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TheChromosomalBasisofInheritanceBIOL221
Ch.15
Overview:LocatingGenesAlongChromosomes• Mendel’s“hereditaryfactors” weregenes
• Notknownatthetime
• Todaywecanshowthatgenesarelocatedonchromosomes
• Locationofaparticulargene
• Canbeseenbytaggingisolatedchromosomeswithafluorescent
dyethathighlightsthegene
Fig.15-2
P Generation Yellow-roundseeds (YYRR)
Y
F1 Generation
Y
R R
R Y
´ r
r
r
y
y
y
Meiosis
FertilizationGametes
Green-wrinkledseeds (yyrr)
All F1 plants produceyellow-round seeds (YyRr)
R R
YY
r ry y
Meiosis
R R
Y Y
r r
y y
Metaphase I
Y Y
R Rrr
y yAnaphase I
r r
y Y
Metaphase IIR
Y
R
y
yyy
RR
YY
rrrr
yYY
R R
yRYryrYR1/4 1/4 1/4 1/4
F2 Generation
Gametes
An F1 ´ F1 cross-fertilization
9 : 3 : 3 : 1
LAW OF INDEPENDENTASSORTMENT Alleles of geneson nonhomologouschromosomes assortindependently during gameteformation.
LAW OF SEGREGATIONThe two alleles for each geneseparate during gameteformation.
1
2
33
2
1
2
Morgan’sChoiceofExperimentalOrganism• ThomasHuntMorgan- Embryologist
• Showedgenesareonchromosomes
• Studiedfruitflies
• Convenientorganismforgeneticstudies:
• Theybreedatahighrate
• Agenerationcanbebredeverytwoweeks
• Theyhaveonlyfourpairsofchromosomes
• Wildtype
• Normal,phenotypesthatwerecommoninflypopulations
• Mutantphenotypes
• Traitsalternativetothewildtype
Morgan’sChoiceofExperimentalOrganism
AllelesandBehaviorofaChromosomePair• Matedmaleflieswithwhiteeyes
(mutant)
• Withfemaleflieswithredeyes(wildtype)
• TheF1 generationallhadredeyes
• TheF2 generationshowedthe3:1red:whiteeyeratio
• Butonlymaleshadwhiteeyes
• Thereforewhite-eyedmutantallelemustbeonXchromosome
• Supportedthechromosometheoryofinheritance
PGeneration
Generation
Generation
Generation
Generation
Generation
F1
F2
All offspring had red eyes
SpermEggs
F1
F2
P
SpermEggs
´
´XX
XY
CONCLUSION
EXPERIMENT
RESULTS
w
w
w
w
ww
w w
+
+
+ + +
w
w w w
ww
w
ww
+
++
+ +
+
3
• Inmammals
• twokindsofsexchromosomes- largerX,smallerYchromosome
• RegionsonendsofYchromosome
arehomologouswiththeXchromosome
• TheSRYgeneontheYchromosomecodesforthedevelopmentoftestes
• Someotheranimalshavedifferent
methodsofsexdetermination
• Birds,fish,somecrustaceans,someinsects
• Female:ZW;MaleZZ
Sex-linkedinheritance
InheritanceofSex-LinkedGenes• Sexchromosomes
• Havegenesformany
charactersunrelatedto
sex
• Sex-linkedgene
• Agenelocatedon
eithersex
chromosome
• Inhumans,sex-linked
usuallyreferstoa
geneonthelargerX
chromosome
• CalledX-linked
• Sex-linkedgenesfollowspecificpatternsofinheritance
• Forarecessivesex-linkedtraittobeexpressed
• Afemaleneedstwocopiesoftheallele
• Amaleneedsonlyonecopyoftheallele
• Sex-linkedrecessivedisorders
• Aremuchmorecommoninmalesthaninfemales
Sex-linkedinheritance
(a) (b) (c)
XNXN XnY XNXn´ ´ XNY XNXn ´ XnY
YXnSpermYXNSpermYXnSperm
XNXnEggs XN
XN XNXn
XNY
XNY
Eggs XN
Xn
XNXN
XnXN
XNY
XnY
Eggs XN
Xn
XNXn
XnXn
XNY
XnY
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• CommonX-linkedconditions- Duetorecessivealleles
• Colorblindness
• Red/greenmostcommon
• Mayinclude19chromosomesand56genes
• Duchennemusculardystrophy
• MutantDystrophingeneXp21
• Hemophilia- Failedbloodclotting
• Threetypes
• TwofoundonXchromosome
Sex-linkedinheritance
XInactivationinFemaleMammals• Mammalianfemales
• OneofthetwoXchromosomes
ineachcellisrandomly
inactivatedduringembryonic
development
