THE NORMAL COPY OF THE GOS19-3-ASSOCIATED, CPG ISLAND-CONTAINING, UPSTREAM SEQUENCE IS DOWNSTREAM OF GOS19-2 MIP1-ALPHA IN ASSOCIATION WITHA TRE17 ONCOGENE/

The G0S19-1/MIP1 alpha and G0S19-2/MIP1 alpha genes locate to human ch romosomes 17q and encode similar copies of the beta-chemokine G0S19/MI P1 alpha. The GOS19-3 gene, present in 1 in 4 humans, is a 5' truncate d version of G0S19-2; a CpG island-containing upstream sequence (CpG-U S), rich in potential transcriptional activation motifs, replaces much of the first intron and the first exon. Sequences hybridizing with th e CpG-US sequence, normally exist in all human genomes. Thus, it appea rs that there has been recombination between a duplicated G0S19 gene a nd a duplicated CpG-US-like sequence. We have isolated sequences hybri dizing with the CpG-US sequence from a human genomic library in bacter iophage lambda. Restriction mapping and sequencing shows a CpG-US-like sequence similar to 8 kb downstream of G0S19-2 (hence, named CpG-DS s equence). The sequence is contiguous with a TRE17 oncogene-associated sequence (GenBank locus HSTRE175). Members of the TRE17 family are kno wn to locate to chromosome 17q (Onno et at, 1993b), and have sequence characteristics suggestive of positive Darwinian selection. Linkage wi th a TRE17 oncogene may have arisen by recombination and imply no func tional relationship. However, it is possible that the CpG-DS may norma lly regulate TRE17 expression. PCR and sequencing studies indicate the close proximity of other chemokine-related sequences in the 17q11.2 r egion.