title: Mechanisms for recurrent and complex human genomic rearrangements.
abstract: During the last two decades, the importance of human genome copy number variation (CNV) in disease has become widely recognized. However, much is not understood about underlying mechanisms. We show how, although model organism research guides molecular understanding, important insights are gained from study of the wealth of information available in the clinic. We describe progress in explaining nonallelic homologous recombination (NAHR), a major cause of copy number change occurring when control of allelic recombination fails, highlight the growing importance of replicative mechanisms to explain complex events, and describe progress in understanding extreme chromosome reorganization (chromothripsis). Both nonhomologous end-joining and aberrant replication have significant roles in chromothripsis. As we study CNV, the processes underlying human genome evolution are revealed.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Carvalho
authors.forename: P J
authors.initials: PJ
authors.lastname: Hastings
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000483:Alleles; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations; D059766:DNA End-Joining Repair; D004261:DNA Replication; D015321:Gene Rearrangement; D030342:Genetic Diseases, Inborn / Q000235:genetics; D015894:Genome, Human; D042822:Genomic Instability; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans
chemical_list: D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human