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

An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). T his locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 56 polymorphic microsatellite marker s 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 mark ers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mappe d to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in or der 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 t his study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduce d to a size amenable to an intensive positional cloning effort. (C) 2000 Ac ademic Press.