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CW/HWAssignments6. CH.15VCN(LinkedGenes)7. Ch.15LectureNotes8. GeneDcsWS3
PLANNER • Complete odd #s for Genetics WS 3 (separate paper) • See Ms. Fleming for ALL stamps • Ch. 15 Quiz • Study for genetics test
– Ch. 13-15, with some Ch. 6-7
QuizProtocol
• Clearyourdesks• Noiselevel0• Eyesonyourownpaper• Checkanswerswhenfinished• Flipoverwhenfinished
EssenDalknowledgestandards• 3.A.4:TheinheritancepaSernofmanytraitscannotbeexplainedbysimpleMendeliangene/cs
• 3.C.1:Changesingenotypecanresultinchangesinphenotype
FLT• Iwillbeableto:– Explainwhysex-linkeddiseasesaremore
commoninhumanmalesthanfemales
– disDnguishbetweensex-linkedgenesandlinkedgenes
– Explainhowmeiosisaccountsfor
recombinantphenotypes
– Explainhowlinkagemapsareconstructed
• Bycomple1ngCh.15LectureNotes
Overview• Mendel’s�hereditaryfactors�weregenes,thoughthiswasn’tknownattheDme.
• ThelocaDonofaparDculargenecanbeseenbytaggingisolatedchromosomeswithafluorescent
dyethathighlightsthegene.
9
I.MendelianGeneDcsandChromosomesA. ChromosomeTheoryofInheritance
• Thechromosometheoryofinheritancestates:
– Mendeliangeneshavespecificloci(posi/ons)onchromosomes
– Chromosomesundergosegrega/onandindependentassortment.
• ThebehaviorofchromosomesduringmeiosiswassaidtoaccountforMendel�slawsofsegregaDonandindependentassortment.
10
Mendel�sLawsPGenera/on Yellow-round
seeds(YYRR)
Y
F1Genera/on
Y
R R
R Y
× rr
r
y
y
y
Meiosis
Fer/liza/on
Gametes
Green-wrinkledseeds( yyrr)
AllF1plantsproduceyellow-roundseeds(YyRr)
R R
YYr r
y y
Meiosis
R R
Y Y
r r
y y
MetaphaseI
Y Y
R Rrr
y yAnaphaseI
r r
y Y
MetaphaseIIR
Y
R
y
yyy
RR
YY
rrrr
yYYR R
yRYryrYR1/4 1/4 1/4 1/4
F2Genera/on
Gametes
AnF1×F1cross-fer/liza/on
9 :3 :3 :1
LAWOFINDEPENDENTASSORTMENTAllelesofgenesonnonhomologouschromosomesassortindependentlyduringgameteforma/on.
LAWOFSEGREGATIONThetwoallelesforeachgeneseparateduringgameteforma/on.
1
2
33
2
1
I.MendelianGeneDcsandChromosomesA. MorganandDrosophilaMelanogaster
• ThomasHuntMorganstudiedmutaDonin
Drosophlamelanogaster(fruitflies)• Morgan�sexperimentswithfruitfliesprovidedconvincingevidencethatchromosomesarethe
locaDonofMendel’sheritablefactors
13
I.MendelianGeneDcsandChromosomesA. ChromosomeTheoryofInheritance
B. MorganandDrosophilaMelanogaster
• SeveralcharacterisDcsmakefruitfliesaconvenient
organismforgeneDcstudies:
– Theybreedatahighrate– AgeneraDoncanbebredeverytwoweeks– Theyhaveonlyfourpairsofchromosomes.
14
I.MendelianGeneDcsandChromosomes
A. MorganandDrosophila
Melanogaster
1. Wildtypeandmutant
type
– Differenttraitshavebeen
studied
– Commonly,eyecoloris
lookedat
– Ex/
– Wildtype=red-eyes– Mutanttype=whiteeyes
15
I.MendelianGeneDcsandChromosomesA. MorganandDrosophilaMelanogaster
• Inoneexperiment,Morganmatedmaleflieswithwhiteeyes(mutant)withfemaleflieswithredeyes(wildtype)
– TheF1generaDonallhadredeyes– TheF2generaDonshowedthe3:1red:whiteeyeraDo,butonlymaleshadwhiteeyes.
