Understanding the mechanisms of congenital hydrocephalus using genomic sequencing approaches

先天性脑积水（CH）是一种影响大脑的疾病，由异常积累引起 脑室内的脑脊液（CSF）。目前治疗脑积水的方法是手术 干预措施，这伴随着高失败率。虽然外在因素如出血或感染 可能导致CH，最近的研究已经确定了一些CH相关基因或突变，强调了CH的作用。 然而，这些遗传因素仅占散发CH病例的约22%， 许多案件仍然没有解决。因此，迫切需要通过以下途径加速对CH的了解： 尖端科技如果不利用这些新方法， CH的遗传因素以及准确诊断和治疗的进展可能会受到阻碍。长-- 学期目标是利用正交试验来了解CH的分子机制和潜在后果。 表型组学、遗传学和多组学方法。总体目标是开发和应用新的基因组学 工具，以促进我们对CH的生物学机制的理解。中心假设是， 生殖系或体细胞和/或特定故障细胞类型中的其他遗传变异， 为了验证这一假设，PI和团队将追求以下目标。1)全面 对来自CH患者的生殖系和体细胞组织中所有形式的变异进行表征， 长读全基因组测序。2)识别异常细胞类型并了解其功能 和对CH的贡献。完成后，预计新的变化 无论是在生殖系或体细胞可能有助于CH。

Congenital Hydrocephalus (CH) is a condition that affects the brain and results from an abnormal accumulation of cerebrospinal fluid (CSF) within the cerebral ventricles. The current treatments for hydrocephalus are surgical interventions, which accompanies a high failure rate. Although extrinsic factors such as hemorrhage or infections may cause CH, recent studies have identified some CH-associated genes or mutations, emphasizing the role of genetics in CH. However, these genetic factors only account for approximately 22% of sporadic CH cases, and many cases remain unsolved. Therefore, there is an urgent need to accelerate the understanding of CH through the cutting-edge technologies. Without leveraging these novel methods, the discovery of additional causal genetic factors of CH and the advancement of accurate diagnoses and treatments may be hindered. The long- term goal is to understand the molecular mechanisms and consequences underlying CH using orthogonal phenomic, genetic, and multi-omics approaches. The overall objective is to develop and apply new genomics tools to advance our understanding of the biological mechanisms of CH. The central hypothesis is that there are additional genetic variations in germline or somatic and/or specific malfunctioning cell types that contribute to the etiology of CH. To test this hypothesis, the PIs and team will pursue the following aims. 1) Comprehensive characterization of all forms of variations in both germline and somatic tissue from CH patients with short- and long- read whole genome sequencing. 2) Identification of abnormal cell types and understanding their function and contribution to CH through single-cell genomics analysis. Upon completion, it is expected that new variations either in the germline or somatic may contribute to CH.