Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1988 Jul;7(7):2003–2010. doi: 10.1002/j.1460-2075.1988.tb03039.x

The use of chromosomal translocations to study human immunoglobulin gene organization: mapping DH segments within 35 kb of the C mu gene and identification of a new DH locus.

L Buluwela 1, D G Albertson 1, P Sherrington 1, P H Rabbitts 1, N Spurr 1, T H Rabbitts 1
PMCID: PMC454475  PMID: 3138112

Abstract

We have studied the Burkitt's lymphoma cell line Daudi which carries the translocation t(8;14). The breakpoint of this translocation on the 14q+ chromosome occurs near to a rearranged DH-JH join, and the actual chromosome junction is a few hundred base pairs upstream of the joined DH element. The nucleotide sequence of the rearranged DH segment shows that it does not come from the previously described D cluster. Using this DH sequence as a probe we have identified two separate DH clusters. One of these is the major DH cluster and is located only 20 kb upstream of the JH segments. A pseudo-VH (probably the first VH segment) is also found approximately 98 kb from JH. A second, minor DH locus has been found which seems to be located on the distal side of the VH locus on chromosome 14, since there is little evidence for rearrangement or deletion of this locus in any B cell DNA analysed. A single VHIII subgroup gene is located within 25 kb of the newly identified DH element: it is possible that this minor locus occurs near the limit of the Igh locus.

