ANALYSIS OF EXON INTRON STRUCTURE AND 400 KB OF GENOMIC SEQUENCE SURROUNDING THE 5'-PROMOTER AND 3'-TERMINAL ENDS OF THE HUMAN GLYPICAN 3 (GPC3) GENE/

GPC3, the gene modified in the Simpson-Golabi-Behmel gigantism/overgro wth syndrome (SGBS), is shown to span more than 500 kb of genomic sequ ence, with the transcript beginning 197 bp 5' of the translational sta rt site. The Xq26.1 region containing GPC3 as the only known gene has been extended to >900 kb by sequence analysis of flanking BAC clones. Two GC isochores (40.6 and 42.6% GC) are observed at the 5' and 3' end s of the locus, with a large repertoire of repetitive sequences that i ncludes an unusual cluster of four L1 elements >92% identical over 2.8 kb. Eight exons, accounting for the full 2.4-kb GPC3 cDNA, have been sequenced along with neighboring intronic regions. PCR assays have bee n developed to amplify each exon and exon/intron junction sequence, to help discriminate instances of SGBS among individuals with overgrowth syndromes and to facilitate mutational analysis of lesions in the gen e. (C) 1997 Academic Press.