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. 1990 Apr 25;18(8):2101–2107. doi: 10.1093/nar/18.8.2101

Structural features of transposed human VK genes and implications for the mechanism of their transpositions.

P Borden 1, R Jaenichen 1, H G Zachau 1
PMCID: PMC330689  PMID: 2159639

Abstract

The genes encoding the variable, joining and constant regions of human immunoglobulin light chains have been localized to the short arm of chromosome 2. However, several VK genes lie outside of the locus: a single copy cluster of five VK genes is located on chromosome 22; an isolated but amplified VkI gene is found on chromosome 1; and several isolated VkI genes are on as-yet-unidentified chromosomes other than chromosome 2. Vk genes not contained within the kappa locus are termed orphons. We have attempted to gain insight into the mechanism of transposition of both the chromosome 22 cluster and the several amplified VkI genes by searching in the kappa locus for a parent copy of the former, and by analyzing the junctions between transposed VKI-containing segments and adjacent non-amplified regions. The chromosome 22 orphon cluster must have been non-duplicatively transposed. Sequence features at the junctions of this and other orphon regions are direct and inverted repeats, and, in one case, an Alu repeat. These unusual features may have predisposed the orphon regions to transposition by serving as target sites for enzymes involved in recombination.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer H. G., Pech M., Zachau H. G. Characterization of a group of transposed human V kappa genes. Biol Chem Hoppe Seyler. 1986 Aug;367(8):751–755. doi: 10.1515/bchm3.1986.367.2.751. [DOI] [PubMed] [Google Scholar]
  2. Brown W. R. A physical map of the human pseudoautosomal region. EMBO J. 1988 Aug;7(8):2377–2385. doi: 10.1002/j.1460-2075.1988.tb03082.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen P. P., Kabat E. A., Wu T. T., Fong S., Carson D. A. Possible involvement of human D minigenes in the first complementarity-determining region of kappa light chains. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2125–2127. doi: 10.1073/pnas.82.7.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Childs G., Maxson R., Cohn R. H., Kedes L. Orphons: dispersed genetic elements derived from tandem repetitive genes of eucaryotes. Cell. 1981 Mar;23(3):651–663. doi: 10.1016/0092-8674(81)90428-1. [DOI] [PubMed] [Google Scholar]
  5. Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
  6. Finnegan D. J. Eukaryotic transposable elements and genome evolution. Trends Genet. 1989 Apr;5(4):103–107. doi: 10.1016/0168-9525(89)90039-5. [DOI] [PubMed] [Google Scholar]
  7. Heartlein M. W., Latt S. A. Amplified inverted duplications within and adjacent to heterologous selectable DNA. Nucleic Acids Res. 1989 Feb 25;17(4):1697–1716. doi: 10.1093/nar/17.4.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hodgson C. P., Fisk R. Z. Hybridization probe size control: optimized 'oligolabelling'. Nucleic Acids Res. 1987 Aug 11;15(15):6295–6295. doi: 10.1093/nar/15.15.6295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hyrien O., Debatisse M., Buttin G., de Saint Vincent B. R. A hotspot for novel amplification joints in a mosaic of Alu-like repeats and palindromic A + T-rich DNA. EMBO J. 1987 Aug;6(8):2401–2408. doi: 10.1002/j.1460-2075.1987.tb02518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hyrien O., Debatisse M., Buttin G., de Saint Vincent B. R. The multicopy appearance of a large inverted duplication and the sequence at the inversion joint suggest a new model for gene amplification. EMBO J. 1988 Feb;7(2):407–417. doi: 10.1002/j.1460-2075.1988.tb02828.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jaenichen H. R., Pech M., Lindenmaier W., Wildgruber N., Zachau H. G. Composite human VK genes and a model of their evolution. Nucleic Acids Res. 1984 Jul 11;12(13):5249–5263. doi: 10.1093/nar/12.13.5249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kariya Y., Kato K., Hayashizaki Y., Himeno S., Tarui S., Matsubara K. Revision of consensus sequence of human Alu repeats--a review. Gene. 1987;53(1):1–10. doi: 10.1016/0378-1119(87)90087-4. [DOI] [PubMed] [Google Scholar]
