Differential DNA Methylation in Purified Human Blood Cells Implications for Cell Lineage and Studies on Disease Susceptibility 英文参考文献.docVIP

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Differential DNA Methylation in Purified Human Blood Cells Implications for Cell Lineage and Studies on Disease Susceptibility 英文参考文献.doc

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Differential DNA Methylation in Purified Human Blood Cells Implications for Cell Lineage and Studies on Disease Susceptibility 英文参考文献

DifferentialDNAMethylationinPurifiedHumanBlood Cells:ImplicationsforCellLineageandStudieson DiseaseSusceptibility LovisaE.Reinius1,NathalieAcevedo2,MaaikeJoerink2,Go¨ranPershagen3,Sven-ErikDahle′n3, DarioGreco1,CillaSo¨derha¨ll1,AnnikaScheynius2,JuhaKere1,4,5* 1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden, 2Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden, 3Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 4Science for Life Laboratory, Stockholm, Sweden, 5DepartmentofMedicalGenetics,UniversityofHelsinkiandFolkha¨lsan InstituteofGenetics,Helsinki,Finland Abstract MethylationofcytosinesatCpGsitesisacommonepigeneticDNAmodificationthatcanbemeasuredbyalargenumberof methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysisisbecomingwidelypopularincomplexdisorders,forexample,tounderstandpartofthe‘‘missingheritability’’.The DNAsamplesmostreadilyavailableformethylationstudiesarederivedfromwholeblood.However,bloodconsistsofmany functionallyanddevelopmentallydistinctcellpopulationsinvaryingproportions.Westudiedwhethersuchvariationmight affecttheinterpretationofmethylationstudiesbasedonwholebloodDNA.Wefoundinhealthymaleblooddonorsthereis important variation in the methylation profiles of whole blood, mononuclear cells, granulocytes, and cells from seven selected purified lineages. CpG methylation between mononuclear cells and granulocytes differed for 22% of the 8252 probescoveringtheselected343genesimplicatedinimmune-relateddisordersbygenome-wideassociationstudies,and at least one probe was differentially methylated for 85% of the genes, indicating that whole blood methylation results mightbeunintelligible.Forindividualgenes,eveniftheoverallmethylationpatternsmightappearsimilar,afewCpGsites in the regulatory regions may have opposite methylation patterns (i.e., hypo/hyper) in the main blood