Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/20277 |
Resumo: | Intellectual disability (ID) is a complex condition, with a world-wide prevalence of 1-3%. Although many etiological factors associated with ID remain unclear, about 25-50% of the cases are due to genetic contributions. In this context, copy number variation (CNV) at Xq28 encompassing methyl-CpG-binding protein 2 gene (MECP2) is one of the most common cause of severe ID in males. MECP2 is highly expressed in neurons and encodes a chromatin-associated protein, which functions as a transcriptional regulator. Therefore, copy number variation in MECP2 can affect the expression of different genes in brain, leading to abnormal neurological phenotypes. In this view, in this study we conducted a CNV screening of MECP2 gene in a large cohort of 920 unrelated males with idiopathic ID. Genomic DNA was isolated from peripheral blood and MECP2 target sequences were amplified by TaqMan copy number assay®. A total of three individuals (0,33%) exhibiting duplications at MECP2 locus were detected. The duplications ranged from 420 Kb to 2 Mb and delimitation of small region of overlap demonstrated the presence of MECP2 and other seven genes (IRAK1, OPN1LM, TEX28, OPN1MW, TKTL1, FLNA and EMD). Subsequently, the segregation analysis of the duplications demonstrated that the rearrangement is de novo in the proband 565, whereas in 4219 patient the duplication was inherited from his mother, which presented an extreme skewed of X-inactivation pattern. Expression analysis in these two patients demonstrated that patient 565 has an increased expression of MECP2 gene, whereas patient 4219 has normal expression levels of this gene. Previous studies conducted in North American and European populations indicate a prevalence of 1-2% of MECP2 duplications among males with ID. Nonetheless, corroborating our results, large cohorts analysis had a lower detection rate of 0.3-0.4%. In addition, such studies indicated that duplications involving MECP2 lead to increased expression of this gene. However, considering that apparently normal expression levels of MECP2 were observed in patient 4219, our data suggests that duplications involving MECP2 gene may lead to the development of the phenotypes through other molecular mechanisms in addition to gene dosage. Alternatively, other genes involved in the rearrangements may contribute to cognitive impairments. Taken together, these data suggest that MECP2 duplications represent an important cause of idiopathic ID in males and confirms that TaqMan copy number assay® is a sensitive method to assess these duplications. |
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Santos-Rebouças, Cíntia Barroshttp://lattes.cnpq.br/5415426502606671Pimentel, Márcia Mattos Gonçalveshttp://lattes.cnpq.br/9409055728849608Leonor Gusmão http://lattes.cnpq.br/2495323064167358 4790298272Simão, Tatiana de Almeidahttp://lattes.cnpq.br/4257729756468950Vargas, Fernando Reglahttp://lattes.cnpq.br/1796505221055428http://lattes.cnpq.br/1446808493153778Abdala, Bianca Barbosaabdala.bianca@gmail.com2023-09-06T16:12:33Z2018-02-27ABDALA, Bianca Barbosa. Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens. 2018. 100 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018.http://www.bdtd.uerj.br/handle/1/20277Intellectual disability (ID) is a complex condition, with a world-wide prevalence of 1-3%. Although many etiological factors associated with ID remain unclear, about 25-50% of the cases are due to genetic contributions. In this context, copy number variation (CNV) at Xq28 encompassing methyl-CpG-binding protein 2 gene (MECP2) is one of the most common cause of severe ID in males. MECP2 is highly expressed in neurons and encodes a chromatin-associated protein, which functions as a transcriptional regulator. Therefore, copy number variation in MECP2 can affect the expression of different genes in brain, leading to abnormal neurological phenotypes. In this view, in this study we conducted a CNV screening of MECP2 gene in a large cohort of 920 unrelated males with idiopathic ID. Genomic DNA was isolated from peripheral blood and MECP2 target sequences were amplified by TaqMan copy number assay®. A total of three individuals (0,33%) exhibiting duplications at MECP2 locus were detected. The duplications ranged from 420 Kb to 2 Mb and delimitation of small region of overlap demonstrated the presence of MECP2 and other seven genes (IRAK1, OPN1LM, TEX28, OPN1MW, TKTL1, FLNA and EMD). Subsequently, the segregation analysis of the duplications demonstrated that the rearrangement is de novo in the proband 565, whereas in 4219 patient the duplication was inherited from his mother, which presented an extreme skewed of X-inactivation pattern. Expression analysis in these two patients demonstrated that patient 565 has an increased expression of MECP2 gene, whereas patient 4219 has normal expression levels of this gene. Previous studies conducted in North American and European populations indicate a prevalence of 1-2% of MECP2 duplications among males with ID. Nonetheless, corroborating our results, large cohorts analysis had a lower detection rate of 0.3-0.4%. In addition, such studies indicated that duplications involving