Comparative architectural aspects of regions of conserved synteny on humanchromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1)

Human chromosome 11p15.3 is associated with chromosome aberrations in the B eckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor types including lung cancer and leukemias. To date, only single tumor -relevant genes with linkage to this region (e.g. LMO1) have been found sug gesting that this region may harbor additional potential disease associated genes. Although this genomic area has been studied for years, the exact or der of genes/chromosome markers between D11S572 and the WEE1 gene locus rem ained unclear. Using the FISH technique and PAC clones of the flanking mark ers we determined the order of the genomic markers. Based on these clones w e established a PAC contig of the respective region. To analyse the chromos ome area in detail the synteny of the orthologous region on distal mouse ch romosome 7 was determined and a corresponding mouse clone contig establishe d, proving the conserved order of the genes and markers in both species: "c en-WEE1-D11S2043-ZNF143-RANBP7-CEGF1-ST5-D11S932-LMO1-D11S572-TUB-tel", wit h inverted order of the murine genes with respect to the telomere/centromer e orientation. The region covered by these contigs comprises roughly 1.6 MB in human as well as in mouse. The genomic sequence of the two subregions ( around WEE1 and LMO1) in both species was determined using a shotgun sequen cing strategy. Comparative sequence analysis techniques demonstrate that th e content of repetitive elements seems to decline from centromere to telome re (52.6% to 34.5%) in human and in the corresponding murine region from te lomere to centromere (41.87% to 27.82%). Genomic organisation of the region s around WEE1 and LMO1 was conserved, although the length of gene regions v aried between the species in an unpredictable ratio. CpG islands were found conserved in putative promoter regions of the known genes but also in regi ons which so far have not been described as harboring expressed sequences. Copyright (C) 2001 S. Karger AG, Basel.