Using Xenopus to discover new candidate genes involved in BOR and other congenital hearing loss syndromes
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Published on: January 4, 2017
Scott J Neal1, Anindita Rajasekaran1, Nisveta Jusić1
1Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York, USA.
Insights
Researchers identified new genes linked to congenital hearing loss by studying Six1 in animal models. This research aims to improve genetic screening for early diagnosis and intervention in infants.
Area of Science:
- Developmental Biology
- Genetics
- Otic Development
Background:
- Infant hearing is crucial for brain development, language acquisition, and social interaction.
- Early diagnosis of hearing loss enables timely interventions.
- Branchio-oto-renal syndrome (BOR) is a common inherited hearing loss associated with craniofacial and kidney defects, often caused by mutations in SIX1, SIX5, and EYA1.
Purpose of the Study:
- To identify novel candidate genes for congenital hearing loss.
- To uncover new Six1 transcriptional targets and interacting proteins involved in otic development.
- To enhance genetic screening panels for congenital hearing loss.
Main Methods:
- Utilized Drosophila mutants and protein biochemical assays.
- Leveraged Xenopus as an aquatic animal model for its genomic similarity to humans.
- Employed transcriptomic, yeast two-hybrid, and proteomic approaches.
Main Results:
- Identified a substantial number of new candidate genes potentially involved in otic development.
- Revealed potential Six1 transcriptional targets and interacting proteins.
- Began elucidating the interaction mechanisms of Six1 and co-factors in otic development.
Conclusions:
- The study successfully identified novel candidate genes for congenital hearing loss.
- Findings contribute to understanding the molecular mechanisms of otic development regulated by Six1.
- The identified genes can be considered for inclusion in future genetic screening panels for hearing loss.
Abstract:
Hearing in infants is essential for brain development, acquisition of verbal language skills, and development of social interactions. Therefore, it is important to diagnose hearing loss soon after birth so that interventions can be provided as early as possible. Most newborns in the United States are screened for hearing deficits and commercially available next-generation sequencing hearing loss panels often can identify the causative gene, which may also identify congenital defects in other organs. One of the most prevalent autosomal dominant congenital hearing loss syndromes is branchio-oto-renal syndrome (BOR), which also presents with defects in craniofacial structures and the kidney. Currently, mutations in three genes, SIX1, SIX5, and EYA1, are known to be causative in about half of the BOR patients that have been tested. To uncover new candidate genes that could be added to congenital hearing loss genetic screens, we have combined the power of Drosophila mutants and protein biochemical assays with the embryological advantages of Xenopus, a key aquatic animal model with a high level of genomic similarity to human, to identify potential Six1 transcriptional targets and interacting proteins that play a role during otic development. We review our transcriptomic, yeast 2-hybrid, and proteomic approaches that have revealed a large number of new candidates. We also discuss how we have begun to identify how Six1 and co-factors interact to direct developmental events necessary for normal otic development.
