title: Refining the DFNB7-DFNB11 deafness locus using intragenic polymorphisms in a novel gene, TMEM2.
abstract: The combined DFNB7-DFNB11 deafness locus maps to chromosome 9q13-q21 between markers D9S1806 and D9S769. We have determined the cDNA sequence and genomic structure of a novel gene, TMEM2, that maps to this interval and is expressed in the cochlea. The mouse orthologue of this gene (Tmem2) maps to the murine dn (deafness) locus on mouse chromosome 19. Screens for transmembrane helices reveal the presence of at least one putative transmembrane domain in the TMEM2 protein. To determine whether mutations in TMEM2 cause hearing loss at the DFNB7-DFNB11 locus, we screened the coding region of this gene in DFNB7-DFNB11 affected families by direct sequencing. All DNA variants that segregated with the deafness and changed the predicted amino acid sequence of TMEM2 were common polymorphisms, as demonstrated by allele-specific amplification of pooled control DNA. Northern blot analysis showed no difference in transcript size or expression level of Tmem2 in dn/dn and control mice. The intragenic polymorphisms in TMEM2 represent a novel centromeric boundary for the DFNB7-DFNB11 interval.
authors.affiliation: Howard Hughes Medical Institute, Iowa City, IA 52242-1078, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Scott
authors.forename: S
authors.initials: S
authors.lastname: Drury
authors.forename: R A
authors.initials: RA
authors.lastname: Sundstrom
authors.forename: J
authors.initials: J
authors.lastname: Bishop
authors.forename: R E
authors.initials: RE
authors.lastname: Swiderski
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: A
authors.initials: A
authors.lastname: Ramesh
authors.forename: K
authors.initials: K
authors.lastname: Elbedour
authors.forename: C R
authors.initials: CR
authors.lastname: Srikumari Srisailapathy
authors.forename: B J
authors.initials: BJ
authors.lastname: Keats
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003051:Cochlea / Q000196:embryology / Q000378:metabolism; D020451:Contig Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005091:Exons; D005192:Family Health; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution
chemical_list: C408224:CEMIP2 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; C485807:Tmem2 protein, mouse; D004247:DNA