Much of the hospital's success in identifying and treating children with hearing loss is the result of the rapid transfer of research findings from laboratories to clinic and bedside.

Areas of Research - Hereditary Communication Disorders - Gene Identification

Research Program

This laboratory is an extension of the Gene Markers Lab with separate research programs headed by Drs. William Kimberling and Philip Kelley. The Gene Identification laboratory and the Gene Markers laboratory use the positional candidate cloning strategy to identify genes causing hearing loss.

The Gene Markers laboratory uses the tools of linkage mapping and haplotype mapping to identify regions of the human genome linked to hearing loss genes. The Gene Identification laboratory constructs physical maps of the critical region, identifies candidate genes in that region, and searches for mutations in those candidate genes.

Current projects focus on identification of genes causing:

Branchio-Oto-Renal Syndrome
Usher Syndromes (Type I, Type II and Type III) (Dr. Kimberling)
Non-Syndromic Recessive Deafness (Drs. Kimberling and Kelley)
Dominant Progressive Hearing Loss (Dr. Kelley)
Non-syndromic Recessive Auditory Neuropathy (Dr. Kelley)

(See also Gene Markers)

Facilities

The laboratory is equipped with a cell culture facility which includes a laminar flow tissue culture hood, CO2 incubator, inverted microscope, centrifuge and refrigerator. The lab has a separate sterile hood for DNA/RNA and PCR work. It has required power supplies for hetero-duplex analysis and a wide variety of DNA, RNA gel electrophoresis gel system. The laboratory also has a Pulsed-field gel electrophoresis system, thermocyclers, circulators, water bath, microcentrifuge, -80°C freezer, balances, shakers, and incubators.

The gene identification laboratory shares an ABI Prism 877 Integrated Thermal Cycler robotic system and an ABI Prism 377 DNA Sequencer.

Representative Publications

Kumar, S., Kimberling, et al. (1992). Autosomal dominant branchio-

oto-renal syndrome: Localization of a disease gene to chromosome

8q by linkage in a Dutch family. Hum. Mol. Genet. 1, 491-495.

Kumar, S., Kimberling, W.J., et al. (1996). Narrowing the genetic

interval and yeast artificial chromosome map in the branchio-oto-

renal region on chromosome 8q. Genomics 31, 71-79.

Kelley, P.M., Harris, D.J., Comer, B.C., Askew, J.W., Fowler, T., Smith,

S.D. & Kimberling, W.J. (1998). Novel mutations in the connexin 26

gene (GJB 2 ) that cause autosomal recessive (DFNB 1 ) hearing loss.

Am. J. Hum. Genet. 62 , 792-799.

Kumar, S., Deffenbacher, K., Cremers, C.W.R.J., Van Camp, G. &

Kimberling, W.J. (1998). Branchio-oto-renal syndrome:

Identification of novel mutations, molecular characterization,

mutation distribution and prospects for genetic testing. Genet.

Test. 1 , 243-251.

Kelley, P.M., Abe, S., Askew, J.W., Smith, S.D., Usami, S. &

Kimberling, W.J. (1999). Human connexin 30 (GJB 6 ), a candidate

gene for nonsyndromic hearing loss: Molecular cloning, tissue-

specific expression, and assignment to chromosome 13 q 12 .

Genomics 62 , 172-176.

Kumar, S., Deffenbacher, K., Marres, H., Cremers, C.W.R.J. &

Kimberling, W.J. (2000). Genomewide search and genetic

localization of a second gene associated with autosomal dominant

branchio-oto-renal (BOR) syndrome: Clinical and genetic

implications. Am. J. Hum. Genet. 77, 1715-1720.

Kelley, P.M., Cohn, E. & Kimberling, W.J. (2000). Connexin 26:

Required for normal auditory function, Brain Res. Brain Res. Rev.

32 , 184-188.

Coucke, P.J., Van Laer, L., Meyers, J., Van Hauwe, P., Ottschytsch,

N., Wauters, J.G. & Kelley, P. et al. (2000). Identification a new

connexin gene GJA 11 (Cx 59 ) using degenerate PCR primers.

GeneScreen 1, 35-40.