학술논문

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes
Original Article
Document Type
Report
Author
Loviglio, M NLeleu, MMännik, KPasseggeri, MGiannuzzi, Gvan der Werf, IWaszak, S MZazhytska, MRoberts-Caldeira, IGheldof, NMigliavacca, EAlfaiz, A AHippolyte, LMaillard, A MLoviglio, Maria NiclaMännik, Katrinvan der Werf, IlseGiannuzzi, GiulianaZazhytska, MariannaGheldof, NeleMigliavacca, EugeniaAlfaiz, Ali ARoberts-Caldeira, InêsHippolyte, LoyseMaillard, Anne MFerrarini, AlessandraButschi, Florence NielConrad, BernardAddor, Marie-ClaudeBelfiore, MarcoRoetzer, KatharinaDijck, Anke VanBlaumeiser, BettinaKooy, FrankRoelens, FilipDheedene, AnneliesChiaie, Barbara DelleMenten, BjörnOostra, AnnCaberg, Jean-HubertCarter, MelissaKellam, BarbaraStavropoulos, Dimitri JMarshall, ChristianScherer, Stephen WWeksberg, RosannaCytrynbaum, CherylBassett, AnneLowther, ChelseaGillis, JaneMacKay, SaraBache, IbenOusager, Lilian BSmerdel, Maja PatriciaGraakjaer, JesperKjaergaard, SusanneMetspalu, AndresMathieu, MicheleBonneau, DominiqueGuichet, AgnesParent, PhilippeFérec, ClaudeGerard, MarionPlessis, GhislaineLespinasse, JamesMasurel, AliceMarle, NathalieFaivre, LaurenceCallier, PatrickLayet, ValerieMeur, Nathalie LeLe Goff, CélineDuban-Bedu, BénédicteSukno, SylvieBoute, OdileAndrieux, JorisBlanchet, PatriciaGeneviève, DavidPuechberty, JacquesSchneider, AnouckLeheup, BrunoJonveaux, PhilippeMercier, SandraDavid, AlbertLe Caignec, Cédricde Pontual, LoicPipiras, EvaJacquette, AureliaKeren, BorisGilbert-Dussardier, BrigitteBilan, FredericGoldenberg, AliceChambon, PascalToutain, AnnickTill, MarianneSanlaville, DamienLeube, BarbaraRoyer-Pokora, BrigitteGrabe, Hans JörgenSchmidt, Carsten OliverSchurmann, ClaudiaHomuth, GeorgThorleifsson, GudmarThorsteinsdottir, UnnurBernardini, LauraNovelli, AntonioMicale, LuciaMerla, GiuseppeZollino, MarcellaMari, FrancescaRizzo, Caterina LoRenieri, AlessandraSilengo, MargheritaVulto-van Silfhout, Anneke TSchouten, MeykePfundt, Rolphde Leeuw, NicoleVansenne, FleurMaas, Saskia MBarge-Schaapveld, Daniela QCMKnegt, Alida CStadheim, BarbroRodningen, OlaugHouge, GunnarPrice, SueHawkes, LaraCampbell, CarolynKini, UshaVogt, JulieWalters, RobinBlakemore, AlexandraGusella, James FShen, YipingScott, DarylBacino, Carlos ATsuchiya, KarenLadda, RogerSell, SusanAsamoah, AlexanderHamati, Aline IRosenfeld, Jill AShaffer, Lisa GMitchell, ElyseHodge, Jennelle CBeckmann, Jacques SJacquemont, SébastienReymond, AlexandreEwans, Lisa JMowat, DavidWalker, JanAmor, David JEsch, Hilde VanLeroy, PatriciaBamforth, John-StevenBabu, DeeptiIsidor, BertrandDiDonato, NataliyaHackmann, KarlPasseggeri, MarziaHaeringen, Arie vanSmith, RosemarieEllingwood, SaraFarber, Darren MPuri, VinayZadeh, NedaWeaver, David DMiller, MandyWilks, TimothyJorgez, Carolina JLafayette, DeeDeeVan Dijck, AKooy, R FSanlaville, DRosenfeld, J AShaffer, L GAndrieux, JMarshall, CScherer, S WShen, YGusella, J FThorsteinsdottir, UThorleifsson, GDermitzakis, E TDeplancke, BBeckmann, J SRougemont, JJacquemont, SReymond, A
Source
Molecular Psychiatry. June 2017, Vol. 22 Issue 6, 836
Subject
Diagnosis
Genetic aspects
Health aspects
Chromosomes -- Health aspects
Cephalometry -- Genetic aspects
Body mass index -- Genetic aspects
Autism -- Genetic aspects -- Diagnosis
Language
English
ISSN
1359-4184
Abstract
Author(s): M N Loviglio [1]; M Leleu [2, 3]; K Männik [1, 4]; M Passeggeri [5]; G Giannuzzi [1]; I van der Werf [1]; S M Waszak [2, 3, 6]; [...]
Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts%apos; maps could uncover functionally and clinically related genes. Molecular Psychiatry (2017) 22, 836-849; doi: 10.1038/mp.2016.84; published online 31 May 2016