Nucleic Acids Research, 1990, Vol. 18, No. 11 3261
© 1990
GENOME STRUCTURE AND MAPPING |
Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q
Laboratory of Pathology, National Cancer Instiute, Nation Institutes of Health Bethesda, MD 20892, USA 1Bernhard Nocht Institute for Tropical Medicine Bernhard Nocht Strasse 74, D–2000 Hamburg, 4, FRG 2Department of Internal Medicine, University of Minnesota Hospital nad clinic Harvard St and E. River Rd, Minneapolis, MN 55455 3Laboratory of Biochemistry, National Cancer Institute,National Institutes of Health Bethesda, MD 20892 4Department of Pathology, Brigham and Women's Hospital, Harvard medical School 75 Francis St, Boston, MA 02115 5Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National institutes of Health Bethesda, MD 20892, USA
*To Whom correspondence should be addressed
Received February 23, 1990. Accepted May 4, 1990.
Mitogenic stimulation of resting T cells results in the de novo transcription of a large number of genes including those encoding regulatory molecules such as lymphokines. The genomlc organization of two newly described induced lymphokine genes, 464.1 and 744.1, has been determined. 464.1 and 744.1 appear to be the human homologues of the recently cloned murine macrophage inflammatory proteins, MIP–1
and MIP–1/ß, respectively. The 464.1 and 744.1 genes share 55% amino acid homology and demonstrate parallel regulation of induced expression in T cells. It was therefore of interest to observe that these genes are closely linked in the human genome, separated by 14 kb, and are organized in a head to head fashion. Each of the genes is present in an additional nonallelic copy (referred to as 464.2 and 744.2) as part of an apparent amplification unit In the genome of many individuals. The 464.2 gene is expressed and potentially encodes a protein highly related to 464.1, varying in 5 of 92 amino acids. As expected, 464.2 and 744.2 are also closely linked to each other as determined by population linkage disequilibrium studies. Individuals bearing a chromosome with a third amplification event, involving a 464–related gene but not a 744–related gene, are also infrequently observed. These genes are all located on chromosome 17 in bands q11–q21, the region implicated in von Recklinghausen neurofibromatosis (NF1) and in acute promyelocytic leukemia (AML-M3).
+Present address. Department of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA
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