A Universal Mechanism Ties Genotype to Phenotype in Trinucleotide Diseases

摘要: Trinucleotide hereditary diseases such as Huntington disease and Friedreich ataxia are cureless associated with inheriting an abnormally large number of DNA trinucleotide repeats in a gene. The genes different unrelated harbor repeat functional regions; therefore, it is striking that many these have similar correlations between their genotype, namely the inherited age onset progression phenotype. These remain unexplained despite more than decade research. Although mechanisms been proposed for several diseases, none proposals, being disease-specific, can account commonalities among diseases. Here, we propose universal mechanism which length-dependent somatic expansion occurs during patient's lifetime toward pathological threshold. Our uniformly explains first time to our knowledge genotype–phenotype common well-supported by both experimental clinical data. In addition, mathematical analysis provides simple explanations wide range phenomena exponential decrease age-of-onset curve, but faster patients homozygous versus heterozygous mutation, correlation length short allele not long ataxia. If proves be core component actual specific would open search uniform treatment all possibly delaying process.