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11161796

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pubmed-article:11161796pubmed:abstractTextTo discover new cochlea-specific genes as candidate genes for nonsyndromic hearing impairment, we searched in The Institute of Genome Research database for expressed sequence tags isolated from the cochlea only. This led to the cloning and characterization of a human gene named melanoma inhibitory activity-like (MIAL; HGMW-approved symbol OTOR alias MIAL) gene. In situ hybridization revealed MIAL expression in a cell layer beneath the sensory epithelium of cochlea and vestibule of human fetal inner ear. No other human tissue, except fetal brain, showed expression of MIAL when analyzed by in situ hybridization or reverse transcription-polymerase chain reaction. The cDNA of the mouse homologue was also cloned and mapped about 80 cM from the top of mouse chromosome 2. In mouse, Mial was also expressed in the cochlea and the vestibule of the inner ear, as well as in brain, eye, limb, and ovary. Expression in mammalian cell cultures showed that MIAL is translated as an approximately 15-kDa polypeptide that is assembled into a covalently linked homodimer, modified by sulfation, and secreted from the cells via the Golgi apparatus. In the human MIAL gene, a frequent polymorphism was discovered in the translation initiation codon (ACG instead of ATG). Of 505 individuals, 48 (9.5%) were ATG/ACG heterozygous and 1 (0.2%) was homozygous for ACG. No MIAL protein was synthesized in cells transfected with cDNA of the ACG allele. The inner ear-restricted expression pattern and the existence of an inactive allele suggest that MIAL may contribute to inner-ear dysfunction in humans.lld:pubmed
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pubmed-article:11161796pubmed:copyrightInfoCopyright 2001 Academic Press.lld:pubmed
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pubmed-article:11161796pubmed:articleTitleIdentification and characterization of an inner ear-expressed human melanoma inhibitory activity (MIA)-like gene (MIAL) with a frequent polymorphism that abolishes translation.lld:pubmed
pubmed-article:11161796pubmed:affiliationDepartment of Medical Genetics, Institute of Medical Biochemistry and Genetics, University of Copenhagen, N, 2200, Denmark.lld:pubmed
pubmed-article:11161796pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11161796pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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