Alanine tracts: the expanding story of human illness and trinucleotide repeats

Abstract

Expansions of polyglutamine repeats are known to cause a variety of human neurodegenerative diseases. More recently, expansions of alanine tracts, particularly in transcription factor genes, have been shown to cause at least nine human conditions, including mental retardation and malformations of the brain, digits and other structures. Present knowledge suggests that alanine tract expansions generally, but not always, arise through unequal recombination as opposed to replication slippage, the most likely mechanism in other triplet repeat expansions. The function of alanine tracts is unknown but when alanine expansions occur in transcription factor genes, alanine tracts can result in either loss-of-function or gain of an abnormal function. Given the frequency of alanine tracts in proteins, it is likely that more alanine tract expansions will be discovered in disease genes.