Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements.
Document Type
Article
Publication Date
8-3-2017
JAX Source
Am J Hum Genet 2017 Aug 3; 49(8):1427-1439
Volume
101
Issue
2
First Page
206
Last Page
217
ISSN
1537-6605
PMID
28735859
DOI
https://doi.org/10.1016/j.ajhg.2017.06.011
Abstract
Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly associated with the subjects' phenotypes. We confirm gene-expression changes for a couple of candidate genes to exemplify the utility of our analysis of position effect. These results highlight the important interplay between chromosomal structure and disease and demonstrate the need to utilize chromatin conformational data for the prediction of position effects in the clinical interpretation of non-coding chromosomal rearrangements. Am J Hum Genet 2017 Aug 3; 49(8):1427-1439.
Recommended Citation
Zepeda-Mendoza C,
Ibn-Salem J,
Kammin T,
Harris D,
Rita D,
Gripp K,
MacKenzie J,
Gropman A,
Graham B,
Shaheen R,
Alkuraya F,
Brasington C,
Spence E,
Masser-Frye D,
Bird L,
Spiegel E,
Sparkes R,
Ordulu Z,
Talkowski M,
Andrade-Navarro M,
Robinson P,
Morton C.
Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements. Am J Hum Genet 2017 Aug 3; 49(8):1427-1439