1. EXTENSIONS OF MENDELIAN GENETICS

2. What happens when inheritance doesn’t follow the patterns observed by Mendel?
There are many reasons why traits might deviate from expected.

3. Alleles Alter Phenotypes in Different Ways
Main Concepts
Alleles Alter Phenotypes in Different Ways
Incomplete Dominance
Codominance
Multiple Alleles
Lethal Alleles
Phenotypes Often Affected by More Than One Gene (Polygenic)
A Single Gene May Have Multiple Effects (Pleiotropy)
Sex Linked Traits
Sex-Limited and Sex-Influenced Inheritance

4. Different types of mutations can alter alleles (or produce new ones)
How are alleles formed?
MUTATION
Wild-type allele: occurs most frequently in nature and is usually dominant
Different types of mutations can alter alleles (or produce new ones)

5. Mutations
Loss of function mutation: a mutation that causes the reduction/loss of the specific wild-type function
If the loss is complete, the mutation has resulted in what is called a null allele
Gain of function mutation: a mutation that enhances the function of the wild-type allele

6. Incomplete Dominance
Incomplete dominance – heterozygotes show a distinct intermediate phenotype different from homozygous genotypes
Neither trait is dominant

7. Symbols
Alleles that are incompletely dominant are written using a superscript letter.
Flower color:
CWCW (white) plant X CRCR (red) plant will produce all CRCW offspring

11. Are these traits blended?
NO … the alleles are particulate (they remain separate and do not influence each other).
How do we know?
A cross of two pink individuals will produce red, white and pink individuals.
The phenotypic ratio will be 1:2:1, like the genotypic ratio

12. Figure 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 4-1 Incomplete dominance shown in the flower color of snapdragons.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

13. Incomplete Dominance

14. What is really going on?
White allele is most likely a “loss of function” mutation
Wild type (red) “codes” for synthesis of red pigment
Mutant allele (white) cannot synthesize the pigment
Therefore, the heterozygote only produces ½ the amount of pigment (pink)

15. True incomplete dominance is rare
Individuals may appear completely dominant until viewed at the molecular level
Tay-Sachs disease
Homozygous recessive = severely affected, death before age 3
Heterozygotes appear normal, but only produce about 50% of normal enzymes
Threshold effect

16. The threshold effect - normal phenotypic expression occurs whenever a certain level (≤ 50%) of gene product is attained.

17. Codominance
Codominance – 2 alleles affect the phenotype in separate, distinguishable ways
Alleles for curly hair and straight hair are codominant
Curly hair = homozygous for curly hair alleles
Straight hair = homozygous for straight hair alleles
Heterozygous individuals have wavy hair

21. Incomplete Dominance vs. Codominance
With incomplete dominance we get a reduced function of the dominant trait (due to recessive), so that the third phenotype is something in the middle (red x white = pink).
In codominance, the "recessive" & "dominant" traits appear together in the phenotype of hybrid organisms – appears to be a “blend”

22. Dominance = common?
Polydactyly – an allele that is dominant to the recessive allele for 5 digits
Recessive allele more common – 99% have 5 digits

23. Multiple Alleles Can only be studied in populations WHY?
Because individuals can only have 2 alleles for a gene!
Example of trait covered by multiple alleles?
Human Blood Type
ABO antigens

24. I stands for “isoagglutinogen”, which is another word for antigen.
ABO blood groups in humans are determined by three alleles, IA, IB, and IO (also referred to as i)
Both the IA and IB alleles are dominant to the IO allele
The IA and IB alleles are codominant to each other
I stands for “isoagglutinogen”, which is another word for antigen.

25. How many blood types are possible?
Because each individual carries two alleles, there are six possible genotypes and four possible blood types
IA IA or IAIO- type A
IB IB or IBIO- type B
IA IB - type AB
IOIO - type O

26. Table 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.
Table 4.1 Potential Phenotypes in the Offspring of Parents with All Possible ABO Blood Group Combinations, Assuming Heterozygosity Whenever Possible
Table Copyright © 2006 Pearson Prentice Hall, Inc.

