Molecular-evolutionary mechanisms for genomic disorders

Curr Opin Genet Dev. 2002 Jun;12(3):312-9. doi: 10.1016/s0959-437x(02)00304-0.


Molecular studies of unstable regions in the human genome have identified region-specific low-copy repeats (LCRs). Unlike highly repetitive sequences (e.g. Alus and LINEs), LCRs are usually of 10-400 kb in size and exhibit > or = 95-97% similarity. According to computer analyses of available sequencing data, LCRs may constitute >5% of the human genome. Through the process of non-allelic homologous recombination using paralogous genomic segments as substrates, LCRs have been shown to facilitate meiotic DNA rearrangements associated with disease traits, referred to as genomic disorders. In addition, this LCR-based complex genome architecture appears to play a major role in both primate karyotype evolution and human tumorigenesis.

Publication types

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

MeSH terms

  • Animals
  • Charcot-Marie-Tooth Disease / genetics
  • Evolution, Molecular*
  • Gene Conversion
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Myelin Proteins / genetics
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Sequence Deletion
  • Williams Syndrome / genetics


  • Myelin Proteins
  • PMP22 protein, human