Loss of splice consensus signal is responsible for the removal of the entire C(H)1 domain of the functional camel IGG2A heavy-chain antibodies

The molecular basis for the absence of the C(H)1 domain in naturally occurr ing heavy-chain antibodies of the camelids was assessed by determining the entire Camelus dromedarius gamma 2a heavy-chain constant gene. The organiza tion of the camel gamma 2a constant heavy-chain gene obtained from a liver genomic library appears to be typical of all other mammalian gamma genes se quenced to date. It contains the switch, C(H)1, hinge, C(H)2, C(H)3, M1 and M2 exons. In contrast to the case in mouse and human heavy chain diseases, the camel gamma 2a gene shows no major structural defect, and its equivale nt C(H)1 exon is intact. However, sequence analysis has revealed that the s plicing site, immediately after the C(H)1 exon, is defective due to point m utations, especially the G(+1) to A(+1) transversion seems to be detrimenta l. It is concluded that the loss of the splice consensus signal is responsi ble for the removal of the entire C(H)1 domain in camel gamma 2a heavy-chai n immunoglobulins. Additionally, a closer analysis of the hinge exon sugges ts the possible involvement of transposons in the genetic variation of mamm alian Cy hinges. (C) 1999 Elsevier Science Ltd. All rights reserved.