Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy.
Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy.
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DOI：
10.1186/gm500
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Craig JM
中科院分区：
文献类型：
--
作者：
Cruickshank MN;Oshlack A;Theda C;Davis PG;Martino D;Sheehan P;Dai Y;Saffery R;Doyle LW;Craig JM
早产给幸存者带来长期不良健康后果的高风险，但其潜在的分子机制尚不清楚。我们假设早产的影响可以通过整个发育过程中可测量的表观基因组变化来调节。因此，我们使用纵向出生队列来测量出生时和18岁时DNA甲基化的表观遗传学标志，比较极早产的幸存者和足月出生的婴儿。使用12例极端早产病例和12例匹配的足月对照，我们从存档的新生儿血点和18岁时以类似方式收集的血液中提取DNA。使用Infinium HM450阵列测量了基因组中347,789个常染色体位置的DNA甲基化。Sequenom Massarray EpiTYPER证实了具有代表性的甲基化差异。在出生时，我们发现1,555个位点在足月儿和早产儿的甲基化方面存在显著差异。在18岁时，这些差异已基本消除，这表明出生时DNA甲基化差异主要是由与胎龄有关的因素驱动的，如细胞组成和/或成熟度。使用匹配的纵向样本，我们发现了与早产相关的表观遗传遗产的证据，确定了10个基因组座位上持续的甲基化差异。对出生时和18岁时DNA甲基化的纵向比较发现，出生时差异甲基化的位点和那些随年龄变化的位点之间存在显著重叠。然而，我们注意到，在妊娠和衰老过程中，重叠的位点可能是相同的(300/1,555)，也可能是相反的(431/1,555)。我们提出的证据表明，极早产儿和足月儿在出生时普遍存在甲基化差异，这些差异在18岁之前基本上可以解决。这些结果与这些时间点的血细胞发育、细胞成分、免疫诱导和年龄相关的甲基化变化是一致的。最后，我们确定了10个与早产个体显著相关的探针，并且在出生时和18个月时甲基化不一致超过5%，这可能反映了早产的长期表观遗传遗产。
Preterm birth confers a high risk of adverse long term health outcomes for survivors, yet the underlying molecular mechanisms are unclear. We hypothesized that effects of preterm birth can be mediated through measurable epigenomic changes throughout development. We therefore used a longitudinal birth cohort to measure the epigenetic mark of DNA methylation at birth and 18 years comparing survivors of extremely preterm birth with infants born at term. Using 12 extreme preterm birth cases and 12 matched, term controls, we extracted DNA from archived neonatal blood spots and blood collected in a similar way at 18 years of age. DNA methylation was measured at 347,789 autosomal locations throughout the genome using Infinium HM450 arrays. Representative methylation differences were confirmed by Sequenom MassArray EpiTYPER. At birth we found 1,555 sites with significant differences in methylation between term and preterm babies. At 18 years of age, these differences had largely resolved, suggesting that DNA methylation differences at birth are mainly driven by factors relating to gestational age, such as cell composition and/or maturity. Using matched longitudinal samples, we found evidence for an epigenetic legacy associated with preterm birth, identifying persistent methylation differences at ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18 years uncovered a significant overlap between sites that were differentially-methylated at birth and those that changed with age. However, we note that overlapping sites may either differ in the same (300/1,555) or opposite (431/1,555) direction during gestation and aging respectively. We present evidence for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age. These results are consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points. Finally, we identified ten probes significantly associated with preterm individuals and with greater than 5% methylation discordance at birth and 18 years that may reflect a long term epigenetic legacy of preterm birth.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
3.7
作者：
Aberg, Karolina A.;Xie, Lin Y.;van den Oord, Edwin J. C. G.
通讯作者：
van den Oord, Edwin J. C. G.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2.9
作者：
Hardin, Jill;Finnell, Richard H.;Shaw, Gary M.
通讯作者：
Shaw, Gary M.