Construction of P1-Derived Artificial Chromosome and Yeast Artificial Chromosome Contigs Encompassing the DFNB7 andDFNB11 Region of Chromosome 9q13–21

DFNB7 and DFNB11, two loci for autosomal recessive nonsyndromic hearing loss (ARNSHL), have been mapped to chromosome 9q13–21 in separate consanguineous families. Using a radiation hybrid map, we have determined the correct marker order in the DFNB7/11 region and have demonstrated that theDFNB11 locus resides within a redefined DFNB7interval. The gene(s) responsible for ARNSHL at these loci resides within an ∼1 cM interval bounded by markers D9S1806(centromeric) and D9S769 (telomeric). A recently discovered Indian family confirms the new telomeric boundary. To assist in the identification and cloning of candidate genes, YAC and PAC contigs were constructed. A total of 19 YAC and 23 PAC clones were utilized to span the affected region and ensure double coverage throughout. Twenty-two previously published STSs and 21 new STSs were used to determine marker order and confirm the integrity of the contig. Using a positional cloning strategy we have identified three cochlear expressed genes that map to the DFNB7/11 interval.