Computational and Experimental Analysis of Genetic Variants
Computational and Experimental Analysis of Genetic Variants
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DOI：
10.1002/cphy.c210012
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发表时间：
2022-04-01
影响因子：
5.8
通讯作者：
Bupp, Caleb P.
中科院分区：
文献类型：
--
作者：
Prokop, Jeremy W.;Jdanov, Vladislav;Bupp, Caleb P.
基因组学在过去十年中呈指数级增长。常见的变异与生理变化通过统计策略，如全基因组关联研究（GWAS）和定量跟踪基因座（QTL）。通过广泛的过滤工具，包括群体基因组学和基于trio的测序（父母和先证者），罕见变异与疾病相关。然而，基因组关联需要后续分析来缩小因果变异，识别受影响的基因，并确定生理变化。存在大量数据，可用于将变异与基因变化、细胞类型、蛋白质途径、临床表型和建立生理基因组学的动物模型联系起来。这些数据与生物信息学相结合，包括进化分析，结构见解和基因调控，可以产生可验证的假设，基因组变异的机制。分子生物学，生物化学，细胞培养，CRISPR编辑和动物模型可以测试假设，以给出分子变异机制。变异表征可以是通过教授遗传学的基本概念和术语，同时学习独立的研究假设设计，在本科，研究生或医学培训课程中教育未来专业人员的重要组成部分。本文通过计算和实验分析策略的变体表征，并提供了这些工具在出版物中应用的例子。(c)2022年美国生理学会。
Genomics has grown exponentially over the last decade. Common variants are associated with physiological changes through statistical strategies such as Genome-Wide Association Studies (GWAS) and quantitative trail loci (QTL). Rare variants are associated with diseases through extensive filtering tools, including population genomics and trio-based sequencing (parents and probands). However, the genomic associations require follow-up analyses to narrow causal variants, identify genes that are influenced, and to determine the physiological changes. Large quantities of data exist that can be used to connect variants to gene changes, cell types, protein pathways, clinical phenotypes, and animal models that establish physiological genomics. This data combined with bioinformatics including evolutionary analysis, structural insights, and gene regulation can yield testable hypotheses for mechanisms of genomic variants. Molecular biology, biochemistry, cell culture, CRISPR editing, and animal models can test the hypotheses to give molecular variant mechanisms. Variant characterizations can be a significant component of educating future professionals at the undergraduate, graduate, or medical training programs through teaching the basic concepts and terminology of genetics while learning independent research hypothesis design. This article goes through the computational and experimental analysis strategies of variant characterization and provides examples of these tools applied in publications. (c) 2022 American Physiological Society.