Intra- and interindividual epigenetic variation in human germ cells
Intra- and interindividual epigenetic variation in human germ cells
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DOI：
10.1086/504729
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发表时间：
2006-07-01
影响因子：
9.8
通讯作者：
Petronis, Arturas
中科院分区：
文献类型：
--
作者：
Flanagan, James M.;Popendikyte, Violeta;Petronis, Arturas
表观遗传学代表了一种次要遗传系统，在人类生物学中的研究很差。这项研究的目的是对正常雄性的细菌之间和内部的DNA甲基化变化进行全面分析。首先，在以下疾病基因的启动子区域中，使用基于双足石修饰的测序映射甲基化的胞嘧啶：Presenilins（PSEN1和PSEN2），乳腺癌（BRCA1和BRCA2），肌动型营养不良（DM1）和亨廷顿病（HD）。在样品中检测到主要的表观遗传变异，因为同一个体的大多数精子都表现出独特的DNA甲基化谱。在个人间分析中，61个成对比较中有41个揭示了独特的DNA甲基化曲线（至6.8 x 10（-14））。第二，微阵列。使用12,198-Feature CpG Island微阵列进行了同一精子样品的基于P = .036的表观遗传分析。微阵列分析已经确定了生殖细胞基因组中的许多DNA甲基化变量位置。分别在单拷贝DNA片段和重复元素之间检测到启动子CpG岛和周围层颗粒卫星的最大变化程度。许多基因，例如EED，CTNNA2，CALM1，CDH13和STMN2，都表现出与年龄相关的DNA甲基化变化。最后，检测到CDH13中的等位基因特异性甲基化模式。这项研究提供了人类生殖细胞显着的表观遗传变异性的证据，这些证据值得进一步研究，以确定这种表观遗传模式是否可以在世代上有效地传播，以及遗传性表观遗传的个性对健康和疾病的表型结果可能产生什么影响。
Epigenetics represents a secondary inheritance system that has been poorly investigated in human biology. The objective of this study was to perform a comprehensive analysis of DNA methylation variation between and within the germlines of normal males. First, methylated cytosines were mapped using bisulphite modification-based sequencing in the promoter regions of the following disease genes: presenilins ( PSEN1 and PSEN2), breast cancer ( BRCA1 and BRCA2), myotonic dystrophy ( DM1), and Huntington disease ( HD). Major epigenetic variation was detected within samples, since the majority of sperm cells of the same individual exhibited unique DNA methylation profiles. In the interindividual analysis, 41 of 61 pairwise comparisons revealed distinct DNA methylation profiles ( to 6.8 x 10(-14)). Second, microarray. P = .036 based epigenetic profiling of the same sperm samples was performed using a 12,198-feature CpG island microarray. The microarray analysis has identified numerous DNA methylation-variable positions in the germ cell genome. The largest degree of variation was detected within the promoter CpG islands and pericentromeric satellites among the single-copy DNA fragments and repetitive elements, respectively. A number of genes, such as EED, CTNNA2, CALM1, CDH13, and STMN2, exhibited age-related DNA methylation changes. Finally, allele-specific methylation patterns in CDH13 were detected. This study provides evidence for significant epigenetic variability in human germ cells, which warrants further research to determine whether such epigenetic patterns can be efficiently transmitted across generations and what impact inherited epigenetic individuality may have on phenotypic outcomes in health and disease.