LONG-RANGE RESTRICTION MAP OF THE VONHIPPEL-LINDAU GENE REGION ON HUMAN CHROMOSOME-3P

Von Hippel-Lindau disease is a heritable tumour syndrome caused by the loss of the function of a tumour suppressor gene on the short arm of human chromosome 3. The interval RAF1-D3S18 (3p25-3p26) has been ident ified by genetic linkage studies to harbour the von Hippel-Lindau gene . We have constructed a long range restriction map of this region and have succeeded in demonstrating the physical linkage of loci D3S726 (D NA probe LIB31-38), D3S18 (c-LIB-1, L162E5), D3S601 (LIB19-63) and D3S 587 (LIB12-48). Since multipoint analysis has located D3S601 proximal to D3S726, the physical map should be oriented with D3S726 towards the telomere. The order and distances of probes within the von Hippel-Lin dau gene region is as follows: telomere - LIB31-38 - (<280 kb) - c-LIB -1 - (overlapping) - L162E5 - (900-1600 kb) - (LIB19-63, LIB12-48) - c entromere. In tissues that included blood, semen and Epstein-Barr-viru s-transformed lymphocytes, we detected a putative CpG island flanking D3S18.