Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism.
Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism.
复制标题
DOI：
10.1186/2040-2392-4-2
复制
发表时间：
2013-01-25
期刊：
影响因子：
6.2
通讯作者：
Giulivi C
中科院分区：
文献类型：
--
作者：
Napoli E;Wong S;Giulivi C
线粒体基因组（mtDNA）特别容易受到活性氧（ROS）介导的损伤。虽然在自闭症谱系障碍儿童的组织中发现了ROS产生增加和氧化应激生物标志物升高，但缺乏线粒体DNA损伤的证据。在加州大学戴维斯分校参加儿童期自闭症风险基因与环境研究（CHARGE）的2-5岁完全型自闭症儿童（Au; n = 67）、典型发育儿童（TD; n = 46）及其父母中分离的外周血单核细胞（PBMC）中评估mtDNA缺失。在来自Au和TD儿童（n = 10;各）及其母亲的mtDNA片段中评估序列变体，其代表整个人类线粒体基因组的31.2%覆盖率。Au儿童线粒体DNA损伤增加的证据是：（i）线粒体DNA缺失频率较高（2倍），（ii）GC→AT转换数目较高（2.4倍），是GC优选的氧化损伤位点，和（iii）更高频率的G，C，T→A转换（1.6倍）表明聚合酶γ在旁路脱嘌呤/脱嘧啶位点主要掺入A的发生率较高，可能是氧化应激引起的最后两个结果与他们的母亲相同，表明遗传了与氧化损伤增加一致的模板，而Au儿童的mtDNA缺失频率与他们的父亲相似。这些结果表明，遗传和表观遗传因素的结合，发生在围产期，导致自闭症儿童的mtDNA模板类似于老年人的预期。
The mitochondrial genome (mtDNA) is particularly susceptible to damage mediated by reactive oxygen species (ROS). Although elevated ROS production and elevated biomarkers of oxidative stress have been found in tissues from children with autism spectrum disorders, evidence for damage to mtDNA is lacking. mtDNA deletions were evaluated in peripheral blood monocytic cells (PBMC) isolated from 2–5 year old children with full autism (AU; n = 67), and typically developing children (TD; n = 46) and their parents enrolled in the CHildhood Autism Risk from Genes and Environment study (CHARGE) at University of California Davis. Sequence variants were evaluated in mtDNA segments from AU and TD children (n = 10; each) and their mothers representing 31.2% coverage of the entire human mitochondrial genome. Increased mtDNA damage in AU children was evidenced by (i) higher frequency of mtDNA deletions (2-fold), (ii) higher number of GC→AT transitions (2.4-fold), being GC preferred sites for oxidative damage, and (iii) higher frequency of G,C,T→A transitions (1.6-fold) suggesting a higher incidence of polymerase gamma incorporating mainly A at bypassed apurinic/apyrimidinic sites, probably originated from oxidative stress. The last two outcomes were identical to their mothers suggesting the inheritance of a template consistent with increased oxidative damage, whereas the frequency of mtDNA deletions in AU children was similar to that of their fathers. These results suggest that a combination of genetic and epigenetic factors, taking place during perinatal periods, results in a mtDNA template in children with autism similar to that expected for older individuals.
登录
查看更多内容
影响因子：
11.2
作者：
HOLT, IJ;HARDING, AE;MORGANHUGHES, JA
通讯作者：
MORGANHUGHES, JA
影响因子：
7.1
作者：
James, S. Jill;Melnyk, Stepan;Gaylor, David W.
通讯作者：
Gaylor, David W.
影响因子：
4.8
作者：
Davey, GP;Peuchen, S;Clark, JB
通讯作者：
Clark, JB
影响因子：
4.8
作者：
James, S. Jill;Rose, Shannon;Gaylor, David W.
通讯作者：
Gaylor, David W.
影响因子：
3.5
作者：
Hao, HL;Morrison, LE;Moraes, CT
通讯作者：
Moraes, CT