The Normal Copy of the GOS19-3 -Associated,CpG Island-Containing,Upstream Sequence Is Downstream of GOS19-2/MIP1 α in Association With a TRE17 Oncogene

The GOS19-1/MIP1α and GOS19-2/MIP1α genes locate to human chromosomes 17q and encode similar copies of the β-chemokine GOS19/MIP1α. The GOS19-3 gene, present in 1 in 4 humans, is a 5′ truncated version of GOS19-2; a CpG island-containing upstream sequence (CpG-US), rich in potential transcriptional activation motifs, replaces much of the first intron and the first exon. Sequences hybridizing with the CpG-US sequence, normally exist in all human genomes. Thus, it appears that there has been recombination between a duplicated GOS19 gene and a duplicated CpG-US-like sequence. We have isolated sequences hybridizing with the CpG-US sequence from a human genomic library in bacteriophage lambda. Restriction mapping and sequencing shows a CpG-US-like sequence ̃8 kb downstream of GOS19-2 (hence, named CpG-DS sequence). The sequence is contiguous with a TRE17 oncogene-associated sequence (GenBank locus HSTRE175). Members of the TRE17 family are known to locate to chromosome 17q (Onno et al., 1993b), and have sequence characteristics suggestive of positive Darwinian selection. Linkage with a TRE17 oncogene may have arisen by recombination and imply no functional relationship. However, it is possible that the CpG-DS may normally regulate TRE17 expression. PCR and sequencing studies indicate the close proximity of other chemokine-related sequences in the 17q11.2 region.