title: Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma.
abstract: Mutations in the human PAX3 gene have previously been associated with two distinct diseases, Waardenburg syndrome and alveolar rhabdomyosarcoma. In this report we establish that the normal human PAX3 gene is encoded by 8 exons. Intron-exon boundary sequences were obtained for PAX3 exons 5, 6, 7, and 8 and together with previous work provide the complete genomic sequence organization for PAX3. Difficulties in obtaining overlapping genomic clone coverage of PAX3 were circumvented in part by RARE cleavage mapping, which showed that the entire PAX3 gene spans 100 kb of chromosome 2. Sequence analysis of the last intron of PAX3, which contains the previously mapped t(2;13)(q35;q14) translocation breakpoints of alveolar rhabdomyosarcoma, revealed the presence of a pair of inverted Alu repeats and a pair of inverted (GT)n-rich microsatellite repeats within a 5-kb region. This work establishes the complete structure of PAX3 and will permit high-resolution analyses of this locus for mutations associated with Waardenburg syndrome, alveolar rhabdomyosarcoma, and other phenotypes for which PAX3 may be a candidate locus.
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Macina
authors.forename: F G
authors.initials: FG
authors.lastname: Barr
authors.forename: N
authors.initials: N
authors.lastname: Galili
authors.forename: H C
authors.initials: HC
authors.lastname: Riethman
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012091:Repetitive Sequences, Nucleic Acid; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse