title: Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes.
abstract: Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.
authors.affiliation: Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112, USA.
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: E D
authors.initials: ED
authors.lastname: Green
authors.forename: H
authors.initials: H
authors.lastname: Massa
authors.forename: B J
authors.initials: BJ
authors.lastname: Trask
authors.forename: C A
authors.initials: CA
authors.lastname: Morris
authors.forename: M T
authors.initials: MT
authors.lastname: Keating
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004252:DNA Mutational Analysis; D015342:DNA Probes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004549:Elastin / Q000235:genetics; D019204:GTP-Binding Proteins; D017353:Gene Deletion; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D011506:Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015293:Transducin / Q000235:genetics; D018980:Williams Syndrome / Q000235:genetics*
chemical_list: C116387:BCL7B protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015342:DNA Probes; D004268:DNA-Binding Proteins; C116385:MLXIPL protein, human; D008565:Membrane Proteins; D011506:Proteins; C402405:TBL2 protein, human; D004549:Elastin; D019204:GTP-Binding Proteins; D015293:Transducin