人类基因组变异与多基因疾病相关的功能特征分析。
Functional characterization of human genomic variation linked to polygenic diseases.
机构信息
Program in Epithelial Biology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Graduate Program in Genetics, Stanford University, Stanford, CA, USA; Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Program in Epithelial Biology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Graduate Program in Genetics, Stanford University, Stanford, CA, USA; Stanford University School of Medicine, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.
出版信息
Trends Genet. 2023 Jun;39(6):462-490. doi: 10.1016/j.tig.2023.02.014. Epub 2023 Mar 28.
The burden of human disease lies predominantly in polygenic diseases. Since the early 2000s, genome-wide association studies (GWAS) have identified genetic variants and loci associated with complex traits. These have ranged from variants in coding sequences to mutations in regulatory regions, such as promoters and enhancers, as well as mutations affecting mediators of mRNA stability and other downstream regulators, such as 5' and 3'-untranslated regions (UTRs), long noncoding RNA (lncRNA), and miRNA. Recent research advances in genetics have utilized a combination of computational techniques, high-throughput in vitro and in vivo screening modalities, and precise genome editing to impute the function of diverse classes of genetic variants identified through GWAS. In this review, we highlight the vastness of genomic variants associated with polygenic disease risk and address recent advances in how genetic tools can be used to functionally characterize them.
人类疾病的负担主要在于多基因疾病。自 21 世纪初以来，全基因组关联研究（GWAS）已经确定了与复杂性状相关的遗传变异和基因座。这些变异包括编码序列中的变异、启动子和增强子等调控区域的突变，以及影响 mRNA 稳定性和其他下游调节剂（如 5'和 3'非翻译区（UTR）、长非编码 RNA（lncRNA）和 miRNA）的突变。遗传学的最新研究进展结合了计算技术、高通量体外和体内筛选模式以及精确的基因组编辑，以推断通过 GWAS 鉴定的不同类别的遗传变异的功能。在这篇综述中，我们强调了与多基因疾病风险相关的基因组变异的广泛性，并讨论了如何利用遗传工具来对其进行功能特征描述的最新进展。
Zotero 插件