Construction of P1-Derived Artificial Chromosome and Yeast Artificial Chromosome Contigs Encompassing the DFNB7 andDFNB11 Region of Chromosome 9q13–21
- John H. Greinwald, Jr.1,9,
- Daryl A. Scott2,9,
- Jacquie R. Marietta1,9,
- Rivka Carmi1,4,
- Jose Manaligod1,
- Arabandi Ramesh3,
- Ross I.S. Zbar1,
- Michelle L. Kraft1,
- Khalil Elbedour4,
- Yael Yairi5,
- Maurice Musy6,
- Anne B. Skvorak7,
- Guy Van Camp8,
- C.R. Srikumari Srisailapathy3,
- Michael Lovett6,
- Cynthia C. Morton7,
- Val C. Sheffield2,10, and
- Richard J.H. Smith1,10
- 1Molecular Otolaryngology Research Laboratories, Department of Otolaryngology–Head and Neck Surgery and the 2Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242; 3Department of Genetics, University of Madras, Madras, India; 4Genetics Institute, 5Faculty of Health Sciences, Soroka Medical Center, Ben Gurion University of Negev, Beer-Sheva, Israel; 6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235; 7Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; 8Department of Medical Genetics, University of Antwerp, 2610 Antwerpen, Belgium
Abstract
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.
