Abstract
Four DNA sequences that reveal restriction fragment length polymorphisms (RFLPs) on the short arm of human chromosome 6 have been identified. Two of these sequences were isolated from recombinant DNA libraries enriched for DNA from human chromosome 6, one was isolated as a subclone from a human DNA segment having homology to an HLA class I sequence, and one was isolated by virtue of its homology to part of the insulin gene. Genetic linkage was determined among these four polymorphic sequences and several genes known to be on chromosome 6: glyoxylase I (GLO1), HLA-DR alpha, HLA-DQ alpha, and HLA-B. Additionally, two of the four RFLPs were regionally localized by using 53 deletion cell lines that had been typed for HLA-A, -B, and -DR, and for glyoxylase I. A genetic map of the short arm of chromosome 6 has been constructed on the basis of linkage studies with the eight markers. The map spans a minimum of 60 recombinational units and will be useful in the study of HLA-associated diseases.
Full text
PDF![3909](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5dd/323634/5a75cdc7b70f/pnas00315-0350.png)
![3910](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5dd/323634/b2f2867042a5/pnas00315-0351.png)
![3911](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5dd/323634/777811f59390/pnas00315-0352.png)
![3912](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5dd/323634/9dcd52fc6f33/pnas00315-0353.png)
![3913](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5dd/323634/c24967907d8e/pnas00315-0354.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Auffray C., Ben-Nun A., Roux-Dosseto M., Germain R. N., Seidman J. G., Strominger J. L. Polymorphism and complexity of the human DC and murine I-A alpha chain genes. EMBO J. 1983;2(1):121–124. doi: 10.1002/j.1460-2075.1983.tb01392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Auffray C., Kuo J., DeMars R., Strominger J. L. A minimum of four human class II alpha-chain genes are encoded in the HLA region of chromosome 6. Nature. 1983 Jul 14;304(5922):174–177. doi: 10.1038/304174a0. [DOI] [PubMed] [Google Scholar]
- Bakker E., Pearson P. L., Meera Khan P., Schreuder G. M., Madan K. Orientation of major histocompatibility (MHC) genes relative to the centromere of human chromosome 6. Clin Genet. 1979 Feb;15(2):198–202. doi: 10.1111/j.1399-0004.1979.tb01762.x. [DOI] [PubMed] [Google Scholar]
- Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bell G. I., Pictet R., Rutter W. J. Analysis of the regions flanking the human insulin gene and sequence of an Alu family member. Nucleic Acids Res. 1980 Sep 25;8(18):4091–4109. doi: 10.1093/nar/8.18.4091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boncinelli E., Goyns M. H., Scotto L., Simeone A., Harris P., Kellow J. E., Young B. D. Isolation of a series of HLA class I clones from a human chromosome 6 genomic library. Mol Biol Med. 1984 Feb;2(1):1–14. [PubMed] [Google Scholar]
- Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
- Cann H. M., Ascanio L., Paul P., Marcadet A., Dausset J., Cohen D. Polymorphic restriction endonuclease fragment segregates and correlates with the gene for HLA-B8. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1665–1668. doi: 10.1073/pnas.80.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cavenee W., Leach R., Mohandas T., Pearson P., White R. Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13. Am J Hum Genet. 1984 Jan;36(1):10–24. [PMC free article] [PubMed] [Google Scholar]
- DeMars R., Chang C. C., Rudersdorf R. A. Dissection of the D-region of the human major histocompatibility complex by means of induced mutations in a lymphoblastoid cell line. Hum Immunol. 1983 Oct;8(2):123–139. doi: 10.1016/0198-8859(83)90008-3. [DOI] [PubMed] [Google Scholar]
- DeMars R., Chang C. C., Shaw S., Reitnauer P. J., Sondel P. M. Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens. Hum Immunol. 1984 Oct;11(2):77–97. doi: 10.1016/0198-8859(84)90047-8. [DOI] [PubMed] [Google Scholar]
