Germline rates of de novo meiotic deletions and duplications causing several genomic disorders.
Germline rates of de novo meiotic deletions and duplications causing several genomic disorders.
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DOI：
10.1038/ng.2007.40
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发表时间：
2008-01
期刊：
影响因子：
30.8
通讯作者：
Hurles, Matthew E.
中科院分区：
文献类型：
--
作者：
Turner, Daniel J.;Miretti, Marcos;Rajan, Diana;Fiegler, Heike;Carter, Nigel P.;Blayney, Martyn L.;Beck, Stephan;Hurles, Matthew E.
高度相似的重复序列之间的减数分裂重组（非等位基因同源重组，NAHR）产生缺失、重复、倒位和易位，并且是称为“基因组疾病”的遗传疾病的原因，其中大多数是由剂量敏感基因的拷贝数改变引起的。NAHR热点已在一些重复序列中被鉴定。我们已经开发了基于精子的测定来测量在4个NAHR热点处的相互缺失和重复的从头发生率。我们使用这些测定来剖析不同重复序列对之间NAHR的相对比率。我们表明：（i）这些NAHR热点对减数分裂是特异性的，（ii）在雄性生殖系中缺失的发生率高于其相互复制，（iii）这些基因组疾病中的一些可能在临床上未被充分确定，最值得注意的是7 q11的重复，Williams-Beuren综合征缺失的倒数。
Meiotic recombination between highly-similar duplicated sequences (non-allelic homologous recombination, NAHR) generates deletions, duplications, inversions, and translocations, and is responsible for genetic diseases known as ‘genomic disorders’, most of which are caused by altered copy number of dosage sensitive genes. NAHR Hotspots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at 4 NAHR hotspots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that: (i) these NAHR hotspots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been under-ascertained clinically, most notably the duplication of 7q11, the reciprocal of the Williams-Beuren Syndrome deletion.
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