PubMed_ArguminSci  

PubMed:15198993 JSONTXT 4 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 138-230 DRI_Approach denotes The expansion of CAG.CTG repeat sequences is the cause of several inherited human disorders.
T2 231-416 DRI_Background denotes Longer alleles are associated with an earlier age of onset and more severe symptoms, and are highly unstable in the germline and soma with a marked tendency towards repeat length gains.
T3 417-627 DRI_Challenge denotes Germinal expansions underlie anticipation; whereas age-dependent, tissue-specific, expansion-biased somatic instability probably contributes toward the progressive nature and tissue-specificity of the symptoms.
T4 628-777 DRI_Outcome denotes The mechanism(s) of repeat instability is not known, but recent data have implicated mismatch-repair (MMR) gene mutS homologues in driving expansion.
T5 778-963 DRI_Outcome denotes To gain further insight into the expansion mechanism, we have determined the levels of somatic mosaicism of a transgenic expanded CAG.CTG repeat in mice deficient for the Pms2 MMR gene.
T6 964-1063 DRI_Challenge denotes Pms2 is a MutL homologue that plays a critical role in the downstream processing of DNA mismatches.
T7 1064-1145 DRI_Background denotes The rate of somatic expansion was reduced by approximately 50% in Pms2-null mice.
T8 1146-1235 DRI_Background denotes A higher frequency of rare, but very large, deletions was also detected in these animals.
T9 1236-1424 DRI_Background denotes No significant differences were observed between Pms2(+/+) and Pms2(+/-) mice, indicating that a single functional Pms2 allele is sufficient to generate normal levels of somatic mosaicism.
T10 1425-1636 DRI_Outcome denotes These findings reveal that as well as MMR enzymes that directly bind mismatched DNA, proteins that are subsequently recruited to the complex also play a central role in the accumulation of repeat length changes.
T11 1637-1834 DRI_Outcome denotes These data suggest that somatic expansion results not by replication slippage, single stranded annealing or simple MutS-mediated stabilization of secondary structures, but by inappropriate DNA MMR.