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. 1985 Sep;4(9):2231–2237. doi: 10.1002/j.1460-2075.1985.tb03919.x

The human HLA class II alpha chain gene DZ alpha is distinct from genes in the DP, DQ and DR subregions.

J Trowsdale, A Kelly
PMCID: PMC554490  PMID: 3000765

Abstract

A new human HLA class II alpha gene DZ alpha was sequenced. The structure and organisation of the gene was similar to other alpha chain genes except for a particularly small intron (95 bp) after the exon encoding the alpha 2 domain, and the position of the stop codon, which was on a different exon to that encoding the cytoplasmic portion of the molecule. Comparison of the DZ alpha sequence with other class II genes showed that the gene is about as distantly related to alpha chain genes in the DP, DQ and DR subregions as they are to each other. The DZ alpha gene results in an unusually large mRNA transcript of greater than 3.0 kb, detected on Northern blots of B cell lines. From the sequence, there are no obvious features that would render DZ alpha a pseudogene, except for an unusual poly(A)+ addition signal, ACTAAA. Analysis of Northern blots shows that sequences downstream (3') of this signal are present in mature mRNA. The large transcripts are probably due to defects in the signals for processing of the mRNA transcript at the 3' end.

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Selected References

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

  1. Auffray C., Lillie J. W., Arnot D., Grossberger D., Kappes D., Strominger J. L. Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes. Nature. 1984 Mar 22;308(5957):327–333. doi: 10.1038/308327a0. [DOI] [PubMed] [Google Scholar]
  2. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. Regions of allelic hypervariability in the murine A alpha immune response gene. Cell. 1983 Aug;34(1):169–177. doi: 10.1016/0092-8674(83)90147-2. [DOI] [PubMed] [Google Scholar]
  3. Berget S. M. Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature. 1984 May 10;309(5964):179–182. doi: 10.1038/309179a0. [DOI] [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Carlson D. P., Ross J. Human beta-globin promoter and coding sequences transcribed by RNA polymerase III. Cell. 1983 Oct;34(3):857–864. doi: 10.1016/0092-8674(83)90543-3. [DOI] [PubMed] [Google Scholar]
  6. Chang H. C., Moriuchi T., Silver J. The heavy chain of human B-cell alloantigen HLA-DS has a variable N-terminal region and a constant immunoglobulin-like region. 1983 Oct 27-Nov 2Nature. 305(5937):813–815. doi: 10.1038/305813a0. [DOI] [PubMed] [Google Scholar]
  7. Dembic Z., Ayane M., Klein J., Steinmetz M., Benoist C. O., Mathis D. J. Inbred and wild mice carry identical deletions in their E alpha MHC genes. EMBO J. 1985 Jan;4(1):127–131. doi: 10.1002/j.1460-2075.1985.tb02326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Ford J. P., Hsu M. T. Transcription pattern of in vivo-labeled late simian virus 40 RNA: equimolar transcription beyond the mRNA 3' terminus. J Virol. 1978 Dec;28(3):795–801. doi: 10.1128/jvi.28.3.795-801.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Higgs D. R., Goodbourn S. E., Lamb J., Clegg J. B., Weatherall D. J., Proudfoot N. J. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24;306(5941):398–400. doi: 10.1038/306398a0. [DOI] [PubMed] [Google Scholar]
  11. Hofer E., Hofer-Warbinek R., Darnell J. E., Jr Globin RNA transcription: a possible termination site and demonstration of transcriptional control correlated with altered chromatin structure. Cell. 1982 Jul;29(3):887–893. doi: 10.1016/0092-8674(82)90450-0. [DOI] [PubMed] [Google Scholar]
  12. Jelinek W. R., Schmid C. W. Repetitive sequences in eukaryotic DNA and their expression. Annu Rev Biochem. 1982;51:813–844. doi: 10.1146/annurev.bi.51.070182.004121. [DOI] [PubMed] [Google Scholar]