• Barrbody
• Thecondensedinactive
X
• Ifafemaleisheterozygousfora
particulargenelocatedontheX
chromosome
• Shewillbeamosaicforthat
character
X chromosomes
Early embryo:
Allele fororange fur
Allele forblack fur
Cell division andX chromosomeinactivationTwo cell
populationsin adult cat:
Active XActive X
Inactive X
Black fur Orange fur
• Eachchromosome
• hashundredsorthousandsofgenes
• linkedgenes
• Geneslocatedonthesamechromosomethattendtobeinherited
togetherarecalled
LinkedGenes
5
HowLinkageAffectsInheritance• Morgandidotherexperimentswithfruitflies
• Toseehowlinkageaffectsinheritanceoftwocharacters
• Crossedflies
• Thatdifferedintraitsofbodycolorandwingsize
b+ vg+
Parents in testcross
Most offspring
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
´
or
Fig.15-9-4
EXPERIMENTP Generation (homozygous)
RESULTS
Wild type(gray body,normal wings)
Double mutant(black body,vestigial wings)´
b b vg vg
b b vg vg
Double mutantTESTCROSS
´
b+ b+ vg+ vg+
F1 dihybrid(wild type)
b+ b vg+ vg
Testcrossoffspring Eggs b+ vg+ b vg b+ vg b vg+
Black-normal
Gray-vestigial
Black-vestigial
Wild type(gray-normal)
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vgPREDICTED RATIOS
If genes are located on different chromosomes:
If genes are located on the same chromosome andparental alleles are always inherited together:
1
1
1
1
1 1
0 0
965 944 206 185
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:
:
:
:
:
:
:
:
• Morganfoundthat
• Bodycolorandwingsize
• Areusuallyinheritedtogetherinspecificcombinations
• FailedLawofSegregation
• Reasonedthattheywereonthesamechromosome
• Thereforelinked
• Theclosertogetheronchromosome
• Morelikelytobeinheritedtogether
Linkedinheritance
RESULTS
Testcrossoffspring Eggs b+ vg+ b vg b+ vg b vg+
Black-normal
Gray-vestigial
Black-vestigial
Wild type(gray-normal)
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg
PREDICTED RATIOSIf genes are located on different chromosomes:
If genes are located on the same chromosome andparental alleles are always inherited together:
1
1
1
1
1 1
0 0
965 944 206 185
:
:
:
:
:
:
:
:
:
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• Afewnon-parentalphenotypeswerealsoproduced
• Geneticrecombination
• Theproductionofoffspringwithcombinationsoftraits
• Differingfromeitherparent
• Ienotgray/normalorblack/vestigial
• Butgray/vestigialorblack/normal
Linkedinheritance
RESULTS
Testcrossoffspring Eggs b+ vg+ b vg b+ vg b vg+
Black-normal
Gray-vestigial
Black-vestigial
Wild type(gray-normal)
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg
PREDICTED RATIOSIf genes are located on different chromosomes:
If genes are located on the same chromosome andparental alleles are always inherited together:
1
1
1
1
1 1
0 0
965 944 206 185
:
:
:
:
:
:
:
:
:
IndependentAssortmentofChromosomes• Mendel- Combinationsoftraitsinsomeoffspringdifferfromeitherparent
• Parentaltypes
• Offspringwithaphenotypematchingoneoftheparentalphenotypes
• Recombinants
• Offspringwithnonparentalphenotypes
• newcombinationsoftraits
• A50%frequencyofrecombinationobservedforanytwogenesondiffchromosomes
• Dueentirelytoindependentassortmentinmetaphase1
YyRr
Gametes from green-wrinkled homozygousrecessive parent ( yyrr)
Gametes from yellow-roundheterozygous parent (YyRr)
Parental-type
offspring
Recombinantoffspring
yr
yyrr Yyrr yyRr
YR yr Yr yR
