The glypicans compose a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans that may play a role in the control of cell division and growth regulation. So far, six members (GPC1-6) of this family are known in vertebrates. We report the construction of a high-resolution 4 Mb sequence-ready BAC/PAC contig of the GPC5/GPC6 gene cluster on chromosome region 13q32. The contig indicates that, like the GPC3/GPC4 genes on Xq26, GPC5 and GPC6 are arranged in tandem array. Both GPC5 and GPC6 are very large genes, with sizes well over 1 Mb. With a size of approximately 2 Mb, GPC5 would be the second largest human gene identified to date. Comparison of the long range gene organisation on 13q and Xq, suggests that these chromosomes share several regions of homology. Mutations and deletions affecting GPC3 are associated with the Simpson-Golabi-Behmel overgrowth syndrome. Mutational analysis of GPC5 and GPC6 in 19 patients with somatic overgrowth failed to reveal pathologic mutations in either of these genes, but identified several coding region polymorphisms.