Tandem repeats in human disorders: mechanisms and evolution

Abstract

One of the most compelling reasons for the study of repetitive DNA sequence in the human genome has been the instability of simple repeat sequences associating with a growing and an interesting group of disorders affecting the neurological, neuromuscular or developmental processes. As a result, the molecular processes that underlie this unique form of mutation and the pathological pathways that lead to the disorders are being uncovered rapidly and are being intensively investigated. Genes with expanded repeats exhibit either loss-of-function or gain-of-function effect at the protein and/or RNA level. In this review, we aim to provide an overview of the recent advances in molecular pathology of disorders associated with heritable changes in the length of the repeat sequences, and examine how dynamism in these repeats is regulated.