• Morgandeterminedthatthewhite-eyedmutantallelemustbelocatedontheXchromosome.
• Morgan’sfindingsupportedthechromosometheoryofinheritance.
17
II.InheritanceofSex-LinkedGenes• Thesexchromosomeshavegenesformany
charactersunrelatedtosex.
• Sex-linkedgene=Agenelocatedononeofthesexchromosomes
• Inhumans,sex-linkedusuallyreferstoageneon
thelargerXchromosome.
19
I.MendelianGeneDcsandChromosomesA. MorganandDrosophilaMelanogaster
• P:Morgancrossedared-eyedfemalewithawhite-
eyedmale
• F1:Allred-eyedoffspring• F2:3red-eyed:1white-eyedmale
• Haveweseenthispadernbefore?
21
I.MendelianGeneDcsandChromosomesNotaDonforX-linkedtraits:
• XA=dominantallele,Xa=recessiveallele
• MalesalwaysexhibitX-linkedtraitstheyinherit(dominantornot)sincetheyonlyhaveoneX
• Examples:
– XRXR=homozygousdominantred-eyedfemale
– XRXr=heterozygousred-eyedfemale
– XrXr=homozygousrecessivewhite-eyedfemale
– XRY=red-eyedmale
– XrY=white-eyedmale
22
II.InheritanceofSex-LinkedGenesA. SexDeterminaDon
• Inhumansandothermammals,therearetwo
varieDesofsexchromosomes:alargerX
chromosomeandasmallerYchromosome.
• OnlytheendsoftheYchromosomehaveregions
thatarehomologouswiththeXchromosome.
• TheSRYgeneontheYchromosomecodesforthedevelopmentoftestes.
25
SystemsofSexDetermina/on
44+XY Parents 44+
XX
22+X
22+X
22+Yor +
44+XX or
Sperm Egg
44+XY
Zygotes(offspring)
(a)TheX-Ysystem
22+XX
22+X
(b)TheX-0system
76+ZW
76+ZZ
(c)TheZ-Wsystem
32(Diploid)
16(Haploid)
(d)Thehaplo-diploidsystem
II.InheritanceofSex-LinkedGenesB.Sex-Linkedinheritedtraits
• Sex-linkedgenesfollowspecificpadernsofinheritance.
• Forarecessivesex-linkedtraittobeexpressed– Afemaleneedstwocopiesoftheallele
– Amaleneedsonlyonecopyoftheallele
• BecausemalesalwaysexpressX-linkedgenes,sex-linkedrecessivedisordersaremuchmorecommoninmalesthaninfemales.
27
(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
N=Normalisdominant
n=disorderisrecessive
II.InheritanceofSex-LinkedGenesC.Hemizygous
=Havingonlyonecopyofagene(insteadoftwo)Ex/MalesaretypicallyhemizygousforX-chromosome
genes
29
II.InheritanceofSex-LinkedGenesD.SomedisorderscausedbyrecessiveallelesontheX
chromosomeinhumans:
1.Musculardystrophy
2.Colorblindness
3.Hemophilia
30
II.InheritanceofSex-LinkedGenesE.X-InacDvaDoninFemales
1.Barrbodies
• Inmammalianfemales,oneofthetwoXchromosomesineachcellisrandomlyinac/vatedduringembryonicdevelopment.
• Theinac/veXcondensesintoaBarrbody.• IfafemaleisheterozygousforaparDculargene
locatedontheXchromosome,shewillbeamosaic
forthatcharacter.
