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The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

2016-11-14Journal article Restricted access
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dc.contributor.authorRedin, Claire
dc.contributor.authorBrand, Harrison
dc.contributor.authorCollins, Ryan L.
dc.contributor.authorKammin, Tammy
dc.contributor.authorMitchell, Elyse
dc.contributor.authorHodge, Jennelle C.
dc.contributor.authorHanscom, Carrie
dc.contributor.authorPillalamarri, Vamsee
dc.contributor.authorSeabra, Catarina M.
dc.contributor.authorAbbott, Mary-Alice
dc.contributor.authorAbdul-Rahman, Omar A.
dc.contributor.authorde Vries, Bert B A.
dc.contributor.authorEarl, Dawn L.
dc.contributor.authorFerguson, Heather L.
dc.contributor.authorHarris, David J.
dc.contributor.authorFisher, Heather
dc.contributor.authorFitzPatrick, David R.
dc.contributor.authorGerrol, Pamela
dc.contributor.authorGiachino, Daniela
dc.contributor.authorGlessner, Joseph T.
dc.contributor.authorGliem, Troy
dc.contributor.authorMargolin, Lauren
dc.contributor.authorGrady, Margo
dc.contributor.authorGraham, Brett H.
dc.contributor.authorGriffis, Cristin
dc.contributor.authorHayden, Mark A.
dc.contributor.authorHill, Rosamund
dc.contributor.authorHochstenbach, Ron
dc.contributor.authorHoffman, Jodi D.
dc.contributor.authorHopkin, Robert J.
dc.contributor.authorHubshman, Monika W.
dc.contributor.authorMoya, Graciela
dc.contributor.authorMason, Tamara
dc.contributor.authorInnes, A Micheil
dc.contributor.authorIrons, Mira
dc.contributor.authorIrving, Melita
dc.contributor.authorJacobsen, Jessie C.
dc.contributor.authorJanssens, Sandra
dc.contributor.authorJewett, Tamison
dc.contributor.authorJohnson, John P.
dc.contributor.authorJongmans, Marjolijn C.
dc.contributor.authorKahler, Stephen G.
dc.contributor.authorKoolen, David A.
dc.contributor.authorMasser-Frye, Diane
dc.contributor.authorNieuwint, Aggie W.
dc.contributor.authorKorzelius, Jerome
dc.contributor.authorKroisel, Peter M.
dc.contributor.authorLacassie, Yves
dc.contributor.authorLawless, William
dc.contributor.authorLemyre, Emmanuelle
dc.contributor.authorLeppig, Kathleen
dc.contributor.authorLevin, Alex V.
dc.contributor.authorLi, Haibo
dc.contributor.authorLi, Hong
dc.contributor.authorParkash, Sandhya
dc.contributor.authorLiao, Eric C.
dc.contributor.authorOrdulu, Zehra
dc.contributor.authorLim, Cynthia
dc.contributor.authorLose, Edward J.
dc.contributor.authorLucente, Diane
dc.contributor.authorMacera, Michael J.
dc.contributor.authorManavalan, Poornima
dc.contributor.authorMandrile, Giorgia
dc.contributor.authorMarcelis, Carlo L.
dc.contributor.authorMcClellan, Michael W.
dc.contributor.authorMendoza, Cinthya J. Zepeda
dc.contributor.authorMenten, Björn
dc.contributor.authorMiddelkamp, Sjors
dc.contributor.authorMikami, Liya R.
dc.contributor.authorMoe, Emily
dc.contributor.authorWiley, Susan
dc.contributor.authorMohammed, Shehla
dc.contributor.authorMononen, Tarja
dc.contributor.authorMortenson, Megan E.
dc.contributor.authorPauker, Susan P.
dc.contributor.authorPereira, Shahrin
dc.contributor.authorPerrin, Danielle
dc.contributor.authorPhelan, Katy
dc.contributor.authorAguilar, Raul E Piña
dc.contributor.authorPoddighe, Pino J.
dc.contributor.authorAberg, Erika
dc.contributor.authorWilson, Anna
dc.contributor.authorPregno, Giulia
dc.contributor.authorRaskin, Salmo
dc.contributor.authorReis, Linda
dc.contributor.authorRhead, William
dc.contributor.authorRita, Debra
dc.contributor.authorRenkens, Ivo
dc.contributor.authorRoelens, Filip
dc.contributor.authorRuliera, Jayla
dc.contributor.authorRump, Patrick
dc.contributor.authorSchilit, Samantha L.P.
