A complete physical contig and partial transcript map of the Williams syndrome critical region.

Williams syndrome (WS) is a contiguous gene syndrome caused by hemizygosity for a chromosomal deletion at 7q11.23. The range of phenotypes includes mental retardation, dysmorphic facies, heart abnormalities, short stature, a specific cognitive profile, hyperacusis, and infantile hypercalcaemia. To identify all the deleted genes, we have constructed a detailed physical map and complete BAC/PAC contig of the critical region, extending a distance of approximately 2 Mb and delimited by the nondeleted markers D7S1816 and D7S489A. Somatic cell hybrids of WS patients were made and used to define the centromeric and telomeric deletion breakpoints, enabling the size of the WS deletion to be defined as approximately 1.4 Mb. Genes previously mapped to the region have been located on the contig, and we have isolated eight transcripts, two of which have been characterized as the genes CPETR1 and CPETR2. This contig and expressed sequence map will form the basis for the construction of a complete transcription map of the deleted region and will enable genotype-phenotype correlations to be attempted to identify the individual components of WS.

[1]  P. Kaplan,et al.  Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion. , 1998, Genomics.

[2]  C. Morris,et al.  A novel human gene, WSTF, is deleted in Williams syndrome. , 1998, Genomics.

[3]  B. Trask,et al.  Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes , 1998, Human Genetics.

[4]  A. Schinzel,et al.  High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions. , 1998, Human molecular genetics.

[5]  U. Francke,et al.  A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. , 1998, Human molecular genetics.

[6]  C. Inglehearn,et al.  Analysis of a human gene homologous to rat ventral prostate.1 protein. , 1997, Genomics.

[7]  J. Katahira,et al.  Clostridium perfringens Enterotoxin Utilizes Two Structurally Related Membrane Proteins as Functional Receptors in Vivo * , 1997, The Journal of Biological Chemistry.

[8]  E. Green,et al.  A p47-phox pseudogene carries the most common mutation causing p47-phox- deficient chronic granulomatous disease. , 1997, The Journal of clinical investigation.

[9]  S. Scherer,et al.  PMS2-related genes flank the rearrangement breakpoints associated with Williams syndrome and other diseases on human chromosome 7. , 1997, Genomics.

[10]  S. Scherer,et al.  Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome. , 1997, American journal of human genetics.

[11]  R. Nusse,et al.  A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. , 1997, Human molecular genetics.

[12]  S. Scherer,et al.  Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. , 1996, Genomics.

[13]  Mark Noble,et al.  LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition , 1996, Cell.

[14]  A. Marks.  Cellular functions of immunophilins. , 1996, Physiological reviews.

[15]  M. Tassabehji,et al.  LIM–kinase deleted in Williams syndrome , 1996, Nature Genetics.

[16]  U. Francke,et al.  The gene for replication factor C subunit 2 (RFC2) is within the 7q11.23 Williams syndrome deletion. , 1996, American journal of human genetics.

[17]  Cécile Fizames,et al.  A comprehensive genetic map of the human genome based on 5,264 microsatellites , 1996, Nature.

[18]  C. Morris,et al.  Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. , 1995, American journal of human genetics.

[19]  L. Shaffer,et al.  Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. , 1995, American journal of human genetics.

[20]  C. Morris,et al.  Williams syndrome: autosomal dominant inheritance. , 1993, American journal of medical genetics.

[21]  L. Sadler,et al.  The Williams syndrome: evidence for possible autosomal dominant inheritance. , 1993, American journal of medical genetics.

[22]  Patricia Spallone,et al.  Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome , 1993, Nature Genetics.

[23]  A. Poustka,et al.  A strategy for the selection of transcribed sequences in the Xq28 region. , 1992, Human molecular genetics.

[24]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[25]  D. Le Paslier,et al.  Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Riley,et al.  A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. , 1990, Nucleic acids research.

[27]  J. Riley,et al.  A 3.5 genome equivalent multi access YAC library: construction, characterisation, screening and storage. , 1990, Nucleic acids research.

[28]  A. Beuren,et al.  Supravalvular Aortic Stenosis in Association with Mental Retardation and a Certain Facial Appearance , 1962, Circulation.

[29]  J. B. Lowe,et al.  Supravalvular Aortic Stenosis , 1961, Circulation.

[30]  A. Karmiloff-Smith,et al.  Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. , 1999, American journal of human genetics.