title: DNA instability and human disease.
abstract: It is now well established that non-Mendelian examples of DNA instability are associated with human disease. Most malignancies are associated with various chromosomal instabilities, such as aneuploidy, gene amplification, and chromosomal deletion. Furthermore, widespread microsatellite instability (MSI) is associated with a variety of tumors, and instability at specific dynamic repeat expansions underlies a family of neurologic disorders. Inactivation of DNA mismatch repair genes results in genomic instabilities affecting microsatellite regions. Mutations in genes involved in DNA polymerization or Okazaki fragment processing are also associated with MSI. Such instabilities convey a 'mutator' phenotype which is pathogenic. The mechanisms controlling trinucleotide repeat expansions are less well understood. Why this type of genomic instability is particularly pathogenic to neurons is also not clear. An understanding of what normally maintains stability is the first step towards preventing such loss of control and maintaining health.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Canada.
authors.forename: S E
authors.initials: SE
authors.lastname: Andrew
authors.forename: A C
authors.initials: AC
authors.lastname: Peters
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D018911:Trinucleotide Repeats
chemical_list: D004247:DNA