Duplications of the AZFa region of the human Y chromosome are mediated by homologous recombination between HERVs and are compatible with male fertility
Duplications of the AZFa region of the human Y chromosome are mediated by homologous recombination between HERVs and are compatible with male fertility
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DOI：
10.1093/hmg/ddg031
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发表时间：
2003-02-01
影响因子：
3.5
通讯作者：
Jobling, MA
中科院分区：
文献类型：
--
作者：
Bosch, E;Jobling, MA
人类Y染色体长臂上AZFa区域的缺失导致男性不育。先前的工作已经表明，这是基因组疾病的一个例子，因为大多数缺失是由780 kb区域侧翼的内源性逆转录病毒元件（HERV）之间的非等位基因同源重组引起的。这些删除事件的相互产物，AZFa重复，迄今尚未报告。在这里，我们表明，重复染色体存在于人口样本中检测Y染色体短串联重复序列（YSTR）等位基因重复的AZFa区域内，并通过显示，携带这些重复等位基因的两条染色体含有第三个连接特异性HERV序列。这些病例最可能代表独立的重复事件，其序列分析显示断点与缺失断点位于HERV间序列同一性的相同区域，因此重复机制确实是缺失的倒数。考虑到AZFa区域的重复拷贝之间累积的Y-STR等位基因多样性，表明重复染色体之一已经在群体中存在至少17代，因此必须与男性生育力相容。
Deletions of the AZFa region on the long arm of the human Y chromosome cause male infertility. Previous work has shown that this is an example of a genomic disorder, since most deletions are caused by non-allelic homologous recombination between endogenous retroviral elements (HERVs) flanking the 780 kb region. The reciprocal products of these deletion events, AZFa duplications, have not been reported to date. Here we show that duplication chromosomes exist in population samples by detecting Y-chromosomal short tandem repeat (YSTR) allele duplications within the AZFa region, and by showing that two chromosomes carrying these duplicated alleles contain a third junction-specific HERV sequence. Sequence analysis of these cases, which most likely represent independent duplication events, shows that breakpoints lie in the same region of inter-HERV sequence identity as do deletion breakpoints, and thus that the mechanism of duplication is indeed the reciprocal of deletion. Consideration of the accumulated Y-STR allele diversity between duplicated copies of the AZFa region indicates that one of the duplication chromosomes has been in the population for at least 17 generations, and therefore must be compatible with male fertility.