Transmission-ratio distortion of X chromosomes among male offspring of females with skewed X-inactivation.
We have begun a search for heritable variation in X-chromosome inactivation pattern in normal females to determine whether there is a genetic effect on the imprinting of X-chromosome inactivation in humans. We have performed a quantitative analysis of X-chromosome inactivation in lymphocytes from mothers in normal, three-generation families. Eight mothers and 12 grandmothers exhibited evidence of highly skewed patterns of X-chromosome inactivation. We observed that the male offspring of females with skewed X-inactivation patterns were three times more likely to inherit alleles at loci that were located on the inactive X chromosome (Xi) than the active X chromosome (Xa). The region of the X chromosome for which this phenomenon was observed extends from Xp11 to -Xq22. We have also examined X-chromosome inactivation patterns in 21 unaffected mothers of male bilateral sporadic retinoblastoma patients. Six of these mothers had skewed patterns of X-chromosome inactivation. In contrast to the tendency for male offspring of skewed mothers from nondisease families to inherit alleles from the inactive X chromosome, five of the six affected males inherited the androgen receptor alleles from the active X chromosome of their mother.
Naumova
A K
AK
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Olien
L
L
Bird
L M
LM
Slamka
C
C
Fonseca
M
M
Verner
A E
AE
Wang
M
M
Leppert
M
M
Morgan
K
K
Sapienza
C
C
D001483:Base Sequence; D017931:DNA Primers; D004303:Dosage Compensation, Genetic; D005260:Female; D014644:Genetic Variation; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D012175:Retinoblastoma / Q000235:genetics; D014960:X Chromosome
D017931:DNA Primers