Download Gene Interactions

Gene Interactions
Chapter 4
I. Genotype-Phenotype Relationship
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Pleiotrophy
Polygeny
I A. Pleiotrophy
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One gene locus can affect several different aspects of phenotype
Diachete mutation in Drosophila has both dominant and recessive effects
Dominant effects:
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Lateral wings
Missing hair on thorax
I A. Pleiotrophy
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Recessive effects:
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Lethal when homozygous
Sickle-cell anemia
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Spleen damage
Joint pain
Tower skull
Anemia
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Sickle-cell anemia effects
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Effect of dominant mutation in rats
I B. Polygeny
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One phenotype dependent upon action of many different genes
Quantitative inheritance
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Height
Weight
II. Complementation Test
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Determines if mutants that alter phenotype are allelic (one locus) OR are from
different loci
Used for recessive alleles
II. Complementation Test
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Produce heterozygote and examine phenotype
If phenotype wild-type (non-mutant), alleles are complementary and are from
different loci
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If phenotype mutant, alleles are non complementary and affect same locus (allelic)
II. Complementation Test
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F1 hybrid a’/a’’
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Mutant phenotype (no wild dominant alleles)
Non-complementary, ONE locus
II. Complementation Test
• F1 hybrid a1/a2
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Wild-type phenotype (mutations in different genes)
Complementary mutations, TWO loci
II. Complementation Test
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Harebell example
Wild flowers blue
Mutant flowers white
Three mutant white homozygous strains
When each strain crossed with blue
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F1 blue
F2 3:1 blue:white  monogenic
II. Complementation Test
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Are the three mutants allelic (monogenic) or from different loci?
Mutants
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$ (dollar)
£ (pound)
¥ (yen)
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II. Complementation Test
If allelic
• Have no wild type alleles
• Thus get mutant phenotype (white)
II. Complementation Test
If different loci
• Each mutant supplies wild type allele for other locus
• F1 is dihybrid
• Have dominant allele at each locus
• Have wild type phenotype  complementary
$x£
• F1 white
• No complementation
• $ and £ allelic
£x¥
• F1 blue
• Complementation
• £ and ¥ not allelic
• Each mutant provides wild allele for other locus
• Two loci
$x¥
• What would F1 be?
• Complementary or non comp?
• $ and ¥ allelic or not allelic?
• One or two loci?
III. Lethal Alleles
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Can alter Mendelian ratios if lethal embryonically
Yellow and wild-type mice
III. Lethal Alleles
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Yellow x Yellow
F1 2/3 Yellow, 1/3 Wild-type
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Why?
Two alleles
AY – yellow
A – wild type
III. Lethal Alleles
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Yellow x Yellow
AY A AY A
III. Lethal Alleles
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Sublethals: reduce viability, but not by 100%
Also called semi-lethal
III. Lethal Alleles
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Aa x aa
Expect 1:1 ratio
May consistently 55 (Aa) : 45 (aa)
aa not lethal but reduces viability
IV. Gene Interaction and Modified Dihybrid Ratios
Normal dihybrid ratio:
• 9/16 A_B_
• 3/16 A_bb
• 3/16 aaB_
• 1/16 aabb
IV. Gene Interaction and Modified Dihybrid Ratios
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If two loci interact 9:3:3:1 ratio modified
Modified ratios still on basis of “16”
Result of epistasis
Genotype at one locus masks or modifies expression of alleles at second locus
Broad definition, includes “suppressor” loci discussed in textbook
IV A. Co-epistasis
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Interacting genes, different biochemical pathways
Keep 9:3:3:1 ratio
Each “part” of ratio has distinct phenotype
Two different biochemical pathways
IV A. Co-epistasis: Corn Snake Coloration
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Two loci
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o+ = orange color; o = no orange
b+ = black color; b = no black
IV A. Co-epistasis: Corn Snake Coloration
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orange x
o+o+ b/b
black
o/o b+b+
IV A. Co-epistasis: Corn Snake Coloration
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F1
camouflaged
o+o b+/b
IV A. Co-epistasis: Corn Snake Coloration
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F2
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o+_
o+_
oo
oo
b+_
bb
b+_
bb
camouflaged
orange
black
albino
IV A. Co-epistasis: Corn Snake Coloration
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Two separate biochemical pathways
b+
precursor  black pigment
camouflaged
precursor  orange pigment
o+
IV B. Interacting Genes in SAME Pathway
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Will examine mutations
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With same phenotype
With different phenotypes
IV B 1. Mutations with SAME Phenotype
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Harebell: blue or white flowers
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• Dihybrid cross of w1 w1 w2 w2
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w1+_ w2_
blue
• F2
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w1+_ w2w2 white
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w1w1 w2+_ white
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w1w1 w2w2 white
IV B 1. Mutations with SAME Phenotype
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Thus, get 9:7 ratio of blue:white
Duplicate recessive epistasis
