|
Title
|
|
|
|
Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes
| |
|
Author
|
|
|
|
| |
|
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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Molecular psychiatry. - London
| |
|
Publication
|
|
|
|
London
:
2017
| |
|
ISSN
|
|
|
|
1359-4184
| |
|
DOI
|
|
|
|
10.1038/MP.2016.84
| |
|
Volume/pages
|
|
|
|
22
:6
(2017)
, p. 836-849
| |
|
ISI
|
|
|
|
000401702800007
| |
|
Pubmed ID
|
|
|
|
27240531
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|