Biology 2250 Principles of Genetics

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Biology 2250Principles of Genetics

• Announcements
• Lab 4 Information B2250 (Innes) webpage
• download and print before lab.
• Virtual fly log in and practice
• http//biologylab.awlonline.com/

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Test 2 Thursday Nov. 17

• http//webct.mun.ca8900/
• All quizzes on WebCT for Review
• Office Hours 130 230 Tue, Wed., Thr
• or by appointment 737-4754, dinnes_at_mun.ca

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Mendelian Genetics

• Topics
• -Transmission of DNA during cell division
• Mitosis and Meiosis
• - Segregation
• - Sex linkage (problem how to get a
  white-eyed female)
• - Inheritance and probability
• - Independent Assortment
• - Mendelian genetics in humans
• - Linkage
• - Gene mapping

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• Gene mapping in other organisms
• (fungi, bacteria)
• - Extensions to Mendelian Genetics
• - Gene mutation
• - Chromosome mutation
• (- Quantitative and population genetics)
• B2900

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Penetrance, expressivity and 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.
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Mutation

• Source of genetic variation
• Gene Mutation (Phenotypic effects)
• - somatic, germinal
• Chromosome mutations (Ch. 11 prob. 1, 2)
• - structure
• - number

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Mutation

• Gene Mutation
• a------gta Forward mutation
• a ------gta Reverse mutation
• 1. Somatic mutation
• - not transmitted to progeny
• 2. Germinal Mutation
• - transmitted to next generation

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Somatic Mutations
Petal colour Rr red rr white
Plant genotype Rr mutation Rr
rr
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Somatic mutations
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Germinal mutations
AA (blue) mutation Aa ? self ?
aa(white)
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Mutant Phenotypes

• Morphological
• Lethal
• Biochemical
• Resistance
• Conditional - DTS (David T. Suzuki)
• (permissive and restrictive conditions)

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Mutation Frequency
Drosophila eye-colour w ? w 4 x 10-5 per
gamete Humans Hemophilia (X-linked
recessive) 4 x 10-5 per gamete

(1 in 25,000)
It is estimated that up to 30 of cases of
hemophilia have no known family history. Many of
these cases are the result of new mutations. This
means that hemophilia can affect any family.
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Mutation Frequency
Drosophila eye-colour w ? w 4 x 10-5 per
gamete Mutation rate for a particular gene
very low (efficient repair) but, Large number of
genes in a genome mutations occur every
generation 4 x 10-5 x 50,000 genes 2
mutations
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Gene Mutation

• Mutations are rare and random
• Ultimate source of genetic variation
• Cancer Proto-oncogene ?oncogene ? cancer
• mutation
• in an oncogene mutation, the activity of the
  mutant oncoprotein has been uncoupled from its
  normal regulatory pathway, leading to its
  continuous unregulated expression. ? tumor growth

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Chromosome Mutations

• Gene mutation detected
  genetically
• Chromosome Mutations detected genetically and
• 
  cytologically
• 1. Structure
• 2. Number

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Chromosome Mutations

• 1. Structure Ch. 11 363 372
• 2. Number Ch. 11 p. 350 - 363

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1. Chromosome Structure

• Karyotype
• 1. size and number
• 2. centromere position
• telocentric
• acrocentric
• metacentric
• submetacentric
• acentric

(lost)
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Chromosome Structure

• 3. Heterochromatin pattern
• - heterochromatin (dark)
• - euchromatin (light)
• 4. Banding patterns
• a) staining Giemsa bands
• b) polytene chromosomes (flies)

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G-bands
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Paint of Chr-22
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Paint
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Structural Abnormalities

• Normal a b c d e f
• 1. Deletion a c d e f
• 2. Duplication a b b c d e f
• 3. Inversion a e d c b f
• 4. Translocation
• a b c d j k g h i
  e f

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Structural Abnormalities

• 1. Deletions
• deletion homozygote----gtusually lethal
• deletion heterozygote----gt viable
• deletion loop b
• (pairing of a c d
• homologues) a c d
• deletion

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Deletion heterozygote
deletion loop
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Pseudodominance

• Deletion Heterozygote
• deletion loop b
• (pairing of a c d
• homologues)
• deletion

Phenotype b
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Deletion Mapping
Prune pn
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Structural Abnormalities

• Deletion notch-wing (Drosophila)
• Phenotype
• Genotype wing survival
• N N normal alive
• N N notch alive
• N N - dead
• 
  (recessive lethal)

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Genetics of Deletions

• Reduced map distance ( chromosome shortened)
• Recessive lethal
• Deletion loop (detected during meiosis)

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Structural Abnormalities

• 2. Duplications
• tandem duplication
• a b b c d
• maintain original evolve new
• function function

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Unequal crossing over
deletion
Tandem duplication
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Bar Eye Mutation (Dominant)
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Gene Duplication and Evolution

• Gene duplication - Evolution of new function
• Example Hemoglobin genes - duplication
• Express in different stages
• embryo fetus adult

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Hemoglobin Alpha Beta Gamma ..
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Structural Abnormalities

• 3. Inversions - different gene order
• - usually viable
• a 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 f
• homozygote heterozygote homozygote
• N N N I
  I I
• normal (N) inversion (I)

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Cytological consequences of an Inversion Heterozyg
ote Inversion Loop
a b c d e
a d c b e
Fig. 11-21
crossover
X
Inversion Loop
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• Cytological consequences of an Inversion
• Heterozygote Inversion Loop
• Cross-over within an inversion
• dicentric bridge (broken)
• acentric fragment (lost)
• deletions

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Inversion heterozygotewith crossing over
Fig. 11-22
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Inversion Heterozygote

