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Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes
Open accessAbstract
Summary Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) chromosomes formed by homologous crossing-over between opposing arms of palindromes on sister chromatids. These ectopic recombination events occur at nearly all Y-linked palindromes. Based on our findings, we propose that intrapalindrome sequence identity is maintained via noncrossover pathways of homologous recombination. DNA double-strand breaks that initiate these pathways can be alternatively resolved by crossing over between sister chromatids to form idicY chromosomes, with clinical consequences ranging from spermatogenic failure to sex reversal and Turner syndrome. Our observations imply that crossover as well as noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes.
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Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy
Hassold, T., & Chiu, D. (1985) · Human Genetics · doi:10.1007/bf00389450 · Cited by 481
Sun, C., Skaletsky, H., Rozen, S., Gromoll, J., Nieschlag, E., Oates, R., & Page, D. C. (2000) · Human Molecular Genetics · doi:10.1093/oxfordjournals.hmg.a018920 · Cited by 247
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Metadata
- Authors
- Lange, J., Skaletsky, H., van Daalen, S. K. M., Embry, S. L., Korver, C. M., Brown, L. G., Oates, R. D., Silber, S., Repping, S., & Page, D. C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 138
- Issue
- 5
- Pages
- 855-869
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2103339246
- Cited by
- 244
- References
- 2
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Lange, J., Skaletsky, H., van Daalen, S. K. M., Embry, S. L., Korver, C. M., Brown, L. G., Oates, R. D., Silber, S., Repping, S., & Page, D. C. (2009). Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes. Cell. https://doi.org/10.1016/j.cell.2009.07.042
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