Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_8773892CB036
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.
Journal
Molecular Psychiatry
Working group(s)
2p15 Consortium, 16p11.2 Consortium
Contributor(s)
Loviglio M.N., Männik K., van der Werf I., Giannuzzi G., Zazhytska M., Gheldof N., Migliavacca E., Alfaiz A.A., Roberts-Caldeira I., Hippolyte L., Maillard A.M., Ferrarini A., Butschi F.N., Conrad B., Addor M.C., Belfiore M., Roetzer K., Dijck A.V., Blaumeiser B., Kooy F., Roelens F., Dheedene A., Chiaie B.D., Menten B., Oostra A., Caberg J.H., Carter M., Kellam B., Stavropoulos D.J., Marshall C., Scherer S.W., Weksberg R., Cytrynbaum C., Bassett A., Lowther C., Gillis J., MacKay S., Bache I., Ousager L.B., Smerdel M.P., 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 N.L., 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 H.J., Schmidt C.O., Schurmann C., Homuth G., Thorleifsson G., Thorsteinsdottir U., Bernardini L., Novelli A., Micale L., Merla G., Zollino M., Mari F., Rizzo C.L., Renieri A., Silengo M., Vulto-van Silfhout A.T., Schouten M., Pfundt R., de Leeuw N., Vansenne F., Maas S.M., Barge-Schaapveld D.Q., Knegt A.C., Stadheim B., Rodningen O., Houge G., Price S., Hawkes L., Campbell C., Kini U., Vogt J., Walters R., Blakemore A., Gusella J.F., Shen Y., Scott D., Bacino C.A., Tsuchiya K., Ladda R., Sell S., Asamoah A., Hamati A.I., Rosenfeld J.A., Shaffer L.G., Mitchell E., Hodge J.C., Beckmann J.S., Jacquemont S., Reymond A., Reymond A., Ewans L.J., Mowat D., Walker J., Amor D.J., Esch H.V., Leroy P., Caberg J.H., Bamforth J.S., Babu D., Till M., Sanlaville D., Geneviève D., Puechberty J., Isidor B., DiDonato N., Hackmann K., Passeggeri M., Haeringen A.V., Rosenfeld J.A., Shaffer L.G., Smith R., Ellingwood S., Farber D.M., Puri V., Zadeh N., Weaver D.D., Miller M., Wilks T., Jorgez C.J., Lafayette D., Jacquemont S.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
22
Number
6
Pages
836-849
Language
english
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2016 9:42
Last modification date
20/08/2019 14:46
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