1. Genetics: From Genes to Genomes
Powerpoint to accompany
Genetics: From Genes to Genomes
Third Edition
Hartwell ● Hood ● Goldberg ● Reynolds ● Silver ● Veres
Chapter 3
Prepared by Malcolm Schug
University of North Carolina Greensboro
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2. Complexities in Relating Genotype to Phenotype
Extensions to Mendel
Complexities in Relating
Genotype to Phenotype
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3. Outline of extensions to Mendel’s analysis
Single-gene inheritance
In which pairs of alleles show deviations from complete dominance and recessiveness
In which different forms of the gene are not limited to two alleles
Where one gene may determine more than one trait
Multifactorial inheritance in which the phenotype arises from the interaction of one or more genes with the environment, chance, and each other.
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4. Dominance is not always complete
Crosses between true-breeding strains can produce hybrids with phenotypes different from both parents.
Incomplete dominance
F1 hybrids that differ from both parents express an intermediate phenotype. Neither allele is dominant or recessive to the other.
Phenotypic ratios are same as genotypic ratios
Codominance
F1hybrids express phenotype of both parents equally.
Phenotypic ratios are same as genotypic ratios.
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5. Summary of dominance relationships
Figure 3.2
Fig. 3.2
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6. Incomplete dominance in snapdragons
Figure 3.3
Fig. 3.3
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7. Codominant lentil coat patterns
Figure 3.4a
Fig. 3.4a
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8. Codominant blood group alleles
Figure 3.4b
Fig. 3.4b
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9. Do variations on dominance relations negate Mendel’s law of segregation?
Dominance relations affect phenotype and have no bearing on the segregation of alleles.
Alleles still segregate randomly.
Gene products control expression of phenotypes differently.
Mendel’s law of segregation still applies.
Interpretation of phenotype/genotype relation is more complex.
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10. A gene can have more than two alleles
Genes may have multiple alleles that segregate in populations.
Although there may be many alleles in a population, each individual carries only 2 of the alternatives.
ABO blood group
3 alleles
6 possible ABO genotypes: IAIA, IBIB, IAIB, IAi, IBi, or ii
Dominance relations are unique to a pair of alleles.
Dominance or recessiveness is always relative to a second allele.
IA is completely dominant to i but codominant to IB.
6 genotypes generate 4 phenotypes.
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11. How do we establish dominance relations between multiple alleles?
Perform reciprocal crosses between pure breeding lines of all phenotypes
Fig. 3.6
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12. Mutations are the source of new alleles
Multiple alleles arise spontaneously in nature due to chance alterations in genetic material – mutations.
Mutation rate varies from 1 in 10,000 to 1 in 1,000,000 per gamete per generation.
Allele frequency is the percentage of the total number of gene copies represented by one allele.
Wild-type – allele whose frequency is more than 1%
Mutant allele – allele whose frequency is less than 1%
Monomorphic – gene with only one wild-type allele
Polymorphic – gene with more than one wild-type allele
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13. One gene may contribute to several visible characteristics
Pleitropy – single gene determines more than one distinct and seemingly unrelated characteristics
Some alleles may cause lethality.
Type of pleitropy where alleles produce a visible phenotype and affect viability
Alleles that affect viability often produce deviations from a 1:2:1 genoptypic and 3:1 phenotypic ratio predicted by Mendel’s Laws.
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14. Pleitropy – inheritance of coat color in mice
a. Inbred agouti X yellow yields 1:1 agouti:yellow
Yellow must be AYA and AY is dominant to A
B. Yellow x yellow mice do not breed true.
AY is a recessive lethal. AYAY die in utero and do not show up as progeny
Fig. 3.9
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16. Sickle-cell syndrome Multiple alleles Pleitropy
Normal wild-type is HbbA
More than 400 mutant alleles identified so far
HbbS allele specifies abnormal peptide causing sickling among red blood cells
Pleitropy
HbbS affects more than one trait
Sickling
Resistance to malaria
Recessive lethality
Different dominance relations
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17. Pleitropy of Sickle-cell syndrome
Fig. 3.10
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18. Two genes can interact to determine one trait
Novel phenotypes can emerge from the combination of alleles of two genes.
