Linkage mapping of the human CSF2 and IL3 genes.
Journal: 1991/July - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 1675789
Abstract:
Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etudé du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.
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Proc Natl Acad Sci U S A 88(11): 4821-4824

Linkage mapping of the human CSF2 and IL3 genes.

Abstract

Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etudé du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.

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  • Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Palaszynski E, et al. Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol. 1983 Jul;131(1):282–287. [PubMed] [Google Scholar]
  • Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola NA, Burgess AW, Dunn AR. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature. 309(5971):763–767. [PubMed] [Google Scholar]
  • Wong GG, Witek JS, Temple PA, Wilkens KM, Leary AC, Luxenberg DP, Jones SS, Brown EL, Kay RM, Orr EC, et al. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. [PubMed] [Google Scholar]
  • Fung MC, Hapel AJ, Ymer S, Cohen DR, Johnson RM, Campbell HD, Young IG. Molecular cloning of cDNA for murine interleukin-3. Nature. 1984 Jan 19;307(5948):233–237. [PubMed] [Google Scholar]
  • Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG, et al. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. [PubMed] [Google Scholar]
  • Donahue RE, Wang EA, Stone DK, Kamen R, Wong GG, Sehgal PK, Nathan DG, Clark SC. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. Nature. 321(6073):872–875. [PubMed] [Google Scholar]
  • Kindler V, Thorens B, de Kossodo S, Allet B, Eliason JF, Thatcher D, Farber N, Vassalli P. Stimulation of hematopoiesis in vivo by recombinant bacterial murine interleukin 3. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1001–1005.[PMC free article] [PubMed] [Google Scholar]
  • Pettenati MJ, Le Beau MM, Lemons RS, Shima EA, Kawasaki ES, Larson RA, Sherr CJ, Diaz MO, Rowley JD. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Proc Natl Acad Sci U S A. 1987 May;84(9):2970–2974.[PMC free article] [PubMed] [Google Scholar]
  • Le Beau MM, Epstein ND, O'Brien SJ, Nienhuis AW, Yang YC, Clark SC, Rowley JD. The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5913–5917.[PMC free article] [PubMed] [Google Scholar]
  • Nienhuis AW, Bunn HF, Turner PH, Gopal TV, Nash WG, O'Brien SJ, Sherr CJ. Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome. Cell. 1985 Sep;42(2):421–428. [PubMed] [Google Scholar]
  • Le Beau MM, Westbrook CA, Diaz MO, Larson RA, Rowley JD, Gasson JC, Golde DW, Sherr CJ. Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science. 1986 Feb 28;231(4741):984–987. [PubMed] [Google Scholar]
  • Dean M, O'Connell P, Leppert M, Park M, Amos JA, Phillips DG, White R, Vande Woude GF. Three additional DNA polymorphisms in the met gene and D7S8 locus: use in prenatal diagnosis of cystic fibrosis. J Pediatr. 1987 Oct;111(4):490–495. [PubMed] [Google Scholar]
  • Lander ES, Green P, Abrahamson J, Barlow A, Daly MJ, Lincoln SE, Newberg LA, Newburg L. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics. 1987 Oct;1(2):174–181. [PubMed] [Google Scholar]
  • Ott J. A computer program for linkage analysis of general human pedigrees. Am J Hum Genet. 1976 Sep;28(5):528–529.[PMC free article] [PubMed] [Google Scholar]
  • Huebner K, Nagarajan L, Besa E, Angert E, Lange BJ, Cannizzaro LA, van den Berghe H, Santoli D, Finan J, Croce CM, et al. Order of genes on human chromosome 5q with respect to 5q interstitial deletions. Am J Hum Genet. 1990 Jan;46(1):26–36.[PMC free article] [PubMed] [Google Scholar]
  • Grimaldi JC, Meeker TC. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood. 1989 Jun;73(8):2081–2085. [PubMed] [Google Scholar]
  • Jaquet K, Kreipe H, Felgner J, Radzun HJ, Parwaresch MR. A BglII RFLP demonstrated for the Il-3 gene in normal human blood cells and leukemias. Nucleic Acids Res. 1989 May 11;17(9):3620–3620.[PMC free article] [PubMed] [Google Scholar]
  • MORTON NE. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318.[PMC free article] [PubMed] [Google Scholar]
  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, Keith TP, Bowden DW, Smith DR, Lander ES, et al. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. [PubMed] [Google Scholar]
  • Barlow DP, Bućan M, Lehrach H, Hogan BL, Gough NM. Close genetic and physical linkage between the murine haemopoietic growth factor genes GM-CSF and Multi-CSF (IL3). EMBO J. 1987 Mar;6(3):617–623.[PMC free article] [PubMed] [Google Scholar]
  • Gough NM, Kelso A. GM-CSF expression is preferential to multi-CSF (IL-3) expression in murine T lymphocyte clones. Growth Factors. 1989;1(4):287–298. [PubMed] [Google Scholar]
  • Rowley JD, Golomb HM, Vardiman JW. Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood. 1981 Oct;58(4):759–767. [PubMed] [Google Scholar]
  • Mitelman F, Nilsson PG, Brandt L, Alimena G, Gastaldi R, Dallapiccola B. Chromosome pattern, occupation, and clinical features in patients with acute nonlymphocytic leukemia. Cancer Genet Cytogenet. 1981 Nov;4(3):197–214. [PubMed] [Google Scholar]
  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. [PubMed] [Google Scholar]
  • Lee WH, Bookstein R, Hong F, Young LJ, Shew JY, Lee EY. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science. 1987 Mar 13;235(4794):1394–1399. [PubMed] [Google Scholar]
  • Zbar B, Brauch H, Talmadge C, Linehan M. Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature. 327(6124):721–724. [PubMed] [Google Scholar]
  • Rose EA, Glaser T, Jones C, Smith CL, Lewis WH, Call KM, Minden M, Champagne E, Bonetta L, Yeger H, et al. Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms' tumor gene. Cell. 1990 Feb 9;60(3):495–508. [PubMed] [Google Scholar]
  • Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. [PubMed] [Google Scholar]
  • Le Beau MM, Pettenati MJ, Lemons RS, Diaz MO, Westbrook CA, Larson RA, Sherr CJ, Rowley JD. Assignment of the GM-CSF, CSF-1, and FMS genes to human chromosome 5 provides evidence for linkage of a family of genes regulating hematopoiesis and for their involvement in the deletion (5q) in myeloid disorders. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):899–909. [PubMed] [Google Scholar]
  • Dean M, Park M, Le Beau MM, Robins TS, Diaz MO, Rowley JD, Blair DG, Vande Woude GF. The human met oncogene is related to the tyrosine kinase oncogenes. Nature. 318(6044):385–388. [PubMed] [Google Scholar]
  • Estivill X, Farrall M, Scambler PJ, Bell GM, Hawley KM, Lench NJ, Bates GP, Kruyer HC, Frederick PA, Stanier P, et al. A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature. 326(6116):840–845. [PubMed] [Google Scholar]
M.M. Shemyakin Institute of Bio-organic Chemistry, Academy of Sciences of the U.S.S.R., Moscow.
M.M. Shemyakin Institute of Bio-organic Chemistry, Academy of Sciences of the U.S.S.R., Moscow.
Abstract
Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etudé du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.
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