27. The blood types differ due to the molecules that are present on the outside of RBC (antigens)

29. Lethal Alleles Loss of function mutation
Can (sometimes) be tolerated in heterozygous state
Can have a mutant phenotype (acts dominant) when heterozygous
BUT… may be lethal in the homozygous state

31. Figure 4-4 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 4-4 Inheritance patterns in three crosses involving the normal wild-type agouti allele (A) and the mutant yellow allele in the mouse. Note that the mutant allele behaves dominantly to the normal allele in controlling coat color, but it also behaves as a homozygous recessive lethal allele. The genotype does not survive.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

33. Lethal alleles
In some cases, the lethal allele is DOMINANT, so even heterozygotes will die.
Why does this allele persist in the population?
Late acting (Huntington’s)
Individuals reproduce before allele takes affect

34. Polygenic Traits
Many traits with a distinct phenotype are affected by more than one gene
The cellular function of numerous gene products contributes to the development of a common phenotype
Ex - skin color in humans is controlled by at least 3 different genes

35. AABBCC (dark) and aabbcc (light)
Imagine - each gene has 2 alleles, (light/dark), demonstrate incomplete dominance
AABBCC (dark) and aabbcc (light)
Cross between 2 AaBbCc (intermediate) produces wide range of shades

37. Epistasis
Epistasis - a gene at one locus alters the phenotypic expression of a gene at a second locus
One gene can mask the effect of the other gene
Two gene pairs can complement each other, such that one dominant allele is required at each locus to express a certain phenotype

38. Epistasis example
Mice (and many other mammals) - coat color depends on two genes
One (epistatic gene), determines whether pigment will be deposited in hair
Presence (C) is dominant to absence (c)
Second determines whether pigment deposited is black (B) or brown (b)
The black allele is dominant to the brown allele
Individual with cc has a white (albino) coat regardless of the genotype of the 2nd gene

41. Epistasis – more complex
In cats (and other mammals), a pattern of hair termed “agouti” is an example of epistasis
Some cats have hairs in which there is more than one color distributed along the hair shaft (banded – agouti)
Agouti fur color is typical of many wild animals such as mice squirrels and rabbits – good for camouflage!

42. Agouti is determined by the dominant agouti allele, A
Hairs on non-agouti cats are unbanded, producing a solidly colored coat
Such a cat is homozygous for the non-agouti allele (aa) at the agouti locus
Again – regardless of color. SO … you could have an agouti brown, agouti black, etc.

44. Epistasis Ratios
When studying a single characteristic, a ratio expressed in 16 parts (e.g., 3:6:3:4) suggests that epistasis is occurring.

45. Pleiotropy
Pleiotropy occurs when expression of a single gene has multiple phenotypic effects, and it is quite common
For example, the wide-ranging symptoms of sickle-cell disease are due to a single gene

47. Marfan syndrome
What US president may have had Marfan?

51. The Environment
Phenotype is not always a direct expression of genotype
The environment plays a role in a gene’s expression.

54. Environmental Mutations
Conditional or temperature-sensitive mutations - mutations affected by temperature
useful in studying mutations that affect essential processes
Nutritional mutations – mutations affected by diet
may prevent phenotype from reflecting genotype. Ex -mutations in a biosynthetic pathway

55. X-linked or Sex linked traits
Genes are located on the X chromosome
Present a unique pattern of inheritance due to the presence of only one X chromosome in males
Females (XX) can be heterozygous (carriers), while their sons (XY) can express the disease/trait.

56. Drosophila (fruit fly) eye color was one of the first examples of X-linkage described
Drosophila was a favorite model organism for Thomas Hunt Morgan
Morgan studied eye color in fruit flies – the trait did not have normal Mendelian ratios

57. Crosses between F1 produced classic 3:1 ratio
Crosses of white-eyed male with a red-eyed female - all F1 offspring had red eyes
The red allele appeared dominant
Crosses between F1 produced classic 3:1 ratio
Surprisingly, the white-eyed trait appeared only in males
All the females and half the males had red eyes
Morgan concluded that a fly’s eye color was linked to its sex

59. Figure 4-11 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 4-11 The F1 and F2 results of T. H. Morgan’s reciprocal crosses involving the X-linked white mutation in Drosophila melanogaster. The actual data are shown in parentheses. The photographs show white eye and the brick-red wild-type eye color.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

60. Figure 4-12 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 4-12 The chromosomal explanation of the results of the X-linked crosses shown in Figure 4–11.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

61. Table 4-3 Copyright © 2006 Pearson Prentice Hall, Inc.
Table 4.3 Human X-Linked Traits
Table Copyright © 2006 Pearson Prentice Hall, Inc.

62. Lethal X-linked recessive disorders are observed only in males, since females can only be heterozygous carriers that do not develop the disorders.