THE HUMAN IMMUNOGLOBULIN-KAPPA LOCUS CONSISTS OF 2 COPIES THAT ARE ORGANIZED IN OPPOSITE POLARITY

The κ locus is a largely duplicated structure from which a 600-kb C(κ) proximal (p) and a 440-kb distal (d) contig have been cloned. In parallel with the cloning and sequencing work, the κ locus and its surroundings were mapped by pulsed-field gel electrophoresis (PFGE) with the help of 13 rare-cutter restriction nucleases and 15 unique hybridization probes. The distance between the two contigs was determined to be about 800 kb and the size of the entire locus about 2.0 Mb. The map extends 1.5 Mb toward the centromere and 3.5 Mb toward the telomere (including the CD8α locus; see accompanying paper by Weichhold et al. (91993b) Genomics 16.512-514), yielding a continuously mapped region of 7 Mb. The detailed map of the κ locus and its close vicinity allows a number of conclusions to be drawn: (1) The κ locus comprises two copies that include the above contigs. It constitutes a structure that, starting from a center in the still uncloned region, is largely symmetrical for about 850 kb to each side. The two contigs are therefore arranged in opposite 5'-3' polarity; this explains the structures of the products of V(κ)-J(κ) rearrangements found in lymphoid cells arising by deletions or inversions, respectively. (2) The organization of the κ locus and its surroundings is very similar, although of course not identical, in three cell lines and 12 individuals. (3) In the so-called haplotype 11, which was found in one individual in homozygous form and in several others in heterozygous form, about 1.0 Mb of DNA including the entire distal copy comprising 36 V(κ) genes is absent. The breakpoints of homology between haplotypes 11 and the other haplotypes were narrowed down to small regions. (4) The mechanisms that may have led to the duplicated structure of the κ locus and to the subsequent formation of haplotype 11 are discussed. © 1993 Academic Press. All rights reserved.