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Biology 2250Biology 2250Principles of GeneticsPrinciples of Genetics
AnnouncementsAnnouncements
Lab 4 Information: B2250 (Innes) webpageLab 4 Information: B2250 (Innes) webpage
download and print before lab.download and print before lab.
Virtual fly: log in and practiceVirtual fly: log in and practice
http://biologylab.awlonline.com/http://biologylab.awlonline.com/
Test 2 Test 2 Thursday Nov. 17Thursday Nov. 17http://http://webctwebct..munmun.ca:8900/.ca:8900/
All quizzes on WebCT for ReviewAll quizzes on WebCT for Review
Office Hours: 1:30 – 2:30 Tue, Wed., ThrOffice Hours: 1:30 – 2:30 Tue, Wed., Thr
or by appointment: 737-4754, [email protected] by appointment: 737-4754, [email protected]
Mendelian GeneticsMendelian Genetics
Topics:Topics: -Transmission of DNA during cell division-Transmission of DNA during cell division
Mitosis and MeiosisMitosis and Meiosis
- Segregation - Segregation
- Sex linkage (- Sex linkage (problem: how to get a white-eyed femaleproblem: how to get a white-eyed female))
- Inheritance and probability- Inheritance and probability
- Independent Assortment- Independent Assortment
- Mendelian genetics in humans- Mendelian genetics in humans
- Linkage- Linkage
- Gene mapping- Gene mapping
-Gene mapping in other organismsGene mapping in other organisms
(fungi, bacteria)(fungi, bacteria)
- Extensions to Mendelian Genetics- Extensions to Mendelian Genetics
- Gene mutation- Gene mutation
- Chromosome mutation- Chromosome mutation
(- Quantitative and population genetics)(- Quantitative and population genetics)
B2900B2900
Penetrance, expressivity Penetrance, expressivity and G X Eand G X E
PURPOSE: To provide a concise review for human cancer risk related to low-penetrance genes and their effects on environmental carcinogen exposure.
CONCLUSION: Sporadic cancers are caused by gene-environment interactions rather than a dominant effect by a specific gene or environmental exposure.
MutationMutation
Source of genetic variation:Source of genetic variation:
Gene Mutation (Phenotypic effects) Gene Mutation (Phenotypic effects)
- somatic, germinal- somatic, germinal
Chromosome mutations (Ch. 11 prob. 1, Chromosome mutations (Ch. 11 prob. 1, 2)2)
- structure - structure
- number - number
MutationMutation
Gene Mutation:Gene Mutation:
aa++------>a Forward mutation------>a Forward mutation
aa ------>a------>a++ Reverse mutation Reverse mutation
1. Somatic mutation1. Somatic mutation
- not transmitted to progeny- not transmitted to progeny
2. Germinal Mutation2. Germinal Mutation
- transmitted to next generation- transmitted to next generation
Somatic MutationsSomatic Mutations
Petal colour:Petal colour:Rr Rr redredrr whiterr white
Plant genotype: RrPlant genotype: Rr mutation: Rr rrmutation: Rr rr
Somatic mutationsSomatic mutations
Germinal mutationsGerminal mutations
AA (blue)AA (blue)
mutationmutation
Aa Aa self self aa(white)aa(white)
Mutant PhenotypesMutant Phenotypes
Morphological Morphological
LethalLethal
Biochemical Biochemical
ResistanceResistance
Conditional - DTSConditional - DTS (David T. Suzuki) (David T. Suzuki)
(permissive and restrictive conditions)(permissive and restrictive conditions)
Mutation FrequencyMutation Frequency
Drosophila Drosophila eye-colour weye-colour w++ w 4 x 10 w 4 x 10-5-5 per gamete per gamete
Humans Hemophilia (X-linked recessive) 4 x 10Humans Hemophilia (X-linked recessive) 4 x 10-5-5 per gamete per gamete
(1 in 25,000)(1 in 25,000)
““It is estimated that up to 30% of cases of hemophilia have It is estimated that up to 30% of cases of hemophilia have no known family history. Many of these cases are the no known family history. Many of these cases are the result of new mutations. This means that hemophilia can result of new mutations. This means that hemophilia can affect any family.”affect any family.”
