Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders
Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders
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DOI：
10.1126/sciadv.aay8299
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发表时间：
2020-06-01
期刊：
影响因子：
13.6
通讯作者：
Ryten, Mina
中科院分区：
文献类型：
--
作者：
Zhang, David;Guelfi, Sebastian;Ryten, Mina
越来越多的证据表明，人类基因注释仍然不完整；然而，目前尚不清楚这如何影响不同的组织和我们对不同疾病的理解。在这里，我们从41个人体组织的基因型组织表达RNA测序数据中检测了先前未注释的转录。我们将这种未注释的转录与已知基因联系起来，证实人类基因注释仍然不完整，即使是在研究得很好的基因中，包括63%的在线孟德尔遗传在人类疾病目录和317个神经变性相关基因。我们发现在大脑中无注释的转录量最大，在大脑中高表达的基因更容易被重新注释。我们探索了重新注释的疾病基因的例子，例如SNCA，我们通过实验验证了以前未识别的，脑特异性的，潜在的蛋白质编码外显子。我们通过vizER: http://rytenlab.com/browser/app/vizER释放所有组织特异性转录组。我们期望这一资源将促进更准确的遗传分析，对我们对孟德尔和复杂神经遗传疾病的理解产生最大的影响。
Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of different disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 human tissues. We connect this unannotated transcription to known genes, confirming that human gene annotation remains incomplete, even among well-studied genes including 63% of the Online Mendelian Inheritance in Man-morbid catalog and 317 neurodegeneration-associated genes. We find the greatest abundance of unannotated transcription in brain and genes highly expressed in brain are more likely to be reannotated. We explore examples of reannotated disease genes, such as SNCA, for which we experimentally validate a previously unidentified, brain-specific, potentially protein-coding exon. We release all tissue-specific transcriptomes through vizER: http://rytenlab.com/browser/app/vizER . We anticipate that this resource will facilitate more accurate genetic analysis, with the greatest impact on our understanding of Mendelian and complex neurogenetic disorders.