MOLECULARMECHANISMS FORGENOMICDISORDERS
- 1 September 2002
- journal article
- review article
- Published by Annual Reviews in Annual Review of Genomics and Human Genetics
- Vol. 3 (1), 199-242
- https://doi.org/10.1146/annurev.genom.3.032802.120023
Abstract
▪ Abstract Genomic rearrangements play a major role in the pathogenesis of human genetic diseases. Nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) that flank unique genomic segments results in changes of genome organization and can cause a loss or gain of genomic segments. These LCRs appear to have arisen recently during primate speciation via paralogous segmental duplication, thus making the human species particularly susceptible to genomic rearrangements. Genomic disorders are defined as a group of diseases that result from genomic rearrangements, mostly mediated by NAHR. Molecular investigations of genomic disorders have revealed genome architectural features associated with susceptibility to rearrangements and the recombination mechanisms responsible for such rearrangements. The human genome sequence project reveals that LCRs may account for 5% of the genome, suggesting that many novel genomic disorders might still remain to be recognized.Keywords
This publication has 102 references indexed in Scilit:
- Recombination at Double-Strand Breaks and DNA Ends: Conserved Mechanisms from Phage to HumansMolecular Cell, 2001
- Positive selection of a gene family during the emergence of humans and African apesNature, 2001
- Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome armsGenes, Chromosomes and Cancer, 2001
- Integration of cytogenetic landmarks into the draft sequence of the human genomeNature, 2001
- Initial sequencing and analysis of the human genomeNature, 2001
- Fine-Scale Comparative Mapping of the Human 7q11.23 Region and the Orthologous Region on Mouse Chromosome 5G: The Low-Copy Repeats That Flank the Williams–Beuren Syndrome Deletion Arose at Breakpoint Sites of an Evolutionary Inversion(s)Genomics, 2000
- Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndromeNature Genetics, 1997
- Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1Nature Genetics, 1997
- Chromsome synapsis and genetic recombination: their roles in meiotic chromsome segregationTrends in Genetics, 1990
- Contiguous gene syndromes: A component of recognizable syndromesThe Journal of Pediatrics, 1986