MECP2 lead to increased expression of this gene. However, considering that apparently normal expression levels of MECP2 were observed in patient 4219, our data suggests that duplications involving MECP2 gene may lead to the development of the phenotypes through other molecular mechanisms in addition to gene dosage. Alternatively, other genes involved in the rearrangements may contribute to cognitive impairments. Taken together, these data suggest that MECP2 duplications represent an important cause of idiopathic ID in males and confirms that TaqMan copy number assay® is a sensitive method to assess these duplications.A deficiência intelectual (DI) é uma condição complexa, com uma prevalência de 1-3%. Embora muitos fatores etiológicos associados à DI ainda sejam desconhecidos, cerca de 25-50% dos casos ocorrem devido a contribuições genéticas. Assim sendo, variações do número de cópias (VNC) em Xq28, englobando o gene methyl-CpG-binding protein 2 (MECP2) são uma das causas mais comuns de DI severa em homens. O gene MECP2 é altamente expresso nos neurônios e codifica uma proteína associada à cromatina, atuando como um regulador transcricional. Sendo assim, VNCs no MECP2 podem afetar a expressão de diferentes genes no cérebro, levando a fenótipos neurológicos anormais. Neste sentido, neste estudo foi conduzido o rastreamento de VNCs no gene MECP2 em uma amostra ampla de 920 indivíduos não aparentados portadores de DI idiopática. O DNA genômico foi isolado do sangue periférico e as sequências alvo no gene MECP2 foram amplificadas pelo sistema de TaqMan copy number assay®. Ao todo, três indivíduos (0,33%) exibindo duplicações envolvendo o gene MECP2 foram detectados. As duplicações variaram de 420 Kb a 2 Mb e a delimitação da região de sobreposição mínima demonstrou a presença de sete genes, além do MECP2 (IRAK1, OPN1LM, TEX28, OPN1MW, TKTL1, FLNA e EMD). Posteriormente, a análise de segregação das duplicações demonstrou que o rearranjo é de novo no probando 565, enquanto que no paciente 4219 a duplicação foi herdada da mãe, a qual apresentou desvio extremo de inativação do cromossomo X. A avaliação da expressão nesses dois pacientes demostrou que o paciente 565 apresentou aumento de expressão do gene MECP2, enquanto que o paciente 4219 exibiu níveis normais de expressão desse gene. Estudos anteriores realizados em populações norte-americanas e européias indicaram a prevalência de 1-2% de duplicações no gene MECP2 em homens portadores de DI. No entanto, corroborando nossos resultados, análises em amostras amplas apresentaram uma taxa de detecção de 0,3-0,4%. Além disso, tais estudos mostraram que duplicações envolvendo o gene MECP2 levaram ao aumento de expressão desse gene. Todavia, na análise funcional do paciente 4219 não foi verificado, aparentemente, um aumento de expressão, sugerindo que as duplicações envolvendo o gene MECP2 podem levar ao desenvolvimento dos fenótipos através de outros mecanismos moleculares, além de dosagem gênica. Alternativamente, outros genes envolvidos nos rearranjos podem ter uma contribuição no comprometimento cognitivo. Em conjunto, esses dados sugerem que as duplicações no gene MECP2 representam uma causa importante da DI idiopática em homens e ratificam que o sistema TaqMan copy number assay® é um método sensível para avaliar essas duplicações.Submitted by Heloísa CB/A (helobdtd@gmail.com) on 2023-09-06T16:12:33Z No. of bitstreams: 1 Dissertação - Bianca Barbosa Abdala - 2018 - Completa.pdf: 5575840 bytes, checksum: 12e97718f7a5407ead0f1a4cc7b7fb48 (MD5)Made available in DSpace on 2023-09-06T16:12:33Z (GMT). No. of bitstreams: 1 Dissertação - Bianca Barbosa Abdala - 2018 - Completa.pdf: 5575840 bytes, checksum: 12e97718f7a5407ead0f1a4cc7b7fb48 (MD5) Previous issue date: 2018-02-27Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBrasilCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesIntellectual disabilityDuplicationMECP2CNV screeningDeficiência IntelectualDuplicaçãoMECP2Rastreamento de VNCsCIENCIAS BIOLOGICAS::GENETICAVariação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homensCopy number variation in MECP2 gene and its relation with intelectual disability in malesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDissertação - Bianca Barbosa Abdala - 2018 - Completa.pdfDissertação - Bianca Barbosa Abdala - 2018 - Completa.pdfapplication/pdf5575840http://www.bdtd.uerj.br/bitstream/1/20277/2/Disserta%C3%A7%C3%A3o+-+Bianca+Barbosa++Abdala+-+2018+-+Completa.pdf12e97718f7a5407ead0f1a4cc7b7fb48MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/20277/1/license.txte5502652da718045d7fcd832b79fca29MD511/202772024-02-26 11:39:25.233oai:www.bdtd.uerj.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:39:25Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
dc.title.alternative.eng.fl_str_mv |
Copy number variation in MECP2 gene and its relation with intelectual disability in males |
title |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
spellingShingle |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens Abdala, Bianca Barbosa Intellectual disability Duplication MECP2 CNV screening Deficiência Intelectual Duplicação MECP2 Rastreamento de VNCs CIENCIAS BIOLOGICAS::GENETICA |
