Identification and characterization of genes for human retrocochlear hearing disorders

通过对人类家族和不同动物模型中听力障碍遗传形式的遗传分析，已经鉴定出大量对听力不可或缺的基因/蛋白质。这尤其适用于主要在耳蜗细胞和结构中表达和功能相关的分子。相反，关于耳蜗后听力障碍的遗传和分子基础的知识非常有限，比如所谓的听神经病变和中枢性听觉处理障碍。该项目的主要目标是查明并与这一优先规划的其他成员合作，进一步确定与这种人工耳蜗后人类听力障碍发展有关的基因特征。为了实现这一目标，我们将在受不同形式神经性听力障碍影响的家庭/患者中应用系统的全基因组连锁和测序方法，并随后在合适的细胞或动物模型中研究鉴定的基因/遗传变异。潜在疾病基因的识别将有助于提高我们对人类中枢听觉信息加工的分子和生理基础的理解。

The genetic analysis of hereditary forms of hearing impairment in human families and diverse animal models has led to the identification of a large number of genes/proteins that are indispensable for hearing. This holds especially true for molecules which are primarily expressed and functionally relevant in cells and structures of the cochlea itself. On the contrary, there is only very limited knowledge about the genetic and molecular basis of retrocochlear hearing disorders like for example for the so called auditory neuropathy and central auditory processing disorders. The main goal of this project is to identify and - in collaboration with other members of this priority programme - further characterize genes involved in the development of such retrocochlear human hearing disorders. To achieve this aim we will apply systematic and genome-wide linkage and sequencing approaches in families/patients affected by different forms of neural hearing disorders and subsequently investigate the identified genes/genetic variants in suited cell or animal models. The identification of underlying disease genes will help to improve our understanding about the molecular and physiological basis of central auditory information processing in humans.