Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes

被引：193

作者：

Lange, Julian ^{[1
,2
]}

Skaletsky, Helen ^{[1
,2
]}

van Daalen, Saskia K. M. ^{[3
]}

Embry, Stephanie L. ^{[4
]}

Korver, Cindy M. ^{[3
]}

Brown, Laura G. ^{[1
,2
]}

Oates, Robert D. ^{[5
]}

Silber, Sherman ^{[6
]}

Repping, Sjoerd ^{[3
]}

Page, David C. ^{[1
,2
]}

机构：

[1] MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02142 USA

[3] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynecol, Ctr Reprod Med, NL-1012 WX Amsterdam, Netherlands

[4] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA

[5] Boston Univ, Dept Urol, Med Ctr, Boston, MA 02118 USA

[6] St Lukes Hosp, Infertil Ctr St Louis, St Louis, MO 63107 USA

来源：

CELL | 2009年 / 138卷 / 05期

基金：

美国国家卫生研究院;

关键词：

NATURALLY-OCCURRING DELETIONS; TESTIS-DETERMINING GENE; ROBERTSONIAN TRANSLOCATIONS; MATERNAL AGE; INTRACHROMOSOMAL RECOMBINATION; FUNCTIONAL CENTROMERES; DICENTRIC CHROMOSOMES; TURNER-SYNDROME; SERTOLI-CELLS; X-CHROMOSOMES;

D O I：

10.1016/j.cell.2009.07.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 and noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes.

引用

页码：855 / 869

页数：15

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