小柯机器人

德国欧洲分子生物学实验室Jan O. Korbel等研究人员合作发现，人类中反复出现的倒位多态性与遗传不稳定性和基因组紊乱有关。这一研究成果于2022年5月6日在线发表在国际学术期刊《细胞》上。

通过整合多种基因组技术，研究人员在41个人类基因组中发现了729个倒位现象。大约85%小于2kbp的倒位是在L1逆转座过程中通过twin-priming形成的；80%的较大反转是平衡的，并且影响的核苷酸数量是拷贝数变异（CNV）的两倍。平衡倒位显示出过多的普通变体，72%的倒位被节段性重复（SD）或逆转座子所包围。由于侧翼的重复会促进非等位的同源重组，研究人员开发了互补的方法来识别反复出现的倒位形成。

研究人员描述了包括0.6%的基因组在内的40个复发性倒位，并显示每代每个基因座的倒位率高达2.7×10^-4。反复出现的倒位表现出性染色体的偏向，并与基因组紊乱的关键区域共定位。研究人员提出，倒位复发导致杂合子携带者和结构性SD多样性的数量增加，这增加了群体的突变性，使特定的单倍型容易出现致病的CNV。

据悉，与CNV不同，反转仍然是一个未被充分探索的遗传变异类别。

附：英文原文

Title: Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders

Author: David Porubsky, Wolfram Hps, Hufsah Ashraf, PingHsun Hsieh, Bernardo Rodriguez-Martin, Feyza Yilmaz, Jana Ebler, Pille Hallast, Flavia Angela Maria Maggiolini, William T. Harvey, Barbara Henning, Peter A. Audano, David S. Gordon, Peter Ebert, Patrick Hasenfeld, Eva Benito, Qihui Zhu, Charles Lee, Francesca Antonacci, Matthias Steinrücken, Christine R. Beck, Ashley D. Sanders, Tobias Marschall, Evan E. Eichler, Jan O. Korbel

Issue&Volume: 2022-05-06

Abstract: Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 104 per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs.

DOI: 10.1016/j.cell.2022.04.017

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00464-0