31
XInac/va/onisRandominFemaleMammalCells
Xchromosomes
Earlyembryo:
Allelefororangefur
Alleleforblackfur
CelldivisionandXchromosomeinac/va/onTwocell
popula/onsinadultcat:
Ac/veXAc/veX
Inac/veX
Blackfur Orangefur
III.ChromosomalRecombinaDonA. LinkedGenes• Linkedgenes=genesonthesamechromosomethattendtobeinheritedtogetherduetoproximity
• Morgandidotherexperimentswithfruitfliestosee
howlinkageaffectsinheritanceoftwocharacters.
• Morgancrossedfliesthatdifferedintraitsofbody
colorandwingsize.
36
Morgan:LinkedGenes
b+ vg+
Parentsintestcross
Mostoffspring
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
×
or
EXPERIMENT
Morgan: Linked Genes P Generation (homozygous)
RESULTS
Wild type (gray body, normal wings)
Double mutant (black body, vestigial wings) ×
b b vg vg
b b vg vg
Double mutant TESTCROSS
×
b+ b+ vg+ vg+
F1 dihybrid (wild type)
b+ b vg+ vg
Testcross offspring 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 RATIOS
If genes are located on different chromosomes:
If genes are located on the same chromosome and parental alleles are always inherited together:
1
1
1
1
1 1
0 0
965 944 206 185
:
:
:
:
:
:
:
:
:
III.ChromosomalRecombinaDonB.GeneDcRecombinaDon
• Evenwhengenesarelinked,geneDcrecombinaDon
canoccur
– Thismeansthatnewphenotypes(non-parentalphenotypes)areproduced
• Gene/crecombina/on=Parentsproduceoffspringwithamixoftraits(notiden/caltoparents)
• ThegeneDcfindingsofMendelandMorganrelate
tothechromosomalbasisofrecombina/on.
39
ParentalTypesandRecombinants
YyRr
Gametesfromgreen-wrinkledhomozygousrecessiveparent(yyrr)
Gametesfromyellow-roundheterozygousparent(YyRr)
Parental-type
offspring
Recombinantoffspring
yr
yyrr Yyrr yyRr
YR yr Yr yR
Crossing Over: Separates Linked Genes Recombinant Frequency Calculated
Testcross parents
Replication of chromo- somes
Gray body, normal wings (F1 dihybrid)
Black body, vestigial wings (double mutant)
Replication of chromo- somes
b+ vg+
b+ vg+
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
b vg b vg
b vg
b+ vg+
b+ vgb vg+
b vg
Recombinant chromosomes
Meiosis I and II
Meiosis I
Meiosis II
b vg+b+ vgb vg b+ vg+ Eggs
Testcross offspring
965 Wild type
(gray-normal)
944 Black-
vestigial
206 Gray-
vestigial
185 Black- normal
b+ vg+
b vg b vg
b vg b+ vg
b vg b vg
b vg+
Sperm
b vg
Parental-type offspring Recombinant offspring
Recombination frequency = 391 recombinants
2,300 total offspring × 100 = 17%
III.ChromosomalRecombinaDonE.CrossingOver–
1.RecombinaDonFrequency=%ofrecombinant
offspringproducedinageneDccross
• Genesondifferentchromosomesà50%recombina/onfrequency
• Ifgenesarelinked,thentheymaynotassortindependentlyduringmeiosis.Thus,LESSTHAN50%recombina/onfrequency
44
IV.GeneDcMaps&CrossingOverData• AlfredSturtevant,oneofMorgan�sstudents,constructedagene/cmap,anorderedlistofthegeneDclocialongaparDcularchromosome
• Sturtevantpredictedthatthefartheraparttwogenesare,thehighertheprobabilitythatacrossoverwilloccurbetweenthemandthereforethehighertherecombina9onfrequency.
46
IV.GeneDcMaps&CrossingOverDataA. Linkagemap/Mapunits
• Linkagemap=mappinggenesonachromosomebasedonrecombina/onfrequencies
• Distancesbetweengenescanbeexpressedasmap
units;onemapunit,orcenDmorgan,representsa
1%recombinaDonfrequency.
