人类外显子的广泛自然变异有助于基因解读

Hannah Jacobs, Bram Gorissen, Jeremy Guez, Masahiro Kanai, Hilary Finucane, Christopher Burge
{"title":"人类外显子的广泛自然变异有助于基因解读","authors":"Hannah Jacobs, Bram Gorissen, Jeremy Guez, Masahiro Kanai, Hilary Finucane, Christopher Burge","doi":"10.1101/2024.09.09.612029","DOIUrl":null,"url":null,"abstract":"Most mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific mammalian lineages, but differences in splicing within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 exons which are included in mRNAs in some individuals but entirely excluded from others, which we term 'naturally variable exons' (NVEs). NVEs impact three quarters of protein-coding genes, occur at all population frequencies, and are often absent from reference annotations. NVEs are more abundant in genes depleted of genetic loss-of-function mutations and aid in the interpretation of causal genetic variants. Genetic variants modulate the splicing of many NVEs, and 5'UTR and coding-region NVEs are often associated with increased and decreased gene expression, respectively. Together, our findings characterize abundant splicing variation in the human population, with implications for a range of human genetic analyses.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Widespread naturally variable human exons aid genetic interpretation\",\"authors\":\"Hannah Jacobs, Bram Gorissen, Jeremy Guez, Masahiro Kanai, Hilary Finucane, Christopher Burge\",\"doi\":\"10.1101/2024.09.09.612029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Most mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific mammalian lineages, but differences in splicing within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 exons which are included in mRNAs in some individuals but entirely excluded from others, which we term 'naturally variable exons' (NVEs). NVEs impact three quarters of protein-coding genes, occur at all population frequencies, and are often absent from reference annotations. NVEs are more abundant in genes depleted of genetic loss-of-function mutations and aid in the interpretation of causal genetic variants. Genetic variants modulate the splicing of many NVEs, and 5'UTR and coding-region NVEs are often associated with increased and decreased gene expression, respectively. Together, our findings characterize abundant splicing variation in the human population, with implications for a range of human genetic analyses.\",\"PeriodicalId\":501246,\"journal\":{\"name\":\"bioRxiv - Genetics\",\"volume\":\"6 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.09.09.612029\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.09.612029","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

大多数哺乳动物基因都会发生替代剪接。一些外显子的剪接在特定的哺乳动物血统中获得或丢失,但人类群体中剪接的差异却很少被描述。利用来自 838 个个体的 GTEx 组织转录组,我们发现了 56,415 个外显子,这些外显子在某些个体中包含在 mRNA 中,但在另一些个体中则完全被排除在外,我们称之为 "自然可变外显子"(NVEs)。自然可变外显子影响四分之三的蛋白质编码基因,在所有种群中都会出现,而且往往不在参考注释中。在基因功能缺失突变消失的基因中,自然可变外显子更为丰富,有助于解释因果遗传变异。遗传变异会调节许多 NVE 的剪接,5'UTR 和编码区 NVE 通常分别与基因表达的增加和减少有关。我们的研究结果共同描述了人类群体中丰富的剪接变异,对一系列人类遗传学分析具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Widespread naturally variable human exons aid genetic interpretation
Most mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific mammalian lineages, but differences in splicing within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 exons which are included in mRNAs in some individuals but entirely excluded from others, which we term 'naturally variable exons' (NVEs). NVEs impact three quarters of protein-coding genes, occur at all population frequencies, and are often absent from reference annotations. NVEs are more abundant in genes depleted of genetic loss-of-function mutations and aid in the interpretation of causal genetic variants. Genetic variants modulate the splicing of many NVEs, and 5'UTR and coding-region NVEs are often associated with increased and decreased gene expression, respectively. Together, our findings characterize abundant splicing variation in the human population, with implications for a range of human genetic analyses.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues Mitochondrial superoxide acts in the intestine to extend longevity AyurPhenoClusters define common molecular roots for rare diseases and uncover ciliary dysfunctions in syndromic conditions Screening and identification of gene expression in large cohorts of clinical lung cancer samples unveils the major involvement of EZH2 and SOX2 LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1