Mutation FrequencyMutation Frequency
Drosophila Drosophila eye-colour weye-colour w++ w 4 x 10 w 4 x 10-5-5 per gamete per gamete
Mutation rate for a particular gene: very low (efficient repair)Mutation rate for a particular gene: very low (efficient repair)
but,but,
Large number of genes in a genome: mutations occur every Large number of genes in a genome: mutations occur every generationgeneration
4 x 104 x 10-5-5 x 50,000 genes = 2 mutations x 50,000 genes = 2 mutations
Gene MutationGene Mutation
Mutations are rare and randomMutations are rare and random
Ultimate source of genetic variationUltimate source of genetic variation
Cancer: Proto-oncogene Cancer: Proto-oncogene oncogene oncogene cancer cancer
mutationmutation
“…“…in an oncogene mutation, the activity of the mutant oncoprotein has been in an oncogene mutation, the activity of the mutant oncoprotein has been uncoupled from its normal regulatory pathway, leading to its continuous uncoupled from its normal regulatory pathway, leading to its continuous unregulated expression.” unregulated expression.” tumor growth tumor growth
Chromosome MutationsChromosome Mutations
Gene mutationGene mutation: : detected geneticallydetected genetically
Chromosome MutationsChromosome Mutations: detected genetically and: detected genetically and
cytologicallycytologically
1. Structure1. Structure
2. Number2. Number
Chromosome MutationsChromosome Mutations
1. Structure Ch. 11 363 – 3721. Structure Ch. 11 363 – 372
2. Number Ch. 11 p. 350 - 3632. Number Ch. 11 p. 350 - 363
1. Chromosome Structure1. Chromosome Structure
Karyotype:Karyotype:
1. size and number1. size and number
2. centromere position:2. centromere position:
telocentrictelocentric
acrocentricacrocentric
metacentricmetacentric
submetacentricsubmetacentric
acentricacentric (lost)(lost)
Chromosome StructureChromosome Structure
33. Heterochromatin pattern. Heterochromatin pattern
- heterochromatin- heterochromatin (dark) (dark)
- euchromatin- euchromatin (light) (light)
44. Banding patterns:. Banding patterns:
a) staining a) staining Giemsa bandsGiemsa bands
b) polytene chromosomes (flies)b) polytene chromosomes (flies)
G-bandsG-bands
Paint of Chr-22Paint of Chr-22
““Paint”Paint”
Structural AbnormalitiesStructural Abnormalities Normal a b c d e fNormal a b c d e f
1. Deletion a c d e f1. Deletion a c d e f
2. Duplication a b b c d e f2. Duplication a b b c d e f
3. Inversion a e d c b f3. Inversion a e d c b f
4. Translocation4. Translocation
a b c d j k g h i e fa b c d j k g h i e f
Structural AbnormalitiesStructural Abnormalities
1. Deletions:1. Deletions:
deletion homozygote---->usually lethaldeletion homozygote---->usually lethal
deletion heterozygote----> viabledeletion heterozygote----> viable
deletion loop deletion loop bb
(pairing of(pairing of a c d a c d
homologues)homologues) a c d a c d
deletiondeletion
Deletion heterozygoteDeletion heterozygote
deletion loopdeletion loop
PseudodominancePseudodominance
Deletion Heterozygote:Deletion Heterozygote:
deletion loop deletion loop bb
(pairing of(pairing of a c d a c d
homologues)homologues) + + + + + +
deletiondeletion
Phenotype:
+ b + ++ b + +
Deletion MappingDeletion Mapping
Prune pn
Structural AbnormalitiesStructural Abnormalities
Deletion:Deletion: notch-wing ( notch-wing (DrosophilaDrosophila))
PhenotypePhenotype
GenotypeGenotype wing survivalwing survival
NN+ + NN++ normal alive normal alive
NN++ N notch alive N notch alive
N N - deadN N - dead
(recessive lethal)(recessive lethal)
Genetics of DeletionsGenetics of Deletions
• Reduced map distance ( chromosome Reduced map distance ( chromosome shortened)shortened)
• Recessive lethalRecessive lethal• Deletion loop (detected during meiosis)Deletion loop (detected during meiosis)
Structural AbnormalitiesStructural Abnormalities
2. Duplications:2. Duplications:
tandem duplicationtandem duplication
a b b c da b b c d
maintain original evolve newmaintain original evolve new
function functionfunction function
deletiondeletion
Tandem duplicationTandem duplication
Unequal crossing overUnequal crossing over
Bar Eye Mutation (Dominant) Bar Eye Mutation (Dominant)
Gene Duplication Gene Duplication and Evolutionand Evolution
Gene duplication - Evolution of new functionGene duplication - Evolution of new function
Example: Hemoglobin genes - duplicationExample: Hemoglobin genes - duplication
Express in different stages:Express in different stages:
embryo – fetus – adult embryo – fetus – adult
Hemoglobin:
Alpha
Beta
Gamma
………..
