Mar. 24, 1998 A team led by geneticist Dr. Karen Avraham of Tel Aviv University has discovered a defective gene that causes progressive hearing loss in a large Israeli family.
Rapid advances in genetics enabled Avraham's group, in collaboration with Dr. Mary-Claire King and Dr. Eric Lynch at University of Washington in Seattle and Dr. Robert Morell and Dr. Thomas Friedman* at the National Institute on Deafness and Other Communication Disorders (part of the National Institutes of Health), to pinpoint the location of this gene in only a year.
The discovery is reported in the March 20 issue of the journal Science.
Oz Vahava, a graduate student in Avraham's laboratory, initiated the study of the genetics of deafness in a number of generations of the Israeli family. Hearing impairment was traced back five generations to an ancestor born in 1843 in Libya. The family migrated through Tunisia and Egypt, eventually settling in Israel. The researchers identified 12 living family members with progressive hearing loss, and 11 unaffected relatives older than age 40.
Vahava determined the chromosomal location of the defective gene, named DFNA15. It was located on chromosome 5 near another gene for inherited deafness identified by King and Lynch in an extended Costa Rican family only a few months earlier (reported in the Nov. 14, 1997 issue of Science). Avraham contacted the UW geneticists, and the groups began working together.
The investigators took advantage of a shortcut revealed by a mouse. One method for identifying human genes is to examine comparable human and mouse chromosomal regions, searching for genes already known to cause problems in mice similar to those of concern in the human families.
Although the evolutionary paths of mice and humans diverged millions of years ago, segments of their chromosomes contain the same genes. The comparison led the geneticists to a mouse gene known to be crucial for normal development of mouse hearing. When the human form of the same gene was sequenced using DNA from hearing-impaired individuals in the Israeli family, a mutation was found in a critical part of the gene.
Deaf members of the Israeli family carry two forms of the gene: one normal and one mutant. Initially, the normal gene appears to be adequate for hearing, since hearing is normal until around the age of 18. But then, hearing begins to deteriorate, so that by the age of 40, affected individuals cannot hear without a hearing aid. By this age, the geneticists believe, the mutant form of the gene takes over, preventing the protein encoded by the normal gene from functioning properly.
The critical gene codes for a member of a group of proteins called transcription factors, which control expression of other genes by binding to them and allowing them to be turned on or off. In the inner ear, the mutant gene does not properly regulate other crucial genes.
Deafness is the most common form of sensory impairment in humans. One child in 1000 is born deaf, and up to 50 percent of the population will lose at least part of their hearing by the age of 80.
"The identification of this gene adds a piece to the increasingly well understood, intricate function of the inner ear," said King. "The next step is to determine whether this gene is involved in congenital or age-related hearing loss in other deaf individuals, and how knowledge of the gene's normal function can be used to alleviate more common forms of deafness,"
*Avraham, King, Lynch and Morell are Ph.D.s; Friedman is an M.D.
Other social bookmarking and sharing tools:
The above story is based on materials provided by University Of Washington.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Note: If no author is given, the source is cited instead.