Genome architecture, rearrangements and genomic disorders

Trends Genet. 2002 Feb;18(2):74-82. doi: 10.1016/s0168-9525(02)02592-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Behavior / physiology
  • DiGeorge Syndrome / genetics
  • Gene Rearrangement*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Techniques
  • Genome, Human*
  • Humans
  • Prader-Willi Syndrome / genetics
  • Sequence Homology, Nucleic Acid
  • Williams Syndrome / genetics
  • X Chromosome
  • Y Chromosome