New types of multiple and single gene deletions in the humanIgCH locus

Abstract

The locus for human immunoglobulin heavy chain constant region genes (IgCH) is characterized by a significant frequency of deleted or duplicated haplotypes, due to unequal crossing-over events. Four types of deletions and one duplication have been reported so far. We describe here a molecular study of four cases of IgCH deletions. Two of the three types of deletions are reported here for the first time. Analysis of genetic markers associated with the deleted haplotypes pointed to the independent origin of similar deletions and the involvement of intergenic sequences in the mispairing-recombination process. The reduced or absent transcription of the C gamma 4 gene in two C gamma 2-deleted haplotypes offers an insight into the requirements for the isotype switch mechanism.

Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions

“…The multigene deletions have been designated I to VI, in the chronological order of their being found: deletion I (del G1-EP1-A1-GP-G2-G4), deletion II (del EP1-A1-GP), deletion III (del A1-GP-G2-G4-E), deletion IV (del EP1-A1-GP-G2-G4), deletion V (del GP-G2-G4-E-A2) and deletion VI (del G1-EP1-A1-GP-G2). 5,6,8,[10][11][12][13] In an earlier study, the levels of IgA subclasses were investigated in saliva and serum in individuals with homozygous heavy chain constant A1 and A2 gene deletions. 3 The salivary IgA concentrations from two individuals homozygous for the deletion III, therefore without IgA1 and from one individual homozygous for the deletion V, and thus without IgA2, were at the same level as for the controls.…”

Multiple levels of analysis of an IGHG4 gene deletion

“…Deletion Lefranc et al 1982Lefranc et al 1983 EP-A1-GP Deletion Lefranc et al 1983 EP-A1-GP-G2-G4 Deletion Migone et al 1984Chaabani et al 1985 A1-GP-G2-G4-E Deletion Migone et al 1984Bottaro et al 1989b G2 Duplication Bech-Hansen and Cox 1986 Deletion Bottaro et al 1989b GP-G2-G4-E-A2 Deletion Bottaro et al 1989bHendriks et al 1989 G1 Deletion Smith et al 1989 G1-EP-A1-GP-G2 Deletion Smith et al 1989 Deletion characterization has been performed in previous cases by the standard Southern technique. However, this presents at least two limitations: first, it cannot resolve rearrangements, such as gene conversions or intragenic crossovers, involving restricted regions, since CH gene-specific DNA probes are not available, except for the G3 gene (Huck et al 1986); secondly, it does not provide any long-range information about the deletion boundaries and the structure of the rearranged region.…”

“…1. DNA (l~tg) from SPA, from subjects carrying deletions of G2 and G4 (DEM and CRU) or of G2 alone (MOD and TIM) (Bottaro et al 1989b) and from normal controls was subjected to 35 amplification cycles of denaturation (93~ 1rain), annealing (50~ 40s) and synthesis (63~ 40s) using TaqI DNA polymerase (New England Biolabs), and slot-blotted onto nitrocellulose filters. Oligonucleotide probes terminally labelled with T4 polynucleotide kinase (New England Biolabs) were used for hybridization.…”

Novel human immunoglobulin heavy chain constant region gene deletion haplotypes characterized by pulsed-field electrophoresis

“…(FRO) [4] (T17) [5] (SAF) [4] (DEM) [6] (SPA) |8] (D847) [IO] (BAR. MON) [22] (I0i)|9] (CRU) [6] (ABB, MOLZER)(221 (MOD) [6] (HJE)|11| were used in the sludy.…”

“…MON) [22] (I0i)|9] (CRU) [6] (ABB, MOLZER)(221 (MOD) [6] (HJE)|11| were used in the sludy. Samples from Swedish blood donors were used as controls.…”