Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism

doi:10.1289/EHP4812

GSTDTAP > 资源环境科学

DOI	10.1289/EHP4812
	Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism
	Chan, Donovan 1; Shao, Xiaojian 2,3,16; Dumargne, Marie-Charlotte 1,4; Aarabi, Mahmoud 5,6; Simon, Marie-Michelle 7,8; Kwan, Tony 7,8; Bailey, Janice L.9; Robaire, Bernard 10; Kimmins, Sarah 4,10; San Gabriel, Maria C.1,11; Zini, Armand 1,11; Librach, Clifford 12,13; Moskowtsev, Sergey 12,13; Grundberg, Elin 3,14; Bourque, Guillaume 2,3; Pastinen, Tomi 3,14; Trasler, Jacquetta M.1,3,10,15
	2019-08-01
发表期刊	ENVIRONMENTAL HEALTH PERSPECTIVES
ISSN	0091-6765
EISSN	1552-9924
出版年	2019
卷号	127 期号:8
文章类型	Article
语种	英语
国家	Canada; USA
英文摘要	BACKGROUND: The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense legions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements. OBJECTIVES: Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome. METHODS: To characterize variation in sperm DNA methylation, we performed whole genorne bisulfite sequencing (WGBS) on an equimolar pool of sperm DNA from a wide cross section of 30 men varying in age, fertility status, methylenetetrahydrofolate reductase (MTHFR) genotype, and exposures. With our targeted capture panel, in individual samples, we examined the effect of MTHFR genotype (n =13 677CC, n = 8 677TT), as well as high-dose folic acid supplementation (n =6, per genotype, before and after supplementation). RESULTS: Through WGBS we discovered nearly 1 million CpGs possessing intermediate methylation levels (20-80%), termed dynamic sperm CpGs. These dynamic CpGs, along with 2 million commonly assessed CpGs, were used to customize a capture panel for targeted interrogation of the human sperm methylome and test its ability to detect effects of altered folate metabolism. As compared with MTHFR 677CC men, those with the 677TT genotype (50% decreased MTHFR activity) had both hyper- and hypomethylation in their sperm. High-dose folic acid supplement treatment exacerbated hypomethylation in MTHFR 677TT men compared with 677CC. In both cases, >80% of altered methylation was found in dynamic sperm CpGs, uniquely measured by our assay. DISCUSSION: Our sperm panel allowed the discovery of differential methylation following conditions affecting folate metabolism in novel dynamic sperm CpGs. Improved ability to examine variation in sperm DNA methylation can facilitate comprehensive studies of environment-epigenome interactions.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000483734400005
WOS关键词	METHYLENETETRAHYDROFOLATE REDUCTASE ; DEMETHYLATION DYNAMICS ; URINARY PHTHALATE ; MTHFR DEFICIENCY ; READ ALIGNMENT ; RISK-FACTOR ; 5-HYDROXYMETHYLCYTOSINE ; 5-METHYLCYTOSINE ; SPERMATOZOA ; PATTERNS
WOS类目	Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology
WOS研究方向	Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/185564
专题	资源环境科学
作者单位	1.McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada; 2.McGill Univ, Canadian Ctr Computat Genom, Montreal, PQ, Canada; 3.McGill Univ, Dept Human Genet, Montreal, PQ, Canada; 4.McGill Univ, Dept Anim Sci, Montreal, PQ, Canada; 5.Univ Pittsburgh, Med Genet & Genom Labs, Magee Womens Hosp, Med Ctr UPMC, Pittsburgh, PA USA; 6.Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA; 7.McGill Univ, Montreal, PQ, Canada; 8.Genome Quebec Innovat Ctr, Montreal, PQ, Canada; 9.Univ Laval, Fac Sci Agr & Alimentat, Ctr Rech Reprod Dev & Sante Intergenerat, Quebec City, PQ, Canada; 10.McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada; 11.McGill Univ, Dept Surg, Div Urol, Montreal, PQ, Canada; 12.Canadian Reprod Assisted Technol CReATe Fertil Ct, Toronto, ON, Canada; 13.Univ Toronto, Dept Obstet & Gynaecol, Toronto, ON, Canada; 14.Childrens Mercy Kansas City, Ctr Pediat Genom Med, Kansas City, MO USA; 15.McGill Univ, Dept Pediat, Montreal, PQ, Canada; 16.Natl Res Council Canada, Digital Technol Res Ctr, Ottawa, ON, Canada
推荐引用方式 GB/T 7714	Chan, Donovan,Shao, Xiaojian,Dumargne, Marie-Charlotte,et al. Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2019,127(8).
APA	Chan, Donovan.,Shao, Xiaojian.,Dumargne, Marie-Charlotte.,Aarabi, Mahmoud.,Simon, Marie-Michelle.,...&Trasler, Jacquetta M..(2019).Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.ENVIRONMENTAL HEALTH PERSPECTIVES,127(8).
MLA	Chan, Donovan,et al."Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism".ENVIRONMENTAL HEALTH PERSPECTIVES 127.8(2019).