Geschwind Daniel H
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, United States; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States.
Handb Clin Neurol. 2018;147:37-42. doi: 10.1016/B978-0-444-63233-3.00004-X.
Recent advances in exome and genome sequencing in populations are beginning to define the genetic architecture of neurologic and psychiatric disease. At the same time these findings are changing our perspective of genetic variant contributions to disease, implicating both rare and common genetic variation in common diseases. Most of what we know about genetic contributions to disease so far comes from analysis of mutations in protein-coding genes. Since most genetic variation lies in nonprotein-coding regions of the genome whose presumed function is entirely regulatory, understanding gene regulation in a cell type and developmental state-specific manner will be important to connect human genetic variation to disease mechanisms.
群体外显子组和基因组测序的最新进展开始明确神经和精神疾病的遗传结构。与此同时，这些发现正在改变我们对疾病遗传变异贡献的看法，表明罕见和常见遗传变异都与常见疾病有关。到目前为止，我们对疾病遗传贡献的大部分了解来自对蛋白质编码基因突变的分析。由于大多数遗传变异位于基因组的非蛋白质编码区域，其假定功能完全是调节性的，因此以细胞类型和发育状态特异性的方式理解基因调控对于将人类遗传变异与疾病机制联系起来至关重要。