Cross of tan and gray lentils produce brown F1 generation
Cross of F1 generation (brown X brown) produces brown, tan, gray, and green lentils
Explanation emerges from experimental cross ratios which are 9 brown:3 tan:3 gray: 1 green
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19. Two genes, A and B aabb is green and will breed pure
AAbb and Aabb are tan
aaBB and aaBb are green
AABB, AABb, AaBB, and AaBb are brown
Fig. 3.11a
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20. Self pollination of F2 to produce F3 shows interaction between two genes.
Fig. 3.11b
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21. Further crosses support two-gene hypothesis.
Each genotypic class determines a particular phenotype.
Fig. 3.11c
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22. Complementary gene action
Two genes work together to produce a phenotype.
9:7 ratio is a phenotypic signature of complementary gene interaction where dominant alleles of two genes act together to produce a trait while other three genotypic classes do not.
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23. Complementary gene action and color in peas
9:7 ration demonstrates that one dominant allele of each gene must be present to produce purple flowers
Fig. 3.12
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24. Epistasis – One gene’s alleles mask the effects of another gene’s alleles
Labrador retriever example – recessive epistasis
Coat color can be black, chocolate brown, or golden yellow
B allele is dominant and determines black.
b allele is recessive and determines brown if homozygous.
E allele at second gene has no affect on coat color.
e allele is recessive and if homozygous hides effects of black or brown alleles.
BBEE (black pure breeding) X bbee (golden pure breeding) produce BbEe black F1 offspring.
BbEe X BbEe produce 9 black (B_E_) for every 3 brown (bbE_), and 4 gold (__ee).
9:3:4 is a telltale ratio of recessive epistasis.
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25. Molecular explanation for recessive epistasis in human blood groups
Two parents who are apparently type O have offspring that is type A or B on rare occasions.
Bombay phenotype – mutant recessive allele at second gene (hh) masks phenotype of ABO alleles
Fig. 3.14b
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26. Dominance epistasis
Presence of dominant allele at second gene hides effects of alleles at a gene
12:3:1 and 13:3 are telltale ratios for dominance epistasis.
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27. Dominance epistasis in summer squash color and chicken feather color
Fig. 3.15
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28. Heterogeneous traits have multiple genes underlying their expression
It is not always possible to determine which of many genes mutated in a person with a heterogeneous mutant phenotype.
Example – deafness in humans may be caused by a mutant allele at one of more than 50 different genes.
Complementation testing can determine if mutations arise from the same or different genes.
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29. Genetic heterogeneity in human deafness can be from complementary gene action or from alleles at the same gene
Fig. 3.16
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31. Breeding studies help determine inheritance of a trait
How do we know if a trait is caused by one gene or two genes that interact?
Ratios such as 9:7 or 13:3 can indicate potential gene interaction.
Further breeding studies can confirm hypotheses.
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32. Testing two gene and one gene hypothesis – example from mice
Fig. 3.18
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33. Pedigree analysis can be used to test trait inheritance hypotheses in humans
OCA (ocularcutaneous albanism) produces little or no pigmentation in skin, hair, and eyes.
Can you determine the inheritance from pedigrees?
Fig. 3.19
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34. Fig b,c
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35. The same genotype does not always produce the same phenotype
Phenotype often depends on penetrance and expressivity.
Penetrance – percentage of a population with a particular genotype that show the expected phenotype
Penetrance can be complete (100%) or incomplete (e.g., retinoblastoma penetrance is 75%).
Expressivity – degree or intensity with which a particular genotype is expressed in a phenotype
Expressivity can be variable or unvarying.
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36. Environment can affect the phenotypic expression of a genotype.
Modifier genes have subtle, secondary effect on a phenotype from a major gene.
Environment can affect the phenotypic expression of a genotype.
Temperature is a common element of the environment that affects phenotype.
Coat color in Siamese cats is lighter in its extremities (legs, tails, ears, etc.) because of a mutation that renders an enzyme involved in melanin synthesis temperature sensitive.
