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Chapter 14
From Gene to Phenotype
Dominance, epistasis, gene interaction
16 and 18 March, 2004
Overview
• Genetic and environmental contributions
interact to determine phenotype.
• Mutations in same gene usually result in
mutant phenotype when present together.
• Mutations in different genes complement.
• Dominance comes in several types.
• Most characters are determined by sets of
genes that interact with the environment.
• Modified genetic ratios reveal gene
interactions, including epistasis.
Complementation test
• Diagnostic test for allelism
• Mutants are crossed to bring two recessive
mutations together in heterozygous form
– if phenotype is mutant, mutations are in same gene
• they fail to complement
• both have loss of function
– if phenotype is wild-type, mutations are in different
gene
• each mutant contributes normal gene at different locus
• complementation due to interaction of different proteins
• Heterokaryons used in haploid organisms
Interactions between alleles
• Dominant versus recessive
• Incomplete dominance
– intermediate phenotype
– 1:2:1 F2 ratio
– quantitative differences in gene dose
• Codominance
– equal presence of two gene products
– ABO blood groups
– sickle-cell hemoglobin
• HbA dominant for lack of anemia
• HbA and HbB codominant for hemoglobin
Alleles of a single
gene can show
various degrees of
dominance.
Dominance is
determined by type
of molecular
interaction and
level of analysis.
Lethal alleles
• Cause death of organisms
• Recessive lethals masked in heterozygotes
by wild-type allele
• Example: yellow coat color in mice
– AY is dominant for color
– AY is recessive lethal
AY/A  AY/A
25% AY/AY lethal
50% AY/A yellow
25% A/A wild-type
• Example of pleiotropism: gene affects
multiple characters
Lethal mutation
•Change in DNA sequence resulting in change
in amino acid sequence
•Genetic load: total of deleterious and lethal
genes in population
•Often result of lack of activity or abnormal
activity of encoded protein
•Lethality affected by genetic and physical
environment
•Detected by abnormal genetic ratios
Epistasis
•Allele of one gene eliminates expression of
alleles of another gene, substituting its own
phenotype
•Usually indicative of biochemical or
developmental pathway (sequential gene
activity)
•Involves genes at two or more loci
•Results in dihybrid F2 ratios that deviate from
9:3:3:1
Bbb
Eee
Black
Brown
Deposition
No deposition in hairs
Two pathways black, orange
Suppression
• Interaction between two molecules
• Product of one allele of a gene interferes
with product of another gene on a different
pathway
• Numerous causes
– nonsense suppressors
• mutant tRNA that reads premature stop codon
– protein-protein interactions
Coat color in mammals
•Five major genes, A, B, C, D, and S
•A: affects distribution of pigment in hair
–A: agouti, yellow band on dark shaft
–a: nonagouti, no yellow; solid pigment
•B: determines color of melanin
–B = black
b = brown
•C: permits color; c: no color
•D: full intensity; d: dilute color (uneven)
•S: no spots; s: spots (piebald)
Penetrance and expressivity
• Penetrance
– percent individuals with a given allele that show
the phenotype of the allele
– <100% penetrance a result of modifiers,
epistasis, suppressors, environmental conditions
• Expressivity
– extent to which allele is expressed at phenotypic
level
– affected by genetic background and environment
• These phenomena make pedigree analysis
and genetic counseling more difficult
Assignment: Concept map, Solved
Problems1 and 2, All Basic and
Challenging Problems.
Problems are particularly important
for this chapter.