Unravelling the genetic basis of BOR syndrome
A Deafness Research UK PhD student, Bernardo Blanco, working with Dr Tanya Whitfield at the University of Sheffield, has spent three years studying the genetics of Branchio-Oto-Renal Syndrome (BOR), an important cause of inherited deafness.
[PhD Studentship, 2004-2007]
In humans it has been shown that mutations in the genes EYA1 and SIX1 and very recently SIX5 are responsible for the disease. All three genes are transcription factors, which control gene expression and are known to interact with each other during development.
This research project aimed to look at the role of EYA1 in development of the ear and to identify other genes that interact with EYA1 in the hope of finding potential targets for the treatment of BOR syndrome.
The study looked at the expression of these genes in zebrafish. When zebrafish have a mutation in the EYA1 gene, they show a very misshapen ear, so, as in humans, the mutation affects the sensory and non-sensory regions of the ear.
The researchers found that EYA1 is required during the very earliest stage of inner ear development, even before recognisable signs of the future inner ear appear in the developing zebrafish embryo. The mutation seems to disrupt the specification of specialised cell sub-types is affected and as a result the cells receive the wrong information for what to become and the cells of the inner ear fail to develop normally.
The researchers also looked at the SIX1 protein by creating an artificial mutant zebrafish lacking SIX1. They found that compromising the function of SIX1 also perturbs inner ear development but not in the same way as EYA1 affects development.
This study has provided a better understanding of the function of the genes EYA1 and SIX1 in the developing inner ear. An understanding of how these genes work may help to improve the clinical classification of different forms of BOR. It may also lead to the development of new diagnostic tools and, eventually, to new therapies.
Results are currently being written up for publication and we are delighted to report that then PhD student Bernardo is now Dr Blanco and that he has remained in hearing research, using the zebrafish as a model system for the study of ear development and as a model for human deafness.
