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Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Title: Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes
Authors: Loviglio, M. N; Leleu, M.; Männik, K.; Passeggeri, M.; Giannuzzi, G.; van der Werf, I.; Waszak, S. M.; Zazhytska, M.; Roberts Caldeira, I.; Gheldof, N.; Migliavacca, E.; Alfaiz, A. A.; Hippolyte, L.; Maillard, A. M.; van Dijck, A.; Kooy, R. F.; Sanlaville, D.; Rosenfeld, J. A.; Shaffer, L. G.; Andrieux, J.; Marshall, C.; Scherer, S. W.; Shen, Y.; Gusella, J. F.; Thorsteinsdottir, U.; Thorleifsson, G.; Dermitzakis, E. T.; Deplancke, B.; Beckmann, J. S.; Rougemont, J.; Jacquemont, S.; Reymond, A.; Collaborators: Loviglio MN; Männik K; van der Werf I; Giannuzzi G; Zazhytska M; Gheldof N; Migliavacca E; Alfaiz AA; Roberts Caldeira I; Hippolyte L; Maillard AM; Ferrarini A; Butschi FN; Conrad B; Addor MC; Belfiore M; Roetzer K; Dijck AV; Blaumeiser B; Kooy F; Roelens F; Dheedene A; Chiaie BD; Menten B; Oostra A; Caberg JH; Carter M; Kellam B; Stavropoulos DJ; Marshall C; Scherer SW; Weksberg R; Cytrynbaum C; Bassett A; Lowther C; Gillis J; MacKay S; Bache I; Ousager LB; Smerdel MP; Graakjaer J; Kjaergaard S; Metspalu A; Mathieu M; Bonneau D; Guichet A; Parent P; Férec C; Gerard M; Plessis G; Lespinasse J; Masurel A; Marle N; Faivre L; Callier P; Layet V; Meur NL; Le Goff C; Duban Bedu B; Sukno S; Boute O; Andrieux J; Blanchet P; Geneviève D; Puechberty J; Schneider A; Leheup B; Jonveaux P; Mercier S; David A; Le Caignec C; de Pontual L; Pipiras E; Jacquette A; Keren B; Gilbert Dussardier B; Bilan F; Goldenberg A; Chambon P; Toutain A; Till M; Sanlaville D; Leube B; Royer Pokora B; Grabe HJ; Schmidt CO; Schurmann C; Homuth G; Thorleifsson G; Thorsteinsdottir U; Bernardini L; Novelli A; Micale L; Merla G; Zollino M; MARI, FRANCESCA; Rizzo CL; RENIERI, ALESSANDRA; Silengo M; Vulto van Silfhout AT; Schouten M; Pfundt R; de Leeuw N; Vansenne F; Maas SM; Barge Schaapveld DQ; Knegt AC; Stadheim B; Rodningen O; Houge G; Price S; Hawkes L; Campbell C; Kini U; Vogt J; Walters R; Blakemore A; Gusella JF; Shen Y; Scott D; Bacino CA; Tsuchiya K; Ladda R; Sell S; Asamoah A; Hamati AI; Rosenfeld JA; Shaffer LG; Mitchell E; Hodge JC; Beckmann JS; Jacquemont S; Reymond A; Ewans LJ; Mowat D; Walker J; Amor DJ; Esch HV; Leroy P; Bamforth JS; Babu D; Isidor B; DiDonato N; Hackmann K; Passeggeri M; Haeringen AV; Smith R; Ellingwood S; Farber DM; Puri V; Zadeh N; Weaver DD; Miller M; Wilks T; Jorgez CJ; Lafayette D; Jacquemont S.
Contributors: Loviglio, M. N; Leleu, M.; Männik, K.; Passeggeri, M.; Giannuzzi, G.; van der Werf, I.; Waszak, S. M.; Zazhytska, M.; Roberts Caldeira, I.; Gheldof, N.; Migliavacca, E.; Alfaiz, A. A.; Hippolyte, L.; Maillard, A. M.; van Dijck, A.; Kooy, R. F.; Sanlaville, D.; Rosenfeld, J. A.; Shaffer, L. G.; Andrieux, J.; Marshall, C.; Scherer, S. W.; Shen, Y.; Gusella, J. F.; Thorsteinsdottir, U.; Thorleifsson, G.; Dermitzakis, E. T.; Deplancke, B.; Beckmann, J. S.; Rougemont, J.; Jacquemont, S.; Reymond, A.; Collaborators: Loviglio, Mn; Männik, K; van der Werf, I; Giannuzzi, G; Zazhytska, M; Gheldof, N; Migliavacca, E; Alfaiz, Aa; Roberts Caldeira, I; Hippolyte, L; Maillard, Am; Ferrarini, A; Butschi, Fn; Conrad, B; Addor, Mc; Belfiore, M; Roetzer, K; Dijck, Av; Blaumeiser, B; Kooy, F; Roelens, F; Dheedene, A; Chiaie, Bd; Menten, B; Oostra, A; Caberg, Jh; Carter, M; Kellam, B; Stavropoulos, Dj; Marshall, C; Scherer, Sw; Weksberg, R; Cytrynbaum, C; Bassett, A; Lowther, C; Gillis, J; Mackay, S; Bache, I; Ousager, Lb; Smerdel, Mp; Graakjaer, J; Kjaergaard, S; Metspalu, A; Mathieu, M; Bonneau, D; Guichet, A; Parent, P; Férec, C; Gerard, M; Plessis, G; Lespinasse, J; Masurel, A; Marle, N; Faivre, L; Callier, P; Layet, V; Meur, Nl; Le Goff, C; Duban Bedu, B; Sukno, S; Boute, O; Andrieux, J; Blanchet, P; Geneviève, D; Puechberty, J; Schneider, A; Leheup, B; Jonveaux, P
Publication Year: 2017
Collection: Università degli Studi di Siena: USiena air
Subject Terms: Molecular Biology; Cellular and Molecular Neuroscience; Psychiatry and Mental Health
Description: 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’ maps could uncover functionally and clinically related genes.Molecular Psychiatry advance online publication, 31 May 2016; doi:10.1038/mp.2016.84.
Document Type: article in journal/newspaper
File Description: STAMPA
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/27240531; info:eu-repo/semantics/altIdentifier/wos/WOS:000401702800007; volume:22; issue:6; firstpage:836; lastpage:849; numberofpages:14; journal:MOLECULAR PSYCHIATRY; http://hdl.handle.net/11365/1010224; https://www.nature.com/articles/mp201684
DOI: 10.1038/mp.2016.84
Availability: http://hdl.handle.net/11365/1010224; https://doi.org/10.1038/mp.2016.84; https://www.nature.com/articles/mp201684
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.9DA7AA5C
Database: BASE