Expansion of polyalanine tracts cause at least 9 inherited human diseases. Eight of these nine diseases are due to expansions in transcription factors and give rise to congenital disorders, many with neurocognitive phenotypes. Disease‑causing expansions vary in length depending upon the gene...

Because natural selection is commonly presumed to minimize mutation rates, the discovery of mutationally unstable simple sequence repeats (SSRs) in many functional genomic locations came as a surprise to many biologists. Whether such SSRs persist in spite of or because of their intrinsic...

Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disease caused by a CAG repeat expansion in exon 1 of the Huntington gene ( HD ) also known as IT15 . Despite the disease being caused by dysfunction of a single gene, expressed as an expanded polyglutamine in...

Kennedy’s disease (KD) or spinobulbar muscular atrophy is a hereditary X‑linked, progressive neurodegenerative condition caused by an expansion of the CAG triplet repeat in the first exon of the androgen receptor gene. The phenotype in its full form is only expressed in males and presents...

Over 100 human cellular proteins contain a repetitive polyglutamine tract, however, only nine of these proteins are associated with disease. In these proteins, the expanded polyQ tract perturbs the native conformation, resulting in an ordered aggregation process that leads to the formation of...

Polyglutamine (polyQ)‑expansions in different proteins cause nine neurodegenerative diseases. While polyQ aggregation is a key pathological hallmark of these diseases, how aggregation relates to pathogenesis remains contentious. In this chapter, we review what is known about the aggregation...

Fragile X syndrome (FXS), a severe neurodevelopmental anomaly, and one of the earliest disorders linked to an unstable (‘dynamic’) mutation, is caused by the large (>200) CGG repeat expansions in the noncoding portion of the FMR1 (Fragile X Mental Retardation‑1) gene. These expansions,...

Microsatellites in and around genes have been shown to modulate levels of gene expression in multiple organisms, ranging from bacteria to humans. Here we will discuss promoter microsatellites known to modulate gene expression, with a few key examples related to the human brain. Many of the...

Dynamic mutations are those caused by the expansion of existing polymorphic DNA repeat sequences beyond a copy number threshold. These genetic mutations can give rise to dominant, recessive or X‑linked disorders, dependent upon the location of the repeat sequence with respect to the genes...

Friedreich ataxia (FRDA), the most common of the hereditary ataxias, is an autosomal recessive, multisystem disorder characterised by progressive ataxia, sensory symptoms, weakness, scoliosis and cardiomyopathy. FRDA is caused by a GAA expansion in intron one of the FXN gene, leading to...

Tandem repetitive DNA elements (tandem repeats), including microsatellites and simple sequence repeats, are extremely common throughout the genomes of a wide range of species. Tandem repeat expansions have been found to cause a range of monogenic diseases, such as Huntington’s disease,...

The most well known effect of single amino acid repeat expansion, beyond a certain threshold, is the development of a specific disease, depending on the protein in which the expansion has occurred. For example, the expansion of the glutamine repeat in huntingtin leads to the debilitating...