New horizons in the understanding of hereditary neuropathies – screening the genome for causative genes and gene mutations

确定潜在的遗传原因对于了解发病机制和开发治疗方法至关重要。遗传性神经疾病包括各种各样的疾病模式，所有这些疾病都有一个逐渐丧失能力的过程。为了通过分析全基因组和转录组数据来识别新的致病基因和修饰基因，申请者的目标是在一个为期两年的博士后研究奖学金的框架内成为“大数据”测序方法的专家。在整个外显子组测序方法取得巨大成功后，包括重复扩增在内的非编码变异的作用仍有待进一步关注，特别是因为目前所有轴突形式的遗传性神经病的诊断差距约为50%，阻碍了临床进展，并最终阻碍了未来精确基因疗法的应用。在本项目中，申请者将评估在佛罗里达迈阿密大学约翰·P·赫斯曼人类基因组研究所建立的测序数据，使用复杂的生物信息学工具和数据库来筛选遗传性神经疾病中的新基因和基因突变。该项目专注于新的基因组调控变体，并评估它们对组织特异性转录本中蛋白质表达的影响。它将导致与美国和德国的合作伙伴以及相关个人建立一个合作网络，并促进专业知识的转移和资源的共享。

To identify the underlying genetic cause is crucial for the understanding of pathomechanisms and the development of treatment. Hereditary neuropathies comprise a wide variety of disease patterns, which all share a progressively disabling course. With the intention to identify new causative and modifier genes by analyzing whole genome and transcriptome data, the applicant aims to become an expert of the "big data" sequencing approach within the frame of a two-year post-doctoral research fellowship.After the great success of the whole exome sequencing approach, the role of non-coding variation including repeat expansions has yet to be further focused on, especially since the current diagnostic gap of ~50% for all axonal forms of hereditary neuropathies hinders clinical progress and ultimately the application of future precise genetic therapies. In the present project, the applicant will evaluate sequencing data established at the John P. Hussman Institute for Human Genomics at the University of Miami, Florida, using elaborate bioinformatic tools and databases to filter for novel genes and gene mutations in hereditary neuropathies. The project focusses on novel genomic regulatory variants and assesses their effect on protein expression in tissue-specific transcriptomes. It will lead to a collaborative network with the US and German partners and involved individuals and fosters the transfer of specialized knowledge and sharing of resources.