title: Physical mapping of the mouse tilted locus identifies an association between human deafness loci DFNA6/14 and vestibular system development.
abstract: The tilted (tlt) mouse carries a recessive mutation causing vestibular dysfunction. The defect in tlt homozygous mice is limited to the utricle and saccule of the inner ear, which completely lack otoconia. Genetic mapping of tlt placed it in a region orthologous with human 4p16.3-p15 that contains two loci, DFNA6 and DFNA14, responsible for autosomal dominant, nonsyndromic hereditary hearing impairment. To identify a possible relationship between tlt in mice and DFNA6 and DFNA14 in humans, we have refined the mouse genetic map, assembled a BAC contig spanning the tlt locus, and developed a comprehensive comparative map between mouse and human. We have determined the position of tlt relative to 17 mouse chromosome 5 genes with orthologous loci in the human 4p16.3-p15 region. This analysis identified an inversion between the mouse and human genomes that places tlt and DFNA6/14 in close proximity.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, Missouri 63110, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hurle
authors.forename: K
authors.initials: K
authors.lastname: Lane
authors.forename: J
authors.initials: J
authors.lastname: Kenney
authors.forename: L M
authors.initials: LM
authors.lastname: Tarantino
authors.forename: M
authors.initials: M
authors.lastname: Bucan
authors.forename: B H
authors.initials: BH
authors.lastname: Brownstein
authors.forename: D M
authors.initials: DM
authors.lastname: Ornitz
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D020451:Contig Mapping; D003638:Deafness / Q000235:genetics*; D020224:Expressed Sequence Tags; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010037:Otolithic Membrane / Q000002:abnormalities*; D020161:Physical Chromosome Mapping; D014722:Vestibule, Labyrinth / Q000002:abnormalities / Q000502:physiology*