Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 Mar;74(3):1147–1151. doi: 10.1073/pnas.74.3.1147

Assignment of the major histocompatibility complex to a region of the short arm of human chromosome 6.

U Francke, M A Pellegrino
PMCID: PMC430627  PMID: 265561

Abstract

Interspecific cell hybrids containing defined parts of human chromosome 6 were used for regional mapping of gene loci previously assigned to chromosome 6: the human leukocyte antigens (HLA) region, phosphoglucomutase-3 (PGM3; alpha-D-glucose-1,6-bisphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1) and malic enzyme-1 [malic dehydrogenase(decarboxylating) (NADP+), L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 1.1.1.40]. Human fibroblasts containing a balanced reciprocal translocation between the short arms of chromosome 1 and chromosome 6--designated t(1;6) (p3200;p2100)--were fused with an established line of Chinese hamster cells. Hybrid clones with segregating human chromosomes were studied for the presence of the translocation chromosomes 1T and 6T and their normal homologues 1 and 6. Six clones that had retained 1T, three clones with 6T, and three clones with 6 and 6T as controls, were analyzed by a microabsorption test for expression of the allelic antigens HLA-A2 and HLA-A3, both of which were present on the human parental cells. HLA-A2 segregated with the 1T translocation chromosome and HLA-A3 with the normal chromosome 6. Hybrid clones with 6T did not possess an HLA-A gene. In contrast, human PGM3 and malic enzyme-1 expression segregated with the 6T translocation chromosome. These results indicate the location of the major histocompatibility complex in region 6p2100 leads to 6pter of the short arm of chromosome 6. The genes for PGM2 and malic enzyme-1 map in region 6p2100 leads to 6qter. The HLA:PGM3 genetic map distance is 15 centimorgans in males, as established by family studies. This allows rather precise mapping of both loci because HLA is distal and PGM3 proximal to the translocation breakpoint in band 6p2100. The findings are consistent with earlier conclusions that HLA is proximal to 6p22. Quantitative correlation between the density of HLA antigens on the hybrid cell surface and the number of copies of the respective HLA gene-bearing chromosome suggests a gene dose effect for cell surface molecules, as it exists for intracellular gene products.

