基因英语与中文哈哈.docx
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基因英语与中文哈哈.docx
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基因英语与中文哈哈
TheMicronutrientGenomicsProject:
acommunity-driven
knowledgebaseformicronutrientresearch
BenvanOmmen*AhmedEl-Sohemy*JohnHesketh*JimKaput*MichaelFenech*ChrisT.EveloHarryJ.McArdle*JildauBouwman*GeorgLietz*JohnC.Mathers*SueFairweather-Tait*HenkvanKranen*RuanElliott*SuzanWopereis*LynnetteR.Ferguson*CatherineMe′plan*GiudittaPerozzi*LindsayAllen*DamarizRivero*TheMicronutrientGenomicsProjectWorkingGroup
Received:
17July2010/Accepted:
13October2010/Publishedonline:
30October2010TheAuthor(s)2010.ThisarticleispublishedwithopenaccessatSAbstractMicronutrientsinfluencemultiplemetabolicsystematicallyandarethusnotoptimallydisseminated.pathwaysincludingoxidativeandinflammatoryprocesses.TheMicronutrientGenomicsProject(MGP)wasestab-Optimummicronutrientsupplyisimportantforthemain-lishedasacommunity-drivenprojecttofacilitatethetenanceofhomeostasisinmetabolismand,ultimately,fordevelopmentofsystematiccapture,storage,management,maintaininggoodhealth.Withadvancesinsystemsbiologyanalyses,anddisseminationofdataandknowledgegen-andgenomicstechnologies,itisbecomingfeasibletoeratedbybiologicalstudiesfocusedonmicronutrient–assesstheactivityofsingleandmultiplemicronutrientsgenomeinteractions.Specifically,theMGPcreatesaintheircompletebiologicalcontext.Existingresearchcol-publicportalandopen-sourcebioinformaticstoolboxforlectsfragmentsofinformation,whicharenotstoredall‘‘omics’’informationandevaluationofmicronutrientandhealthstudies.Thecoreoftheprojectfocusesonaccessto,groupisorwillbeestablishedcombiningthevariousrelevantareas(includinggenetics,nutrition,biochemistry,
andepidemiology).Eachexpertgroupwill
(1)collectallavailableknowledge,
(2)collaboratewithbioinformaticsteamstowardsconstructingthepathwaysandbiologicalnetworks,and(3)publishtheirfindingsonaregularbasis.Theprojectiscoordinatedinatransparentmanner,reg-ularmeetingsareorganizedanddisseminationisarrangedthroughtools,atoolboxwebportal,acommunications
websiteanddedicatedpublications.andvisualizationof,genetic/genomic,tran-TheMicronutrientGenomicsProjectWorkingGroupisacommunityscriptomic,proteomicandmetabolomicinformationrela-effort-basedresearchconsortiumwithagrowingnumberofactive.
tedtomicronutrients.Foreachmicronutrient,anexpertparticipants,aslistedathttp:
//www.micronutrientgenomics.org/40661.
B.vanOmmen(&)_J.Bouwman_S.WopereisTNOQualityofLife,P.O.box360,3700AJZeist,TheNetherlandse-mail:
ben.vanommen@tno.nl
J.Bouwman
e-mail:
jildau.bouwman@tno.nl
A.El-Sohemy
DepartmentofNutritionalSciences,UniversityofToronto,150CollegeStreet,Toronto,ONM5S3E2,Canadae-mail:
a.el.sohemy@utoronto.ca
J.Hesketh_C.Me´plan
InstituteforCellandMolecularBiosciences,NewcastleUniversityMedicalSchoolandHumanNutritionResearchCentre,Newcastle-upon-TyneNE24HH,UKe-mail:
j.e.hesketh@ncl.ac.uk
C.Me´plan
e-mail:
Catherine.meplan@ncl.ac.uk
J.Kaput
DivisionofPersonalizedNutritionandMedicine,NationalCenterforToxicologicalResearch,FoodandDrug
Administration,3900NCTRRoad,Jefferson,AR72079,USAe-mail:
james.kaput@fda.hhs.gov
M.Fenech
CSIROFoodandNutritionalSciences,POBox10041,AdelaideBC,SA5000,Australia
C.T.Evelo
DepartmentofBioinformatics—BiGCaT,MaastrichtUniversity,Maastricht,TheNetherlandse-mail:
chris.evelo@bigcat.unimaas.nl
H.J.McArdle
RowettInstituteofNutritionandHealth,UniversityofAberdeen,AberdeenAB219SB,UKe-mail:
h.mcardle@abdn.ac.uk
G.Lietz
HumanNutritionResearchCentre,SchoolofAgriculture,FoodandRuralDevelopment,NewcastleUniversity,KingsRoad,AgricultureBuilding,NewcastleuponTyneNE17RU,UKe-mail:
Georg.lietz@ncl.ac.uk
J.C.Mathers
HumanNutritionResearchCentre,InstituteforAgeingandHealth,NewcastleUniversity,NewcastleuponTyneNE24HH,UKe-mail:
john.mathers@newcastle.ac.uk。
KeywordsMicronutrientBioinformaticsDatabaseGenomics
Theintroductionofgenomicsinmicronutrientresearch
Micronutrientsreessentialregulatorsofimportantmeta-bolicandphysiologicalprocessesinhumans.Micronutrientdeficienciescausespecificillnesses.Suboptimalintakesmaycontributetothedevelopmentandseverityofchronicdiseases.Anincreasingnumberofstudiesalsodemon-stratestheundesirabilityofhighmicronutrientdoses(by
Supplementsintakeforexample)infavourofoptimaldoses(e.g.[17]).Basedontheseobservations,acontinuousprocessofre-assessingdietaryrequirementsanduppersafetylimitsformicronutrientsistakingplaceinthecon-textofpublichealthnutrition[1].Thesenewreviewsarebasedonbestavailablescience,includingconsiderationsondifferentialrecommendationsforsubgroups(e.g.,
