Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder

Abstract Background Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for...

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Autores principales:	Rebeca Borges-Monroy, Chong Chu, Caroline Dias, Jaejoon Choi, Soohyun Lee, Yue Gao, Taehwan Shin, Peter J. Park, Christopher A. Walsh, Eunjung Alice Lee
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Transposable elements Retrotransposons Autism spectrum disorder de novo insertions Polymorphic insertions de novo rates Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8f9cee324ba7466e90e75f9ca6ee92f3
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spelling	oai:doaj.org-article:8f9cee324ba7466e90e75f9ca6ee92f32021-11-28T12:22:13ZWhole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder10.1186/s13100-021-00256-w1759-8753https://doaj.org/article/8f9cee324ba7466e90e75f9ca6ee92f32021-11-01T00:00:00Zhttps://doi.org/10.1186/s13100-021-00256-whttps://doaj.org/toc/1759-8753Abstract Background Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for this analysis has only recently become available. Results We analyzed WGS data from a cohort of 2288 ASD families from the Simons Simplex Collection by establishing a scalable computational pipeline for retrotransposon insertion detection. We report 86,154 polymorphic retrotransposon insertions—including > 60% not previously reported—and 158 de novo retrotransposition events. The overall burden of de novo events was similar between ASD individuals and unaffected siblings, with 1 de novo insertion per 29, 117, and 206 births for Alu, L1, and SVA respectively, and 1 de novo insertion per 21 births total. However, ASD cases showed more de novo L1 insertions than expected in ASD genes. Additionally, we observed exonic insertions in loss-of-function intolerant genes, including a likely pathogenic exonic insertion in CSDE1, only in ASD individuals. Conclusions These findings suggest a modest, but important, impact of intronic and exonic retrotransposon insertions in ASD, show the importance of WGS for their analysis, and highlight the utility of specific bioinformatic tools for high-throughput detection of retrotransposon insertions.Rebeca Borges-MonroyChong ChuCaroline DiasJaejoon ChoiSoohyun LeeYue GaoTaehwan ShinPeter J. ParkChristopher A. WalshEunjung Alice LeeBMCarticleTransposable elementsRetrotransposonsAutism spectrum disorderde novo insertionsPolymorphic insertionsde novo ratesGeneticsQH426-470ENMobile DNA, Vol 12, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Transposable elements Retrotransposons Autism spectrum disorder de novo insertions Polymorphic insertions de novo rates Genetics QH426-470
spellingShingle	Transposable elements Retrotransposons Autism spectrum disorder de novo insertions Polymorphic insertions de novo rates Genetics QH426-470 Rebeca Borges-Monroy Chong Chu Caroline Dias Jaejoon Choi Soohyun Lee Yue Gao Taehwan Shin Peter J. Park Christopher A. Walsh Eunjung Alice Lee Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
description	Abstract Background Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for this analysis has only recently become available. Results We analyzed WGS data from a cohort of 2288 ASD families from the Simons Simplex Collection by establishing a scalable computational pipeline for retrotransposon insertion detection. We report 86,154 polymorphic retrotransposon insertions—including > 60% not previously reported—and 158 de novo retrotransposition events. The overall burden of de novo events was similar between ASD individuals and unaffected siblings, with 1 de novo insertion per 29, 117, and 206 births for Alu, L1, and SVA respectively, and 1 de novo insertion per 21 births total. However, ASD cases showed more de novo L1 insertions than expected in ASD genes. Additionally, we observed exonic insertions in loss-of-function intolerant genes, including a likely pathogenic exonic insertion in CSDE1, only in ASD individuals. Conclusions These findings suggest a modest, but important, impact of intronic and exonic retrotransposon insertions in ASD, show the importance of WGS for their analysis, and highlight the utility of specific bioinformatic tools for high-throughput detection of retrotransposon insertions.
format	article
author	Rebeca Borges-Monroy Chong Chu Caroline Dias Jaejoon Choi Soohyun Lee Yue Gao Taehwan Shin Peter J. Park Christopher A. Walsh Eunjung Alice Lee
author_facet	Rebeca Borges-Monroy Chong Chu Caroline Dias Jaejoon Choi Soohyun Lee Yue Gao Taehwan Shin Peter J. Park Christopher A. Walsh Eunjung Alice Lee
author_sort	Rebeca Borges-Monroy
title	Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
title_short	Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
title_full	Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
title_fullStr	Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
title_full_unstemmed	Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
title_sort	whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8f9cee324ba7466e90e75f9ca6ee92f3
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Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder

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