RecombinationofLinkedGenes:CrossingOver• Morgandiscoveredthatgenescanbelinked
• Butthelinkagewasincomplete
• Evidentfromrecombinantphenotypes
• Proposedthatsomeprocessmustsometimesbreakthephysical
connectionbetweengenesonthesamechromosome
• crossingoverofhomologouschromosomeswasthatmechanism
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MappingtheDistanceBetweenGenes• AlfredSturtevant
• StudentofMorgan
• Constructedageneticmap
• anorderedlistofthegeneticloci
alongaparticularchromosome
• Predictedthat
• Thefartheraparttwogenesare
• thehighertheprobabilitythatacrossoverwilloccurbetween
them
• andthereforethehighertherecombinationfrequency
Recombinationfrequencies
Chromosome9% 9.5%
17%
b cn vg
• Linkagemap
• geneticmapofachromosome
basedonrecombinationfrequencies
• Mapunits
• Expressionofdistancesbetweengenes
• onemapunit,or
centimorgan,representsa1%recombination
frequency
• Mapunitsindicaterelativedistanceandorder,notpreciselocationsof
genes
LinkageMap
• Genesthatarefarapartonthesame
chromosome
• Canhavearecombination
frequencynear50%
• Suchgenesarephysicallylinked,but
geneticallyunlinked,
• Andbehaveasiffoundon
differentchromosomes
LinkageMap
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• Sturtevant- usedrecombinationfrequenciestomakelinkagemapsoffruitflygenes
• Chromosomalbanding
• Stainingmethodtoidentifyregionsofchromosomes
• Geneticistscandevelopcytogeneticmapsofchromosomes
• Cytogeneticmaps
• Indicatethepositionsofgeneswithrespecttochromosomalfeatures
• Ie– bandsduetodenselypackagedgene-freeregionsofchromosomes
GeneMapping
Mutant phenotypesShortaristae
Blackbody
Cinnabareyes
Vestigialwings
Browneyes
Redeyes
Normalwings
Redeyes
Graybody
Long aristae(appendageson head) Wild-type phenotypes
0 48.5 57.5 67.0 104.5
Meiosis I
Nondisjunction
(a) Nondisjunction of hom ologouschrom osom es in m eiosis I
(b) Nondisjunction of sisterchrom atids in m eiosis II
Meiosis II
Nondisjunction
Gam etes
Num ber of chrom osom es
n + 1 n + 1 n + 1n – 1 n – 1 n – 1 n n
Alterationsofchromosomenumberorstructure• Large-scalechromosomalalterations
• Oftenleadtospontaneousabortions(miscarriages)
• Orcauseavarietyofdevelopmentaldisorders
• Nondisjunction
• Pairsofhomologouschromosomesor sisterchromatidsdonotseparatenormallyduringmeiosis
• Asaresultonegametereceivestwoofthesametypeofchromosome
• Andanothergametereceivesnocopy
• Aneuploidy
• Resultsfromthefertilizationofgametesinwhichnondisjunction
occurred
• Offspringwiththisconditionhaveanabnormalnumberofaparticular
chromosome
AbnormalChromosomeNumber
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• Monosomiczygote
• hasonlyonecopyofaparticularchromosome
• Trisomiczygote
• hasthreecopiesofaparticularchromosome
AbnormalChromosomeNumber
• Polyploidy
• conditioninwhichanorganismhas
morethantwocompletesetsof
chromosomes
• Triploidy(3n)isthreesetsof
chromosomes
• Tetraploidy(4n)isfoursetsof
chromosomes
• commoninplants
• butnotanimals
• Polyploidsaremorenormalinappearance
thananeuploids
ChromosomeNumber
AlterationsofChromosomeStructure• Breakageofachromosomecanleadtofourtypesofchangesinchromosome
structure:
• Deletionremovesachromosomalsegment
• Duplicationrepeatsasegment
• Inversionreversesasegmentwithinachromosome
• Translocationmovesasegmentfromonechromosometoanother
DeletionA B C D E F G H A B C E F G H(a)
(b)
(c)
(d)
Duplication
Inversion
