De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.

Neurodevelopmental and psychiatric disorders are a highly disabling and heterogeneous group of developmental and mental disorders, resulting from complex interactions of genetic and environmental risk factors. The nature of multifactorial traits and the presence of comorbidity and polygenicity in th...

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Detalles Bibliográficos
Autores: Wang, Weidi, Corominas Castiñeira, Roser, Lin, Guan Ning
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/165097
Acceso en línea:https://hdl.handle.net/2445/165097
Access Level:acceso abierto
Palabra clave:Trastorns del desenvolupament
Psicopatologia
Developmental disabilities
Pathological psychology
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spelling De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.Wang, WeidiCorominas Castiñeira, RoserLin, Guan NingTrastorns del desenvolupamentPsicopatologiaDevelopmental disabilitiesPathological psychologyNeurodevelopmental and psychiatric disorders are a highly disabling and heterogeneous group of developmental and mental disorders, resulting from complex interactions of genetic and environmental risk factors. The nature of multifactorial traits and the presence of comorbidity and polygenicity in these disorders present challenges in both disease risk identification and clinical diagnoses. The genetic component has been firmly established, but the identification of all the causative variants remains elusive. The development of next-generation sequencing, especially whole exome sequencing (WES), has greatly enriched our knowledge of the precise genetic alterations of human diseases, including brain-related disorders. In particular, the extensive usage of WES in research studies has uncovered the important contribution of de novo mutations (DNMs) to these disorders. Trio and quad familial WES are a particularly useful approach to discover DNMs. Here, we review the major WES studies in neurodevelopmental and psychiatric disorders and summarize how genes hit by discovered DNMs are shared among different disorders. Next, we discuss different integrative approaches utilized to interrogate DNMs and to identify biological pathways that may disrupt brain development and shed light on our understanding of the genetic architecture underlying these disorders. Lastly, we discuss the current state of the transition from WES research to its routine clinical application. This review will assist researchers and clinicians in the interpretation of variants obtained from WES studies, and highlights the need to develop consensus analytical protocols and validated lists of genes appropriate for clinical laboratory analysis, in order to reach the growing demands.Frontiers Media2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/165097Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fgene.2019.00258Frontiers In Genetics, 2019, vol. 10, p. 258https://doi.org/10.3389/fgene.2019.00258cc-by (c) Wang, Weidi et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1650972026-05-27T06:46:51Z
dc.title.none.fl_str_mv De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
title De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
spellingShingle De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
Wang, Weidi
Trastorns del desenvolupament
Psicopatologia
Developmental disabilities
Pathological psychology
title_short De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
title_full De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
title_fullStr De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
title_full_unstemmed De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
title_sort De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.
dc.creator.none.fl_str_mv Wang, Weidi
Corominas Castiñeira, Roser
Lin, Guan Ning
author Wang, Weidi
author_facet Wang, Weidi
Corominas Castiñeira, Roser
Lin, Guan Ning
author_role author
author2 Corominas Castiñeira, Roser
Lin, Guan Ning
author2_role author
author
dc.subject.none.fl_str_mv Trastorns del desenvolupament
Psicopatologia
Developmental disabilities
Pathological psychology
topic Trastorns del desenvolupament
Psicopatologia
Developmental disabilities
Pathological psychology
description Neurodevelopmental and psychiatric disorders are a highly disabling and heterogeneous group of developmental and mental disorders, resulting from complex interactions of genetic and environmental risk factors. The nature of multifactorial traits and the presence of comorbidity and polygenicity in these disorders present challenges in both disease risk identification and clinical diagnoses. The genetic component has been firmly established, but the identification of all the causative variants remains elusive. The development of next-generation sequencing, especially whole exome sequencing (WES), has greatly enriched our knowledge of the precise genetic alterations of human diseases, including brain-related disorders. In particular, the extensive usage of WES in research studies has uncovered the important contribution of de novo mutations (DNMs) to these disorders. Trio and quad familial WES are a particularly useful approach to discover DNMs. Here, we review the major WES studies in neurodevelopmental and psychiatric disorders and summarize how genes hit by discovered DNMs are shared among different disorders. Next, we discuss different integrative approaches utilized to interrogate DNMs and to identify biological pathways that may disrupt brain development and shed light on our understanding of the genetic architecture underlying these disorders. Lastly, we discuss the current state of the transition from WES research to its routine clinical application. This review will assist researchers and clinicians in the interpretation of variants obtained from WES studies, and highlights the need to develop consensus analytical protocols and validated lists of genes appropriate for clinical laboratory analysis, in order to reach the growing demands.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/165097
url https://hdl.handle.net/2445/165097
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fgene.2019.00258
Frontiers In Genetics, 2019, vol. 10, p. 258
https://doi.org/10.3389/fgene.2019.00258
dc.rights.none.fl_str_mv cc-by (c) Wang, Weidi et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Wang, Weidi et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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