Full text

PDF
2003

Images in this article

Selected References

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

  1. Albertson D. G. Localization of the ribosomal genes in Caenorhabditis elegans chromosomes by in situ hybridization using biotin-labeled probes. EMBO J. 1984 Jun;3(6):1227–1234. doi: 10.1002/j.1460-2075.1984.tb01957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albertson D. G. Mapping muscle protein genes by in situ hybridization using biotin-labeled probes. EMBO J. 1985 Oct;4(10):2493–2498. doi: 10.1002/j.1460-2075.1985.tb03961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707–1711. doi: 10.1073/pnas.80.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baer R., Boehm T., Yssel H., Spits H., Rabbitts T. H. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments. EMBO J. 1988 Jun;7(6):1661–1668. doi: 10.1002/j.1460-2075.1988.tb02993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baer R., Chen K. C., Smith S. D., Rabbitts T. H. Fusion of an immunoglobulin variable gene and a T cell receptor constant gene in the chromosome 14 inversion associated with T cell tumors. Cell. 1985 Dec;43(3 Pt 2):705–713. doi: 10.1016/0092-8674(85)90243-0. [DOI] [PubMed] [Google Scholar]
  6. Baer R., Forster A., Rabbitts T. H. The mechanism of chromosome 14 inversion in a human T cell lymphoma. Cell. 1987 Jul 3;50(1):97–105. doi: 10.1016/0092-8674(87)90666-0. [DOI] [PubMed] [Google Scholar]
  7. Bakhshi A., Wright J. J., Graninger W., Seto M., Owens J., Cossman J., Jensen J. P., Goldman P., Korsmeyer S. J. Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2396–2400. doi: 10.1073/pnas.84.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cleary M. L., Meeker T. C., Levy S., Lee E., Trela M., Sklar J., Levy R. Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma. Cell. 1986 Jan 17;44(1):97–106. doi: 10.1016/0092-8674(86)90488-5. [DOI] [PubMed] [Google Scholar]
  9. Coulson A., Sulston J., Brenner S., Karn J. Toward a physical map of the genome of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7821–7825. doi: 10.1073/pnas.83.20.7821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Edwards Y. H., Parkar M., Povey S., West L. F., Parrington J. M., Solomon E. Human myosin heavy chain genes assigned to chromosome 17 using a human cDNA clone as probe. Ann Hum Genet. 1985 May;49(Pt 2):101–109. doi: 10.1111/j.1469-1809.1985.tb01681.x. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. Flanagan J. G., Rabbitts T. H. The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J. 1982;1(5):655–660. doi: 10.1002/j.1460-2075.1982.tb01223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gibson T. J., Rosenthal A., Waterston R. H. Lorist6, a cosmid vector with BamHI, NotI, ScaI and HindIII cloning sites and altered neomycin phosphotransferase gene expression. Gene. 1987;53(2-3):283–286. doi: 10.1016/0378-1119(87)90017-5. [DOI] [PubMed] [Google Scholar]
  14. Haluska F. G., Finver S., Tsujimoto Y., Croce C. M. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature. 1986 Nov 13;324(6093):158–161. doi: 10.1038/324158a0. [DOI] [PubMed] [Google Scholar]
  15. Haluska F. G., Tsujimoto Y., Croce C. M. The t(8;14) chromosome translocation of the Burkitt lymphoma cell line Daudi occurred during immunoglobulin gene rearrangement and involved the heavy chain diversity region. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6835–6839. doi: 10.1073/pnas.84.19.6835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hamlyn P. H., Rabbitts T. H. Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983 Jul 14;304(5922):135–139. doi: 10.1038/304135a0. [DOI] [PubMed] [Google Scholar]
  17. Heisterkamp N., Groffen J., Stephenson J. R., Spurr N. K., Goodfellow P. N., Solomon E., Carritt B., Bodmer W. F. Chromosomal localization of human cellular homologues of two viral oncogenes. Nature. 1982 Oct 21;299(5885):747–749. doi: 10.1038/299747a0. [DOI] [PubMed] [Google Scholar]
  18. Karn J., Matthes H. W., Gait M. J., Brenner S. A new selective phage cloning vector, lambda 2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI. Gene. 1984 Dec;32(1-2):217–224. doi: 10.1016/0378-1119(84)90049-0. [DOI] [PubMed] [Google Scholar]
  19. Kielty C. M., Povey S., Hopkinson D. A. Regulation of expression of liver-specific enzymes. III. Further analysis of a series of rat hepatoma X human somatic cell hybrids. Ann Hum Genet. 1982 Oct;46(Pt 4):307–327. doi: 10.1111/j.1469-1809.1982.tb01582.x. [DOI] [PubMed] [Google Scholar]
  20. Kodaira M., Kinashi T., Umemura I., Matsuda F., Noma T., Ono Y., Honjo T. Organization and evolution of variable region genes of the human immunoglobulin heavy chain. J Mol Biol. 1986 Aug 20;190(4):529–541. doi: 10.1016/0022-2836(86)90239-1. [DOI] [PubMed] [Google Scholar]
  21. Krawinkel U., Rabbitts T. H. Comparison of the hinge-coding segments in human immunoglobulin gamma heavy chain genes and the linkage of the gamma 2 and gamma 4 subclass genes. EMBO J. 1982;1(4):403–407. doi: 10.1002/j.1460-2075.1982.tb01182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  23. Matthyssens G., Rabbitts T. H. Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6561–6565. doi: 10.1073/pnas.77.11.6561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nabholz M., Miggiano V., Bodmer W. Genetic analysis with human--mouse somatic cell hybrids. Nature. 1969 Jul 26;223(5204):358–363. doi: 10.1038/223358a0. [DOI] [PubMed] [Google Scholar]
  25. Phillips I. R., Shephard E. A., Povey S., Davis M. B., Kelsey G., Monteiro M., West L. F., Cowell J. A cytochrome P-450 gene family mapped to human chromosome 19. Ann Hum Genet. 1985 Oct;49(Pt 4):267–274. doi: 10.1111/j.1469-1809.1985.tb01702.x. [DOI] [PubMed] [Google Scholar]
  26. Rabbitts T. H., Forster A., Hamlyn P., Baer R. Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma. Nature. 1984 Jun 14;309(5969):592–597. doi: 10.1038/309592a0. [DOI] [PubMed] [Google Scholar]
  27. Rabbitts T. H., Forster A., Milstein C. P. Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences. Nucleic Acids Res. 1981 Sep 25;9(18):4509–4524. doi: 10.1093/nar/9.18.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rabbitts T. H. The human immunoglobulin genes. The nineteenth Colworth medal lecture. Biochem Soc Trans. 1983 Apr;11(2):119–126. [PubMed] [Google Scholar]
  29. Ravetch J. V., Siebenlist U., Korsmeyer S., Waldmann T., Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell. 1981 Dec;27(3 Pt 2):583–591. doi: 10.1016/0092-8674(81)90400-1. [DOI] [PubMed] [Google Scholar]
  30. Reth M. G., Alt F. W. Novel immunoglobulin heavy chains are produced from DJH gene segment rearrangements in lymphoid cells. 1984 Nov 29-Dec 5Nature. 312(5993):418–423. doi: 10.1038/312418a0. [DOI] [PubMed] [Google Scholar]
  31. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  32. Siebenlist U., Ravetch J. V., Korsmeyer S., Waldmann T., Leder P. Human immunoglobulin D segments encoded in tandem multigenic families. Nature. 1981 Dec 17;294(5842):631–635. doi: 10.1038/294631a0. [DOI] [PubMed] [Google Scholar]
  33. Solomon E., Bobrow M., Goodfellow P. N., Bodmer W. F., Swallow D. M., Povey S., Noël B. Human gene mapping using an X/autosome translocation. Somatic Cell Genet. 1976 Mar;2(2):125–140. doi: 10.1007/BF01542626. [DOI] [PubMed] [Google Scholar]
  34. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  35. Staden R. The current status and portability of our sequence handling software. Nucleic Acids Res. 1986 Jan 10;14(1):217–231. doi: 10.1093/nar/14.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Swallow D. M., Solomon E., Pajunen L. Immunochemical analysis of the N-acetyl hexosaminidases in human-mouse hybrids made using a double selective system. Cytogenet Cell Genet. 1977;18(3):136–148. doi: 10.1159/000130758. [DOI] [PubMed] [Google Scholar]
  37. Tunnacliffe A., Buluwela L., Rabbitts T. H. Physical linkage of three CD3 genes on human chromosome 11. EMBO J. 1987 Oct;6(10):2953–2957. doi: 10.1002/j.1460-2075.1987.tb02600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  39. Whitehead A. S., Solomon E., Chambers S., Bodmer W. F., Povey S., Fey G. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5021–5025. doi: 10.1073/pnas.79.16.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wood C., Tonegawa S. Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: implications for the joining mechanism. Proc Natl Acad Sci U S A. 1983 May;80(10):3030–3034. doi: 10.1073/pnas.80.10.3030. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES