Mapping cosmid contigs to intervals on chromosome 9q34 by FISH

To date, fifty-seven cosmid contigs, eleven containing known genes and seven containing known markers have been localized by FISH to one of four intervals on chromosome 9q34. A further two genes and five markers have also been mapped but as yet they do not form part of a contig. We have achieved this by using metaphase chromosomes from three lymphoblastoid cell lines with balanced reciprocal translocations. Cell line SD-1 has the characteristic Philadelphia breakpoint at 9q34.1 and cell lines 9T12 and 9T01 both have breakpoints within 9q34.3. Cosmid contigs mapping proximal to the Philadelphia breakpoint include the genes PBX3, FPGS, and PAPPA and the markers D9S61 and D9S62. The genes and markers localized to the interval between the translocation breakpoint for SD-1 and 9T12 include CAN, ABO, DBH, CEL, D9S113, D9S148, D9S64, D9S149, D9S150, D9S10, D9S66 and D9S14. Those localized to the interval between the 9T12 and 9T01 breakpoint include RXRA, COL5A1, D9S298 and D9S67. Finally, those mapping distal to the 9T01 breakpoint include TANI, PAEP, GRINI and D9S207. The flanking markers for the tuberous sclerosis gene on chromosome 9q34 (TSCI) are D9S149 and D9S114. These markers have been mapped on the interval between the SD-1 and 9T12 breakpoint, andmore » therefore contigs from this region are currently being searched for expressed sequences by exon trapping. One such exon which is derived from the D9S10/D9S66 contig shows homology to the VAV proto-oncogene and we are now investigating its potential as a candidate gene.« less