TY - JOUR
T1 - Structural variation in the 3D genome
AU - Spielmann, Malte
AU - Lupiáñez, Darío G.
AU - Mundlos, Stefan
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Ltd., part of Springer Nature. All rights reserved.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Structural and quantitative chromosomal rearrangements, collectively referred to as structural variation (SV), contribute to a large extent to the genetic diversity of the human genome and thus are of high relevance for cancer genetics, rare diseases and evolutionary genetics. Recent studies have shown that SVs can not only affect gene dosage but also modulate basic mechanisms of gene regulation. SVs can alter the copy number of regulatory elements or modify the 3D genome by disrupting higher-order chromatin organization such as topologically associating domains. As a result of these position effects, SVs can influence the expression of genes distant from the SV breakpoints, thereby causing disease. The impact of SVs on the 3D genome and on gene expression regulation has to be considered when interpreting the pathogenic potential of these variant types.
AB - Structural and quantitative chromosomal rearrangements, collectively referred to as structural variation (SV), contribute to a large extent to the genetic diversity of the human genome and thus are of high relevance for cancer genetics, rare diseases and evolutionary genetics. Recent studies have shown that SVs can not only affect gene dosage but also modulate basic mechanisms of gene regulation. SVs can alter the copy number of regulatory elements or modify the 3D genome by disrupting higher-order chromatin organization such as topologically associating domains. As a result of these position effects, SVs can influence the expression of genes distant from the SV breakpoints, thereby causing disease. The impact of SVs on the 3D genome and on gene expression regulation has to be considered when interpreting the pathogenic potential of these variant types.
UR - http://www.scopus.com/inward/record.url?scp=85045905339&partnerID=8YFLogxK
U2 - 10.1038/s41576-018-0007-0
DO - 10.1038/s41576-018-0007-0
M3 - Scientific review articles
C2 - 29692413
AN - SCOPUS:85045905339
SN - 1471-0056
VL - 19
SP - 453
EP - 467
JO - Nature Reviews Genetics
JF - Nature Reviews Genetics
IS - 7
ER -