Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
12Activity
0 of .
Results for:
No results containing your search query
P. 1
94 - Gene Mutations

94 - Gene Mutations

Ratings: (0)|Views: 1,439|Likes:
Published by Manan Bhatt

More info:

Published by: Manan Bhatt on Nov 23, 2008
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

01/08/2013

pdf

text

original

 
to
Fa*sbm@
crg
B.v
aoo
Remember-DNAatul RNAarepoltmersoJ'rtucleotidas.lesigtrutedytlu, etters J'tlrciritt'oeetk)usase ,A(acleritrc.T(htnitte.LIw'acil.C(c't'tosirre)ndG(guattittc).Tlrc bascsarean'anged nto threcsrtrukirtgrp lrccoclortslic'ltarerlrcwits of tlrcgetrcticode.Particularcoclorrs eusa lrc rtsertiottofspcciJ'ic ntirtoaciclsttto tlrcpolryeptidesso lrut J hecoclotts re altcrecl.lrcut'ortganinoaciclrut'bausertctl.AlsorententberlrutAis conrylemetrtarto T ittDliA ardtoLItt RIVA.Gis contplenrcnter'\'o C irtbcttltRNAarrclDNA. Conryslenrcntctt'\'teenstlrut tlteyu'illconbineogcrlterr htdt'ogert torrclirtg.In sickle ellanaemiahemutationflects heaminoacidsequencefpartof theB-globinproteinhainof thehaemoglobinFig2).Tliisresultsn thelormationof abnormalaemogiobin-S hichinconditionsf low oxyuentension auseshe edbloodcells o collapsc ntosickleshapes.Fig 2. The mutation whichresults inSickle Cell AnaemiaInsicklecell anaemia,hebaseT marked inthe normaldiagram)withanarrowssubstitutedwitha baseA. This meanshat he esultantodononthemRNA is GUA instead fGAA andso heaminoacidvalines nsertedintotheproteinnplaceofglutamicacid. This results nthe brmationofhaemoglobin-S. hisypeofgenemutation scalledamissense'mutationand only changesne aminoacidnthepolypeptidehain.Sometimes base lterationna codondoesnotalter heaminoacidsequenceof thepolypeptidemadeby thegene.his s calleda'samesense'mutation.Itoccursbecausehegeneticode s degenerate.egenerate eanshatsomeamino acidscanbe coded or by severalmRNA codonswhich varyntheir hird base.or nstance.erine s coded orby UCU,UCC, UCAandUCG.Ifthe mutationchanged he hirdbasenUCA to make UCU,thenew codonwillstill insertserine ntothepolypeptide.
GeneMutations
stud.ving his Factsheetvoushouldgaina knowledgeof:the natureand causes f'gene mutation:the ef'f'ectsfgenemutations;genemutationas a sourceofvariation whichmavbe of selectivevalue.This Factsheetssumeshat he student asa basic norvledsef thc natureofDNA.RNA. replication.heqeneticcodeandproteinsvnthcsis. hesewerecoverednFactsheet2.Proteinl,nthesis-nucleiccids mdFactsheet49.ProteinynthesisI-mechanisms.The natureofgenemutationA mutationsa suddennheritable hangenthegeneticmaterial.Genemutation ssometimesalledpointmutationbecausehe mutationmay'only nvolvehange f onenucleotidebase)inhecodonequenceltliegene.ThereplicationofDNAand transcriptionf messengerRNA(mRNA)is not 100%etficientwiththe resultthatq_gg.rqqnqlrrorsoccur.Theserrorsma)'causemutations. he mutationma)/be dueothe nsertionaddition)r deletionf a nucleotide.hesubstitutionl onenucleotideoranother r inversion f two nucleotidesFisI).Fig 1. Typesofpointmutation.Alteringthe base sequencesnthe codclns fthegenemay alterthesequencen whichaminoacidsareassemblednto the polypeptidemadeby thatgene.Thealteredolypeptidemaythenhaveanalteredeftect orfunctionwhichin turn mayalter one or more characteristicsf theorganism. heresultingmutation s harmful,e.g.sickle cell anaemia,orit mayconfer evolutionary/r survival benefit e.g.in industrialmelanismwhichoccursnmany butterlliesand moths. f the mutatedallele ssituated n a sexchromosomehen he mutatedonditionwillbesex-linked.as n haemophiliaand red-greenolour blindness. ntheseconditionshemutatedllele s on theX-chromosome.OriginalDNACorrespondingmRNAInsertion of AasburthnucleotideNew DNAAltered mRNAcodonsDeletionof the hird nucleotide.New DNAAlteredmRNA codonsSubstitutionoffburthnucleotidewithT.Neu,DNAAlteredmRNA codonsInversionof second nd hirdnucleotidesNew DNAAltered mRNAcodonsAGTCCC AAA CCALICA GGGUUU GGUAGT ACCCAA ACC A
L]CA UGGGUU UGGU
AGCCCA AACCAUCGGGU UUG GUAGTTCC AAACCAUCA AGGL]UU GGL'AGCTCC AAACCAUCGAGGUUU GGUNormal
nrino acid sequenceofp-globinchainofhaemoglobin:Codonson mRNA:glutamic
+
Icode
Ior
GAAproineglutamic
++
IcodeIcode
lforIor
CCAGAA
t
I
I
CTT
tr
ll
rl
GGTCTT
proline valineglutamiccida
+ +t.^,-.t
IcodesIcodes| "1.'I =IorlforIorIi
CCA GUAGAA
acida
A;
l'"
t:l=
IF
a7
&i
tr.=ffi,w'i
aF
9.
ffihE
g:ff!.jF
t
I
I
CTT
tt
tl
tl
GGTCAT
acid
Baseson DNA:Aminoacid sequenceofp-globinchainof haemoglobin:Codons on mRNA:
+
Sickle Cell
BasesonDNA:
The substitution f A tor Tsivesvalinensteadfclutamicacid
 
