Abstract
Structural variant (SV) differences between human genomes can cause germline and mosaic disease as well as inter-individual variation. De-regulation of accurate DNA repair and genomic surveillance mechanisms results in a large number of SVs in cancer. Analysis of the DNA sequences at SV breakpoints can help identify pathways of mutagenesis and regions of the genome that are more susceptible to rearrangement. Large-scale SV analyses have been enabled by high-throughput genome-level sequencing on humans in the past decade. These studies have shed light on the mechanisms and prevalence of complex genomic rearrangements. Recent advancements in both sequencing and other mapping technologies as well as calling algorithms for detection of genomic rearrangements have helped propel SV detection into population-scale studies, and have begun to elucidate previously inaccessible regions of the genome. Here, we discuss the genomic organization of simple and complex SVs, the molecular mechanisms of their formation, and various ways to detect them. We also introduce methods for characterizing SVs and their consequences on human genomes.
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Abbreviations
- GRCh38:
-
Genome Reference Consortium Human Build 38
- HGR:
-
human genome reference
- HTS:
-
high-throughput sequencing
- WGS:
-
whole-genome sequencing
- SNV:
-
single-nucleotide variant (1 bp)
- InDel:
-
insertion and deletion (1 – 49 bp)
- SV:
-
structural variant (≥ 50 bp)
- DSB:
-
double-strand break
- CNV:
-
copy number variant
- bp:
-
base pair
- DEL:
-
deletion
- INS:
-
insertion
- MEI:
-
mobile element insertion
- DUP:
-
duplication
- TRP:
-
triplication
- INV:
-
inversion
- TRA:
-
translocation
- CGR:
-
complex genomic rearrangement
- LOH:
-
loss of heterozygosity
- SNP:
-
single-nucleotide polymorphism
- NHEJ:
-
non-homologous end joining
- NAHR:
-
non-allelic homologous recombination
- FoSTeS:
-
fork stalling and template switching
- MMBIR:
-
microhomology-mediated break-induced replication
- SSA:
-
single-strand annealing
- FISH:
-
fluorescence in situ hybridization
- aCGH:
-
array comparative genomic hybridization
- SCE:
-
sister chromatid exchange
- PacBio:
-
Pacific Biosciences
- CCS:
-
circular concensus sequencing
- CLR:
-
continuous long read
- ONT:
-
Oxford nanopore technologies
- SMRT:
-
single-molecule real time
- BrdU:
-
bromodeoxyuridine
- GEM:
-
gel-bead in emulsion
- IGV:
-
Integrative Genomics Viewer
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Acknowledgements
We thank the members of the Beck lab for reading and editing the review, in particular Alex V. Nesta. This work was supported in part by the National Institute of General Medical Sciences grants R00GM120453 and R35GM133600 and startup funds from the University of Connecticut Health and the Jackson Laboratory to Christine R. Beck.
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Balachandran, P., Beck, C.R. Structural variant identification and characterization. Chromosome Res 28, 31–47 (2020). https://doi.org/10.1007/s10577-019-09623-z
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DOI: https://doi.org/10.1007/s10577-019-09623-z