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Early results of next-gen cytogenetics implementation in Portugal

2016-05Conference object Open access
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dc.contributor.authorDavid, Dezső
dc.contributor.authorFreixo, João
dc.contributor.authorMarques, Bárbara
dc.contributor.authorCarvalho, Inês
dc.contributor.authorTkachenko, Natália
dc.contributor.authorOliva-Teles, Natália
dc.contributor.authorMarques, Mariana
dc.contributor.authorCardoso, Manuela
dc.contributor.authorFino, Joana
dc.contributor.authorAlves, Cristina
dc.contributor.authorFortuna, Ana
dc.contributor.authorSófia, Dória
dc.contributor.authorPinto de Moura, Carla
dc.contributor.authorCorreia, Hildeberto
dc.contributor.authorMarques Carreira, Isabel
dc.contributor.authorSá, Joaquim
dc.contributor.authorGonçalves, Rui Miguel
dc.contributor.authorLavinha, João
dc.contributor.authorKay, Teresa
dc.contributor.authorTalkowski, Michael
dc.contributor.authorMorton, Cynthia
dc.date.accessioned2017-03-03T16:32:29Z
dc.date.available2017-03-03T16:32:29Z
dc.date.issued2016-05
dc.descriptionAbstract publicado em: Eur J Hum Gen.2016;24(S1):228. P11.027pt_PT
dc.description.abstractBackground: Most approaches are insensitive to the full mutational spectrum of chromosome rearrangements associated with human developmental abnormalities. Therefore, our aim is to introduce next-generation sequencing (NGS) into clinical cytogenetics, creating a sequence-based NextGen Cytogenetics to catalyze a dramatic advancement in clinical diagnostics. Methods: Twenty families with chromosome rearrangement-associated diseases, including two prenatal (PN) cases, have been enrolled. Fourteen of these were also analyzed by NGS using large-insert paired-end libraries. Results: The majority of these cases were confirmed to be balanced reciprocal rearrangements, whereas 4 were complex chromosomal rearrangements including 1 of chromothripsis. Thus far, over 50 breakpoints were identified disrupting protein coding genes, lncRNAs, or intergenic regions, thus revealing candidate genes or genomic loci. These cases are further assessed for pathogenicity from positional effects on genes located within topological domains (TADs) containing the breakpoints using DECIPHER predictions of haploinsufficiency. In one PN case, the 16q24 breakpoint disrupts ANKRD11, etiologic in the autosomal dominant KBG syndrome (OMIM #148050), predicting an abnormal phenotype. The chromothripsis case, submitted as 46,XY,t(7;14)(q22;q32.1),inv(15)(q21.2q26.1), proved by NGS to carry two further deletions, at 3p12 (5.3 Mb) and 15q14 (488 kb), as well as an insertion of 644.4 kb from 15q14 into 3p14. The inv(15) is in fact a complex rearrangement of 15q with eight breakpoints. Conclusions: We demonstrate that NGS-based chromosomal rearrangement characterization leads to major improvements in identification of chromosomal aberrations and in prediction of clinical outcomes of postnatally and prenatally detected genomic rearrangements, and to contributions to human genome annotation.pt_PT
dc.description.sponsorshipFCT HMSP-ICT/0016/2013pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/4457
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectChromosome Rearrangementspt_PT
dc.subjectDevelopmental Abnormalitiespt_PT
dc.subjectANKRD11pt_PT
dc.subjectDoenças Genómicaspt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectPortugal
dc.titleEarly results of next-gen cytogenetics implementation in Portugalpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0016%2F2013/PT
oaire.citation.conferencePlaceBarcelona, Espanhapt_PT
oaire.citation.titleEuropean Journal Human Genetics Conference, 21-24 May 2016pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication55f3392d-71be-4224-bedd-9feb4a06c428
relation.isProjectOfPublication.latestForDiscovery55f3392d-71be-4224-bedd-9feb4a06c428

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