dc.contributor.authorYerena-de Vega, Maria de la Concepcion A.
dc.contributor.authorAdley, Rhett
dc.contributor.authorShaheen, Ranad
dc.contributor.authorSparkes, Rebecca
dc.contributor.authorSpiegel, Erica
dc.contributor.authorStevens, Blair
dc.contributor.authorStone, Matthew R.
dc.contributor.authorTagoe, Julia
dc.contributor.authorThakuria, Joseph V.
dc.contributor.authorvan Bon, Bregje W.
dc.contributor.authorvan de Kamp, Jiddeke
dc.contributor.authorAlkuraya, Fowzan S.
dc.contributor.authorvan Der Burgt, Ineke
dc.contributor.authorAlcaraz-Estrada, Sofia L.
dc.contributor.authorvan Essen, Ton
dc.contributor.authorvan Ravenswaaij-Arts, Conny M.
dc.contributor.authorvan Roosmalen, Markus J.
dc.contributor.authorVergult, Sarah
dc.contributor.authorVolker-Touw, Catharina M.L.
dc.contributor.authorWarburton, Dorothy P.
dc.contributor.authorWaterman, Matthew J.
dc.contributor.authorZori, Roberto T.
dc.contributor.authorLevy, Brynn
dc.contributor.authorBrunner, Han G.
dc.contributor.authorde Leeuw, Nicole
dc.contributor.authorKloosterman, Wigard P.
dc.contributor.authorThorland, Erik C.
dc.contributor.authorGripp, Karen W.
dc.contributor.authorMorton, Cynthia C.
dc.contributor.authorGusella, James F.
dc.contributor.authorTalkowski, Michael E.
dc.contributor.authorAn, Yu
dc.contributor.authorAnderson, Mary-Anne
dc.contributor.authorAntolik, Caroline
dc.contributor.authorAnyane-Yeboa, Kwame
dc.contributor.authorAtkin, Joan F.
dc.contributor.authorBartell, Tina
dc.contributor.authorBernstein, Jonathan A.
dc.contributor.authorGropman, Andrea L.
dc.contributor.authorBeyer, Elizabeth
dc.contributor.authorBlumenthal, Ian
dc.contributor.authorBongers, Ernie M.H.F.
dc.contributor.authorBrilstra, Eva H.
dc.contributor.authorBrown, Chester W.
dc.contributor.authorBrüggenwirth, Hennie T.
dc.contributor.authorCallewaert, Bert
dc.contributor.authorChiang, Colby
dc.contributor.authorCorning, Ken
dc.contributor.authorCox, Helen
dc.contributor.authorHanson-Kahn, Andrea
dc.contributor.authorCuppen, Edwin
dc.contributor.authorCurrall, Benjamin B.
dc.contributor.authorCushing, Tom
dc.contributor.authorDavid, Dezső
dc.contributor.authorDeardorff, Matthew A.
dc.contributor.authorDheedene, Annelies
dc.contributor.authorD'Hooghe, Marc
dc.date.accessioned2017-03-03T17:09:28Z
dc.date.available2017-03-03T17:09:28Z
dc.date.issued2016-11-14
dc.description.abstractDespite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Genet. 2017 Jan;49(1):36-45. doi: 10.1038/ng.3720. Epub 2016 Nov 14.pt_PT
dc.identifier.doi10.1038/ng.3720pt_PT
dc.identifier.issn1061-4036
dc.identifier.urihttp://hdl.handle.net/10400.18/4461
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relation.publisherversionhttp://www.nature.com/ng/journal/v49/n1/full/ng.3720.htmlpt_PT
dc.subjectCytogeneticspt_PT
dc.subjectStructural Variationpt_PT
dc.subjectBalanced Chromosomal Abnormalitypt_PT
dc.subjectCongenital Anomalypt_PT
dc.subjectIntellectual Disabilitypt_PT
dc.subjectAutismpt_PT
dc.subjectTranslocationpt_PT
dc.subjectInversionpt_PT
dc.subjectChromothripsispt_PT
dc.subjectTopologically Associated Domain (TAD)pt_PT
dc.subjectMEF2Cpt_PT
dc.subjectCytogenetic Abnormalitiespt_PT
dc.subjectHuman Congenital Anomaliespt_PT
dc.subjectDoenças Genómicaspt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleThe genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomaliespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage45pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage36pt_PT
oaire.citation.titleNature Geneticspt_PT
oaire.citation.volume49pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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