title: Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region.
abstract: An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 50 polymorphic microsatellite markers in 21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10 has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mapped to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in order from centromere to telomere: White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and eliminated as candidates for DFNB10. The new microsatellite markers and single nucleotide polymorphisms identified in this study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduced to a size amenable to an intensive positional cloning effort.
authors.affiliation: Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Ramat-Aviv, 69978, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Berry
authors.forename: H S
authors.initials: HS
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: Kudoh
authors.forename: I
authors.initials: I
authors.lastname: Talior
authors.forename: M
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: M
authors.initials: M
authors.lastname: Wattenhofer
authors.forename: M
authors.initials: M
authors.lastname: Guipponi
authors.forename: C
authors.initials: C
authors.lastname: Barras
authors.forename: C
authors.initials: C
authors.lastname: Rossier
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Kawasaki
authors.forename: S
authors.initials: S
authors.lastname: Asakawa
authors.forename: S
authors.initials: S
authors.lastname: Minoshima
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Antonarakis
authors.forename: B
authors.initials: B
authors.lastname: Bonné-Tamir
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003638:Deafness / Q000151:congenital / Q000235:genetics*; D005192:Family Health; D005260:Female; D005796:Genes / Q000235:genetics*; D005808:Genes, Recessive; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D000071164:Trefoil Factor-2
chemical_list: C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; D004247:DNA