Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/11402 |
Resumo: | Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA /Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil |
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Fonseca, Claudia Marcia Benedetto de CarvalhoVasanth, ShivakumarShinawi, MarwanRussell, ChadRamocki, Melissa B.Brown, Chester W.Graakjaer, JesperBine Skytte, AnneMorgante, Angela Maria ViannaKrepischi, Ana Cristina VictorinoPatel, Gayle S.Immken, LaDonnaAleck, KyrieckosLim, CynthiaCheung, Sau WaiRosenberg, CarlaKatsanis, Nicholas2015-07-23T16:05:33Z2015-07-23T16:05:33Z2014CARVALHO, Claudia Marcia Benedetto et al. Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes. Am J Hum Genet. 2014 Nov 6;95(5):565-78.0002-9297https://www.arca.fiocruz.br/handle/icict/1140210.1016/j.ajhg.2014.10.006engElsevier IncDosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA /Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, BrazilDuke University. Center for Human Disease Modeling.Durham, NC, USAWashington University . Division of Genetics and Genomic Medicine. Department of Pediatrics. St Louis, MO, USADuke University. Center for Human Disease Modeling.Durham, NC, USABaylor College of Medicine. Department of Pediatrics. Houston, TX, USA/ Texas Children’s Hospital. Houston, TX , USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA /Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/ Texas Children’s Hospital. Houston, TX , USAVejle Hospital. Clinical Genetics Department. Vejle, DenmarkVejle Hospital. Clinical Genetics Department. Vejle, DenmarkUniversidade de São Paulo. Instituto de Biociencias. Departamento de Genetica e Evolução Biologica. Sao Paulo, SP, BrazilUniversidade de São Paulo. Instituto de Biociencias. Departamento de Genetica e Evolução Biologica. Sao Paulo, SP, BrazilTexas Oncology. Austin, TX, USASpecially for Children. Austin, TX, USAPhoenix Children’s Hospital. Phoenix, AZ, USAPhoenix Children’s Hospital. Phoenix, AZ, USABaylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USAUniversidade de São Paulo. Instituto de Biociencias. Departamento de Genetica e Evolução Biologica. Sao Paulo, SP, BrazilDuke University. Center for Human Disease Modeling. Durham, NC, USAThe 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO.Abnormalities, Multiple/geneticsChromosomes, Human, Pair 17/geneticsMolecular Sequence DataSequence Analysis, DNAinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11402/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALDosage Changes of a Segment at 17p13.1 Lead.pdfDosage Changes of a Segment at 17p13.1 Lead.pdfapplication/pdf1645159https://www.arca.fiocruz.br/bitstream/icict/11402/2/Dosage%20Changes%20of%20a%20Segment%20at%2017p13.1%20Lead.pdfe83119eec1267cdcf9dc571d78ff4028MD52TEXTDosage Changes of a Segment at 17p13.1 Lead.pdf.txtDosage Changes of a Segment at 17p13.1 Lead.pdf.txtExtracted texttext/plain68031https://www.arca.fiocruz.br/bitstream/icict/11402/3/Dosage%20Changes%20of%20a%20Segment%20at%2017p13.1%20Lead.pdf.txt063a6c4e2a472cbc301843f955b1ac33MD53icict/114022019-06-19 10:12:10.541oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:12:10Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| title |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| spellingShingle |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes Fonseca, Claudia Marcia Benedetto de Carvalho Abnormalities, Multiple/genetics Chromosomes, Human, Pair 17/genetics Molecular Sequence Data Sequence Analysis, DNA |
| title_short |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| title_full |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| title_fullStr |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| title_full_unstemmed |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| title_sort |
Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes |
| author |
Fonseca, Claudia Marcia Benedetto de Carvalho |
| author_facet |
Fonseca, Claudia Marcia Benedetto de Carvalho Vasanth, Shivakumar Shinawi, Marwan Russell, Chad Ramocki, Melissa B. Brown, Chester W. Graakjaer, Jesper Bine Skytte, Anne Morgante, Angela Maria Vianna Krepischi, Ana Cristina Victorino Patel, Gayle S. Immken, LaDonna Aleck, Kyrieckos Lim, Cynthia Cheung, Sau Wai Rosenberg, Carla Katsanis, Nicholas |
| author_role |
author |
| author2 |
Vasanth, Shivakumar Shinawi, Marwan Russell, Chad Ramocki, Melissa B. Brown, Chester W. Graakjaer, Jesper Bine Skytte, Anne Morgante, Angela Maria Vianna Krepischi, Ana Cristina Victorino Patel, Gayle S. Immken, LaDonna Aleck, Kyrieckos Lim, Cynthia Cheung, Sau Wai Rosenberg, Carla Katsanis, Nicholas |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Fonseca, Claudia Marcia Benedetto de Carvalho Vasanth, Shivakumar Shinawi, Marwan Russell, Chad Ramocki, Melissa B. Brown, Chester W. Graakjaer, Jesper Bine Skytte, Anne Morgante, Angela Maria Vianna Krepischi, Ana Cristina Victorino Patel, Gayle S. Immken, LaDonna Aleck, Kyrieckos Lim, Cynthia Cheung, Sau Wai Rosenberg, Carla Katsanis, Nicholas |
| dc.subject.en.pt_BR.fl_str_mv |
Abnormalities, Multiple/genetics Chromosomes, Human, Pair 17/genetics Molecular Sequence Data Sequence Analysis, DNA |
| topic |
Abnormalities, Multiple/genetics Chromosomes, Human, Pair 17/genetics Molecular Sequence Data Sequence Analysis, DNA |
| description |
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA /Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil |
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2014 |
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2014 |
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2015-07-23T16:05:33Z |
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2015-07-23T16:05:33Z |
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info:eu-repo/semantics/article |
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CARVALHO, Claudia Marcia Benedetto et al. Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes. Am J Hum Genet. 2014 Nov 6;95(5):565-78. |
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https://www.arca.fiocruz.br/handle/icict/11402 |
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0002-9297 |
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10.1016/j.ajhg.2014.10.006 |
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CARVALHO, Claudia Marcia Benedetto et al. Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes. Am J Hum Genet. 2014 Nov 6;95(5):565-78. 0002-9297 10.1016/j.ajhg.2014.10.006 |
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