Till recently, mutations in genes were described in textbooks as deletions or point mutations. These mutations can be inherited from a parent or they are de novo alterations. The discovery in 1991 that human disease can be caused by large-scale ex pansion of highly unstable trinucleotide repeats has elucidated a new mutation mechanism, heritable unstable DNA. In the subsequent years more then 10 such disease genes have been identified. All dynamic mutations have been iden tified in neurological disorders. There are ten possible trinucleotide repeats at the DNA level, but only 3 have been identified as being involved in human dis eases. The rather frequent occurence of triplet repeats in the human genome indicates that other loci subject to unstable expansions may be discovered. The identification of repeat instability and the identification of disease genes containing trinucleotide repeats has helped to answer intriguing questions. The diseases share the unusual characteristic of inheritance with increased disease severity in successive gernerations, a phenomenon called anticipation. Trinu cleotide repeat diseases are ideal subjects for direct testing because the muta tion is almost exclusively of the same type and there is an extremely low occur ance of new mutations in these diseases. The anticipation can now be explained by the correlation of increasing repeat length with increased disease serverity. It can be speculated that other neurological disorders showing anticipation will be caused by unstable repeats as well.

Describes the common molecular basis of a diverse series of human diseases, and how this knowledge can be used in diagnosis

Klappentext

The discovery in 1991 that human diseases can be caused by large-scale expansion of highly unstable trinucleotide repeats has elucidated a new mutation mechanism: heritable unstable DNA. There are ten possible trinucleotide repeats at the DNA level, but only three have been identified to be involved in human diseases. On the basis of three disease genes, this book provides an overview of the different types of repeat instability in genes and describes how this knowledge can be used diagnostically. The diseases share the unusual characteristic of inheritance with increased severity in successive generations, a phenomenon called anticipation. The anticipation can now be explained by the correlation of increasing repeat length with increased disease severity.

Inhalt
The Fragile X Syndrome and Other Fragile Site Disorders.- Molecular Genetics of Huntington's Disease.- Myotonic Dystrophy.- Instabilities of Triplet Repeats: Factors and Mechanisms.