title: The mouse region syntenic for human spinal muscular atrophy lies within the Lgn1 critical interval and contains multiple copies of Naip exon 5.
abstract: Spinal muscular atrophy (SMA) is a relatively common, autosomal recessively inherited neurodegenerative disorder that maps to human chromosome 5q13. This region of the human genome has an intricate genomic structure that has complicated the evaluation of SMA candidate genes. We have chosen to study the mouse region syntenic for human SMA in the hope that the homologous mouse interval would contain the same genes as human 5q13 on a simpler genomic background. Here, we report the mapping of such a region to mouse chromosome 13 and to the critical interval for Lgn1, a mouse locus responsible for modulating the intracellular replication and pathogenicity of the bacterium Legionella pneumophila. We have generated a mouse YAC contig across the Lgn1/Sma interval and have mapped the two flanking gene markers for the human SMA locus, MAP1B and CCNB1, onto this contig. In addition, we have localized the two SMA candidate genes, SMN and NAIP, to the Lgn1 critical region, making these two genes candidates for the Lgn1 phenotype. Upon subcloning of the YAC contig into P1s and BACs, we have detected a large, low copy number repeat that contains at least one copy of Naip exon 5. Identification of the Lgn1 gene will either provide a novel function for SMN or NAIP or reveal the existence of another, yet uncharacterized gene in the SMA critical region. Mutations in such a gene might help to explain some of the phenotypic variability among the human SMAs.
authors.affiliation: Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA. dietrich@rascal.med.harvard.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Scharf
authors.forename: D
authors.initials: D
authors.lastname: Damron
authors.forename: A
authors.initials: A
authors.lastname: Frisella
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: W F
authors.initials: WF
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005091:Exons / Q000235:genetics; D005808:Genes, Recessive; D006801:Humans; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein