公共基因组数据库中高度受限基因的独特特征

Pankaj Agrawal, Klaus E Schmitz-Abe, Qifei Li, Sunny Greene, Michela Borrelli, Shiyu Luo, Madesh Ramesh
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引用次数: 0

摘要

公开可用的基因组数据库和遗传约束评分对于了解人类群体变异和识别可能对人类疾病产生有害影响的变异至关重要。我们利用最大的公开数据库之一 gnomAD,确定了仅 LoF、仅 missense 和 LoF/missense 变异高度受限的基因,识别了它们的独特特征,并探讨了它们与人类疾病的因果关系。利用多个公开数据库对这些基因的独特模式进行了评估,包括其染色体位置、组织水平表达、基因本体分析和基因家族分类。对于这些与人类疾病相关的高度受限基因,我们确定了其独特的遗传模式、蛋白质大小以及在不同分子通路中的富集情况。此外,我们还发现了一批目前还不知道会导致人类疾病的高度受限基因,我们建议将这些基因作为新型疾病相关基因进行研究。总之,这些见解不仅阐明了高度受限基因的生物通路,扩大了我们对关键细胞蛋白的了解,还推动了罕见疾病的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unique Signatures of Highly Constrained Genes Across Publicly Available Genomic Databases
Publicly available genomic databases and genetic constraint scores are crucial in understanding human population variation and the identification of variants that are likely to have a deleterious impact causing human disease. We utilized the one of largest publicly available databases, gnomAD, to determine genes that are highly constrained for only LoF, only missense, and both LoF/missense variants, identified their unique signatures, and explored their causal relationship with human conditions. Those genes were evaluated for unique patterns including their chromosomal location, tissue level expression, gene ontology analysis, and gene family categorization using multiple publicly available databases. Those highly constrained genes associated with human disease, we identified unique patterns of inheritance, protein size, and enrichment in distinct molecular pathways. In addition, we identified a cohort of highly constrained genes that are currently not known to cause human disease, that we suggest will be candidates to pursue as novel disease-associated genes. In summary, these insights not only elucidate biological pathways of highly constrained genes that expand our understanding of critical cellular proteins but also advance research in rare diseases.
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