Abstract
To test whether the differentiation events that lead to the embryonal layers and their derived organs produce divergent X-chromosome activation ratios among the different tissues, the X-chromosome activation ratios in leucocytes and muscle (mesodermal origin), thyroid gland (endodermal origin) and medulla of the suprarenal glands (ectodermal origin) from ten deceased females were surveyed. Analysis of the degree of methylation of the polymorphic alleles recognized by the probes M27β and pSPT-PGK showed that the ratios for the medulla of the suprarenals correlated well with those of all other tissues except for leucocytes; the thyroid gland showed limited correlation with muscle, whereas leucocytes showed correlation only with muscle. The results of this preliminary study suggest that differentiation events result in considerable variation in the activation ratios in different tissues. As a consequence caution should be taken in extrapolating from the activation ratios observed in leucocytes or fibroblasts to tissues of endodermal or ectodermal origin.
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Abbadi N, Philippe C, Cherry M, Gilgenkrantz H, Tome F, Collin H, Theau D, Recan D, Bronx O, Fardeau M, Kaplan JC, Gilgenkrantz S (1994) Additional case of female monozygotic twins discordant for the clinical manifestation of Duchenne Muscular Dystrophy due to opposite X-chromosome inactivation. Am J Med Genet 52:198–206
Azofeifa J, Voit T, Hübner C, Cremer M (1995) X-chromosome methylation in manifesting and healthy carriers of dystrophinopathies: concordance of activation ratios among first degree female relatives and skewed inactivation ratios as cause of the affected phenotypes. Hum Genet 96:167–176
Boyd Y, Fraser NJ (1990) Methylation patterns at the hypervariable X-chromosome locus DXS255(M27β): correlation with X-inactivation status. Genomics 7:182–187
Bushby KMD, Goodship JA, Nicholson LVB, Johnson MA, Haggerty ID, Gardner-Medwin D (1993) Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. Neuromusc Disord 3:57–64
Fearon ER, Winkelstein JA, Civin CI, Pardol DM, Vogelstein B (1987) Carrier detection in X-linked agammaglobulinema by analysis of X-chromosome inactivation. N Engl J Med 316:427–431
Fialkow BJ (1973) Primordial cell pool size and lineage relationships of five human cell types. Ann Hum Genet 37:39–48
Glass IA, Nicholson LVB, Watkiss E, Johnson MA, Roberts RG, Abbs S, Brittain-Jones S, Boddie HG (1992) Investigation of a female manifesting Becker muscular dystrophy. J Med Genet 29:578–582
Grant SJ, Chapmann VM (1988) Mechanisms of X-chromosome regulation. Annu Rev Genet 22:199–233
Hendriks RW, Hinds H, Chen CZ, Craig IW (1992) The hypervariable DXS255 locus contains a LINE-1 repetitive element with a CpG island that is extensively methylated only on the active X chromosome. Genomics 14:598–603
Hermann BG, Frischauf AM (1987) Isolation of genomic DNA. Methods Enzymol 152:180–183
Ingerslev J, Schwartz M, Lamm LU, Kruse TA, Bukh A, Stenbjerg S (1989) Female haemophilia A in a family with seeming extreme bidirectional lyonization tendency: abnormal premature X-chromosome inactivation? Clin Genet 35:41–48
Jørgensen AL, Philip J, Raskind WH, Matsushita M, Christensen B, Dreyer V, Motulsky A (1992) Different patterns of X inactivation in MZ twins discordant for red-green color-vision deficiency. Am J Hum Genet 51:291–298
Keith DH, Singer-Sam J, Riggs AD (1986) Active X-chromosome DNA is unmethylated at eight CCGG sites clustered in a guanine-plus-cytosine-rich island at the 5′ end of the gene for phosphoglycerate kinase. Mol Cell Biol 6:4122–4125
Pegoraro E, Schimke RN, Arahata K, Hayashi Y, Stern H, Marks H, Glasberg MR, Carroll JE, Taber JW, Wessel HB, Bauserman SC, Marks WA, Toriello HW, Higgins JV, Appleton S, Schwartz L, García CA, Hoffman EP (1994) Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females. Am J Hum Genet 54:989–1003
Puck JM, Stewart CC, Nussbaum RL (1992) Maximum-likelihood analysis of human T-cell X chromosome inactivation patterns: normal women versus carriers of X-linked severe combined immunodeficiency. Am J Hum Genet 50:742–748
Richards CS, Watkins SC, Hoffmann EP, Schneider NR, Milsark IW, Katz KS, Cook JD, Kunkel LM, Cortada JM (1990) Skewed X inactivation in a female MZ twin results in Duchenne muscular dystrophy. Am J Hum Genet 46:672–681
Tihy F, Vogt N, Recan D, Malfoy B, Leturq F, Coquet M, Serville F, Fontan D, Guillard JM, Kaplan JC, Dutrillaux B, Lemieux N (1994) Skewed inactivation of an X chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter. Hum Genet 93:563–567
Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP (1985) Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science 227:642–644
Vogelstein B, Fearon ER, Hamilton SR, Preisinger AC, Willard HF, Michelson AM, Riggs A, Orkin SH (1987) Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res 47:4806–4813
Wadelius C, Lindstedt M, Pigg M, Egberg N, Petterson U, Anvret M (1993) Hemophilia B in a 46,XX female probably caused by non-random X inactivation. Clin Genet 43:1–4
Watkiss E, Webb T, McDermott K (1994) X inactivation studies in Anderson-Fabry disease and X linked ectodermal dysplasia. J Med Genet 31:169
Winchester B, Young E, Geddes S, Genet S, Hurst J, Middelton-Price H, Williams N, Webb M, Habel A, Malcolm S (1992) Female twin with Hunter disease due to nonrandom inactivation of the X chromosome: A consequence of twinning. Am J Med Genet 44:834–838
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Azofeifa, J., Cremer, M. & Waldherr, R. X-chromosome methylation ratios as indicators of chromosomal activity: Evidence of intraindividual divergencies among tissues of different embryonal origin. Hum Genet 97, 330–333 (1996). https://doi.org/10.1007/BF02185765
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DOI: https://doi.org/10.1007/BF02185765