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DNA methylation represents an important link between structural genetic variation and complex phenotypes. The study of genome-wide CpG methylation and its relation to traits relevant to psychiatry has become increasingly important. Here, we analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319 mentally healthy young adults. For 25% of all CpGs we observed medium to large common epigenetic variation. These CpGs were overrepresented in open sea and shore regions, as well as in intergenic regions. They also showed a strong enrichment of significant hits in association analyses. Furthermore, a significant proportion of common DNA methylation is at least partially genetically driven and thus may be observed similarly across tissues. These findings could be of particular relevance for studies of complex neuropsychiatric traits, which often rely on proxy tissues. 相似文献
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Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the ‘plastic’ characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients. 相似文献
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外周T细胞淋巴瘤(PTCL)是一组高度异质且预后极差的恶性肿瘤,基因异常和分子生物学改变是其发生、发展的重要因素.目前,PTCL的治疗仍然借鉴侵袭性B细胞淋巴瘤的化疗方案,但是疗效并不显著.表观遗传学作为一门涉及基因表达调控的新兴学科,为PTCL的发生、发展机制的研究与临床诊断治疗提供了新的思路.同时,针对PTCL的新型表观遗传学靶向药物的研发及新药联合应用方案的研究亦在进行中.因此,表观遗传学调控为PTCL的诊断及治疗提供了新的治疗切入点.笔者拟就PTCL的表观遗传学机制研究及相关靶向新药的应用前景进行综述. 相似文献
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New blood cells are continually produced from the hematopoietic stem cells (HSCs) that reside in the bone marrow. Throughout the life-span of the organism, this stem cell reservoir sustains life. Although HSCs can persist in vivo longer than one life-span (Harrison et al., 1978), with aging, HSC regenerative potential diminishes and skewing from lymphopoiesis toward myelopoiesis occurs. The expansion in the HSC pool with aging provides sufficient, yet abnormal, blood production. Examination of gene expression changes in aged HSCs has provided a link between aging and genomic instability. Furthermore, studies on the effects of reactive oxygen species (ROS) on HSC aging has given more insight into the reasons for HSC failure. Understanding of the interactions between niche cells and HSCs and changes in them with aging, may give us insights into the lineage skewing phenotype observed in the aged, and also other immune dysfunctions. 相似文献
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表观遗传(epigenetics)指所有不通过DNA序列改变就能影响基因表达(从而决定细胞乃至个体表型)的、可遗传的(即可伴随细胞分裂传递下去)调控方式,包括DNA甲基化、组蛋白修饰、染色质重塑、miRNA、朊病毒等。表观遗传调控在干细胞自我更新、定向分化、器官发育等生命过程中起着至关重要的作用:每一个多细胞生物个体都是由一个受精 相似文献
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