Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements
| Autor: | Lynne M. Bird, Fowzan S. Alkuraya, Jennifer MacKenzie, Rebecca Sparkes, Andrea L. Gropman, Cinthya J. Zepeda-Mendoza, Brett H. Graham, Campbell K. Brasington, Diane Masser-Frye, Zehra Ordulu, Debra Rita, Karen W. Gripp, Edward J. Spence, Jonas Ibn-Salem, Erica Spiegel, Ranad Shaheen, Michael E. Talkowski, Tammy Kammin, Cynthia C. Morton, Miguel A. Andrade-Navarro, Peter N. Robinson, David J. Harris |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Candidate gene diagnosis 030105 genetics & heredity Medical and Health Sciences cytogenetics Translocation Genetic chromosomal translocation Chromosome Breakpoints chromatin conformation balanced chromosomal rearrangement 2.1 Biological and endogenous factors Chromosomes Human Genetics(clinical) Aetiology Genetics (clinical) In Situ Hybridization In Situ Hybridization Fluorescence long-range effect Genetics Genetics & Heredity Gene Rearrangement Genome Chromosome Mapping Biological Sciences Chromatin Position effect Phenotype Medical genetics HPO Human distal effect medicine.medical_specialty Chromosome engineering chromosomal rearrangement Karyotype Translocation Chromosomal rearrangement Biology Chromosomes Fluorescence Article Chromosomal Position Effects 03 medical and health sciences Genetic Clinical Research medicine Humans Genetic Predisposition to Disease Gene Genome Human Human Genome Genetic Variation 030104 developmental biology Gene Expression Regulation Human genome clinical genetics |
| Zdroj: | American journal of human genetics, vol 101, iss 2 Zepeda-Mendoza, C J, Ibn-Salem, J, Kammin, T, Harris, D J, Rita, D, Gripp, K W, MacKenzie, J J, Gropman, A L, Graham, B H, Shaheen, R, Alkuraya, F S, Brasington, C K, Spence, E J, Masser-Frye, D, Bird, L M, Spiegel, E, Sparkes, R L, Ordulu, Z, Talkowski, M E, Andrade-Navarro, M A, Robinson, P N & Morton, C C 2017, ' Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements ', American Journal of Human Genetics . https://doi.org/10.1016/j.ajhg.2017.06.011 |
| ISSN: | 1537-6605 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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