Absence of somatic mosaicism in 17 families with hemophilia B: An analysis with a sensitivity 10- to 1000-fold greater than that of sequencing gels

Antje Knöll, Rhett P. Ketterling, Steve S. Sommer

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Most estimates of germ-line mosaicism have been derived from families in which there has been transmission of a mutated allele to two or more children by an unaffected individual. Previously, analyses for somatic mosaicism detected five such individuals by PCR-based sequencing and haplotype analysis at a sensitivity of approximately 1 mutant per 10 wild-type alleles. To determine whether mutations that occur later in embryogenesis also give rise to somatic mosaicism, we analyzed leukocyte DNA from 17 individuals in whom a mutation in the factor IX gene was known to have originated. Methods capable of detecting 1 mutant allele in 100-10000 were utilized, and no further examples of somatic mosaicism were detected. If confirmed by future studies, the paucity of somatic mosaicism with mutant:wild-type allele frequencies ranging from 1:10 to 1:1000 (relative to the 11% of somatic mosaicism detected with mutant:wild-type allele frequencies of 1:1 to 1:10) may reflect a higher mutation rate and/or germ-line lineage allocation very early in embryogenesis.

Original languageEnglish (US)
Pages (from-to)539-545
Number of pages7
JournalHuman genetics
Volume98
Issue number5
DOIs
StatePublished - Dec 5 1996

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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