GeneMutations
BioFactsbeet
A'nonsense'mutationchanges namino-acicl-speciliingoclon nto achain-terminatingodon.Fornstance.fUCA.whichcodesorserine.ssubstituted,a-kingGA. then his sa codonwhichhaltsvnthcsis fthepoll,peptide.A'fiameshift'mutations a mutationuising rorn he nsertionrdeletionof oneor morenucieotidesotherhan n multiplesf three)hatcauseshegeneobemisreacluringtranslationntothepolvpeptide.nthist1,pe fmutatictn.eeralor all of the codonsafter hc mutationare alteredndscrscveralor all of the aminoacids assernbleclogether re incorrect.Theresultingol-vpepticleillprobabll,beompletel\,inactivcndbiologicalll'useless.Causesofmutationl.Spontaneousmutations esult iomerrors ntheeplication1'DNA.ReplicationfDNAis acomplicatedrocessnvolvinsDNApoll,meraseand a larsenumberof otherenzvmes. heseenzvmesmake aremistakesandhe ecauseasechanges n thecomrrositionfDNA.2.Induced mutationsare chan-eein the DNAcaused-v he efl-ects 1'mutagens'.Thesema1,eadiationlr hemicaln naturendcauscenesto mutateatrateshataremuch hishcrthantheir spontaneous'ate.Examplesre:ionising adiations.e.g.X-rays.cosmic ays romspace.lpha(u)raysheliumnuclei).etaF)ra1'selectronsrpositrons)ndgamma(])rayswhichareelectromagnetic.lpha.betaandsammaaysaretrom radioactiveources. he1,c1 l,directlvbreakinghegeneticmoleculesndby breakingupwatermoleculesnto reactiveonisedlragmentshiit can damage lie DNA indirectiy.non-ionisingradiations. Thecommonestxample sultra-violetIightbetweenwavelengths-50o 170pm.This sabsorbedi,, henitrogenousases n DNA andmodifieshem nvariousways.Onernaineffect s tliat thyminedimersareproducedadjacent hvminebases none DNA strandcoupleogether atherhanwiththecomplementarydenines n the otherstrand. hustheDNAhelixdevelops bulgewheret is notcoupled. uckilythere s a i-eht epairsystem hat ntheightusesepairenzymesomakegoodheDNAdamage. owever,somepeopleaveagenemutationwhichcausesthe repairenzyme obedamaged. hesepeopleare at risk lromdeveloping kincancerxerodermaigmentosum)f they sunbathe.chemicals.Mustardgass analkylatingagent','liichddsa methvlorsimilaralkylgroupoguanine.ltering tsability o baseair.Thiscauseshe eleasefguaninerom DNAso hat hepositionccupiedb1,uaninecan henbe llled byanother ase.Manyother chemicalsarebasenalogueshichhavesirniiartructuresothenormalbasesandsocanbecome ncorporated nto he DNA inplaceofthemduringrcplication.n examples5-bromouracil.thermutagenichemicalsincludedioxin, colchicine.afteine. omeesticidesndseveralobaccoproducts.GenemutationandnaturalselectionManygenemutationsreharmful,suchas hehumanonditionsf sickle-cell anaemia, aemophilia,musculardystrophy. lbinoism.halassaemia,fibrocysticdiseaseof thepancreasand Huntington'schorea.Withoutmedicaltreatmentand support, he individualssuffering romtheseconditionsprobablywouldnot survive.However.manygenemutationscanbeof advanta_ee.For example.hemutantsickle-cell lleleorhaemoglobin-Ss codominantto the normal haemoglobin-Aallele.Althoughan