1. Genetics and Evolution
Welcome to IB 201!
Genetics and Evolution

2. IB 201: Review Question
A phenotype ratio of 9:3:3:1 in the offspring of a mating between two individuals that are heterozygous for two traits occurs when:
A. the genes reside on the same chromosome
B. each gene contains two mutations
C. the gene pairs assort independently during meiosis
D. only recessive traits are scored
E. none of the above

3. Course Outline Genetic Data Analysis: Probability & Statistics
Deviations from Mendelism:
Epistasis; Unusual Modes of Inheritance
Chromosomal Inheritance:
Chromosomal Abnormalities; Sex Determination
Mapping:
Gene and Genome Mapping
Traits Affected by Genes & Environment
Quantitative Traits
Genes in Populations
Genetic Mechanisms of Evolution; Population Genetics of Disease and Disease resistance

4. Genetic Data Analysis II
Some simple rules of probability

5. Sum Rule
The combined probability of two events that are mutually exclusive is the sum of the individual probabilities. Clue: look for “or”
Q: What’s the probability of rolling a ‘five’ or a ‘six’ on one six-sided die?
A: 1/6 + 1/6 = 1/3

6. Genetic Example: Monohybrid Cross
P: GG x gg
F1: Gg
Gg x Gg ==>
F2: 1/4 GG: 1/2 Gg: 1/4 gg
What is the probability that the F2 offspring has the dominant phenotype (is either GG or Gg)?
1/4 GG + 1/2 Gg = 3/4 G-

7. Genetic Example 2: Dihybrid Cross
P: GG ww x gg WW
F1: Gg Ww
Gg Ww x Gg Ww ==>
F2: 9/16 G-W- 3/16 G-ww 3/16 ggW- 1/16 ggww
What is the probability that an F2 offspring will have the dominant phenotype (G-ww or ggW-) for only one of the two traits?
3/16 G-ww + 3/16 ggW- = 6/16=3/8

8. Product Rule
The probability of several independent events is the product of the individual probabilities.
Two events are independent if the occurrence of the first event has no effect on the probability of the second event. Clue: look for “and”.
Q: You roll two dice. What’s the probability of getting a ‘two’ on the first one and a ‘five’ on the second one.
A: 1/6 * 1/6 = 1/36

9. Genetic example of product rule
P: AA bb CC DD ee ff x aa BB cc dd EE FF
F1: Aa Bb Cc Dd Ee Ff x Aa Bb Cc Dd Ee Ff
Q: What proportion of F2 progeny will be
AA bb Cc DD ee Ff ?
A: 1/4 * 1/4 * 1/2 * 1/4 * 1/4 * 1/2 = 1/1024

10. Deviations from Mendelism
Lethal Alleles
Epistasis
Unusual sex linkage
Sex influenced inheritance
Genetic Anticipation

11. Manx Cats

12. Lethal alleles F1: Mm x Mm F1: 1 MM 2 Mm 1 mm
F2: Lethal: 2 Manx: 1 Normal
F2 phenotypic ratio: 2:1 instead of 3:1

13. Other lethal mutations
Achondroplasia (humans)
Yellow body color (domestic mice)
Curly wings (Drosophila)

14. Epistasis Genetic interaction between two (or more) loci.
One gene modifies the phenotypic effects of another gene.

15. Agouti: wild type Figure: 04-00CO Caption:
Agouti, yellow, and black mice.

16. F2: 9/16 B- C- 3/16 bb C- 3/16 B- cc 1/16 bb cc agouti black albino
BB CC x bb cc
P: agouti albino
Bb Cc
F1: agouti
Simple dominant phenotype?
F2: 9/16 B- C- 3/16 bb C- 3/16 B- cc 1/16 bb cc
agouti
black
albino
albino
F2 Phen. ratio: 9 agouti : 3 black : 4 albino
novel phenotype

17. Epistasis Normal dihybrid ratio is altered from 9:3:3:1 to 9:3:4
C and B gene have an epistatic interaction

18. Epistasis Locus 1 Locus 2 BB Bb bb CC Cc cc
agouti agouti black no effect no effect albino

19. Biochemical model
CC or Cc: tyrosinase is produced (involved in production of melanin)
BB or Bb: controls distribution of the pigment

20. rrYY RRyy Codominance? R-Y- R-Y- rrY- R-yy rryy
Figure 10.18b
Crosses between pure lines produce novel colors.
Parental
generation
rrYY RRyy X
Yellow
Brown
Codominance?
F1 generation
R-Y-
Red
Self-fertilization
Figure: 10.18b
Caption:
Inheritance of Fruit Color in Bell Peppers
F2 generation
R-Y- rrY R-yy rryy
Red
Yellow
Brown
Green
9/16
3/16
3/16
1/16

21. yellow ----------------> green -----------------> brown pepper
Figure 10.18c
Model to explain 9 : 3 : 3 : 1 pattern observed above: Two genes interact to produce pepper color.
yellow > green > brown pepper
yy? chlorophyll R? red pigment
yellow > yellow > orange
Y? No chlorophyll R? red pigment
Genotype
Color
Explanation of color
R-Y-
Red
Red pigment + no chlorophyll
rrY-
Yellow
Yellow pigment + no chlorophyll
R-yy
Brown
Red pigment + chlorophyll
rryy
Green
Yellow pigment + chlorophyll
Gene 1
Figure: 10.18c
Caption:
Inheritance of Fruit Color in Bell Peppers
Gene 2
R = Red
Y = Absence of green (no chlorophyll)
r = Yellow
y = Presence of green (+ chlorophyll)
(-) = R or r
(-) = Y or y

