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Correlation of intercentromeric distance, mosaicism, and sexual phenotype: Molecular localization of breakpoints in isodicentric Y chromosomes

Authors

  • Mélanie Beaulieu Bergeron,

    1. Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada
    2. Département de Pathologie, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
    3. Centre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
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  • Pierre Brochu,

    1. Département de Pathologie, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
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  • Emmanuelle Lemyre,

    1. Centre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
    2. Département de Pédiatrie, Université de Montréal, Montréal, Québec, Canada
    3. Service de Génétique, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
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  • Nicole Lemieux

    Corresponding author
    1. Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada
    2. Département de Pathologie, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
    3. Centre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada
    • Département de pathologie et biologie cellulaire, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Québec H3C 3J7, Canada.
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  • How to Cite this Article: Beaulieu Bergeron M, Brochu P, Lemyre E, Lemieux N. 2011. Correlation of intercentromeric distance, mosaicism, and sexual phenotype: Molecular localization of breakpoints in isodicentric Y chromosomes. Am J Med Genet Part A 155: 2705–2712.

Abstract

Isodicentric chromosomes are among the structural abnormalities of the Y chromosome that are commonly identified in patients. The simultaneous 45,X cell line that is generated in cell division due to instability of the isodicentric Y chromosome [idic(Y)] has long been hypothesized to explain the variable sexual development of these patients, although gonads have been studied in only a subset of cases. We report here on the molecular localization of breakpoints in ten patients with an idic(Y). Breakpoints were mapped by FISH using BACs; gonads and fibroblasts were also analyzed when possible to evaluate the level of mosaicism. First, we demonstrate great tissue variability in the distribution of idic(Y). Second, palindromes and direct repeats were near the breakpoint of several idic(Y), suggesting that these sequences play a role in the formation of idic(Y). Finally, our data suggest that intercentromeric distance has a negative influence on the stability of idic(Y), as a greater proportion of cells with breakage or loss of the idic(Y) were found in idic(Y) with a greater intercentromeric distance. Females had a significantly greater intercentromeric distance on their idic(Y) than did males. In conclusion, our study indicates that the Y chromosome contains sequences that are more prone to formation of isodicentric chromosomes. We also demonstrate that patients with an intercentromeric distance greater than 20 Mb on their idic(Y) are at increased risk of having a female sexual phenotype. © 2011 Wiley Periodicals, Inc.

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