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

被引:10
作者
Knoll, A [1 ]
Ketterling, RP [1 ]
Sommer, SS [1 ]
机构
[1] MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOL BIOL,ROCHESTER,MN 55905
关键词
D O I
10.1007/s004390050256
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:539 / 545
页数:7
相关论文
共 23 条
[21]   SOMATIC MOSAICISM AND FEMALE-TO-FEMALE TRANSMISSION IN A KINDRED WITH HEMOPHILIA-B (FACTOR-IX DEFICIENCY) [J].
TAYLOR, SAM ;
DEUGAU, KV ;
LILLICRAP, DP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) :39-42
[22]   PARENTAL ORIGIN AND GERMLINE MOSAICISM OF DELETIONS AND DUPLICATIONS OF THE DYSTROPHIN GENE - A EUROPEAN STUDY [J].
VANESSEN, AJ ;
ABBS, S ;
BAIGET, M ;
BAKKER, E ;
BOILEAU, C ;
VANBROECKHOVEN, C ;
BUSHBY, K ;
CLARKE, A ;
CLAUSTRES, M ;
COVONE, AE ;
FERRARI, M ;
FERLINI, A ;
GALLUZZI, G ;
GRIMM, T ;
GRUBBEN, C ;
JEANPIERRE, M ;
KAARIAINEN, H ;
LIECHTIGALLATI, S ;
MELIS, MA ;
VANOMMEN, GJB ;
PONCIN, JE ;
SCHEFFER, H ;
SCHWARTZ, M ;
SPEER, A ;
STUHRMANN, M ;
VERELLENDUMOULIN, C ;
WILCOX, DE ;
TENKATE, LP .
HUMAN GENETICS, 1992, 88 (03) :249-257
[23]   NUCLEOTIDE-SEQUENCE OF THE GENE FOR HUMAN FACTOR-IX (ANTIHEMOPHILIC FACTOR-B) [J].
YOSHITAKE, S ;
SCHACH, BG ;
FOSTER, DC ;
DAVIE, EW ;
KURACHI, K .
BIOCHEMISTRY, 1985, 24 (14) :3736-3750