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X Chromosome Inactivation Patterns Correlate with Fetal-Placental Anatomy in Monozygotic Twin Pairs: Implications for Immune Relatedness and Concordance for Autoimmunity

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Abstract

Background

Monozygotic (MZ) twinning is a poorly understood phenomenon that may result in subtle biologic differences between twins, despite their identical inheritance. These differences may in part account for discordant expression of disease in MZ twin pairs. Due to their stochastic nature, differences in X chromosome inactivation patterns are one source of such variation in female MZ twins.

Materials and Methods

We investigated X chromosome inactivation patterns in the blood of 41 MZ twin pairs based on methylation of the androgen receptor gene using a Hpa II-PCR assay. Twenty-six female MZ twin pairs with autoimmune disease (rheumatoid arthritis or multiple sclerosis) were studied. In addition, we studied 15 newborn female MZ twin pairs who were characterized at birth with respect to the anatomy of chorionic membranes (dichorionic versus monochorionic).

Results

We found a strong correlation between dichorionic fetal anatomy and differences in X chromosome inactivation patterns between members of an MZ twin pair. In contrast, all monochorionic twin pairs had closely correlated patterns of X chromosome inactivation. X chromosome inactivation patterns did not distinguish between MZ twin pairs who were concordant or discordant for autoimmune disease.

Conclusions

The highly similar patterns of X chromosome inactivation among monochorionic twin pairs may result from their shared placental blood supply during intrauterine life. Alternatively, these patterns may indicate that X chromosome inactivation occurs before the twinning event in this anatomic subgroup of MZ twins. The data further suggest that these factors do not make a major contribution to the high discordance rates for autoimmune disease in MZ twin pairs.

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Acknowledgments

This work was supported by a Pilot Research Grant from the National Multiple Sclerosis Society and by generous donations to P.K.G. from Mr. and Mrs. James C. Dudley and the Guilford Fund. Support was also provided by the Fund for Medical Scientific Research (Belgium). P.K.G. is especially grateful to Drs. Jennifer Puck and Harry Ostrer for helpful discussions and advice during the early phases of this work, to Tom Mack for many informative conversations about twins, and to Daniel Kastner for critical review of the manuscript. We also wish to thank Dr. Robert Pergolizzi for technical support and advice and Francine S. Mandel for help with biostatistics.

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Authors and Affiliations

  1. Departments of Medicine, North Shore University Hospital and Cornell University Medical College, 350 Community Drive, Manhasset, New York, 11030, USA

    Velia Trejo & Peter K. Gregersen

  2. Centrum voor Menselijke Erfelijkheid, Katholieke Universiteit, Leuven, Belgium

    Catherine Derom, Robert Vlietinck & Robert Derom

  3. ARC Epidemiology Research Unit, University of Manchester, Manchester, UK

    William Ollier & Alan Silman

  4. Department of Neurology, University of Western Ontario, London, Ontario, Canada

    George Ebers

Authors
  1. Velia Trejo
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  2. Catherine Derom
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  3. Robert Vlietinck
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  4. William Ollier
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  5. Alan Silman
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  6. George Ebers
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  7. Robert Derom
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  8. Peter K. Gregersen
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Trejo, V., Derom, C., Vlietinck, R. et al. X Chromosome Inactivation Patterns Correlate with Fetal-Placental Anatomy in Monozygotic Twin Pairs: Implications for Immune Relatedness and Concordance for Autoimmunity. Mol Med 1, 62–70 (1994). https://doi.org/10.1007/BF03403532

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  • DOI: https://doi.org/10.1007/BF03403532

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