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The Journal of Immunology, 2000, 165: 6984-6993.
Copyright © 2000 by The American Association of Immunologists

Conservation of Mhc Class III Region Synteny Between Zebrafish and Human as Determined by Radiation Hybrid Mapping1

Holger Sültmann2,*, Akie Sato*, Brent W. Murray*, Naoko Takezaki{dagger}, Robert Geisler{ddagger}, Gerd-Jörg Rauch{ddagger} and Jan Klein3,*

* Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany; {dagger} The Graduate University for Advanced Studies, Department of Biosystems Science, Hayama, Kanagawa, Japan; and {ddagger} Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany

In the HLA, H2, and other mammalian Mhc, the class I and II loci are separated by the so-called class III region comprised of ~60 genes that are functionally and evolutionarily unrelated to the class I/II genes. To explore the origin of this island of unrelated loci in the middle of the Mhc 19 homologues of HLA class III genes, we identified 19 homologues of HLA class III genes as well as 21 additional non-class I/II HLA homologues in the zebrafish and mapped them by testing a panel of 94 zebrafish-hamster radiation hybrid cell lines. Six of the HLA class III and eight of the flanking homologues were found to be linked to the zebrafish class I (but not class II) loci in linkage group 19. The remaining homologous loci were found to be scattered over 14 zebrafish linkage groups. The linkage group 19 contains at least 25 genes (not counting the class I loci) that are also syntenic on human chromosome 6. This gene assembly presumably represents the pre-Mhc that existed before the class I/II genes arose. The pre-Mhc may not have contained the complement and other class III genes involved in immune response.




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