 is the first case of a deletion of type m reported in the Tunisian population . Molecular analysis demonstrates that the T17 deletion occurred betwe en highly homologous regions located downstream of IGHEP1 and IGHE, re spectively In contrast to the EZZ deletion, the recombination occurred near or in the switch regions, since the homologous regions involved in the deletion extend over 4.5 kb of DNA and encompass the I alpha 1- S alpha 1 and I alpha 2-S alpha 2 regions, respectively.