  13. Kelly A., Trowsdale J. Complete nucleotide sequence of a functional HLA-DP beta gene and the region between the DP beta 1 and DP alpha 1 genes: comparison of the 5' ends of HLA class II genes. Nucleic Acids Res. 1985 Mar 11;13(5):1607–1621. doi: 10.1093/nar/13.5.1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larhammar D., Servenius B., Rask L., Peterson P. A. Characterization of an HLA DR beta pseudogene. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1475–1479. doi: 10.1073/pnas.82.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee J. S., Trowsdale J., Bodmer W. F. Synthesis of HLA antigens from membrane-associated messenger RNA. J Exp Med. 1980 Aug 1;152(2 Pt 2):3s–10s. [PubMed] [Google Scholar]
  16. Lee J. S., Trowsdale J., Bodmer W. F. cDNA clones coding for the heavy chain of human HLA-DR antigen. Proc Natl Acad Sci U S A. 1982 Jan;79(2):545–549. doi: 10.1073/pnas.79.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee J. S., Trowsdale J., Travers P. J., Carey J., Grosveld F., Jenkins J., Bodmer W. F. Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization of the corresponding gene. Nature. 1982 Oct 21;299(5885):750–752. doi: 10.1038/299750a0. [DOI] [PubMed] [Google Scholar]
  18. Mason P. J., Jones M. B., Elkington J. A., Williams J. G. Polyadenylation of the Xenopus beta 1 globin mRNA at a downstream minor site in the absence of the major site and utilization of an AAUACA polyadenylation signal. EMBO J. 1985 Jan;4(1):205–211. doi: 10.1002/j.1460-2075.1985.tb02337.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mathis D. J., Benoist C. O., Williams V. E., 2nd, Kanter M. R., McDevitt H. O. The murine E alpha immune response gene. Cell. 1983 Mar;32(3):745–754. doi: 10.1016/0092-8674(83)90060-0. [DOI] [PubMed] [Google Scholar]
  20. Montell C., Fisher E. F., Caruthers M. H., Berk A. J. Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA. Nature. 1983 Oct 13;305(5935):600–605. doi: 10.1038/305600a0. [DOI] [PubMed] [Google Scholar]
  21. Nevins J. R., Blanchard J. M., Darnell J. E., Jr Transcription units of adenovirus type 2. Termination of transcription beyond the poly(A) addition site in early regions 2 and 4. J Mol Biol. 1980 Dec 15;144(3):377–386. doi: 10.1016/0022-2836(80)90096-0. [DOI] [PubMed] [Google Scholar]
  22. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  23. Proudfoot N. The end of the message and beyond. Nature. 1984 Feb 2;307(5950):412–413. doi: 10.1038/307412a0. [DOI] [PubMed] [Google Scholar]
  24. Roux-Dosseto M., Auffray C., Lillie J. W., Boss J. M., Cohen D., DeMars R., Mawas C., Seidman J. G., Strominger J. L. Genetic mapping of a human class II antigen beta-chain cDNA clone to the SB region of the HLA complex. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6036–6040. doi: 10.1073/pnas.80.19.6036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saito H., Maki R. A., Clayton L. K., Tonegawa S. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520–5524. doi: 10.1073/pnas.80.18.5520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Servenius B., Gustafsson K., Widmark E., Emmoth E., Andersson G., Larhammar D., Rask L., Peterson P. A. Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SB alpha (DP alpha) pseudogene. EMBO J. 1984 Dec 20;3(13):3209–3214. doi: 10.1002/j.1460-2075.1984.tb02280.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spielman R. S., Lee J., Bodmer W. F., Bodmer J. G., Trowsdale J. Six HLA-D region alpha-chain genes on human chromosome 6: polymorphisms and associations of DC alpha-related sequences with DR types. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3461–3465. doi: 10.1073/pnas.81.11.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Travers P., Blundell T. L., Sternberg M. J., Bodmer W. F. Structural and evolutionary analysis of HLA-D-region products. Nature. 1984 Jul 19;310(5974):235–238. doi: 10.1038/310235a0. [DOI] [PubMed] [Google Scholar]
  30. Trowsdale J., Kelly A., Lee J., Carson S., Austin P., Travers P. Linkage map of two HLA-SB beta and two HLA-SB alpha-related genes: an intron in one of the SB beta genes contains a processed pseudogene. Cell. 1984 Aug;38(1):241–249. doi: 10.1016/0092-8674(84)90546-4. [DOI] [PubMed] [Google Scholar]
  31. Trowsdale J., Lee J., Carey J., Grosveld F., Bodmer J., Bodmer W. Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1972–1976. doi: 10.1073/pnas.80.7.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]

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