SBT2130Genetics

Lecture1 Klug,W.S.,Cummings, M.R.,Spencer,C.A.,and Palladino,M.A.2009. ConceptsofGenetics. PearsonBenjamin Cummings.779p.

INTRODUCTIONTOGENETICS 1.1FromMendeltoDNAinLessThanaCentury 1.2DiscoveryoftheDoubleHelixLaunchedtheEraofMolecularGenetics 1.3DevelopmentofRecombinantDNATechnologyBegantheEraofCloning 1.4TheImpactofBiotechnologyIsContinuallyExpanding 1.5Genomics,Proteomics,andBioinformaticsAreNewandExpandingFields 1.6GeneticStudiesRelyontheUseofModelOrganisms 1.7WeLiveinthe"AgeofGenetics" Humanmetaphase chromosomes,each composedoftwosister chromatids.

1.1FromMendeltoDNAinLessThanaCentury Mendelshowedthattraitsarepassedfromparentstooffspringinapredictableway.Hisworkformsthe foundationforgenetics.Inmitosis,chromosomesarecopiedanddistributedsothatthetworesulting daughtercellseachreceiveadiploidset.Inmeiosis,thegametesproducedarehaploid.Accordingto thechromosometheoryofinheritance,inheritedtraitsarecontrolledbygenesresidingon chromosomes.Thegenesarefaithfullytransmittedthroughgametes,maintaininggeneticcontinuity fromgenerationtogeneration.Mutationsproduceallelesofageneandarethesourceofgenetic variation.DNA,notprotein,isthecarrierofgeneticinformation.

Themonasterygarden whereGregorMendel conductedhis experiments.In1866, Mendelputforwardthe majorpostulatesof transmissiongenetics.

Humanmetaphase chromosomesvisualized underSEM.

Colorisedimageof humanmalechromosome set(karyotype)

Astageinmitosiswhen thechromosomes (stainedblue)moveapart.

Chromosome1(X chromosome)of Drosophilamelanogaster showingthelocationsof variousgenes.

Thenormalredeyecolor (wildtype)ofD. melanogasterandthe whiteeyedmutant(top).

Anelectronmicrograph showingTphageinfecting acellofthebacterium Escherichiacoli.

1.2DiscoveryoftheDoubleHelixLaunchedtheEraofMolecularGenetics DNAisanantiparellel,doublestrandedhelixmadeupofthenucleotidesA,C,G,andT.Thesugarinits nucleotidesisdeoxyribose.ThesenucleotidesformATandGCbasepairsacrossthehelix(Figure18). RNAissimilartoDNAexceptthatitisusuallysinglestrandedandhasUinplaceofT.Inaddition,the sugarinitsnucleotidesisriboseinsteadofdeoxyribose.DNAistranscribedtoRNA,whichistranslated intoprotein(Figure19)Thisisknownasthecentraldogmaofgenetics.Thegeneticcodeconsistsof tripletnucleotidespresentinmRNA.Eachtripletencodesforinsertionofaspecificaminoacidintoa growingproteinchain.Onceaproteinismade,itsactionorlocationinacellplaysaroleinproducinga phenotype.

Summaryofthestructure ofDNA,illustratingthe arrangementofthe doublehelix(left)andthe chemicalcomponents makingupeachstrand (right). Geneexpressionconsists oftranscriptionofDNA intomRNA,and translationofmRNA(with thehelpofribosome)into aprotein.

Athreedimensional conformationofa protein.

Thehemoglobin molecule,showingthe twochainsandthetwo chains.Amutationin thegeneforthechain producesabnormal hemoglobinandthe sicklecellanemia(below).

Normalredbloodcells (round)andsickledred bloodcells.Thesickled cellsblockcapillariesand smallbloodvessels.

1.3DevelopmentofRecombinantDNATechnologyBegantheEraofCloning RestrictionenzymeshaveallowedtheadventofrecombinantDNAandcloning(Figure114).Genomics analyzesgenomesequencestostudythestructure,function,andevolutionofgenesandgenomes.

Incloning,avectoranda DNAfragmentproduced bycuttingwitha restrictionenzymeare joinedtoproducea recombinantDNA molecule.The recombinantDNAis transferredintoa bacterialcell,whereitis clonedintomanycopies byreplicationofthe recombinantmolecule andbydivisionofthe bacterialcell.

1.4TheImpactofBiotechnologyIsContinuallyExpanding Biotechnologyhasbeenusedforthegeneticmodificationofcropplantsforincreasedherbicide,insect, andviralresistance,aswellasfornutritionalenhancement.Somegeneticallyalteredtraitsincropplants areshowninTable1.1.Themolecularbasisforhundredsofgeneticdisordersisknown(Figure118). Genetherapyandgenetictestingareimportantpartsofmedicine.

Dolly,asheepcloned fromthegeneticmaterial ofanadultmammarycell, shownnexttoherfirst bornlamb,Bonnie.

Oncstrainofmouse,the firstgeneticallymodified organismtobepatented, andissusceptibletomany formsofcancer.These micewredesignedfor studyingcancer developmentandthe designofnewanticancer drugs..

1.5Genomics,Proteomics,andBioinformaticsAreNewandExpandingFields

Diagramofthehumanchromosomeset,showingthelocationofsomegeneswhosemutantformscause hereditarydiseases.ConditionsthatcanbediagnosedusingDNAanalysisareindicatedbyreddots.

AportionofaDNA microarray.DNAfroman individualcanbetested todetectmutantcopies ofgenes.

Acolorizedelectron micrographof Haemophilusinfluenza,a bacteriumthatwasthe firstfreelivingorganism tohaveitsgenome sequenced.This bacteriumcaused respiratoryinfectionsand bacterialmeningitisin humans. SocietyofGenetics, Genomicsand ComputationalBiology Genomics Bioinformatics

Nextgeneration sequencingtechnologies

10thMalaysiaGenetics Congress2013 Themeprobablyon: Genomics,Bioinformatics andComputational Biology

1.6GeneticStudiesRelyontheUseofModelOrganisms Modelorganismsforgeneticstudyareeasytogrow,haveashortlifecycle,andproducemanyoffspring. Alllifehasacommonorigin,andgeneswithsimilarfunctionsindifferentorganismsaresimilarin structureandDNAsequence.RecombinantDNAtechnologyandtheabilitytotransfergenesacross specieshasmadeitpossibletodevelopmodelsofhumandiseases(Table1.2). Modelorganismsusedin geneticanalysis/studies include: Themouse Thefruitfly

Theyeast, Saccharomyces cerevisiae Thebacterium, E.coli

Theroundworm, Caenorhabditis elegans Theplant, Arabidopsis thaliana

Thezebrafish, Daniorerio

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 1.7WeLiveinthe"AgeofGenetics" Geneticsisthecoreofbiologyandthemethodofchoiceforunderstandingthefunctionsand malfunctionsofabiologicalsystem.

AtimelineshowingthedevelopmentofgeneticsfromGregorMendelsworkonpeaplantstocurrent eraofgenomicsanditsmanyapplicationsinresearch,medicine,andsociety. MBO6/10/11

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