repeatsthreenucleotide

Repeatsthreenucleotide, commonly called trinucleotide repeats, are sequences in DNA or RNA in which a three-nucleotide motif is repeated in tandem. The number of repeats varies among individuals and across loci, and most repeats remain stable through generations, while others become unstable and expand or contract.

Expansion mechanisms often involve replication slippage and imperfect DNA repair. When repeats expand beyond a locus-specific threshold, gene function or expression can be disrupted. Expansions in coding regions typically produce proteins with abnormal amino acid tracts, such as polyglutamine, which can confer toxic properties. Expansions in noncoding regions may cause RNA-mediated toxicity, affect transcription, or promote heterochromatin formation and gene silencing.

Clinically, trinucleotide repeat expansions are associated with a group of disorders that frequently exhibit anticipation, where disease onset becomes earlier or more severe in successive generations. Well-known examples include Huntington disease (CAG repeats in HTT leading to polyglutamine-containing protein), myotonic dystrophy type 1 (CTG repeats in DMPK with RNA toxicity), and fragile X syndrome (CGG repeats in FMR1 with gene silencing). Other conditions include various spinocerebellar ataxias (often CAG repeats) and Friedreich ataxia (GAA repeats in FXN).

Diagnosis relies on molecular sizing of repeat lengths, using methods such as PCR for small to moderate expansions and Southern blot for large expansions; sequencing can determine exact counts in some cases. Genetic counseling addresses variable penetrance and transmission risks, which can differ by locus and parental origin.

Research directions include therapies aimed at reducing repeat expression or toxicity, such as antisense oligonucleotides, and approaches to modulate repeat instability.