Full text

PDF
1149

Images in this article

Selected References

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

  1. Chen T. R., McMorris F. A., Creagan R., Ricciuti F., Tischfield J., Ruddle F. Assignment of the genes for malate oxidoreductase decarboxylating to chromosome 6 and peptidase B and lactate dehydrogenase B to chromosome 12 in man. Am J Hum Genet. 1973 Mar;25(2):200–207. [PMC free article] [PubMed] [Google Scholar]
  2. Cohen P. T., Omenn G. S. Human malic enzyme: high-frequency polymorphism of the mitochondrial form. Biochem Genet. 1972 Dec;7(3):303–311. doi: 10.1007/BF00484830. [DOI] [PubMed] [Google Scholar]
  3. Faber H. E., Kucherlapati R. S., Poulik M. D., Ruddle F. H., Smithies O. beta2-microglobulin locus on human chromosome 15. Somatic Cell Genet. 1976 Mar;2(2):141–153. doi: 10.1007/BF01542627. [DOI] [PubMed] [Google Scholar]
  4. Ferrone S., Pellegrino M. A., Reisfeld R. A. A rapid method for direct HL-A typing of cultured lymphoid cells. J Immunol. 1971 Aug;107(2):613–615. [PubMed] [Google Scholar]
  5. Francke U., Busby N., Shaw D., Hansen S., Brown M. G. Intrachromosomal gene mapping in man: assignment of nucleoside phosphorylase to region 14cen leads to 14q21 by interspecific hybridization of cells with a t(X;14) (p22;q21) translocation. Somatic Cell Genet. 1976 Jan;2(1):27–40. doi: 10.1007/BF01539240. [DOI] [PubMed] [Google Scholar]
  6. Francke U. The human gene for beta glucuronidase is on chromosome 7. Am J Hum Genet. 1976 Jul;28(4):357–362. [PMC free article] [PubMed] [Google Scholar]
  7. George D. L., Francke U. Gene dose effect: regional mapping of human nuceloside phosphorylase on chromosome 14. Science. 1976 Nov 19;194(4267):851–852. doi: 10.1126/science.824731. [DOI] [PubMed] [Google Scholar]
  8. Hultén M. Chiasma distribution at diakinesis in the normal human male. Hereditas. 1974;76(1):55–78. doi: 10.1111/j.1601-5223.1974.tb01177.x. [DOI] [PubMed] [Google Scholar]
  9. Jongsma A., van Someren H., Westerveld A., Hagemeijer A., Pearson P. Localization of genes on human chromosomes by studies of human-Chinese hamster somatic cell hybrids. Assignment of PGM3 to chromosome C6 and regional mapping of the PGD, PGM1 and pep-C genes on chromosome A1. Humangenetik. 1973 Dec 10;20(3):195–202. doi: 10.1007/BF00385730. [DOI] [PubMed] [Google Scholar]
  10. Lamm L. U., Friedrich U., Petersen C. B., Jorgensen J., Nielsen J., Therkelsen A. J., Kissmeyer-Nielsen F. Assignment of the major histocompatibility complex to chromosome No. 6 in a family with a pericentric inversion. Hum Hered. 1974;24(3):273–284. doi: 10.1159/000152660. [DOI] [PubMed] [Google Scholar]
  11. Lamm L. U., Svejgaard A., Kissmeyer-Nielsen F. PGM3: HL-A is another linkage in man. Nat New Biol. 1971 May 26;231(21):109–110. doi: 10.1038/newbio231109a0. [DOI] [PubMed] [Google Scholar]
  12. Ott J., Hecht F., Linder D., Lovrien E. W., McCaw B. K. Human centromere mapping using teratoma data. Birth Defects Orig Artic Ser. 1976;12(7):396–398. doi: 10.1159/000130641. [DOI] [PubMed] [Google Scholar]
  13. Pellegrino M. A., Ferrone S., Pellegrino A. A simple microabsorption technique for HL-A typing. Proc Soc Exp Biol Med. 1972 Feb;139(2):484–488. doi: 10.3181/00379727-139-36169. [DOI] [PubMed] [Google Scholar]
  14. SPENCER N., HOPKINSON D. A., HARRIS H. PHOSPHOGLUCOMUTASE POLYMORPHISM IN MAN. Nature. 1964 Nov 21;204:742–745. doi: 10.1038/204742a0. [DOI] [PubMed] [Google Scholar]
  15. Smith M., Gold P., Freedman S. O., Shuster J. Studies of the linkage relationship of beta-2-microglobulin in man-mouse somatic cell hybrids. Ann Hum Genet. 1975 Jul;39(1):21–31. doi: 10.1111/j.1469-1809.1975.tb00104.x. [DOI] [PubMed] [Google Scholar]
  16. Weitkamp L. R., Guttormsen S. A., Greendyke R. M. Genetic linkage between a locus for 6-PGD and the Rh locus: evaluation of possible heterogeneity in the recombination fraction between sexes and among families. Am J Hum Genet. 1971 Sep;23(5):462–470. [PMC free article] [PubMed] [Google Scholar]
  17. van Someren H., Beijersbergen van Henegouwen H., Los W., Wurzer-Figurelli E., Doppert B., Vervloet M., Meera Khan P. Enzyme electrophoresis on cellulose acetate gel. II. Zymogram patterns in man-Chinese hamster somatic cell hybrids. Humangenetik. 1974;25(3):189–201. doi: 10.1007/BF00281426. [DOI] [PubMed] [Google Scholar]
  18. van Someren H., Westerveld A., Hagemeijer A., Mees J. R., Meera Khan P., Zaalberg O. B. Human antigen and enzyme markers in man-Chinese hamster somatic cell hybrids: evidence for synteny between the HL-A, PGM3, ME1, and IPO-B loci. Proc Natl Acad Sci U S A. 1974 Mar;71(3):962–965. doi: 10.1073/pnas.71.3.962. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES