Using Change in Local DNA Sequence Complexity as a Pointer to the Mechanism of Mutagenesis in Inherited Disease


The vast majority of mutations causing human genetic disease are single base-pair substitutions and micro-deletions. However, a substantial proportion of the remainder involves the insertion of novel bases that serve to alter the reading frame leading to premature termination of translation. A relatively uncommon type of mutation is the indel, a complex lesion that appears to represent a combination of micro-deletion and micro-insertion. In the present study, we examine previously postulated mechanisms underlying micro-deletions and micro-insertions such as slipped mispairing and strand switching, secondary loop excision and quasi-palindrome correction, Moebius loop resolution and excision in terms of local DNA sequence complexity. Indels are regarded as being the result of a two-step deletion/insertion process. Data from the Human Gene Mutation Database (HGMD were used to compare and contrast 3767 micro-deletions, 1960 micro-insertions, and 211 indels. The change in complexity was found to be indicative of the type of repeat sequences involved in mediating the deletion/insertion event, which in turn provided pointers as to the possible pathways through which the mutations could have arisen.

Key words

sequence complexity micro-deletion micro-insertion indel mutagenesis 


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Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  1. 1.Department of Computer ScienceCardiff UniversityCardiffUK
  2. 2.Institute of Medical GeneticsUniversity of Wales College of MedicineCardiffUK

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