Transposable elements that have recently been mobile in the human genome

Abstract Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the...

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Autores principales:	Matias I. Autio, Talal Bin Amin, Arnaud Perrin, Jen Yi Wong, Roger S.-Y. Foo, Shyam Prabhakar
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Transposable element Mobile element Insertion Polymorphism Human Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/37cbd73da4dc4bac9f79b35ef2968e33
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spelling	oai:doaj.org-article:37cbd73da4dc4bac9f79b35ef2968e332021-11-08T10:57:24ZTransposable elements that have recently been mobile in the human genome10.1186/s12864-021-08085-01471-2164https://doaj.org/article/37cbd73da4dc4bac9f79b35ef2968e332021-11-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08085-0https://doaj.org/toc/1471-2164Abstract Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the human genome. In this study, we therefore developed a novel statistical test for recently mobile subfamilies (RMSs), based on patterns of overlap with > 100,000 polymorphic indels. Results Our analysis produced a catalogue of 20 high-confidence RMSs, which excludes many false positives in public databases. Intriguingly though, it includes HERV-K, an LTR subfamily previously thought to be extinct. The RMS catalogue is strongly enriched for contributions to germline genetic disorders (P = 1.1e-10), and thus constitutes a valuable resource for diagnosing disorders of unknown aetiology using targeted TE-insertion screens. Remarkably, RMSs are also highly enriched for somatic insertions in diverse cancers (P = 2.8e-17), thus indicating strong correlations between germline and somatic TE mobility. Using CRISPR/Cas9 deletion, we show that an RMS-derived polymorphic TE insertion increased the expression of RPL17, a gene associated with lower survival in liver cancer. More broadly, polymorphic TE insertions from RMSs were enriched near genes with allele-specific expression, suggesting widespread effects on gene regulation. Conclusions By using a novel statistical test we have defined a catalogue of 20 recently mobile transposable element subfamilies. We illustrate the gene regulatory potential of RMS-derived polymorphic TE insertions, using CRISPR/Cas9 deletion in vitro on a specific candidate, as well as by genome wide analysis of allele-specific expression. Our study presents novel insights into TE mobility and regulatory potential and provides a key resource for human disease genetics and population history studies.Matias I. AutioTalal Bin AminArnaud PerrinJen Yi WongRoger S.-Y. FooShyam PrabhakarBMCarticleTransposable elementMobile elementInsertionPolymorphismHumanBiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Transposable element Mobile element Insertion Polymorphism Human Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	Transposable element Mobile element Insertion Polymorphism Human Biotechnology TP248.13-248.65 Genetics QH426-470 Matias I. Autio Talal Bin Amin Arnaud Perrin Jen Yi Wong Roger S.-Y. Foo Shyam Prabhakar Transposable elements that have recently been mobile in the human genome
description	Abstract Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the human genome. In this study, we therefore developed a novel statistical test for recently mobile subfamilies (RMSs), based on patterns of overlap with > 100,000 polymorphic indels. Results Our analysis produced a catalogue of 20 high-confidence RMSs, which excludes many false positives in public databases. Intriguingly though, it includes HERV-K, an LTR subfamily previously thought to be extinct. The RMS catalogue is strongly enriched for contributions to germline genetic disorders (P = 1.1e-10), and thus constitutes a valuable resource for diagnosing disorders of unknown aetiology using targeted TE-insertion screens. Remarkably, RMSs are also highly enriched for somatic insertions in diverse cancers (P = 2.8e-17), thus indicating strong correlations between germline and somatic TE mobility. Using CRISPR/Cas9 deletion, we show that an RMS-derived polymorphic TE insertion increased the expression of RPL17, a gene associated with lower survival in liver cancer. More broadly, polymorphic TE insertions from RMSs were enriched near genes with allele-specific expression, suggesting widespread effects on gene regulation. Conclusions By using a novel statistical test we have defined a catalogue of 20 recently mobile transposable element subfamilies. We illustrate the gene regulatory potential of RMS-derived polymorphic TE insertions, using CRISPR/Cas9 deletion in vitro on a specific candidate, as well as by genome wide analysis of allele-specific expression. Our study presents novel insights into TE mobility and regulatory potential and provides a key resource for human disease genetics and population history studies.
format	article
author	Matias I. Autio Talal Bin Amin Arnaud Perrin Jen Yi Wong Roger S.-Y. Foo Shyam Prabhakar
author_facet	Matias I. Autio Talal Bin Amin Arnaud Perrin Jen Yi Wong Roger S.-Y. Foo Shyam Prabhakar
author_sort	Matias I. Autio
title	Transposable elements that have recently been mobile in the human genome
title_short	Transposable elements that have recently been mobile in the human genome
title_full	Transposable elements that have recently been mobile in the human genome
title_fullStr	Transposable elements that have recently been mobile in the human genome
title_full_unstemmed	Transposable elements that have recently been mobile in the human genome
title_sort	transposable elements that have recently been mobile in the human genome
publisher	BMC
publishDate	2021
url	https://doaj.org/article/37cbd73da4dc4bac9f79b35ef2968e33
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Transposable elements that have recently been mobile in the human genome

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