Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.
Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.
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DOI：
10.1096/fba.2020-00101
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发表时间：
2021-04
影响因子：
2.7
通讯作者：
Affara NA
中科院分区：
文献类型：
--
作者：
Quilter CR;Harvey KM;Bauer J;Skinner BM;Gomez M;Shrivastava M;Doel AM;Drammeh S;Dunger DB;Moore SE;Ong KK;Prentice AM;Bernstein RM;Sargent CA;Affara NA
低出生体重和婴儿时期身高增长减少（发育迟缓）可能至少部分源于不良的早期生活环境，这些环境会触发有利于生存的表观遗传重编程。我们通过对冈比亚农村婴儿群体中调节基因活性的区域进行靶向甲基测序，研究了差异的DNA甲基化模式：(a)低出生体重和高出生体重（DNA分别来自脐带血（n = 16和n = 20）、胎盘滋养细胞组织（n = 21和n = 20）和12月龄婴儿外周血（n = 23和n = 17））， (b)前10%显示产后长度快速增长（高，n = 20），后10%显示产后长度增长缓慢（低，n = 20）。n = 20)，基于出生至12月龄之间的z评分变化（LAZ）（从12月龄婴儿收集的外周血DNA）。使用BiSeq分析来识别显著的甲基化标记，对于出生体重，在滋养细胞DNA中鉴定出4个差异甲基化区域（DMRs），而在脐带血DNA中鉴定出68个差异甲基化区域，在12个月外周血DNA中鉴定出54个差异甲基化区域。在12个月时观察到25个DMRs与年龄长短（LAZ）相关。除了五个位点（与两个不同的基因相关），这些甲基化标记组之间没有重叠。在DMRs中包含的194个CpG甲基化标记中，106个定位于定义的基因调控元件（启动子、CTCF结合位点、转录因子结合位点和增强子），58个定位于基因小体（内含子或外显子），30个定位于基因间DNA。与12个月（接近婴儿期/儿童期生长过渡）收集的DNA相比，在出生时（在宫内生长窗口结束时）收集的DNA中观察到各组之间与出生体重相关的不同甲基化模式。甲基化模式的纵向差异可能来自甲基化调整、血液细胞组成的变化或两者兼而有之，这些变化在关键的出生后生长时期持续存在，也可能是对早期营养和感染性环境暴露的反应，对生长和长期健康结果产生影响。
Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood (n = 16 and n = 20, respectively), from placental trophoblast tissue (n = 21 and n = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age (n = 23 and n = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high, n = 20) and the bottom 10% showing slow postnatal length gain (low, n = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12‐month peripheral blood DNA. Twenty‐five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF‐binding sites, transcription factor‐binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer‐term health outcomes.
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影响因子：
30.8
作者：
Cleaton MA;Dent CL;Howard M;Corish JA;Gutteridge I;Sovio U;Gaccioli F;Takahashi N;Bauer SR;Charnock-Jones DS;Powell TL;Smith GC;Ferguson-Smith AC;Charalambous M
通讯作者：
Charalambous M
影响因子：
7.1
作者：
Adu-Afarwuah, Seth;Lartey, Anna;Dewey, Kathryn G.
通讯作者：
Dewey, Kathryn G.
影响因子：
9.9
作者：
Beecham, Gary W.;Dickson, Dennis W.;Vance, Jeffery M.
通讯作者：
Vance, Jeffery M.
影响因子：
4.8
作者：
Berry, FB;Miura, Y;Tamaoki, T
通讯作者：
Tamaoki, T
影响因子：
4.4
作者：
Affinito, Ornella;Palumbo, Domenico;Cocozza, Sergio
通讯作者：
Cocozza, Sergio