美国威斯康星医学院Paul L. Auer和德克萨斯大学Paul Scheet研究组合作利用全基因组测序分析，揭示了不同祖先血液中镶嵌染色体改变（mCA）。2023年10月30日，国际学术期刊《自然—遗传学》发表了这一成果。

为了更好地了解不同基因人群中mCA的发生率，研究人员分析了美国国家心肺血液研究所Trans-Omics for Precision Medicine计划中67,390个人全基因组测序数据。与基于阵列的数据相比，研究观察到全基因组测序数据在发现低突变细胞分数mCA方面具有更高的灵敏度，并发现与非洲或西班牙人相比，欧洲人的常染色体mCA发生率最高，而X染色体mCA发生率最低。

研究揭示了与X染色体缺失相关的三个位点，常染色体mCA与DCPS、ADM17、PPP1R16B和TET2罕见变异的关联，以及ATM和MPL中与顺式mCA有关的人种特异性变异。

据了解，血液中超多的镶嵌染色体改变是人一系列疾病的预后标志。

附：英文原文

Title: Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing

Author: Jakubek, Yasminka A., Zhou, Ying, Stilp, Adrienne, Bacon, Jason, Wong, Justin W., Ozcan, Zuhal, Arnett, Donna, Barnes, Kathleen, Bis, Joshua C., Boerwinkle, Eric, Brody, Jennifer A., Carson, April P., Chasman, Daniel I., Chen, Jiawen, Cho, Michael, Conomos, Matthew P., Cox, Nancy, Doyle, Margaret F., Fornage, Myriam, Guo, Xiuqing, Kardia, Sharon L. R., Lewis, Joshua P., Loos, Ruth J. F., Ma, Xiaolong, Machiela, Mitchell J., Mack, Taralynn M., Mathias, Rasika A., Mitchell, Braxton D., Mychaleckyj, Josyf C., North, Kari, Pankratz, Nathan, Peyser, Patricia A., Preuss, Michael H., Psaty, Bruce, Raffield, Laura M., Vasan, Ramachandran S., Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Silverman, Edwin K., Smith, Jennifer A., Smith, Aaron P., Taub, Margaret, Taylor, Kent D., Yun, Jeong, Li, Yun, Desai, Pinkal, Bick, Alexander G., Reiner, Alexander P., Scheet, Paul, Auer, Paul L.

Issue&Volume: 2023-10-30

Abstract: Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.

DOI: 10.1038/s41588-023-01553-1

Source: https://www.nature.com/articles/s41588-023-01553-1