Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human Chromosome 7q11.23

Williams syndrome (WS) is a complex neurodevelopmental disorder arising fro m a microdeletion at Chr band 7q11.23, which results in a hemizygous condit ion for a number of genes. Within this region we have completely characteri zed 200 kb containing the genes LIMK1, WBSCR1, and RFC2. Evidence was also found for WBSCR5 in this region, but not the previously proposed genes WSCR 2 and WSCR6. The syntenic region in mouse was also sequenced (115 kb) and c haracterized, and a comparative sequence analysis with a percent identity p lot (PIP) easily allowed us to identify coding exons. This genomic region i s GC rich (50.1% human, 49.9% mouse) and contains an unusually high abundan ce of repetitive elements consisting primarily of Alu (45.4%, one of the hi ghest levels identified to date) in human, and the B family of SINES (30.6% of the total sequence) in mouse. WBSCR1 corresponds to eukaryotic initiati on factor 4H, identified in rabbit, and is herein found to be constitutivel y expressed in both human and mouse, with two RNA and protein products form ed (exon 5 is alternatively spliced). The transcription pattern of WBSCR5 w as also examined and discussed along with its putative amino acid sequence.