title: Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.
abstract: SPG7 is a newly identified gene involved in an autosomal recessive form of hereditary spastic paraplegia (HSP), a genetically heterogeneous group of neurodegenerative disorders. This gene encodes a protein characterized as a nuclear-encoded mitochondrial metalloprotease. The present report describes the genomic structure of the SPG7 gene. It is organized into 17 exons ranging from 78 to 242 bp and spans approximately 52 kb within three overlapping cosmids. The exon/intron boundaries and all splice junctions are consistent with the published consensus sequences for donor and acceptor sites. The provided genomic structure of SPG7 should facilitate the screening for mutations in this gene in patients with HSP and other related mitochondrial disease syndromes. SPG7 has been mapped to chromosome 16q24.3, a region of frequent loss of heterozygosity (LOH) seen in sporadic breast and prostate cancer. We have performed single-strand conformation polymorphism analysis of ten exons of this gene in a number of sporadic breast cancer samples showing LOH at 16q24.3. No mutations were detected; only single nucleotide polymorphisms were observed in exon 11, intron 7, intron 10 and intron 12. An expression analysis study has revealed the differential expression of SPG7 mRNA in various tissues and at different developmental stages.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, Australia. csettasatian@medicine.adelaide.edu.au
authors.forename: C
authors.initials: C
authors.lastname: Settasatian
authors.forename: S A
authors.initials: SA
authors.lastname: Whitmore
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: R L
authors.initials: RL
authors.lastname: Bilton
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: D F
authors.initials: DF
authors.lastname: Callen
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D017398:Alternative Splicing; D001483:Base Sequence; D015152:Blotting, Northern; D002885:Chromosomes, Human, Pair 16; D003360:Cosmids; D005091:Exons; D006801:Humans; D007438:Introns; D008666:Metalloendopeptidases / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities