Transposition of human immunoglobulin V kappa genes within the same chromosome and the mechanism of their amplification.

The variable, joining and constant gene segments of the human immunoglobulin kappa locus (V kappa, J kappa and C kappa) are located on the short arm of chromosome 2 at 2p11-2p12. Here we describe a cluster of 11 V kappa genes on the long arm of chromosome 2 at 2cen-q11. By pulsed-field gel electrophoresis, cosmid cloning and DNA sequencing the cluster was shown to consist of four amplified units (amplicons). The amplicons, each 110-160 kb in size, are organized within 650 kb as an array of inverted repeats with short stretches of non-amplified DNA in between. Cloning and sequencing of three different joints between amplified and non-amplified DNA revealed the existence of parts of Alu repeats at each of the analysed joints. It is suggested that during evolution a group of five V kappa genes was transposed from the short to the long arm of chromosome 2 by a pericentric inversion. Three of the five V kappa genes were then amplified in two subsequent steps to yield the structure found in the majority of the present day population. The possible relation of this structure to a pericentric inversion of chromosome 2 that is seen cytogenetically in a small fraction of today's population is discussed.