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

D. G. Monckton, L. J C Wong, T. Ashizawa, C. T. Caskey

Research output: Contribution to journalArticle

227 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalHuman Molecular Genetics
Volume4
Issue number1
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses'. Together they form a unique fingerprint.

Cite this