冰岛大学Kari Stefansson、Daniel F. Gudbjartsson等研究人员合作揭示单卵双胞胎生殖系基因组之间的差异。相关论文发表在2021年1月7日出版的《自然—遗传学》杂志上。

研究人员发现，单卵双胞胎平均相差5.2个早期发育突变，并且大约15％的单卵双胞胎具有大量特定于其中一个的这些早期发育突变。利用双胞胎的父母和后代，研究人员确定了孪生前的突变。

研究人员观察到在孪生前的细胞团中由单个细胞谱系形成双胞胎的情况，以及由多个细胞谱系形成双胞胎的情况。CpG>TpG突变的发生频率随着胚胎的发育而增加，这与DNA甲基化的增加相吻合。

这些结果表明，在发育过程中细胞的分配塑造了单卵双胞胎之间的基因组差异。

据悉，尽管单卵双胞胎在遗传学研究中发挥了重要作用，但对其基因组差异仍知之甚少。 

附：英文原文

Title: Differences between germline genomes of monozygotic twins

Author: Hakon Jonsson, Erna Magnusdottir, Hannes P. Eggertsson, Olafur A. Stefansson, Gudny A. Arnadottir, Ogmundur Eiriksson, Florian Zink, Einar A. Helgason, Ingileif Jonsdottir, Arnaldur Gylfason, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Doruk Beyter, Thora Steingrimsdottir, Gudmundur L. Norddahl, Olafur Th. Magnusson, Gisli Masson, Bjarni V. Halldorsson, Unnur Thorsteinsdottir, Agnar Helgason, Patrick Sulem, Daniel F. Gudbjartsson, Kari Stefansson

Issue&Volume: 2021-01-07

Abstract: Despite the important role that monozygotic twins have played in genetics research, little is known about their genomic differences. Here we show that monozygotic twins differ on average by 5.2 early developmental mutations and that approximately 15% of monozygotic twins have a substantial number of these early developmental mutations specific to one of them. Using the parents and offspring of twins, we identified pre-twinning mutations. We observed instances where a twin was formed from a single cell lineage in the pre-twinning cell mass and instances where a twin was formed from several cell lineages. CpG>TpG mutations increased in frequency with embryonic development, coinciding with an increase in DNA methylation. Our results indicate that allocations of cells during development shapes genomic differences between monozygotic twins. Whole-genome sequencing of monozygotic twins, along with their parents, spouses and children, identifies postzygotic mutations present in the somatic tissue of one twin, but not the other, and characterizes differences in the number and timing of these mutations.

DOI: 10.1038/s41588-020-00755-1

Source: https://www.nature.com/articles/s41588-020-00755-1