Structural AbnormalitiesStructural Abnormalities
3. Inversions - different gene order3. Inversions - different gene order
- usually viable- usually viable
a b c d e f a b e d c f a b e d c fa b c d e f a b e d c f a b e d c f
a b c d e f a b c d e f a b e d c fa b c d e f a b c d e f a b e d c f
homozygote heterozygote homozygotehomozygote heterozygote homozygote
N N N I I IN N N I I I
normal (N) inversion (I)normal (N) inversion (I)
Cytological consequences of an InversionCytological consequences of an Inversion
Heterozygote: Heterozygote: Inversion LoopInversion Loop
a b c d ea b c d e
a d c b ea d c b e
X
crossovercrossover
Inversion Loop
Fig. 11-21
Cytological consequences of an InversionCytological consequences of an Inversion
Heterozygote: Heterozygote: Inversion LoopInversion Loop
Cross-over within Cross-over within an an inversioninversion
dicentric bridge (broken)dicentric bridge (broken)
acentric fragment (lost)acentric fragment (lost)
deletionsdeletions
Inversion Inversion heterozygoteheterozygotewith crossing with crossing overover
Fig. 11-22
Inversion HeterozygoteInversion Heterozygote
• Reduced recombination frequencyReduced recombination frequency
(suppression of crossing over)(suppression of crossing over)
• SemisterileSemisterile
4. 4. TranslocationTranslocation
a b c d j k g h i e fa b c d j k g h i e f
Translocation HeterozygoteTranslocation Heterozygote (meiosis) (meiosis)
NN11
TT22TT11
NN22
TranslocationTranslocation
TranslocationTranslocation heterozygoteheterozygote
Fig. 11-24
Translocation heterozygoteTranslocation heterozygoteAdjacent segregationAdjacent segregation
T1
N1
N2
T2
inviableinviable
Translocation heterozygoteTranslocation heterozygoteAlternate segregationAlternate segregation
T1
N1 N2
T2
viableviable
TranslocationTranslocation
Change linkage relationshipsChange linkage relationships
(position effects)(position effects)
Change chromosome sizeChange chromosome size
Semisterile - unbalanced meiotic productsSemisterile - unbalanced meiotic products
normalnormal
abortedabortedCorn PollenCorn Pollen
Structural AbnormalitiesStructural Abnormalities Normal a b c d e fNormal a b c d e f
1. Deletion a c d e f1. Deletion a c d e f
2. Duplication a b b c d e f2. Duplication a b b c d e f
3. Inversion a e d c b f3. Inversion a e d c b f
4. Translocation4. Translocation
a b c d j k g h i e fa b c d j k g h i e f
Human Chromosomes
MutationMutation
Source of genetic variation:Source of genetic variation:
Gene Mutation Gene Mutation
- somatic, germinal- somatic, germinal
Chromosome mutations (Ch. 11)Chromosome mutations (Ch. 11)
- structure - structure
- number- number
Chromosome MutationChromosome Mutation(2. changes in number)(2. changes in number)
Euploidy: Euploidy: variation in complete sets ofvariation in complete sets of
chromosomeschromosomes
Aneuploidy: Aneuploidy: variation in parts of chromosomevariation in parts of chromosome
setssets
EuploidyEuploidy
1x 1x monoploid (1 set) = n monoploid (1 set) = n
2x 2x diploid (2 sets) = 2ndiploid (2 sets) = 2n
3x triploid3x triploid
4x tetraploid4x tetraploid
5x pentaploid 5x pentaploid polyploid (> polyploid (> 22 sets) sets)