Homozygous recessive at either locus blocks effects of other locus
w1+
w2+
colorless  colorless  blue pigment
IV B 2. Mutations with Different Phenotypes
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Blue-eyed Mary flower color
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white
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ww m m
magenta
w w mm
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IV B 2. Mutations with Different Phenotypes
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F1
blue
w w m+m
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IV B 2. Mutations with Different Phenotypes
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F2
m+_ blue
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w+_ m_
ww m+_
ww mm
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9:3:4 ratio
Recessive epistasis
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One pathway
Colorless precursor
Intermediate a pigment (magenta)
Final product a pigment (blue)
Block second step, get magenta
Block first step, get white
magenta
white
white
IV C. Interacting Genes in Different Pathways
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Foxglove Flower Petal Coloration
Variation controlled by three loci
M locus
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M  makes anthocyanin (purple)
m  no anthocyanin (white)
IV C. Interacting Genes in Different Pathways
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D locus
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D  makes large amount of anthocyanin (deep purple)
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w+_
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d  makes lesser amount of anthocyanin (light purple)
IV C. Interacting Genes in Different Pathways
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W locus
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W  prevents pigment deposition except in throat spots (speckling effect)
w  allows even pigment deposition all over petal (even color)
IV C. Interacting Genes in Different Pathways
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P
dark purple x
white w/purple spots
MM DD ww
MM dd WW
As homozygous for MM, ignore
IV C. Interacting Genes in Different Pathways
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F1
white w/purple spots
Dd Ww
IV C. Interacting Genes in Different Pathways
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F2
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D_ W_
white w/purple spots
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dd W_ white w/purple spots
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D_ ww dark purple
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dd ww light purple
12:3:1 ratio
Dominant epistasis (W epistatic to D locus)
Various Epistatic Ratios
V. Penetrance and Expressivity
V A. Penetrance
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Percentage of individuals with a genotype who show the phenotype associated with
that genotype
Up to this point, we have assumed full penetrance
V A. Penetrance
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Eyeless mutation in Drosophila
Causes reduction in eye facet number
Homozygous recessive (ee) strains
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85% have reduced eyes
15% appear “wild type”
85% penetrant
V A. Penetrance
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Polydactyly in humans
Extra fingers and toes
Dominant, yet may skip generations in pedigree
V A. Penetrance
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III-2 lacks polydactyly
Some progeny of III-2 polydactylous
V A. Penetrance in Down Syndrome
V A. Penetrance in Klinefelter Syndrome
V B. Expressivity
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Even when genotype has phenotypic effect (penetrant), may be range of phenotypic
variation
Eyeless mutation (ee)
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Of the 85% penetrant, range from no eyes to nearly normal
Most have ¼ to ½ reduction
V B. Expressivity
Polydactyly
• Extra toes only
V B. Expressivity
Polydactyly
• Extra fingers only
V B. Expressivity
Polydactyly
• Extra fingers AND toes
V B. Expressivity
Polydactyly
• Asymmetrical by side
V C. Why is There Variable Penetrance and Expressivity?
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Environmental Effects (norm of reaction)
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Epistasis (broad sense, including modifier and suppressor genes)
Developmental Noise
VI. Conditional Mutants
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Alleles expressed only under narrow range of environmental conditions
Change environment, change phenotype
VI A. Temperature Effects
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C locus of Mammals allows color expression (c blocks color expression)
cc epistatic to other loci  albinism
ch (Himalayan) allele heat sensitive enzyme
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Warm temperature, enzyme inactive, pigment not made
Cooler temperature, enzyme active, pigment made
Himalayan Rabbit
• Abdomen/thorax warmer, enzyme inactive  white
• Ears, nose, paws cooler, enzyme active  black
• If shave hairs on back and cool the region, new hair black
VI B. Nutritional Effects
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Lethal mutant: lack of enzyme in metabolic pathway for some molecule
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Amino acid synthesis
Toxin degradation
VI B. Nutritional Effects
Neurospora
• Leucine deficient (leu-) strain
• Can’t make leucine
VI B. Nutritional Effects
Neurospora
• Grown on minimal media leu- strains can’t grow
• Which of the 20 spots are leu+?
VI B. Nutritional Effects
Neurospora
• Shown are colonies on miminal media + leucine
• Represents leu+ cultures that grew on minimal media
VI B. Nutritional Effects
Neurospora
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So which colonies are leu-?
VI B. Nutritional Effects
Neurospora
• If leucine present, leu- strains live
• If leucine absent, leu- strains die
VI B. pH Effects
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Lousewort
Two color phases, yellow and red
Color differences due to soil pH
VI B. pH Effects
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pH 6.5  yellow
pH 5.8  red
Extract yellow pigment, lower pH to 5.8, turns red
Dr. Newberry
Last revised 8 September 2003
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