Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia Philadelphia, PA, USA ; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia Philadelphia, PA, USA.
Front Genet. 2014 Apr 29;5:105. doi: 10.3389/fgene.2014.00105. eCollection 2014.
Estimates from large scale genome sequencing studies indicate that each human carries up to 20 genetic variants that are predicted to results in loss of function (LOF) of protein-coding genes. While some are known disease-causing variants or common, tolerated, LOFs in non-essential genes, the majority remain of unknown consequence. We explore the possibility of using imputed GWAS data from large biorepositories such as the electronic medical record and genomics (eMERGE) consortium to determine the effects of rare LOFs. Here, we show that two hypocholesterolemia-associated LOF mutations in the PCSK9 gene can be accurately imputed into large-scale GWAS datasets which raises the possibility of assessing LOFs through genomics-linked medical records.
大规模基因组测序研究的估计表明，每个人携带多达 20 种预测会导致蛋白质编码基因功能丧失（LOF）的遗传变异。虽然有些是已知的致病变异或常见的、可耐受的非必需基因中的 LOF，但大多数仍然未知其后果。我们探索了使用大型生物库（如电子病历和基因组学（eMERGE）联盟）中的已推断 GWAS 数据来确定罕见 LOF 的影响的可能性。在这里，我们表明，PCSK9 基因中与低胆固醇血症相关的两种 LOF 突变可以准确地推断到大规模 GWAS 数据集，这增加了通过与基因组相关的医疗记录评估 LOF 的可能性。
