Transposable element-mediated rearrangements are prevalent in human genomes.
Transposable element-mediated rearrangements are prevalent in human genomes.
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DOI：
10.1038/s41467-022-34810-8
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发表时间：
2022-11-19
影响因子：
16.6
通讯作者：
Beck, Christine R.
中科院分区：
文献类型：
--
作者：
Balachandran, Parithi;Walawalkar, Isha A.;Flores, Jacob, I;Dayton, Jacob N.;Audano, Peter A.;Beck, Christine R.
转座元件约占人类基因组的一半，它们通过逆转录转座产生人类变异的作用得到了广泛的研究和赞赏。转座子介导的结构变异，我们称之为转座元件介导的重排(TEMR)，研究得较少，导致它们形成的机制以及它们对人类多样性的更广泛影响也知之甚少。在这里，我们在三个个体的基因组中识别了493个独特的TEMR。虽然同源定向修复是TEMR的主要驱动因素，但我们的序列解析TEMR资源允许我们识别复杂的反转断点、三倍体或其他高拷贝数多态，以及额外的复杂性。TEMR富含基因位点，可以产生潜在的重要风险等位基因，例如已知的癌症生物标记物和治疗靶点TRIM65的缺失。这些发现扩大了我们对这类重要的结构变异的理解，以及它们形成的机制，并将它们确立为人类多样性的重要驱动因素。在这里，作者们表明，可转座元件介导的重排影响平均人类基因组的500kBP以上，是个体变异的来源，进化变化的底物，并可以通过不同的机制发生。
Transposable elements constitute about half of human genomes, and their role in generating human variation through retrotransposition is broadly studied and appreciated. Structural variants mediated by transposons, which we call transposable element-mediated rearrangements (TEMRs), are less well studied, and the mechanisms leading to their formation as well as their broader impact on human diversity are poorly understood. Here, we identify 493 unique TEMRs across the genomes of three individuals. While homology directed repair is the dominant driver of TEMRs, our sequence-resolved TEMR resource allows us to identify complex inversion breakpoints, triplications or other high copy number polymorphisms, and additional complexities. TEMRs are enriched in genic loci and can create potentially important risk alleles such as a deletion in TRIM65, a known cancer biomarker and therapeutic target. These findings expand our understanding of this important class of structural variation, the mechanisms responsible for their formation, and establish them as an important driver of human diversity. Here the authors show that transposable element-mediated rearrangements impact more than 500 kbp of an average human genome, are a source of individual variation, a substrate for evolutionary change, and can occur through diverse mechanisms.
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影响因子：
4.5
作者：
de Koning AP;Gu W;Castoe TA;Batzer MA;Pollock DD
通讯作者：
Pollock DD
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
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作者：
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影响因子：
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作者：
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通讯作者：
Moran, JV