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 |
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Authors: | Antje Knöll Rhett P Ketterling S S Sommer |
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Institution: | (1) Mayo Clinic/Foundation, Department of Biochemistry and Molecular Biology, Rochester, MN 55905, USA Fax: +1-507-284-3383, US |
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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 100–10 000 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.
Received: 14 July 1995 / Revised: 1 April 1996 |
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