individual whoishomozygous bralleleS(genotypeSS)willhavesicklingof all his or herredcells, causinga severe, sually 'atal. naemia,n individualwhoisheterozygous-eenotypeA)willproduce50c/rsickle cellswithhaemoglobin-Snd507c orrnalellswithhaemoglobin-A.his ndividualcan surviveandmay reproduceopassn the sicklecelltrait.Naturalelectionlavsapmtwhenheterozygousickleell rait ndividualsIive nareas'heremalaria sprevalent.hemaliuiaiparasiteivesn normalred cells ancl -eedsn haemoglobin .It cannoteed successlulhonhaemoglohin-Sndlndsdifticultt,inentering icklecledcells.Thussickle-cell carriersdo notsuf-ferrom malaria nareas.l,herc-lauv ormal peclplecontractmalaria.he requencvf the sickle-celllleles raisedn thesemalarialareas bove ts frequencvn malaria-lreereas. hiscould bebecausehesurvival ateandeprocluctiveateof sickle-cellraitcarriers shigher n malarialreas han n non-malarialreas.r because orenormalpcopleieoi'maiariahan ickie-cellraitcarrierso.Aclcarer xamplel'natural ele tionoperating namutated enesshownin theexamplef thcpcpperecloth,Bistottbetularia.Asin-sleeeneocusis involvecl'ithwc.rnainalleles. he recessivellelec)determineshe't1''pical'phenotl,'pen thedouble ecessiveomozygotescc).Thisphenot.""pes lightcoloureclmothswitha'peppering'ofblackspotsonthcwingsandbod"v'-.hescwerehepredominantbrmsof themothpresentin Britain n the irsthalf of thc nineteenthentur),.n 18219dark-colouredvarietvcalleclcarbonarill'\\'asdiscoveredn Manchester.hisphenotvpewasclue o a dominantmutationntoalleleC. Thecarbonaria'mothshadtheeenotypesC or Cc. Between 849and 189,5hecarbonaria'varietyincreasecln trequencl',brming98%ol thepopulationn theManchesterarea.Thisncreasen trequencv\'asssociated iththe ndustrialRevolutioninthenineteentl')enturvand tsassociatedollution.Thecarbonparticlesandsulphurdioxideallingoutiomtactorychimneys illedthe ightcolouredlichenon treeruntris ndocks.and ormeda black.sootycoatingon thesesurlhces. hetvpical'torms of the mothwereno longercamoullagednthesesurfaces nd sowerc predatedn(bvbirdssuch as robinsandthrushes) orc han hecarbonaria'fbrms whichwerecamoufla-sed.husthecarbonaria'lbrms survivedandwereselectedutthetvnical'lormswereeaten ndbecamecarce.Thisphenomenonecame nown asindustrialmelanism'andoccurredin manl'species f butterilies ndmoths.However.tdid not occur nnon-industrial. on-polluted egionsof the countryherchetypical'formssurvived.In 1956 heCleanAir Actu'asntroducedwiththe resulthat ndustrialpollutionbvsootand sulphurdioxidewas greatlycurtailed. hisresultedina return of lichenqrowthand alightningofthe surf'acesf treesandrocks.Thecarbonaria'tbrmsareno ongercamoullagedndnowgeteatenwhilethetypical'tormsarecamouflagedndhaveanmprovedhance fsurvivalFig3.Fig3. Changes n the frequenciesof'typical'and'carbonaria'pepperedmoths in industrialareas of England
+
I
I
:100-.=
.E
-
.J
=JO.,
ra
\i
/t
--J
;typ\ca,l
\
\t-carbonaria185019001950+ ftime/yearstlindustrialcleanrevolutionair act
 
