Determination of clonal status of pulmonary sclerosing hemangioma with X-chromosome inactivation mosaicism and polymorphism of phosphoglycerate kinase and androgen receptor genes

The pattern of expression of the two X chromosomes was investigated in pre-meiotic germ cells from 12½-day-old female embryos heterozygous for the variant electrophoretic forms of the X-linked enzyme phosphoglycerate kinase (PGK-1). If such germ cells carry the preferentially active Searle's translocated X chromosome (Lyon, Searle, Ford & Ohno, 1964), then only the Pgk-1 allele on this chromosome is expressed. This confirms Johnston's evidence (1979,1981) that Pgk-1 expression reflects a single active X chromosome at this time. Extracts of 12½-day germ cells from heterozygous females carrying two normal X chromosomes show both the A and the B forms of PGK; since only one X chromosome in each cell is active, different alleles must be expressed in different cells, suggesting that X-chromosome inactivation is normally random in the germ line. This result makes it unlikely that germ cells are derived from the yolk-sac endoderm where the paternally derived X chromosome is preferentially inactivated. In their pattern of X-chromosome inactivation, germ cells evidently resemble other tissues derived from the epiblast.

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Investigation of variability among mouse aggregation chimaeras and X-chromosome inactivation mosaics

Development ◽

10.1242/dev.84.1.309 ◽

1984 ◽

Vol 84 (1) ◽

pp. 309-329

Author(s):

John D. West ◽

Theodor Bücher ◽

Ingrid M. Linke ◽

Manfred Dünnwald

Keyword(s):

X Chromosome ◽

Phosphoglycerate Kinase ◽

X Chromosome Inactivation ◽

Yolk Sac ◽

X Inactivation ◽

Chromosome Inactivation ◽

Cell Populations ◽

Primitive Endoderm ◽

Female Progeny ◽

Positive Correlations

Mouse aggregation chimaeras were produced by aggregating C3H/HeH and C3H/HeHa—Pgk-1a/Ws embryos. At mid-term the proportions of the two cell populations in these conceptuses and the X-inactivation mosaic female progeny of C3H/HeH ♀ × C3H/HeHa—Pgk-1a/Ws ♂ matings were estimated using quantitative electrophoresis of phosphoglycerate kinase (PGK-1) allozymes. The percentage of PGK-1B was more variable in the foetus, amnion and yolk sac mesoderm of the chimaeras than in the corresponding tissues of the mosaic conceptuses. Positive correlations were found for the percentage of PGK-1B between these three primitive ectoderm tissues in both chimaeras and mosaics and between the two primitive endoderm tissues (yolk sac endoderm and parietal endoderm) of the chimaeras. There was no significant correlation between the primitive ectoderm and primitive endoderm tissues of the chimaeras. The results suggest that unequal allocation of cell populations to the primitive ectoderm and primitive endoderm considerably increases the variability among chimaeras but variation probably exists before this segregation occurs. The variation that arises before and at this allocation event is present before X-chromosome inactivation occurs in the primitive ectoderm lineage and explains why the proportions of the two cell populations are more variable among chimaeras than mosaics. Additional variation arises within the primitive ectoderm lineage, after X-inactivation. This variation may be greater in chimaeras than mosaics but the evidence is inconclusive. The results also have some bearing on the nature of the allocation of cells to the primitive ectoderm and primitive endoderm lineages and the timing of X-chromosome inactivation in the primitive ectoderm lineage.

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Further evidence for the importance of parental source of the Xce allele in X chromosome inactivation

Genetics Research ◽

10.1017/s001667230002961x ◽

1991 ◽

Vol 58 (1) ◽

pp. 63-65 ◽

Cited By ~ 7

Author(s):

Deborah J. Fowlis ◽

John D. Ansell ◽

H. Spedding Micklem

Keyword(s):

X Chromosome ◽

Reciprocal Cross ◽

Phosphoglycerate Kinase ◽

X Chromosome Inactivation ◽

Chromosome Inactivation

SummaryUsing mice that were mosaics for both Xce and phosphoglycerate kinase (Pgk-1) alleles, we present further evidence that the parental source of the X chromosome may affect the probability of that X chromosome remaining active. The reciprocal cross differences in PGK-1 activity described here are intermediate between those published previously for other alleles of Xce.

