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Structural variation mutagenesis of the human genome: Impact on disease and evolution
Author(s) -
Lupski James R.
Publication year - 2015
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21943
Subject(s) - biology , structural variation , copy number variation , genetics , gene duplication , human genome , genome , genome instability , mutagenesis , mendelian inheritance , gene , genomics , chromothripsis , mutation , computational biology , dna , dna damage
Watson‐Crick base‐pair changes, or single‐nucleotide variants (SNV), have long been known as a source of mutations. However, the extent to which DNA structural variation, including duplication and deletion copy number variants (CNV) and copy number neutral inversions and translocations, contribute to human genome variation and disease has been appreciated only recently. Moreover, the potential complexity of structural variants (SV) was not envisioned; thus, the frequency of complex genomic rearrangements and how such events form remained a mystery. The concept of genomic disorders, diseases due to genomic rearrangements and not sequence‐based changes for which genomic architecture incite genomic instability, delineated a new category of conditions distinct from chromosomal syndromes and single‐gene Mendelian diseases. Nevertheless, it is the mechanistic understanding of CNV/SV formation that has promoted further understanding of human biology and disease and provided insights into human genome and gene evolution. Environ. Mol. Mutagen. 56:419–436, 2015. © 2015 Wiley Periodicals, Inc.