DNA methylation profiles in monozygotic and dizygotic twins

被引:474
作者
Kaminsky, Zachary A. [1 ,2 ]
Tang, Thomas [1 ]
Wang, Sun-Chong [1 ,5 ]
Ptak, Carolyn [1 ,2 ]
Oh, Gabriel H. T. [1 ,2 ]
Wong, Albert H. C. [1 ,2 ]
Feldcamp, Laura A. [1 ,2 ]
Virtanen, Carl [8 ]
Halfvarson, Jonas [6 ,7 ]
Tysk, Curt [6 ,7 ]
McRae, Allan F. [4 ]
Visscher, Peter M. [4 ]
Montgomery, Grant W. [4 ]
Gottesman, Irving I. [3 ]
Martin, Nicholas G. [4 ]
Petronis, Art [1 ,2 ]
机构
[1] Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada
[2] Univ Toronto, Toronto, ON M5S 1A1, Canada
[3] Univ Minnesota, Minneapolis, MN 55454 USA
[4] Queensland Inst Med Res, Brisbane, Qld 4029, Australia
[5] Natl Cent Univ, Inst Syst Biol & Bioinformat, Chungli 320, Taiwan
[6] Univ Orebro, Sch Hlth & Med Sci, S-70185 Orebro, Sweden
[7] Orebro Univ Hosp, Dept Med, Div Gastroenterol, S-70185 Orebro, Sweden
[8] Univ Hlth Network Microarray Ctr, Toronto, ON M5G 1L7, Canada
关键词
EPIGENETIC DIFFERENCES; GENE; DISCORDANT; DISEASE; GENOME; ASSOCIATION;
D O I
10.1038/ng.286
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Twin studies have provided the basis for genetic and epidemiological studies in human complex traits(1,2). As epigenetic factors can contribute to phenotypic outcomes, we conducted a DNA methylation analysis in white blood cells (WBC), buccal epithelial cells and gut biopsies of 114 monozygotic (MZ) twins as well as WBC and buccal epithelial cells of 80 dizygotic (DZ) twins using 12K CpG island microarrays(3,4). Here we provide the first annotation of epigenetic metastability of similar to 6,000 unique genomic regions in MZ twins. An intraclass correlation (ICC)-based comparison of matched MZ and DZ twins showed significantly higher epigenetic difference in buccal cells of DZ co-twins (P = 1.2 x 10(-294)). Although such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and animal studies favor the hypothesis that it is due to epigenomic differences in the zygotes, suggesting that molecular mechanisms of heritability may not be limited to DNA sequence differences.
引用
收藏
页码:240 / 245
页数:6
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