6x hexaploid6x hexaploid
n = # chromosomes n = # chromosomes
in the gametesin the gametes
PolyploidsPolyploids
Autopolyploids: Autopolyploids: within one specieswithin one species
Allopolyploids: Allopolyploids: from different, closelyfrom different, closely
related speciesrelated species
PolyploidsPolyploids
Larger Larger than Diploidsthan Diploids
PolyploidsPolyploids
Triploids: = 3nTriploids: = 3n
- problems with pairing during- problems with pairing during
meiosismeiosis
- unbalanced gametes- unbalanced gametes
- usually steril- usually sterilee
Applications:Applications: seedless fruits, sterile fish seedless fruits, sterile fish
aquacultureaquaculture
Formation of TriploidsFormation of Triploids
nn
nn
nn
= = 3n3n
nn
PolarPolarbodiesbodies
nn 22nnnn
= = 3n3n
Triploids (3x)Triploids (3x)
Why can’t a triploid produce viable Why can’t a triploid produce viable gametes ?gametes ?
Fig. 11-5
Triploids (3x)Triploids (3x)
x = 1x = 1 GametesGametes
TriploidsTriploids
x = 2x = 2
GametesGametes
oror
viableviable
Non-Non-viableviable
TriploidsTriploids
Probability (2x or x gamete) =Probability (2x or x gamete) =
( )( )if x = 10 Prob. = 0.002 of viable gametesif x = 10 Prob. = 0.002 of viable gametes
11
22
x - 1x - 1
AutotetraploidAutotetraploid
AutotetraploidAutotetraploid
Doubling of chromosomes: 2x----> 4xDoubling of chromosomes: 2x----> 4x
Even number of chromosomes: normal meiosisEven number of chromosomes: normal meiosis
2<---->2 segregation------> functional 2<---->2 segregation------> functional gametesgametes
Triploid
2n = 42 x = 7
n = 21
2n = 14, n = x = 7
Chromosome sets:
A, B, D
7 7 7
hybrid
Origin of Origin of WheatWheat
Fig. 11-10Fig. 11-10
2n = 28
n = 14
77 1414
AllopolyploidAllopolyploid
PolyploidyPolyploidy
Plants: Plants: speciation speciation
Animals: Animals: - rare (sex determination)- rare (sex determination)
- fish- fish (salmon) (salmon)
- - parthenogenetic parthenogenetic animalsanimals
123 11 22 12 12
Latitute North
30 40 50 60 70 80 90
% P
olyp
loid
s
30
40
50
60
70
80
90Plant PolyploidsPlant Polyploids
Chromosome MutationChromosome Mutation((changes in number)changes in number)
Euploidy: Euploidy: variation in complete sets ofvariation in complete sets of
chromosomeschromosomes
Aneuploidy: Aneuploidy: variation in parts of chromosomevariation in parts of chromosome
setssets
AneuploidyAneuploidy
Nullisomics (2n - 2)Nullisomics (2n - 2)
Monosomics (2n - 1)Monosomics (2n - 1)
Trisomics (2n + 1)Trisomics (2n + 1)
AneuploidyAneuploidy
Nullisomics (2n - 2)Nullisomics (2n - 2)
- lethal in diploids- lethal in diploids
- tolerated in polyploids- tolerated in polyploids
Monosomics (2n - 1)Monosomics (2n - 1)
- disturbs chromosome balance- disturbs chromosome balance
- recessive lethals hemizygous- recessive lethals hemizygous
Trisomics (2n + 1)Trisomics (2n + 1)
- sex chromosomes vs autosomes- sex chromosomes vs autosomes
- size of chromosome- size of chromosome
AneuploidyAneuploidy
Non-disjunction: GametesNon-disjunction: Gametes
Meiosis I n + 1 n - 1Meiosis I n + 1 n - 1
Meiosis II n + 1 n - 1 Meiosis II n + 1 n - 1 nn
n x n - 1 ---------> 2n - 1 monosomicn x n - 1 ---------> 2n - 1 monosomic
