Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses

摘要: In order to characterize the dynamics of CTG repeat instability in somatic and germline tissue from myotonic dystrophy (DM) males we have used small pool polymerase chain reaction (PCR) a detailed quantitative analysis length variation. We demonstrate that heterogeneous smear repeats observed DM patients using standard analyses is comprised multiple unresolved bands may be dissected into discrete alleles derived single cells molecule PCR techniques. Analysis tissues demonstrates bias toward increasing allele lower boundary below which variant are rare, consistent with highly directional expansion pathway soma. Two sperm samples show extensive variation size increase bias, concordant phenomenon anticipation. addition, shows large contractions, including reversions normal range, restricted germline. Detailed intergenerational 'reductions' paternally transmitted two offspring suggests some apparent reductions artifacts parent. Our data indicate addition variation, substantial can also contribute differences usually DM.