title_short |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
title_full |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
title_fullStr |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
title_full_unstemmed |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
title_sort |
Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens |
author |
Abdala, Bianca Barbosa |
author_facet |
Abdala, Bianca Barbosa abdala.bianca@gmail.com |
author_role |
author |
author2 |
abdala.bianca@gmail.com |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Santos-Rebouças, Cíntia Barros |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5415426502606671 |
dc.contributor.advisor-co1.fl_str_mv |
Pimentel, Márcia Mattos Gonçalves |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/9409055728849608 |
dc.contributor.referee1Lattes.fl_str_mv |
Leonor Gusmão http://lattes.cnpq.br/2495323064167358 4790298272 |
dc.contributor.referee2.fl_str_mv |
Simão, Tatiana de Almeida |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/4257729756468950 |
dc.contributor.referee3.fl_str_mv |
Vargas, Fernando Regla |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/1796505221055428 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1446808493153778 |
dc.contributor.author.fl_str_mv |
Abdala, Bianca Barbosa abdala.bianca@gmail.com |
contributor_str_mv |
Santos-Rebouças, Cíntia Barros Pimentel, Márcia Mattos Gonçalves Simão, Tatiana de Almeida Vargas, Fernando Regla |
dc.subject.eng.fl_str_mv |
Intellectual disability Duplication MECP2 CNV screening |
topic |
Intellectual disability Duplication MECP2 CNV screening Deficiência Intelectual Duplicação MECP2 Rastreamento de VNCs CIENCIAS BIOLOGICAS::GENETICA |
dc.subject.por.fl_str_mv |
Deficiência Intelectual Duplicação MECP2 Rastreamento de VNCs |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::GENETICA |
description |
Intellectual disability (ID) is a complex condition, with a world-wide prevalence of 1-3%. Although many etiological factors associated with ID remain unclear, about 25-50% of the cases are due to genetic contributions. In this context, copy number variation (CNV) at Xq28 encompassing methyl-CpG-binding protein 2 gene (MECP2) is one of the most common cause of severe ID in males. MECP2 is highly expressed in neurons and encodes a chromatin-associated protein, which functions as a transcriptional regulator. Therefore, copy number variation in MECP2 can affect the expression of different genes in brain, leading to abnormal neurological phenotypes. In this view, in this study we conducted a CNV screening of MECP2 gene in a large cohort of 920 unrelated males with idiopathic ID. Genomic DNA was isolated from peripheral blood and MECP2 target sequences were amplified by TaqMan copy number assay®. A total of three individuals (0,33%) exhibiting duplications at MECP2 locus were detected. The duplications ranged from 420 Kb to 2 Mb and delimitation of small region of overlap demonstrated the presence of MECP2 and other seven genes (IRAK1, OPN1LM, TEX28, OPN1MW, TKTL1, FLNA and EMD). Subsequently, the segregation analysis of the duplications demonstrated that the rearrangement is de novo in the proband 565, whereas in 4219 patient the duplication was inherited from his mother, which presented an extreme skewed of X-inactivation pattern. Expression analysis in these two patients demonstrated that patient 565 has an increased expression of MECP2 gene, whereas patient 4219 has normal expression levels of this gene. Previous studies conducted in North American and European populations indicate a prevalence of 1-2% of MECP2 duplications among males with ID. Nonetheless, corroborating our results, large cohorts analysis had a lower detection rate of 0.3-0.4%. In addition, such studies indicated that duplications involving MECP2 lead to increased expression of this gene. However, considering that apparently normal expression levels of MECP2 were observed in patient 4219, our data suggests that duplications involving MECP2 gene may lead to the development of the phenotypes through other molecular mechanisms in addition to gene dosage. Alternatively, other genes involved in the rearrangements may contribute to cognitive impairments. Taken together, these data suggest that MECP2 duplications represent an important cause of idiopathic ID in males and confirms that TaqMan copy number assay® is a sensitive method to assess these duplications. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-02-27 |
dc.date.accessioned.fl_str_mv |
2023-09-06T16:12:33Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
ABDALA, Bianca Barbosa. Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens. 2018. 100 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/20277 |
identifier_str_mv |
ABDALA, Bianca Barbosa. Variação no número de cópias no gene MECP2 e sua relação com a deficiência intelectual em homens. 2018. 100 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
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http://www.bdtd.uerj.br/handle/1/20277 |
dc.language.iso.fl_str_mv |
por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biociências |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
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