elderly,children,pregnantwomen).Withrecentadvancesinsystemsbiologyandgenomics
technologies,itisbecomingfeasibletoassessthebiolog-icalactionofamicronutrientinitscompletebiologicalcontext,thatis,inrelationtoitseffectsonmultiplemet-abolicpathways,includinginteractionswithothernutrientsincontextofgeneticmake-up.Thesemechanisticand
integrated(‘systems’)approachesinthemicronutrientandhealthrelationshipmaycomplementthepubichealthrecommendationapproachesandproviderefinementsinspecificcases.Threemajordevelopmentsintheareaofgenomicsnowallowustofurtherstudythemolecularmechanismsinvolvedinthe(optimal)healthrelationshipwithmicronutrients.Theseare
S.Fairweather-Tait
SchoolofMedicine,HealthPolicyandPractice,UniversityofEastAnglia,NorwichNR47TJ,UK
e-mail:
s.fairweather-tait@uea.ac.uk
H.vanKranen
RIVM,Postbus1,3720BABilthoven,TheNetherlandse-mail:
henk.van.kranen@rivm.nl
R.ElliottInstituteofFoodResearch,NorwichResearchPark,
NorwichNR47UA,UK
e-mail:
ruan.elliott@bbsrc.ac.uk
L.R.Ferguson
DisciplineofNutrition,FacultyofMedicalandHealthSciences,TheUniversityofAuckland,Auckland,NewZealande-mail:
l.ferguson@auckland.ac.nz
G.Perozzi
DepartmentofNutritionalSciences—INRAN,NationalResearchInstituteonFood&Nutrition,ViaArdeatina546,00178Rome,Italye-mail:
perozzi@inran.it
L.Allen
USDA,ARSWesternHumanNutritionResearchCenter,UniversityofCalifornia,530W.HealthSciencesDrive,Davis,CA95616,USA
D.Rivero
DepartmentofPharmacology,UniversityofFlorence,
VialePieraccini6,50139Florence,Italy
e-mail:
rivero.damariz@unifi.it
*theabilitytoinexpensivelyanalysegeneticvariationinhumangenesrelatedtomicronutrientuptakeandmetabolism;
*theunravellingofthemolecularcomplexityofthemodesofactionofmicronutrientsusingomicstechnologies
*thegenerationofmultipleinter-relatedbiomarkersanddiagnosticsthataccuratelydefineoptimalmicronutrientintakeforhealthatthemolecularlevel.
TheMicronutrientGenomicsProject(MGP)describedinthispaperisaresearchcommunityprojecttostimulateandfacilitatethemostrecentdevelopmentsbyprovidingtherequiredknowledge-basedinfrastructurefornutritionalrecommendationsatthegeneticsubgroupandindividuallevel.Fourobservationsthatnecessitateintegratingmicronutrientresearchandgenomicsareparticularlyrelevant.
Micronutrientshavecomplexbiologicalactions
Theeffectsofmicronutrientsdependonaseriesofphys-ical,chemical,andphysiologicalprocesses,includingamountingested,mealmatrix,digestion,absorption,dis-tribution,metabolism(biotransformation),excretion(lastfourcollectivelyknownasADME),geneticfactorsinalloftheaboveprocesses,andlast,butnotleast,cellularmechanismsofaction(e.g.,[26,38]).Eachofthesepro-cessesinvolvesacomplexinteractionamonggenes,geneproducts,andenvironmentalfactors.Forexample,thecoreone-carbonpathwaythatproducesS-adenosylmethionineformethylationandotherreactionsutilizefolateandthreeothervitamins(B12,B2,andB6)inconjunctionwithatleasteightenzymesortransporterstoperformthecorereactions.Furthermore,metabolitesinthispathwayareusedinmultiplecriticalcellfunctionssuchasDNAsyn-thesis,maintenancemethylationofDNAsequencesandneurotransmittersynthesis.
Micronutrientshaveoverlappingbiologicalaction
Theaboveexamplealsodemonstratesthatmicronutrientsdonotactindependently.Theneedtoconsidertheimpactofmicronutrientcombinationsonbiologicalprocessesisbecomingincreasinglyevident,sincemicronutrientshaveoverlappingorcomplementingactions,orevenactinconcert(e.g.5-methyltetrahydrofolateassubstrateandvitaminB12ascofactorformethioninesynthase).Sele-nium,zinc,folate,vitaminsD,E,B2,B6,andB12areallinvolveddirectlyorindirectlyintheinnateimmuneresponse,oxidativestressresponse,andDNAmetabolism[25].Manymicronutrientsplayaroleinoxidativestressdefence.Fromareductionistviewpoint,itmakessensetostudyeachpathwayandreactioninanisolatedmanner,asthisprovidesinsightintomechanisms.However,fromaphysiologicalandasystemic(=systemsbiology)view,the
bestapproachistostudytheroleofallactors.
Micronutrientsandgeneticvariations
Untilrecently,micronutrientresearchwasusuallycon-ductedundertheassumptionthattheunderlyingmecha-nismsarethesameinallhumans.About600enzymesforwhichmicronutrientsarecofactorsareknowninthehumanproteome,andthegeneticdiversityofmosthasnotbeenextensivelycharacterized.Asignificanteffortisnowbeingmadetocharacterizeallelesof‘‘micronutrient’’geneswithinthehumanpopulation.Awidelystudiedexampleismet
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