• Reduced recombination frequency
• (suppression of crossing over)
• Semisterile

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4. Translocation

• a b c d j k g h i e
  f

Translocation Heterozygote (meiosis)
N2
N1
T2
T1
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Translocation
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Fig. 11-24
Translocation heterozygote
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Translocation heterozygoteAdjacent segregation
T1
N2
N1
T2
inviable
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Translocation heterozygoteAlternate segregation
N1
N2
T1
T2
viable
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Translocation

• Change linkage relationships
• (position effects)
• Change chromosome size
• Semisterile - unbalanced meiotic products

normal
Corn Pollen
aborted
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Structural Abnormalities

• Normal a b c d e f
• 1. Deletion a c d e f
• 2. Duplication a b b c d e f
• 3. Inversion a e d c b f
• 4. Translocation
• a b c d j k g h i
  e f

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Human Chromosomes
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Mutation

• Source of genetic variation
• Gene Mutation
• - somatic, germinal
• Chromosome mutations (Ch. 11)
• - structure
• - number

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Chromosome Mutation(2. changes in number)

• Euploidy variation in complete sets of
• chromosomes
• Aneuploidy variation in parts of chromosome
• sets

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Euploidy

• 1x monoploid (1 set) n
• 2x diploid (2 sets) 2n
• 3x triploid
• 4x tetraploid
• 5x pentaploid polyploid (gt 2 sets)
• 6x hexaploid
• n chromosomes
• in the gametes

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Polyploids

• Autopolyploids within one species
• Allopolyploids from different, closely
• related species

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Polyploids Larger than Diploids
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Polyploids

• Triploids 3n
• - problems with pairing
  during
• meiosis
• - unbalanced gametes
• - usually sterile
• Applications seedless fruits, sterile fish
• 
  aquaculture

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Formation of Triploids
n
3n
n
n
Polar bodies
3n
n
2n
n
n
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Triploids (3x)

• Why cant a triploid produce viable gametes ?

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Fig. 11-5
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Triploids (3x)
Gametes

• x 1

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Triploids
Gametes

• x 2

viable
or
Non- viable
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Triploids

• Probability (2x or x gamete)
• ( )
• if x 10 Prob. 0.002 of viable gametes

x - 1
1
2
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Autotetraploid
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Autotetraploid

• Doubling of chromosomes 2x----gt 4x
• Even number of chromosomes normal meiosis
• 2lt----gt2 segregation------gt functional gametes

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Origin of WheatFig. 11-10
Allopolyploid
2n 14, n x 7
hybrid
2n 28 n 14
Chromosome sets A, B, D 7 7 7
7
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Triploid
2n 42 x 7 n 21
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Polyploidy

• Plants speciation
• Animals - rare (sex determination)
• - fish (salmon)
• - parthenogenetic animals

123 11 22 12 12
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Plant Polyploids
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Chromosome Mutation(changes in number)

• Euploidy variation in complete sets of
• chromosomes
• Aneuploidy variation in parts of chromosome
• sets

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Aneuploidy

• Nullisomics (2n - 2)
• Monosomics (2n - 1)
• Trisomics (2n 1)

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Aneuploidy

• Nullisomics (2n - 2)
• - lethal in diploids
• - tolerated in polyploids
• Monosomics (2n - 1)
• - disturbs chromosome balance
• - recessive lethals hemizygous
• Trisomics (2n 1)
• - sex chromosomes vs autosomes
• - size of chromosome

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Aneuploidy

• Non-disjunction Gametes
• Meiosis I n 1 n - 1
• Meiosis II n 1 n - 1
  n
• n x n - 1 ---------gt 2n - 1
  monosomic
• n x n 1 ---------gt 2n 1
  trisomic

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Aneuploidy

• Humans (live births)
• Monosomics - XO Turner syndrome
• - no known autosomes
• Trisomics XXY Klinefelter sterile male
• XYY fertile male ( X or
  Y gametes)
• XXX sometimes normal
• 21 Down
• 18 Edwards
  syndromes
• 13 Patau

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G-bands
13
18
21
X
Y
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Downs Births per 1000
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Mutations Causing Death and Disease in Humans

• of live
  births
• Gene mutations 1.2
• Chromosome mutations 0.61

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Chromosome Mutations(Humans)

• of spontaneous
  abortions
• Trisomics 26
• XO 9
• Triploids 9
• Tetraploids 3
• Others 3
• Chromosome 50
• abnormalities

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Chromosome Mutations

• Comparison of euploidy with aneuploidy
• Aneuploids more abnormal than euploids
• likely due to gene imbalance
• Plants more tolerant than animals to aneuploidy
  and polyploidy
• (animal sex determination)

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Summary

• Mutation - gene
• - chromosome
• (structure, number)
• Detecting - cytology
• - phenotype
• Rate of mutation - low
• Mutation - source of genetic variation
• - evolutionary change

genetic analysis
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Chapter References

• Recombination, linkage maps
• Ch. 6 p. 148 165 Prob 1-5, 7, 8, 10,
  11, 14
• Extensions to Mendelian Genetics
• Ch. 14 p. 459 473 Prob 2, 3, 4, 5, 6, 7
• Chromosome Mutations
• Ch. 11 p. 350 377 Prob 1, 2

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Mendelian Genetics

• Topics
• -Transmission of DNA during cell division
• Mitosis and Meiosis
• - Segregation
• - Sex linkage (problem how to get a
  white-eyed female)
• - Inheritance and probability
• - Independent Assortment
• - Mendelian genetics in humans
• - Linkage
• - Gene mapping

?
?
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?

• Gene mapping in other organisms
• (fungi, bacteria)
• - Extensions to Mendelian Genetics
• - Gene mutation
• - Chromosome mutation

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