Conditional lethals
shibire gene in Drosophila melanogaster is lethal at temperatures above 29oC.
Phenocopy – change in phenotype arising from environmental agents that mimics the effect of a mutation at a gene
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37. Continuous variation can be explained by Mendelian analysis
Previous examples of Mendelian inherited traits were discontinuous, clear cut phenotypes.
Continuous traits such as height in humans are determined by segregating alleles of many genes interacting with one another and the environment.
Continuous traits are called quantitative traits by geneticists and are usually polygenic.
The more genes that contribute to a trait, the greater the number of possible phenotypic classes and the greater the similarity to continuous variation.
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38. Height is a continuous trait in humans
Fig. 3.21
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39. Mouse’s coat and tail: example of multiple alleles and multifactorial traits
Gene 1 Agouti and other coat patterns
Agouti gene has multiple alleles
Wild-type A allele specifies bands of yellow and black.
AY gets rid of black and produces solid yellow.
A gets rid of yellow and produces solid black.
At specifies black on the back and yellow on the stomach
Dominance series is AY > A > at > a.
AY is however, recessive to all others for lethality.
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40. Mouse’s coat and tail: example of multiple alleles and multifactorial traits
Gene 2 – black or brown
Second gene specifies whether dark hair from gene one is black or brown.
b is recessive and generates brown.
B is dominant and generates black.
AY alleles completely eliminates dark hair, and thus acts in a dominant epistatic manner to the B gene.
A_B_ produces wild-type agouti with black and yellow hairs.
A_bb generates cinnamon (hairs with strips of brown and yellow)
aabb is all brown.
Atatbb is brown on the back and yellow on the stomach.
AYaBb X AYaBb would produce a ratio of 8 yellow (AY_,__), 3 black (aa, B_), 1 brown (aa, bb). The AYAY class of 4 would be missing because of lethality.
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41. Mouse’s coat and tail: example of multiple alleles and multifactorial traits
Gene 3 – Albino or pigmented
A third gene c, abolishes the function of the enzyme that leads to formation of dark pigment melanin when recessive. It is thus recessive epistatic to all others.
cc is all white, Cc are agouti, black, brown, yellow, or yellow and black, etc. depending on the A and B genes.
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42. Mouse’s coat and tail: example of multiple alleles and multifactorial traits
Gene 4 – Short and long tail
Wild type (++) mice have long tapering tails.
X-ray induced T mice have short tails.
TT mice during gestation making the mutation recessive lethal
T+ mutants have short tails.
Variable expressivity in tail length is due to modifier genes.
May be viewed as a quantitative trait
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43. Essential Concepts
The F1 phenotype generated by a pair of alleles defines the dominance relationship between these alleles.
Incomplete dominance – F1 resembles neither parent
Codominance – F1 resembles components of each parent
One gene can contribute to multiple traits. Dominance relations for these genes can vary.
A single gene may have many alleles. New alleles arise by mutation.
Wild type alleles > 1% in the population.
Mutant alleles < 1% in the population.
Two or more wild-type alleles in the population constitute a polymorphic gene.
A gene with only one wild-type allele is monomorphic.
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44. Essential Concepts
Two or more genes may interact in several ways to produce a phenotype.
Observation of deviations from traditional Mendelian phenotypic ratios often generates an understanding of the gene interactions.
Epistasis is when the action of an allele at one gene hides traits normally caused by alleles at another gene.
Complementary gene action is when dominant alleles of two or more genes are required to generate a trait.
With heterogeneity, mutant alleles at any one of two or more genes are sufficient to elicit a phenotype.
Complementation tests can reveal whether a particular phenotype arises from mutations in the same or separate genes.
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45. Essential Concepts
Expression of phenotypes can be modified by the environment, chance, or other genes.
Incomplete penetrance is when fewer than 100% of individuals with the same genotype express a specific phenotype.
A phenotype may show variable expressivity when it is expressed at a different level in different individuals with the same genotype.
A quantitative, or continuous trait can have any value of expression between two extremes. Most continuous traits are polygenic.
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