Epigenetics in Turner syndrome.
Epigenetics in Turner syndrome.
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DOI：
10.1186/s13148-018-0477-0
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发表时间：
2018
影响因子：
5.7
通讯作者：
Lanes R
中科院分区：
文献类型：
--
作者：
Álvarez-Nava F;Lanes R
X 染色体单体性是人类最常见的遗传异常，因为大约 2% 的受孕胚胎中存在 X 染色体单体性，尽管这些胚胎中 99% 会自然流产。在出生后，特纳综合征的临床特征可能包括典型的畸形特征、身材矮小、性幼稚症以及肾脏、心脏、骨骼、内分泌和代谢异常。特纳综合征是由于第二性染色体部分或全部丢失导致的，导致临床特征高度可变。这种表型可能不仅是由于删除基因的基因组不平衡造成的，还可能是由于对给定基因网络内相关基因的附加影响造成的，第二性染色体的缺失引发了基因表达调节的改变。目前对人类和小鼠模型的研究表明，这种染色体异常会导致表观遗传变化，包括与几种临床和代谢特征相关的途径中特定下游靶基因组中的差异DNA甲基化，主要是在常染色体上。在本文中，我们开始探索遗传和表观遗传因素在 X 染色体单体起源中的潜在参与。我们回顾了 45,X 单体减数分裂和合子后起源之间的争论，主要分析了几项研究的结果，这些研究比较了 45,X 单体与其整倍体和/或 47,XXX 三体细胞对应物在外周血单核细胞、羊水、人成纤维细胞和诱导多能人细胞系上的基因表达。从这些研究中，表观遗传变化的概况似乎是对染色体失衡的反应。所有这些研究的一个有趣发现是，基于甲基化和基于表达的通路分析是互补的，而不是重叠的，并且与 TS 受试者表现出的临床表现相关。澄清这些可能的因果途径可能会对提高这些患者的预期寿命产生未来的影响，并可能为早期药物干预提供信息丰富的目标。
Monosomy of the X chromosome is the most frequent genetic abnormality in human as it is present in approximately 2% of all conceptions, although 99% of these embryos are spontaneously miscarried. In postnatal life, clinical features of Turner syndrome may include typical dysmorphic stigmata, short stature, sexual infantilism, and renal, cardiac, skeletal, endocrine and metabolic abnormalities. Turner syndrome is due to a partial or total loss of the second sexual chromosome, resulting in the development of highly variable clinical features. This phenotype may not merely be due to genomic imbalance from deleted genes but may also result from additive influences on associated genes within a given gene network, with an altered regulation of gene expression triggered by the absence of the second sex chromosome. Current studies in human and mouse models have demonstrated that this chromosomal abnormality leads to epigenetic changes, including differential DNA methylation in specific groups of downstream target genes in pathways associated with several clinical and metabolic features, mostly on autosomal chromosomes. In this article, we begin exploring the potential involvement of both genetic and epigenetic factors in the origin of X chromosome monosomy. We review the dispute between the meiotic and post-zygotic origins of 45,X monosomy, by mainly analyzing the findings from several studies that compare gene expression of the 45,X monosomy to their euploid and/or 47,XXX trisomic cell counterparts on peripheral blood mononuclear cells, amniotic fluid, human fibroblast cells, and induced pluripotent human cell lines. From these studies, a profile of epigenetic changes seems to emerge in response to chromosomal imbalance. An interesting finding of all these studies is that methylation-based and expression-based pathway analyses are complementary, rather than overlapping, and are correlated with the clinical picture displayed by TS subjects. The clarification of these possible causal pathways may have future implications in increasing the life expectancy of these patients and may provide informative targets for early pharmaceutical intervention.
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影响因子：
4.5
作者：
Cheng EY;Hunt PA;Naluai-Cecchini TA;Fligner CL;Fujimoto VY;Pasternack TL;Schwartz JM;Steinauer JE;Woodruff TJ;Cherry SM;Hansen TA;Vallente RU;Broman KW;Hassold TJ
通讯作者：
Hassold TJ
影响因子：
6.6
作者：
Cantini, Giulia;Lombardi, Adriana;Luconi, Michaela
通讯作者：
Luconi, Michaela
影响因子：
10.5
作者：
BEARD, C;LI, E;JAENISCH, R
通讯作者：
JAENISCH, R
影响因子：
64.8
作者：
Cahill, DP;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
5.8
作者：
Bakalov, Vladimir K.;Cheng, Clara;Bondy, Carolyn A.
通讯作者：
Bondy, Carolyn A.