B. Hurle et al., Physical mapping of the mouse tilted locus identifies an association between human deafness loci DFNA6/14 and vestibular system development, GENOMICS, 77(3), 2001, pp. 189-199
The tilted (tlt) mouse carries a recessive mutation causing vestibular dysf
unction. The defect in tlt homozygous mice is limited to the utricle and sa
ccule 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 t
wo 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 gene
tic map, assembled a BAC contig spanning the tlt locus, and developed a com
prehensive comparative map between mouse and human. We have determined the
position of tlt relative to 17 mouse chromosome 5 genes with orthologous lo
ci in the human 4p16.3-p15 region. This analysis identified an inversion be
tween the mouse and human genomes that places tlt and DFNA6/14 in close pro
ximity.