n x n + 1 ---------> 2n + 1 trisomicn x n + 1 ---------> 2n + 1 trisomic
AneuploidyAneuploidyHumans:Humans: (live births) (live births)
Monosomics - XO Turner syndromeMonosomics - XO Turner syndrome
- no known autosomes- no known autosomes
Trisomics XXY Trisomics XXY KKlinefelter sterile malelinefelter sterile male
XYY fertile maleXYY fertile male ( X or Y gametes)( X or Y gametes)
XXX sometimes normalXXX sometimes normal
21 Down21 Down
18 Edwards syndromes18 Edwards syndromes
13 Patau13 Patau
G-bandsG-bands
13 1821 X Y
Maternal Age (years)
20 25 30 35 40 45 50
Dow
ns B
irths
per
100
0
0
5
10
15
20
25Downs Births per 1000Downs Births per 1000
Mutations Causing Death and Mutations Causing Death and Disease in HumansDisease in Humans
% of live births% of live births
Gene mutations: Gene mutations: 1.2 1.2
Chromosome mutationsChromosome mutations:: 0.610.61
Chromosome MutationsChromosome Mutations(Humans)(Humans)
% of spontaneous abortions% of spontaneous abortions
Trisomics 26 %Trisomics 26 %
XO 9 %XO 9 %
Triploids 9 %Triploids 9 %
Tetraploids 3 %Tetraploids 3 %
Others 3 %Others 3 %
Chromosome 50 %Chromosome 50 %
abnormalitiesabnormalities
Chromosome MutationsChromosome Mutations
Comparison of euploidy with aneuploidyComparison of euploidy with aneuploidy
Aneuploids more abnormal than euploids:Aneuploids more abnormal than euploids:
likely due to gene imbalancelikely due to gene imbalance
Plants more tolerant than animals to Plants more tolerant than animals to aneuploidy and polyploidyaneuploidy and polyploidy
(animal sex determination)(animal sex determination)
SummarySummaryMutationMutation - gene - gene
- chromosome- chromosome
(structure, number)(structure, number)
DetectingDetecting - cytology - cytology
- phenotype- phenotype
Rate of mutationRate of mutation - low - low
MutationMutation - source of genetic variation - source of genetic variation
- evolutionary change- evolutionary change
geneticgeneticanalysisanalysis
Chapter Chapter ReferencesReferences
RRecombinationecombination, l, linkage mapsinkage mapsCh. 6 p. 148 – 165 Prob: 1-5, 7, 8, 10, 11, 14Ch. 6 p. 148 – 165 Prob: 1-5, 7, 8, 10, 11, 14
Extensions to Mendelian GeneticsExtensions to Mendelian Genetics
Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7
Chromosome MutationsChromosome Mutations
Ch. 11 p. 350 – 377 Prob: 1, 2Ch. 11 p. 350 – 377 Prob: 1, 2
Mendelian GeneticsMendelian Genetics
Topics:Topics: -Transmission of DNA during cell division-Transmission of DNA during cell division
Mitosis and MeiosisMitosis and Meiosis
- Segregation - Segregation
- Sex linkage (- Sex linkage (problem: how to get a white-eyed femaleproblem: how to get a white-eyed female))
- Inheritance and probability- Inheritance and probability
- Independent Assortment- Independent Assortment
- Mendelian genetics in humans- Mendelian genetics in humans
- Linkage- Linkage
- Gene mapping- Gene mapping
-Gene mapping in other organismsGene mapping in other organisms
(fungi, bacteria)(fungi, bacteria)
- Extensions to Mendelian Genetics- Extensions to Mendelian Genetics
- Gene mutation- Gene mutation
- Chromosome mutation- Chromosome mutation