Mailick Marsha R, Hong Jinkuk, DaWalt Leann Smith, Greenberg Jan S, Movaghar Arezoo, Baker Mei Wang, Rathouz Paul J, Brilliant Murray H
Waisman Center, University of Wisconsin-Madison, Madison, WI, United States.
Wisconsin State Laboratory of Hygiene, Madison, WI, United States.
Front Pediatr. 2020 May 14;8:223. doi: 10.3389/fped.2020.00223. eCollection 2020.
The gene on the X chromosome has varying numbers of CGG repeats. The modal number is 30, and expansion to >200 results in fragile X syndrome, but the copy number extends down to 6. Past research suggests that individuals whose CGGs are in the "low zone" (LZ; defined here as ≤ 25 CGGs) may be more environmentally-reactive than those with normal range repeats (26-40 CGGs)-a gene x environment interaction. Using a population-based DNA biobank, in our primary analysis we compared 96 mothers with LZ CGG repeats on both alleles to 280 mothers who had CGG repeats in the normal range. Secondarily, we conducted parallel analyses on fathers. We investigated how parents in these two CGG repeat categories differentially responded to stress, defined as parenting a child with disabilities. Significant gene x environment interactions indicated that LZ mothers who had children with disabilities had greater limitations (in executive functioning, depression, anxiety, daily health symptoms, and balance) than LZ mothers whose children did not have disabilities. In contrast, mothers with normal-range CGG repeats did not differ based on stress exposure. For fathers, a similar pattern was evident for one phenotype only (hand tremors). Although on average LZ CGGs are not associated with compromised functioning, the average masks differential response to the environment.
X染色体上的基因具有不同数量的CGG重复序列。其模式数为30,当扩展至超过200时会导致脆性X综合征,但拷贝数可低至6。过去的研究表明,CGG处于“低区”(LZ;此处定义为≤25个CGG)的个体可能比具有正常范围重复序列(26 - 40个CGG)的个体对环境更具反应性——这是一种基因与环境的相互作用。利用基于人群的DNA生物样本库,在我们的初步分析中,我们将96位两个等位基因均具有LZ CGG重复序列的母亲与280位具有正常范围CGG重复序列的母亲进行了比较。其次,我们对父亲进行了平行分析。我们研究了这两类CGG重复序列的父母对压力(定义为养育残疾儿童)的不同反应。显著的基因与环境相互作用表明,生育残疾子女的LZ母亲比子女无残疾的LZ母亲有更大的局限性(在执行功能、抑郁、焦虑、日常健康症状和平衡方面)。相比之下,具有正常范围CGG重复序列的母亲在压力暴露方面没有差异。对于父亲来说,仅在一种表型(手部震颤)上出现了类似的模式。尽管平均而言,LZ CGG与功能受损无关,但这个平均值掩盖了对环境的不同反应。