Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling

The etiology of Autism Spectrum Disorders (ASD) remains unknown for most of the cases, in spite of its strong genetic component. A greater knowledge of its genetic basis would result in many benefits, including specific genetic counseling for families and, eventually, the development of personalized...

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Detalles Bibliográficos
Autor: Codina i Solà, Marta
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/388031
Acceso en línea:http://hdl.handle.net/10803/388031
Access Level:acceso abierto
Palabra clave:Trastorns de l'Espectre Autista (TEA)
Seqüenciació d'exoma
Transcriptoma
Assessorament genètic
Variants genètiques
Autism Spectrum Disorders (ASD)
Exome Sequencing
Transcriptome
Genetic Counseling
Genetic variants
616.89
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spelling Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counselingCodina i Solà, MartaTrastorns de l'Espectre Autista (TEA)Seqüenciació d'exomaTranscriptomaAssessorament genèticVariants genètiquesAutism Spectrum Disorders (ASD)Exome SequencingTranscriptomeGenetic CounselingGenetic variants616.89The etiology of Autism Spectrum Disorders (ASD) remains unknown for most of the cases, in spite of its strong genetic component. A greater knowledge of its genetic basis would result in many benefits, including specific genetic counseling for families and, eventually, the development of personalized therapeutic strategies. In this thesis, we have applied several recent sequencing technologies and adapted pipelines to its study. We have investigated the role of rare variants and its transcriptional consequences and explored the contribution of complex rearrangements to its missing heritability. In addition, we have studied second-hit susceptibility genetic factors in a group of individuals with Williams-Beuren syndrome, a genomic disorder associated with a mirror phenotype. Finally, we have explored parental knowledge and the effect of genetic counseling in affected families. Our results reveal that both highly penetrant mutations and inherited variants of milder effect contribute to its susceptibility, following monogenic and oligogenic or multifactorial models, respectively. Each of them may contribute to part of the variability and may explain a subset of cases.Malgrat el fort component genètic dels Trastorns de l’Espectre Autista (TEA), l’etiologia de la majoria de casos es desconeix. Un major coneixement de les seves bases genètiques seria molt beneficiós, ja que permetria un assessorament genètic específic a les famílies i, a la llarga, el desenvolupament d’estratègies terapèutiques personalitzades. En aquesta tesis, s’han aplicat diverses tècniques recents de seqüenciació i estratègies d’anàlisi adaptades. S’ha investigat el paper de variants rares i les seves conseqüències transcripcionals, així com de reordenaments complexos. A més, hem estudiat la presència de variants de susceptibilitat en un grup de persones amb síndrome de Williams, un trastorn genòmic associat a un fenotip oposat. Finalment, hem explorat el coneixement i les opinions en un grup de famílies afectades i, també, l’efecte de l’assessorament genètic. Els resultats obtinguts indiquen que, en el TEA, hi contribueixen tant mutacions altament penetrants, com variants heretades que augmenten lleugerament el risc i poden seguir tant models monogènics com oligogènics. Cada un d’aquests models contribuiria a explicar part de la variabilitat i dels casosPrograma de doctorat en BiomedicinaUniversitat Pompeu FabraPérez Jurado, Luis AlbertoCuscó Martí, IvonUniversitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut201620182016info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion307 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/388031TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/3.0/es/http://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/3880312026-06-14T12:46:07Z
dc.title.none.fl_str_mv Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
title Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
spellingShingle Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
Codina i Solà, Marta
Trastorns de l'Espectre Autista (TEA)
Seqüenciació d'exoma
Transcriptoma
Assessorament genètic
Variants genètiques
Autism Spectrum Disorders (ASD)
Exome Sequencing
Transcriptome
Genetic Counseling
Genetic variants
616.89
title_short Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
title_full Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
title_fullStr Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
title_full_unstemmed Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
title_sort Genetic variation and complex rearrangements in Autism Spectrum Disorders: implications for genetic counseling
dc.creator.none.fl_str_mv Codina i Solà, Marta
author Codina i Solà, Marta
author_facet Codina i Solà, Marta
author_role author
dc.contributor.none.fl_str_mv Pérez Jurado, Luis Alberto
Cuscó Martí, Ivon
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
dc.subject.none.fl_str_mv Trastorns de l'Espectre Autista (TEA)
Seqüenciació d'exoma
Transcriptoma
Assessorament genètic
Variants genètiques
Autism Spectrum Disorders (ASD)
Exome Sequencing
Transcriptome
Genetic Counseling
Genetic variants
616.89
topic Trastorns de l'Espectre Autista (TEA)
Seqüenciació d'exoma
Transcriptoma
Assessorament genètic
Variants genètiques
Autism Spectrum Disorders (ASD)
Exome Sequencing
Transcriptome
Genetic Counseling
Genetic variants
616.89
description The etiology of Autism Spectrum Disorders (ASD) remains unknown for most of the cases, in spite of its strong genetic component. A greater knowledge of its genetic basis would result in many benefits, including specific genetic counseling for families and, eventually, the development of personalized therapeutic strategies. In this thesis, we have applied several recent sequencing technologies and adapted pipelines to its study. We have investigated the role of rare variants and its transcriptional consequences and explored the contribution of complex rearrangements to its missing heritability. In addition, we have studied second-hit susceptibility genetic factors in a group of individuals with Williams-Beuren syndrome, a genomic disorder associated with a mirror phenotype. Finally, we have explored parental knowledge and the effect of genetic counseling in affected families. Our results reveal that both highly penetrant mutations and inherited variants of milder effect contribute to its susceptibility, following monogenic and oligogenic or multifactorial models, respectively. Each of them may contribute to part of the variability and may explain a subset of cases.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/388031
url http://hdl.handle.net/10803/388031
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 307 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat Pompeu Fabra
publisher.none.fl_str_mv Universitat Pompeu Fabra
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425660399714304
score 15.301603

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