There are roughly 20,000 to 25,000 genes in the human body, and for the most part, each gene is supposedly responsible for encoding one particular protein.
However, researchers from the National Institute on Deafness and Other Communication Disorders (NIDCD) and a group of international scientists have found an exception to the rule. The group has uncovered a gene that causes deafness in humans and that makes two completely different proteins. The gene, called LRTOMT, is a fused version of two separate genes that appear in mice and rats: Lrrc51 and Tomt. The study is published in the November 2008 issue of Nature Genetics.
NIDCD geneticists Zubair Ahmed, Ph.D., and Thomas Friedman, Ph.D., together with scientists from the Centre of Biotechnology of Sfax, Tunisia, and from Radboud University in the Netherlands used molecular biology techniques to identify a gene on chromosome 11 responsible for nonsyndromic deafness. The researchers were able to pinpoint the gene from a larger region, called DFNB63, that had previously been found to be associated with nonsyndromic deafness. Nonsyndromic deafness occurs without additional symptoms such as blindness or a kidney or heart disorder. It is the most common form of inherited deafness.
Until now, the gene responsible for DFNB63 deafness in humans was a puzzle to scientists. The researchers found that while the neighboring Lrrc51 and Tomt genes in mice each make separate proteins, in humans, the fused version of these genes still makes two separate proteins. (The first protein is named LRTOMT1 and the second is LRTOMT2.) The researchers also identified four mutations that resulted in deafness in families they studied. All of the mutations primarily affect the LRTOMT2 protein.
Although there have been a few other examples in which one gene can make two different proteins, this is the first example in which mutations in a fusion gene causes a Mendelian disorder, a disorder that exhibits a simple pattern of inheritance. The next goal is to study the function of LRTOMT and determine how mutations of this gene cause deafness in humans.