- DeMars R., Rudersdorf R., Chang C., Petersen J., Strandtmann J., Korn N., Sidwell B., Orr H. T. Mutations that impair a posttranscriptional step in expression of HLA-A and -B antigens. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8183–8187. doi: 10.1073/pnas.82.23.8183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erlich H. A., Stetler D., Saiki R., Gladstone P., Pious D. Mapping of the genes encoding the HLA-DR alpha chain and the HLA-related antigens to a chromosome 6 deletion by using genomic blotting. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2300–2304. doi: 10.1073/pnas.80.8.2300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
- Kan Y. W., Dozy A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5631–5635. doi: 10.1073/pnas.75.11.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kavathas P., Bach F. H., DeMars R. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4251–4255. doi: 10.1073/pnas.77.7.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kavathas P., DeMars R., Bach F. H. Hemizygous HLA mutants of lymphoblastoid cells: a new cell type for histocompatibility testing. Hum Immunol. 1980 Dec;1(4):317–324. doi: 10.1016/0198-8859(80)90107-x. [DOI] [PubMed] [Google Scholar]
- Kömpf J., Bissbort S., Gussmann S., Ritter H. Polymorphism of red cell glyoxalase I (EI: 4.4.1.5); a new genetic marker in man. Investigation of 169 mother-child combinations. Humangenetik. 1975;27(2):141–143. doi: 10.1007/BF00273329. [DOI] [PubMed] [Google Scholar]
- Lange K., Boehnke M. How many polymorphic genes will it take to span the human genome? Am J Hum Genet. 1982 Nov;34(6):842–845. [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
- Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
- Mi M. P., Morton N. E. Blood factor association. Vox Sang. 1966 Jul-Aug;11(4):434–449. doi: 10.1111/j.1423-0410.1966.tb04240.x. [DOI] [PubMed] [Google Scholar]
- Mohandas T., Sparkes R. S., Shulkin J. D., Sparkes M. C., Moedjono S. Assignment of PGM3 to the long arm of human chromosome 6. Studies using Chinese hamster X human cell hybrids containing a human 6/15 translocation. Cytogenet Cell Genet. 1980;28(1-2):116–120. doi: 10.1159/000131519. [DOI] [PubMed] [Google Scholar]
- Orr H. T., Bach F. H., Ploegh H. L., Strominger J. L., Kavathas P., DeMars R. Use of HLA loss mutants to analyse the structure of the human major histocompatibility complex. Nature. 1982 Apr 1;296(5856):454–456. doi: 10.1038/296454a0. [DOI] [PubMed] [Google Scholar]
- Orr H. T., DeMars R. Class I-like HLA genes map telomeric to the HLA-A2 locus in human cells. Nature. 1983 Apr 7;302(5908):534–536. doi: 10.1038/302534a0. [DOI] [PubMed] [Google Scholar]
- Orr H. T., DeMars R. Mapping of class I DNA sequences within the human major histocompatibility complex. Immunogenetics. 1983;18(5):489–502. doi: 10.1007/BF00364390. [DOI] [PubMed] [Google Scholar]
- 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]
- Ryder L. P., Svejgaard A., Dausset J. Genetics of HLA disease association. Annu Rev Genet. 1981;15:169–187. doi: 10.1146/annurev.ge.15.120181.001125. [DOI] [PubMed] [Google Scholar]
- Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Ullrich A., Dull T. J., Gray A., Brosius J., Sures I. Genetic variation in the human insulin gene. Science. 1980 Aug 1;209(4456):612–615. doi: 10.1126/science.6248962. [DOI] [PubMed] [Google Scholar]
- White R., Leppert M., Bishop D. T., Barker D., Berkowitz J., Brown C., Callahan P., Holm T., Jerominski L. Construction of linkage maps with DNA markers for human chromosomes. Nature. 1985 Jan 10;313(5998):101–105. doi: 10.1038/313101a0. [DOI] [PubMed] [Google Scholar]
- Whitehead A. S., Colten H. R., Chang C. C., Demars R. Localization of the human MHC-linked complement genes between HLA-B and HLA-DR by using HLA mutant cell lines. J Immunol. 1985 Jan;134(1):641–643. [PubMed] [Google Scholar]
- Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]