Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients

Journal Article · Sun Sep 01 04:00:00 EDT 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0469· OSTI ID:486319

Osborne, L R; Rommens, J; Tsui, Lap-Chee ^[1]

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1. Hospital for Sick Children, Ontario (Canada)

Williams syndrome (WS) is a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Hemizygosity of the elastin (ELN) gene can account for the vascular and connective tissue abnormalities observed in WS patients, but the genes that contribute to features such as infantile hypercalcemia, dysmorphic facies, and mental retardation remain to be identified. In addition, the size of the genomic interval commonly deleted in WS patients has not been established. In this study we report the characterization of a 500-kb region that was determined to be deleted in our collection of WS patients. A detailed physical map consisting of cosmid, P1 artificial chromosomes, and yeast artificial chromosomes was constructed and used for gene isolation experiments. Using the techniques of direct cDNA selection and genomic DNA sequencing, a three known genes (ELN, LIMK1, and RFC2), a novel gene (WSCR1) with homology to RNA-binding proteins, a gene with homology to restin, and four other putative transcription units were identified. LIMK1 is a protein kinase with two repeats of the LIM/double zinc finger motif, and it is highly expressed in brain. RFC2 is the 40-kDa ATP-binding sub-unit of replication factor C, which is known to play a role in the elongation of DNA catalyzed by DNA polymerase {delta} and {epsilon}. LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients. 56 refs., 4 figs., 3 tabs.

• OSTI ID: 486319
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 2 Vol. 36; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
COSMIDS
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
FLUORESCENCE
GENE MUTATIONS
GENE REGULATION
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 7
MENTAL DISORDERS
PATIENTS
PHOSPHOTRANSFERASES
SIZE
TISSUE DISTRIBUTION
TRANSCRIPTION