GeneMutations
BioFactsbeet
Othcr examplesn naturefgcnemutations liichhaveproducedenetlcialvariationsothe mutatedorganismlre:.thedevelopmentfantibiotic esistaucencertain trainsf bacteria:othedevelopmentl'w,artarinratpoison)esistancen rats:.thedevelopmentfDDTresistancen mosquitocsanclman1,otherspecies f inscct:.thc developmentf camoullagingshell coloursanclbandingontheshellso1'thesnail.CrTa(anentorolis.hisreducesredationbrrthrushes:.thc dcvelopment1 resistanceothc myxclmatosis irusb1,manvrabbits.
Remember:- otltergetrcmutatiotts u'licltlou nru\. beasketl oboutittcluclc lruemopliliu.recl-E'r,ettcolout'ltlintlrrcss.cr.s/ic.fibt'osisandalplru-lattitt't'ltsirtcleJiciartct'u,lticltresultsirtarr irtlrct'itedfor.moJempltvsenta(lwtgcliseasc).You ntot'begircttdata intcrprctatit)nqtteslott u xtttt rttltantttal ott.s.A t'en'conunon en'ot'isto cortlfusease leletiottofgertenurtatiort u'itlrqac cl attttJ'trttnl(s(nrnt tr.
ExamHint:-lnaddition toquestionsabaut thenatureofgenemutationsand their importanceas sourcesofvariationor naturalselectionto act upon,examinersoften setquestionsontheinheritancepatternsofgenemutationsn familytrees.nansweringtheseit is importantthat thegeneticdiagramsarelaidoutinthecorrect,acceptable ormat.Some examplesare shown inthespecimenquestionsand markschemes below.Questions ofteninvolvedatainterpretation.Mostgenemutationsn naturewillhaveonly slighteftectsor unnoticableeff-ects nd mavalso conlersurvivalbenefits.Polygenicystemswithmanydill-erentllelesrobabli'arisesa resultf manysuchenemutationsover ongperiodsf time. Thus.houghanndividualgenemutationgivesriseto discontinuousariation.man)'minor mutationso thesamegeneoverthousands fyearsmaveiveriseo the continuous ariationdue topolygeneshichcanconsistfhundredsfdilferent lleles.PracticeQuestionsl.CysticibrosisCF)s themostommon ecessiveeneticisorderntheUK Caucasianopulation,ithan overallbirthiequencyof aboutIin 2-500. t ischaracterisedv severe espiratory roblemsandinadequateancreaticunction.aused vaccumulationf stickl,mucus.There sno cureatpresentutimprovedreatments an ncreasehelif-e xpectancyo about30years.eathsuallybeingdue o respiratorylailure.Malesu'ithCF are usualll,' terile.Cystic lbrosiss dueo amutation nthegeneencodinghe cystic fibrosisransmembraneconductanceegulatorCFTR).Thisproteinegulateshe ransportfchlorideacross ell membranes.hemutantallelesrecessivendheterozygoteso notexhibit symptoms.The mutantallele occursnabout 4c/rof thepopulationanclusually arisesby deletionof threeadjacent ucleotides.