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The human Vκ locus

1987; Elsevier BV; Volume: 193; Issue: 2 Linguagem: Inglês

10.1016/0022-2836(87)90216-6

1089-8638

Hans‐Dieter Pohlenz, Bernhard Straubinger, Rainer Thiebe Michael Pech, Franz-Josef Zimmer, Hans G. Zachau,

Skin and Cellular Biology Research

As part of the ongoing work in our laboratory on the structural organization of the human Vκ locus we screened cosmid libraries with Vκ gene probes and obtained numerous Vκ gene-containing cosmid clones. Several genomic regions of the Vκ locus were reconstructed from overlapping cosmid inserts and were extended by one step of chromosomal walking. The regions that are called Wa, Wb, Oa, Ob and Ob′ comprise about 370 kb (103 bases) of DNA and contain 24 Vκ genes and pseudogenes. The Vκ genes belong to the three dominant subgroups (VκI, VκII, VκIII) and are arranged to form mixed clusters with members of the different subgroups being intermingled with each other. The distances between the genes range from 1 to 15 kb. Three genes of the Wa and Wb regions that were sequenced turned out to be pseudogenes. Terminal parts of the regions Wa and Ob that do not contain Vκ genes of one of the known subgroups may represent extended spacer regions within the Vκ locus. Wa and Wb are duplicated regions located at different positions of the locus. Region Wb was found to comprise inversely repeated sections of at least 14 kb each that contain Vκ genes oriented in opposite polarity. This finding is consistent with inversion-deletion models of V-J joining; it also shows that the Vκ locus contains not only unique and duplicated but also triplicated parts. The data on the W and O regions are discussed together with those on the L regions and on other regions established in our laboratory. Although the picture of the human Vκ locus with, to date, about 70 different non-allelic Vκ genes is still incomplete, some general features with respect to the organization of the genes and the limited duplication of genomic regions have emerged.