基因英语与中文哈哈.docx

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