Simple sequence repeats: genetic modulators of brain function and behavior

Simple sequence repeats (SSRs), sometimes described as genetic ‘stutters,’ are DNA tracts in which a short base-pair motif is repeated several to many times in tandem (e.g. CAGCAGCAG). These sequences experience frequent mutations that alter the number of repeats. Because SSRs are commonly located in promoters, untranslated regions and even coding sequences, such mutations can directly influence almost any aspect of gene function. Mutational expansion of certain triplet repeats is responsible for several hereditary neurodegenerative disorders, but SSR alleles can also contribute to normal variation in brain and behavioral traits. Here we review studies implicating SSRs not just in disease but also in circadian rhythmicity, sociosexual interaction, aggression, cognition and personality. SSRs can affect neuronal differentiation, brain development and even behavioral evolution.