title: Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9.
abstract: Previously we identified a partial human cDNA for a novel cochlear transcript, hCoch-5B2 (HGMW-approved symbol D14S564E), using subtractive hybridization techniques. Herein we report isolation and characterization of both human and mouse (D12H14S564E) cDNAs for Coch-5B2. Full-length Coch5B2 deduced amino acid sequences reveal a very high degree of conservation in the coding region (89% nucleotide and 94% amino acid identity and a potential signal peptide and two regions of extensive homology to the collagen-binding type A domains of von Willebrand factor, also present in other secreted proteins, including extracellular matrix components. High levels of hCoch-5B2 expression are seen only in human fetal inner ear structures, cochlea, and vestibule, among a large panel of human fetal and adult tissues. Coch-5B2 expression in the mouse is more widespread than in the human, with message detected in mouse adult spleen, cerebrum, cerebellum/medulla, and thymus. In both species very low level expression is detected in total eye. More specifically, mouse retina shows a higher level of mCoch-5B2 message than sclera and choroid. We have mapped hCoch-5B2 to human 14q11.2-q13 by somatic cell hybrid analysis and FISH and, more precisely, using radiation hybrids to a region of markers linked to DFNA9, a nonsyndromic autosomal dominant sensorineural hearing loss with vestibular defects. Furthermore, we detect hCoch-5B2 on three overlapping YACs, two of which also contain one of the markers linked to DFNA9. mCoch-5B2 was genetically mapped in the mouse to chromosome 12, in a region of homologous synteny with human 14q11.2-q13, which contains the asp1 (audiogenic seizure prone) locus in the mouse.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: N G
authors.initials: NG
authors.lastname: Robertson
authors.forename: A B
authors.initials: AB
authors.lastname: Skvorak
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.forename: S
authors.initials: S
authors.lastname: Weremowicz
authors.forename: K R
authors.initials: KR
authors.lastname: Johnson
authors.forename: K A
authors.initials: KA
authors.lastname: Kovatch
authors.forename: J F
authors.initials: JF
authors.lastname: Battey
authors.forename: F R
authors.initials: FR
authors.lastname: Bieber
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003053:Cochlear Duct / Q000378:metabolism; D018076:DNA, Complementary; D003638:Deafness / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C110668:COCH protein, human; C491729:Coch protein, mouse; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D011506:Proteins