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.
Correlation of intercentromeric distance, mosaicism, and sexual phenotype: Molecular localization of breakpoints in isodicentric Y chromosomes†
Article first published online: 30 SEP 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 11, pages 2705–2712, November 2011
How to Cite
Bergeron, M. B., Brochu, P., Lemyre, E. and Lemieux, N. (2011), Correlation of intercentromeric distance, mosaicism, and sexual phenotype: Molecular localization of breakpoints in isodicentric Y chromosomes. Am. J. Med. Genet., 155: 2705–2712. doi: 10.1002/ajmg.a.34260
- Issue published online: 20 OCT 2011
- Article first published online: 30 SEP 2011
- Manuscript Accepted: 18 JUL 2011
- Manuscript Received: 21 OCT 2010
- Le Fonds de Recherche en Santé du Québec (FRSQ)
- La Fondation du CHU Sainte-Justine
- La Fondation des Étoiles
- isodicentric Y chromosome [idic(Y)];
- tissue mosaicism;
- intercentromeric distance;
- chromosome instability;
- disorder of sex development
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.