Reciprocaltranslocation
A B C D E F G H
A B C D E F G H
A B C D E F G H
A B C B C D E F G H
A D C B E F G H
M N O C D E F G H
M N O P Q R A B P Q R
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AneuploidyDownSyndrome(Trisomy21)• Downsyndrome
• Aneuploidconditionthatresultsfromthreecopiesofchromosome21
• Affectsaboutoneoutofevery700children
• IntheUnitedStates
• ThefrequencyofDownsyndromeincreaseswiththeageofthemother
• Acorrelationthathasnotbeenexplained
AneuploidyofSexChromosomes• Nondisjunctionofsexchromosomes
• Producesavarietyofaneuploidconditions
• Klinefeltersyndrome
• XXYmale
• Sterile,smalltestes,somefemalesecondarysexualcharacteristics
• MonosomyX,Turnersyndrome
• X0female
• sterile
• itistheonlyknownviablemonosomyinhumans
StructurallyAlteredChromosomes• criduchat(“cryofthecat”)
• specificdeletioninchromosome5
• mentalretardation
• catlikecry
• usuallydieininfancyorearlychildhood
• Translocationsofchromosomes
• Certaincancers,includingchronic
myelogenousleukemia(CML)
Normal chromosome 9
Normal chromosome 22
Reciprocaltranslocation Translocated chromosome 9
Translocated chromosome 22(Philadelphia chromosome)
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GenomicImprinting• Genomicimprinting
• Variationinphenotype
• dependsonwhichparentpassedalongtheallelesforthosetraits
• Involvesthesilencingofcertaingenes
• thatare“stamped” withanimprintduringgameteproduction
• GenomicImprinting
• Oneformofepigenetics
• Theresultofthemethylation(additionof–CH3)ofDNA
• Thoughttoaffectonlyasmallfractionofmammaliangenes
• Mostimprintedgenesarecriticalforembryonicdevelopment
Norm al Igf2 alleleis expressed
Paternalchrom osom e
Maternalchrom osom e
Norm al Igf2 alleleis not expressed
Mutant Igf2 alleleinherited from m other
(a) Hom ozygote
W ild-type m ouse(norm al size)
Mutant Igf2 alleleinherited from father
Norm al size m ouse(wild type)
Dwarf m ouse(m utant)
Norm al Igf2 alleleis expressed
Mutant Igf2 alleleis expressed
Mutant Igf2 alleleis not expressed
Norm al Igf2 alleleis not expressed
(b) Heterozygotes
InheritanceofOrganelleGenes• Extranucleargenes(orcytoplasmicgenes)
• genesfoundinorganellesinthecytoplasm
• Mitochondria,chloroplasts,andotherplantplastidscarrysmallcircularDNAmolecules
• Extranucleargenes
• inheritedmaternally
• zygote’scytoplasmcomesfromtheegg
• Thefirstevidenceofextranucleargenes
• camefromstudiesontheinheritanceofyelloworwhitepatchesonleaves
• Variegation
• Somedefectsinmitochondrial
genes
• Preventcellsfrommaking
enoughATP
• Andresultindiseases
thataffectthemuscular
andnervoussystems
• Forexample,
mitochondrialmyopathy
andLeber’shereditaryopticneuropathy
• Failureofoxidative
phosphorylation
InheritanceofOrganelleGenes
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Youshouldnowbeableto:
1. Explainthechromosomaltheoryofinheritanceanditsdiscovery
2. Explainwhysex-linkeddiseasesaremorecommoninhumanmalesthanfemales
3. Distinguishbetweensex-linkedgenesandlinkedgenes
4. Explainhowmeiosisaccountsforrecombinantphenotypes
5. Explainhowlinkagemapsareconstructed
6. Explainhownondisjunctioncanleadtoaneuploidy
7. Definetrisomy,triploidy,andpolyploidy
8. Distinguishamongdeletions,duplications,inversions,andtranslocations
9. Explaingenomicimprinting
10. ExplainwhyextranucleargenesarenotinheritedinaMendelianfashion
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