Understanding the Role of C2orf43 in Hearing Loss

描述（由申请人提供）：大约一半的新生儿先天性听力损失是由遗传引起的。识别与听力损失有关的基因对于这种常见异常的精确诊断、遗传咨询和未来治疗至关重要。通过发育基因组解剖计划（DGAP, DGAP .harvard.edu），我们已经确定了一个患有各种发育障碍的受试者，包括先天性听力损失和早发性前列腺癌，其新生染色体易位中断了一个未注释的基因C2orf43。本提案的目的是研究C2orf43在听力中的可能作用，以扩展我在听力生理学和遗传学训练方面的背景。我将通过进一步描述受试者的听力损失，排除其他已知的听力损失遗传原因，并筛选听力损失人群中C2orf43的变异，来分析人类听力损失与C2orf43之间的表型-基因型相关性。人类受试者的研究将辅以斑马鱼和新开发的C2orf43敲除（KO）小鼠模型的基因型-表型相关性研究，并重点研究耳朵和其他器官系统的表达、形态和生理变化。我们所提出的研究应使我们能够验证C2orf43对于正常听力是必要的，阐明C2orf43在听力生理学中的作用，建立分析其他听力损失相关基因的方法，并在年轻的听力研究者中建立遗传学研究背景。

DESCRIPTION (provided by applicant): About half of newborn congenital hearing loss has a genetic cause. Identifying genes involved in hearing loss is essential for precise diagnosis, genetic counseling and future treatment of this common abnormality. Through the Developmental Genome Anatomy Project (DGAP, dgap.harvard.edu), we have identified a subject with various developmental disorders including congenital hearing loss and early onset prostate cancer, whose de novo chromosomal translocation interrupts an unannotated gene, C2orf43. The goal of this proposal is to investigate the possible role of C2orf43 in hearing to extend my background in hearing physiology with genetics training. I will analyze the phenotype-genotype correlation between hearing loss and C2orf43 in humans by further characterizing the subject's hearing loss, excluding other known genetic causes for the hearing loss, and screening hearing loss populations for variations in C2orf43. Human subjects research will be complemented by studies of genotype-phenotype correlation in zebrafish and a newly developed C2orf43 knockout (KO) mouse model and focused on changes in expression, morphology and physiology in the ear and other organ systems. The proposed study should allow us to validate that C2orf43 is necessary for normal hearing, shed light on the role of C2orf43 in hearing physiology, develop methods to analyze other genes associated with hearing loss, and establish a genetics research background in a young hearing investigator.