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Androgen Receptor-Mediated Hypersensitivity to Androgens in Women with Nonhyperandrogenic Hirsutism: Skewing of X-Chromosome Inactivation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.84.3.1091 ◽

1999 ◽

Vol 84 (3) ◽

pp. 1091-1095 ◽

Cited By ~ 20

Author(s):

A. Vottero

Keyword(s):

Androgen Receptor ◽

X Chromosome ◽

X Chromosome Inactivation ◽

Chromosome Inactivation

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Expression of the maternally derived X chromosome in the mural trophoblastof the mouse

Development ◽

10.1242/dev.56.1.179 ◽

1980 ◽

Vol 56 (1) ◽

pp. 179-190

Author(s):

William I. Frels ◽

Verne M. Chapman

Keyword(s):

X Chromosome ◽

Phosphoglycerate Kinase ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Heterozygous Female ◽

Allelic Form ◽

Maternal Tissue ◽

Trophectoderm Cells ◽

Tissue Contamination ◽

Selection Of

Only the maternally derived allelic form of the X-chromosome-linked enzyme phosphoglycerate kinase (PGK-1) is observed in the mural trophoblast of heterozygous female progenyin F3 and backcross matings. We have demonstrated that this expression of the maternally derived PGK-1 is not a result of maternal tissue contamination nor of selection of cells expressing the maternal X chromosome (Xm). Our results suggest that the expression of Xm in mural trophoblast is a consequence of nonrandom X-chromosome inactivation in trophectoderm cells.

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X-Chromosome Inactivation Patterns and Androgen Receptor Functionality Influence Phenotype and Social Characteristics as Well as Pharmacogenetics of Testosterone Therapy in Klinefelter Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1424 ◽

2004 ◽

Vol 89 (12) ◽

pp. 6208-6217 ◽

Cited By ~ 142

Author(s):

Michael Zitzmann ◽

Marion Depenbusch ◽

Jörg Gromoll ◽

Eberhard Nieschlag

Keyword(s):

Androgen Receptor ◽

X Chromosome ◽

Body Height ◽

X Chromosome Inactivation ◽

Cag Repeat ◽

Chromosome Inactivation ◽

Social Characteristics ◽

Social Traits ◽

Arm Span ◽

Androgen Effects

Abstract Klinefelter syndrome is characterized by a vast range of phenotypes related to androgen effects. Testosterone (T) acts via the X-linked androgen receptor gene carrying the CAG repeat (CAGn) polymorphism, the length of which is inversely associated with androgen action and might account for the marked variation in phenotypes. In 77 newly diagnosed and untreated Klinefelter patients with a 47,XXY karyotype we assessed phenotype and social traits in relation to X-weighted biallelic CAGn length using X-chromosome inactivation analysis after digestion of leukocyte DNA with methylation-sensitive HpaII. Forty-eight men were hypogonadal and received T substitution therapy; in these, pharmacogenetic effects were investigated. The shorter CAGn allele was preferentially inactive. CAGn length was positively associated with body height. Bone density and the relation of arm span to body height were inversely related to CAGn length. The presence of long CAGn was predictive for gynecomastia and smaller testes, whereas short CAGn were associated with a stable partnership and professions requiring higher standards of education also when corrected for family background. There was a trend for men with longer CAGn to be diagnosed earlier in life. Under T substitution, men with shorter CAGn exhibited a more profound suppression of LH levels, augmented prostate growth, and higher hemoglobin concentrations. A significant genotype-phenotype association exists in Klinefelter patients: androgen effects on appearance and social characteristics are modulated by the androgen receptor CAGn polymorphism. The effects of T substitution are pharmacogenetically modified. This finding is magnified by preferential inactivation of the more functional short CAGn allele.

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