• Mapunitsindicaterela/vedistanceandorder,notpreciseloca/onsofgenes.
47
CrossingOver-->RecombinantsFrequency-->DistanceApart
RESULTS
Recombina/onfrequencies
Chromosome9% 9.5%
17%
b cn vg
IV.GeneDcMaps&CrossingOverDataA. Linkagemap/Mapunits
• Genesthatarefarapartonthesamechromosomecan
havearecombinaDonfrequencynear50%.
• Suchgenesarephysicallylinked,butgeneDcallyunlinked,andbehaveasiffoundondifferentchromosomes.
• SturtevantusedrecombinaDonfrequenciestomake
linkagemapsoffruitflygenes.
• Usingmethodslikechromosomalbanding,geneDcistscan
developcytogeneDcmapsofchromosomes.
• CytogeneDcmapsindicatetheposiDonsofgeneswith
respecttochromosomalfeatures.
49
Pair-Share-Respond1. Whatismeantbytheterm“linkedgenes”?2. What%recombina/onfrequencywouldbe
expectedforlinkedgenes?3. What%recombina/onfrequencywouldbe
expectedforgenesthatarenotlinked?4. Whatisalinkagemap,andwhatdoesittell
us?
50
V.ChromosomalAlteraDonsA. AlteraDonsinChromosomeNumber
1.Nondisjunc/on=whenhomologouschromosomesdonotseparateduringanaphaseIofmeiosis• Thiscausesonegametetoreceive2copiesofachromosome,andanothergametetohavenocopies
2.Aneuploidy–
3.Polyploidy-
52
Fig.15-13-3
MeiosisI
Nondisjunc/on
(a) Nondisjunction of homologous chromosomes in meiosis I
(b) Nondisjunction of sister chromatids in meiosis II
MeiosisII
Nondisjunc/on
Gametes
Numberofchromosomes
n+1 n+1 n+1n–1 n–1 n–1 n n
V.ChromosomalAlteraDonsA. AlteraDonsinChromosomeNumber
2.Aneuploidy=whenthegametesresul/ngfromnondisjunc/onarefer/lized,anabnormalchromosomenumberresults
• AmonosomiczygotehasonlyonecopyofaparDcularchromosome2n-1
• AtrisomiczygotehasthreecopiesofaparDcularchromosome2n+1
3.Polyploidy-
54
V.ChromosomalAlteraDonsA. AlteraDonsinChromosomeNumber
3.Polyploidy–
• Polyploidy=whenanorganismhasmorethantwocompletesetsofchromosomes– Triploidy(3n)isthreesetsofchromosomes
– Tetraploidy(4n)isfoursetsofchromosomes
• Polyploidyiscommoninplants,butnotanimals
• Polyploidsaremorenormalinappearancethan
aneuploids.
55
V.ChromosomalAlteraDonsB.AlteraDonsofChromosomeStructure
• Breakageofachromosomecanleadtofourtypesof
changesinchromosomestructure:
1. Dele/on=removesachromosomalsegment2. Duplica/on=repeatsasegment3. Inversion=reversesasegmentwithinachromosome4. Transloca/on=movesasegmentfromone
chromosometoanother.5. NonreciprocalCrossover=resultsinonechromosome
havingadele/onandanotheraduplica/on
56
BreakageCausesChange
Dele/onABCDEFGH ABCEFGH(a)
(b)
(c)
(d)
Duplica/on
Inversion
Reciprocaltransloca/on
ABCDEFGH
ABCDEFGH
ABCDEFGH
ABCBCDEFGH
ADCBEFGH
MNOCDEFGH
MNOPQR ABPQR
V.ChromosomalAlteraDonsC.ChromosomalAlteraDonsinHumanDisease
1.AneuploidDisorders=causedbynondisjunc/onofsexchromosomes
58
V.ChromosomalAlteraDons1.AneuploidDisorders
a.DownSyndrome=resultsfromthreecopiesofchromosome21
• Itaffectsaboutoneoutofevery700childrenbornintheUnitedStates.
