title: Genome architecture, rearrangements and genomic disorders.
abstract: An increasing number of human diseases are recognized to result from recurrent DNA rearrangements involving unstable genomic regions. These are termed genomic disorders, in which the clinical phenotype is a consequence of abnormal dosage of gene(s) located within the rearranged genomic fragments. Both inter- and intrachromosomal rearrangements are facilitated by the presence of region-specific low-copy repeats (LCRs) and result from nonallelic homologous recombination (NAHR) between paralogous genomic segments. LCRs usually span approximately 10-400 kb of genomic DNA, share >or= 97% sequence identity, and provide the substrates for homologous recombination, thus predisposing the region to rearrangements. Moreover, it has been suggested that higher order genomic architecture involving LCRs plays a significant role in karyotypic evolution accompanying primate speciation.
authors.affiliation: Dept Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3498, USA.
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D001519:Behavior / Q000502:physiology; D004062:DiGeorge Syndrome / Q000235:genetics; D015321:Gene Rearrangement; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005821:Genetic Techniques; D015894:Genome, Human; D006801:Humans; D011218:Prader-Willi Syndrome / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D018980:Williams Syndrome / Q000235:genetics; D014960:X Chromosome; D014998:Y Chromosome