* 425000

GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR, ALPHA SUBUNIT, Y-CHROMOSOMAL; CSF2RY


HGNC Approved Gene Symbol: CSF2RA

Cytogenetic location: Yp11.2     Genomic coordinates (GRCh38): Y:1,268,814-1,325,218 (from NCBI)


TEXT

By in situ hybridization, Gough et al. (1990) showed that the gene for the alpha subunit of the granulocyte-macrophage colony-stimulating factor (CSF2R) maps to the tip of the short arm of the X chromosome and to the short arm of the Y chromosome, with the most likely location being Xpter-p21 (306250) and Ypter-p11.2. Although this information was consistent with the location of the gene in the pseudoautosomal region (PAR), conclusive proof required study of segregation of the locus with respect to its actual phenotype. In a total of 14 informative male meioses, they found 3 recombination events, i.e., in 2 cases, a daughter had inherited the allele from the paternal Y chromosome, and in 1 case, a son had inherited the allele from the paternal X chromosome. Thus, the CSF2R locus is distal to the MIC2 locus (313470, 450000), which shows only about 2.5% recombination with the sexual phenotype and maps close to the PAR boundary. CSF2R was the first gene of known function to be mapped to the PAR, which encompasses about 2,500 kb. Loss of either the X or the Y chromosome is apparent in 25% of acute myeloid leukemias of the M2 subtype (AML-M2), compared with only 1 to 6% of other AML subtypes, suggesting the involvement of a 'recessive oncogene' in the genesis of M2 AMLs. The presumed gene is likely to be in the PAR, because if it were located in the portion of the X chromosome not shared with the Y, then similar loss of the Y chromosome would not be predicted and vice versa. Gough et al. (1990) suggested that CSF2R may be the gene in question. Loss or inactivation of both copies of the gene in a myeloid progenitor cell would be expected to result in a clone of cells unable to respond to GM-CSF, and hence in the relatively undifferentiated phenotype of the M2 form of leukemia.


REFERENCES

  1. Gough, N. M., Gearing, D. P., Nicola, N. A., Baker, E., Pritchard, M., Callen, D. F., Sutherland, G. R. Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region. Nature 345: 734-736, 1990. [PubMed: 1972780, related citations] [Full Text]


Creation Date:
Victor A. McKusick : 9/14/1992
mimadm : 3/11/1994
carol : 9/22/1992
carol : 9/14/1992

* 425000

GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR, ALPHA SUBUNIT, Y-CHROMOSOMAL; CSF2RY


HGNC Approved Gene Symbol: CSF2RA

Cytogenetic location: Yp11.2     Genomic coordinates (GRCh38): Y:1,268,814-1,325,218 (from NCBI)


TEXT

By in situ hybridization, Gough et al. (1990) showed that the gene for the alpha subunit of the granulocyte-macrophage colony-stimulating factor (CSF2R) maps to the tip of the short arm of the X chromosome and to the short arm of the Y chromosome, with the most likely location being Xpter-p21 (306250) and Ypter-p11.2. Although this information was consistent with the location of the gene in the pseudoautosomal region (PAR), conclusive proof required study of segregation of the locus with respect to its actual phenotype. In a total of 14 informative male meioses, they found 3 recombination events, i.e., in 2 cases, a daughter had inherited the allele from the paternal Y chromosome, and in 1 case, a son had inherited the allele from the paternal X chromosome. Thus, the CSF2R locus is distal to the MIC2 locus (313470, 450000), which shows only about 2.5% recombination with the sexual phenotype and maps close to the PAR boundary. CSF2R was the first gene of known function to be mapped to the PAR, which encompasses about 2,500 kb. Loss of either the X or the Y chromosome is apparent in 25% of acute myeloid leukemias of the M2 subtype (AML-M2), compared with only 1 to 6% of other AML subtypes, suggesting the involvement of a 'recessive oncogene' in the genesis of M2 AMLs. The presumed gene is likely to be in the PAR, because if it were located in the portion of the X chromosome not shared with the Y, then similar loss of the Y chromosome would not be predicted and vice versa. Gough et al. (1990) suggested that CSF2R may be the gene in question. Loss or inactivation of both copies of the gene in a myeloid progenitor cell would be expected to result in a clone of cells unable to respond to GM-CSF, and hence in the relatively undifferentiated phenotype of the M2 form of leukemia.


REFERENCES

  1. Gough, N. M., Gearing, D. P., Nicola, N. A., Baker, E., Pritchard, M., Callen, D. F., Sutherland, G. R. Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region. Nature 345: 734-736, 1990. [PubMed: 1972780] [Full Text: https://doi.org/10.1038/345734a0]


Creation Date:
Victor A. McKusick : 9/14/1992

Edit History:
mimadm : 3/11/1994
carol : 9/22/1992
carol : 9/14/1992