  13. Kenter A. L., Birshtein B. K. Chi, a promoter of generalized recombination in lambda phage, is present in immunoglobulin genes. Nature. 1981 Oct 1;293(5831):402–404. doi: 10.1038/293402a0. [DOI] [PubMed] [Google Scholar]
  14. Krawinkel U., Zoebelein G., Bothwell A. L. Palindromic sequences are associated with sites of DNA breakage during gene conversion. Nucleic Acids Res. 1986 May 12;14(9):3871–3882. doi: 10.1093/nar/14.9.3871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lorenz W., Straubinger B., Zachau H. G. Physical map of the human immunoglobulin K locus and its implications for the mechanisms of VK-JK rearrangement. Nucleic Acids Res. 1987 Dec 10;15(23):9667–9676. doi: 10.1093/nar/15.23.9667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lötscher E., Grzeschik K. H., Bauer H. G., Pohlenz H. D., Straubinger B., Zachau H. G. Dispersed human immunoglobulin kappa light-chain genes. Nature. 1986 Apr 3;320(6061):456–458. doi: 10.1038/320456a0. [DOI] [PubMed] [Google Scholar]
  17. Lötscher E., Siwka W., Zimmer F. J., Grummt F., Zachau H. G. Transposed human immunoglobulin V kappa gene regions carry clusters of conserved sequence elements. Gene. 1988 Sep 30;69(2):225–236. doi: 10.1016/0378-1119(88)90433-7. [DOI] [PubMed] [Google Scholar]
  18. Lötscher E., Zimmer F. J., Klopstock T., Grzeschik K. H., Jaenichen R., Straubinger B., Zachau H. G. Localization, analysis and evolution of transposed human immunoglobulin V kappa genes. Gene. 1988 Sep 30;69(2):215–223. doi: 10.1016/0378-1119(88)90432-5. [DOI] [PubMed] [Google Scholar]
  19. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  20. Passananti C., Davies B., Ford M., Fried M. Structure of an inverted duplication formed as a first step in a gene amplification event: implications for a model of gene amplification. EMBO J. 1987 Jun;6(6):1697–1703. doi: 10.1002/j.1460-2075.1987.tb02420.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pech M., Jaenichen H. R., Pohlenz H. D., Neumaier P. S., Klobeck H. G., Zachau H. G. Organization and evolution of a gene cluster for human immunoglobulin variable regions of the kappa type. J Mol Biol. 1984 Jun 25;176(2):189–204. doi: 10.1016/0022-2836(84)90420-0. [DOI] [PubMed] [Google Scholar]
  22. Pech M., Smola H., Pohlenz H. D., Straubinger B., Gerl R., Zachau H. G. A large section of the gene locus encoding human immunoglobulin variable regions of the kappa type is duplicated. J Mol Biol. 1985 Jun 5;183(3):291–299. doi: 10.1016/0022-2836(85)90001-4. [DOI] [PubMed] [Google Scholar]
  23. Pech M., Zachau H. G. Immunoglobulin genes of different subgroups are interdigitated within the VK locus. Nucleic Acids Res. 1984 Dec 21;12(24):9229–9236. doi: 10.1093/nar/12.24.9229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schon E. A., Rizzuto R., Moraes C. T., Nakase H., Zeviani M., DiMauro S. A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science. 1989 Apr 21;244(4902):346–349. doi: 10.1126/science.2711184. [DOI] [PubMed] [Google Scholar]
  26. Stark G. R., Debatisse M., Giulotto E., Wahl G. M. Recent progress in understanding mechanisms of mammalian DNA amplification. Cell. 1989 Jun 16;57(6):901–908. doi: 10.1016/0092-8674(89)90328-0. [DOI] [PubMed] [Google Scholar]
  27. Straubinger B., Thiebe R., Pech M., Zachau H. G. The Z family, a group of transposed human immunoglobulin V kappa genes. Gene. 1988 Sep 30;69(2):209–214. doi: 10.1016/0378-1119(88)90431-3. [DOI] [PubMed] [Google Scholar]
  28. Sullivan K. M., Lilley D. M. A dominant influence of flanking sequences on a local structural transition in DNA. Cell. 1986 Dec 5;47(5):817–827. doi: 10.1016/0092-8674(86)90524-6. [DOI] [PubMed] [Google Scholar]
  29. van der Feltz M. J., Shivji M. K., Allen P. B., Heisterkamp N., Groffen J., Wiedemann L. M. Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene. Nucleic Acids Res. 1989 Jan 11;17(1):1–10. doi: 10.1093/nar/17.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]

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