• ThefrequencyofDownsyndromeincreaseswith
theageofthemother,acorrelaDonthathasnot
beenexplained.
59
V.ChromosomalAlteraDons1.AneuploidDisorders
b.KlinefelterSyndrome=resultsfromanextrachromosomeinmales(XXY)
• EffectsincludelowIQ,tallerbody,decreasedmusclemass,broadhips,extendedlegs,weaker
bones,etc.
61
V.ChromosomalAlteraDons1.AneuploidDisorders
c.Turnersyndrome=MonosomyX=XOfemales
– Viable,butfemalesaresterile
62
V.ChromosomalAlteraDons1.AneuploidDisorders
d.ExtraY=XYYmales(occursin1/1000malebirths)• Taller,possibleacneissues,butmostlynormal
63
V.ChromosomalAlteraDons1.AneuploidDisorders
e.Metafemales=XXX(about1:1500femalebirths)• Taller,poorcoordinaDon,reproducDveconcerns
64
V.ChromosomalAlteraDonsC.ChromosomalAlteraDonsinHumanDisease
2.StructuralDiseases
a.Criduchat=“cryofthecat”=dele/onofchromosome5
• Resultsinseveredevelopmentaldelays,behavioral
struggles,unusualfacialfeatures,andnervous
systemissues.
65
VI.ExcepDonstoStandardChromosomeTheory
OneexcepDontochromosometheoryinvolvesgenes
locatedinthenucleus
A. GenomicImprin/ng=varia/oninphenotypethatdependsonwhichparentpassedthealleles(mothervs.father)
• GenomicimprinDnginvolvesthesilencingofcertain
genesthatare�stamped�withanimprintduring
gameteproducDon.
66
Genomic Imprinting
Normal Igf2 allele is expressed
Paternal chromosome
Maternal chromosome
Normal Igf2 allele is not expressed
Mutant Igf2 allele inherited from mother
(a) Homozygote
Wild-type mouse (normal size)
Mutant Igf2 allele inherited from father
Normal size mouse (wild type)
Dwarf mouse (mutant)
Normal Igf2 allele is expressed
Mutant Igf2 allele is expressed
Mutant Igf2 allele is not expressed
Normal Igf2 allele is not expressed
(b) Heterozygotes
VI.ExcepDonstoStandardChromosomeTheory
A. GenomicImprinDng:
• ItappearsthatmammaliangenomicimprinDng,
�genesilencing,�istheresultofthemethyla9onofDNA(addiDonof–CH3).
• GenomicimprinDngisthoughttoaffectonlyasmall
fracDonofmammaliangenes.
• MostimprintedgenesarecriDcalforembryonic
development.
68
VI.ExcepDonstoStandardChromosomeTheory
B. OrganelleGenes=extranuclearDNA(suchasthatfoundinmitochondriaandchloroplasts)areinheritedmaternallybecausethezygote’scytoplasmcomesfromtheegg
• Thefirstevidenceofextranucleargenescamefromstudiesontheinheritanceofyelloworwhitepatchesonleavesofanotherwisegreenplant.
69
REVIEW EggSperm
Pgenera/ongametes
CBAD E
F
D
F EA
BCe
d
fcba
d
f
e
cba
ThisF1cellhas2n=6chromosomesandisheterozygousforallsixgenesshown(AaBbCcDdEeFf ).Red=maternal;blue=paternal.
+
Eachchromosomehashundredsorthousandsofgenes.Four(A, B, C, F)areshownonthisone.
Theallelesofunlinkedgenesareeitheronseparatechromosomes(suchasdande)orsofarapartonthesamechromosome(candf )thattheyassortindependently.
Genesonthesamechromo-somewhoseallelesaresoclosetogetherthattheydonotassortindependently(suchasa, b,andc)aresaidtobelinked.