22. Practice Problem
In Labrador retrievers, coat color is controlled by two loci each with two alleles B,b and E,e respectively. When pure breeding Black labs with genotype BB EE are crossed with pure breeding yellow labs of genotype bb ee the resulting F1 offspring are black. F1 offspring are crossed (Bb Ee x Bb Ee). Puppies appear in the ratio:
9/16 black; /16 chocolate; /16=1/4 yellow.
What genotypes correspond to these three phenotypes?
9/16 B- E /16 B- ee 3/16 bb E- 1/16 eebb
B- E- B- ee bb E- and bb ee

23. Other kinds of epistasis
9/16 A-B-
3/16 A-bb
3/16 aaB-
1/16 aabb
Figure: 04-07
Caption:
Basis of modified dihybrid F2 phenotypic ratios.
Hint: usually given numbers, not fractions
27 agouti; 12 albino; 9 black
28 agouti; 11 albino; 4 black

24. Practice Problem
In the summer squash (Cucurbita pepo) fruit shape is determined by two genes. Two different true-breeding spherical types were crossed. The F1's were all disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results.
What’s the first step?
Notice novel phenotype: disk, long.
What’s the next step?
Notice there are three F2 phenotypes. What kind of inheritance will give three F2 phenotypes?
Genetic Model?
Incomplete, codominance
Epistasis
Expected F2 ratio?
1:2:1
Variation on 9:3:3:1

25. Practice Problem, cont.
In the summer squash (Cucurbita pepo) spherical fruit is recessive to disk, True-breeding spherical types from different geographic regions were crossed. The F1's were disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results.
Are the phenotypic ratios closer 1:2:1 or to a variant of 9:3:3:1 ?
If phenotypic ratios closer to a variant of 9:3:3:1, then what variant is it?
Total # of individuals = = 64
64/16 = 4
9*4 = 36
6*4 = 24
1*4 = 4
Phenotypic ratio close to 9:6:1

26. Practice Problem, cont. AA bb aaBB
In the summer squash (Cucurbita pepo) spherical fruit is recessive to disk, True-breeding spherical types from different geographic regions were crossed. The F1's were disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results.
If phenotypic ratios are close to 9:6:1, then what are the genotypes associated with each phenotype?
35 disk spherical long
9/16 A- B /16 A- bb + 3/16 aa B- 1/16 aa bb
What were the genotypes of the original spherical parents?
AA bb aaBB

27. Sex Linkage: mammals, flies
Heterogametic
Sex
Diploid XAXa XAY
Adults
Gametes XA Xa XA Y XA Y
Male XA
XAXA
XAY
Female Xa
XAXa
XaY

29. Sex Linkage: birds, butterflies
Homogametic
Sex
Heterogametic
Sex
Diploid ZBW ZBZb
Adults Female Male
Gametes ZB W ZB Zb ZB Zb
Male ZB
ZBZb
ZBZb
Female W
ZBW
ZbW

30. Y-linked inheritance

31. Hairy ears

32. Male pattern baldness: what kind of inheritance?

33. Sex influenced phenotype
Genotype Female Male
bb Bald Bald
bb’ Not bald Bald
b’b’ Not bald Not bald

34. Environment-dependent dependent expression of a genotype

35. Siamese or “Himalayan”
Different allele of the C locus that causes albinism.
Temperature sensitive.

36. Phenotypes are not always a direct reflection of genotypes
Temperature-sensitive alleles: Siamese color pattern
Nutritional effects: phenylketonuria
Genetic anticipation: several genetic diseases

37. Phenylketonuria Nutritional defect: can’t metabolize phenylalanine.
Can lead to severe physical and mental disorders in children, but only if they consume phenylalanine.
Disease phenotype can be avoided by eliminating phenylalanine from the diet

38. Genetic Anticipation Huntington disease Fragile-X syndrome
Kennedy disease
Myotonic muscular dystrophy

39. Fragile X syndrome
Symptoms: delayed development & mental retardation. More severe in males than females
Caused by expansion of triplet repeat (CGG) in a gene on the long arm of the X chromosome
Named for breakage of X chromosome in cell preparations.

40. Fragile X Normal range: 7-52 (average=30)
“Pre-mutation”: repeats
Full Mutation: > s. DNA becomes abnormally methylated, promoter is inactivated, and gene silenced.
Pre-mutation is unstable: maternally-inherited premutation with >100 repeats almost always expands to a full mutation

41. Genetic Anticipation: Fragile X
Most common kind of inherited mental retardation.
Named for “fragile site”
Due to expansion of 3-base pair repeat (CGG) in a gene near the tip of the long arm of X chromosome.

42. Fragile X
Pre-mutation is unstable: maternally-inherited premutation with >100 repeats almost always expands to a full mutation

43. Genetic Anticipation causes subsequent generations in a family to be more severely affected by a disease. It does this by increasing the number of triplet repeats in the fragile area of the X chromosome through the generations.

44. Huntington Disease Autosomal dominant lethal (chromosome 4)
Progressive neurological deterioration
First symptoms appear after reproductive age
One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats
All show inverse correlation with age of onset and number of repeats.

45. Huntington Disease Autosomal dominant lethal (chromosome 4)
Progressive neurological deterioration
First symptoms appear after reproductive age
One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats
All show inverse correlation with age of onset and number of repeats.

46. Huntington Disease Autosomal dominant lethal (chromosome 4)
Progressive neurological deterioration
First symptoms appear after reproductive age
One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats
All show inverse correlation with age of onset and number of repeats.

47. Which is the pedigree of autosomal dominant (like HD)