(a)(i)Suggest ow thedeletionould occurand influenceheeffectivenessf theCFTRgene.5(ii)Namewoother vpesofsenemutation.2(b) (i)Bv meansof ageneticdiagram.show heprobabilityof twocarrierparentsroducin_eCF child.-5(ii)What wouldbe the expectedercenragencidenceofcysticfibrosis nthepopulation'?xplainyouranswer.5(iii)Sincecystic lbrosiss a Iethalcondition,whydoes ts alielepersistnthepopulation'lI2. Thedrawingsbelou'shou' he appeffancef normal humanedcellsandedcells iomiur ndividual ufferineiomsicklecellanaemia. hecondition s causedv a mutanto-dominantllele.Inhehomozygousconcliticlnhealleleauses ickleellanaemia hichhaserious. tienfatal.eff'ccts nsuf'ferers.vhilentheheterozygousonditiont causessicklccellraitwhichs harmlessndsivesesistlnccagainst nl-ectionbv malarialarasites.heabnormalenelso hangeshepermeabilitl,'o1 eclell membraneso hatheeciells oseDotassiumons.normal edcellssickleells(atThe mutatior-ll-lectshe aminoacid sequencel thep-globinchainofhaemoglobin.he nomralaminoacidsequence.ogetherwiththemRNAanclDNA baseswhichcode brthe sequencere shou'nbelou,.
amino acidsequence: r,alirrehistidine /leuciucthreonineprolineglutamicacid/slutarricacid
mR\Acodons:D\Abases:
GI.IA CAI.I CTC'ACL]CCAGAAGAA
-t.
C,{I CITAC;AC; TC;AC}C;T
c-l-fcTI
+
(i)Ifthe basemarkedwithan rrow waschanged o A(adenine)what wouldbe the eflecton theamino aciclsequencef the-elobin'lExplainvour answer.4(ii)Whatwillbeheprobablellect s thischangenaminoacidsequencen the structuref the haemo_elobin'?xplainvouranswer.2(iii)Namehisypeofgenemutation.I(b)Thesicklecell hacmoglobinsknou'nashaemo-elobin. Thisypeol haemoglobins bundmainly'inpeoplewholiventhemalarialbeltsof theworld.or in theirdescendents.uggestn explanationwhvthissso.4Alkaptonuria sa harmless.are autosomal-eeneticef-ect,ueto amutantallele. n humans.he amilytreebelou'showshepedigreefa tamill'af1'ected1,'alkaptonuria.lndividualsrenumberedto l4)
unaf'fectedf'emaleafl-ected emaleunattected maleallected male
(a)(i)Isthe conditiondominantor recessive?xplainvouranswer(ii)Statehe numbersfall thencliviclualshatare certaino beheterozy-eousor thisgene3(iii)Whatistheprobabilityhat ndividual4 is heterozy-eousbrthisgene?I(b)Alkaptonuriaoccursdueopointmutationof anallele ofa-eene.State wo otherpointmutationdiseasesf humans.2

Activity (12)

You've already reviewed this. Edit your review.
1 hundred reads
1 thousand reads
Zing Harn liked this
Rezki Kadir liked this
Rohan David liked this
reyzmoghary liked this
Rishu Cybergurl liked this
yota_ahly liked this
Marooty liked this
Koo Keung Eng liked this

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->