Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21
- Univ. of Chicago Pritzker School of Medicine, IL (United States); and others
Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity. The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type I IFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16{sup INK4A}) and CDKN2B (p15{sup INK4B}), and several CpG islands. In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2.5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3{prime} untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8-kDa protein in the pet gene (coding for cytochrome bc{sub 1} complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequences of this gene suggest that it codes for the MTAP enzyme. 35 refs., 4 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- FG02-86ER60408
- OSTI ID:
- 96604
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, Issue 14; Other Information: PBD: 3 Jul 1995
- Country of Publication:
- United States
- Language:
- English
Similar Records
Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22
The use of methylthioadenosine phosphorylase activity to select for human chromosome 9 in interspecies and intraspecies hybrid cells