1. The Chromosomal Basis of Inheritance12
The Chromosomal Basis of Inheritance

2. Where are Mendel’s hereditary factors located in a cell?
Figure 12.1
Figure 12.1 Where are Mendel's hereditary factors located in the cell? 2

3. Many biologists remained skeptical about Mendel’s laws of segregation and independent assortment until there was evidence that these principles had a physical basis in chromosomal behavior.
Late 1800s: microscopy allowed parallels to be seen

4. Chromosomal Theory of Inheritance: Mendelian genes have specific loci along chromosomes
It is the chromosomes that undergo segregation and independent assortment

5. P Generation Yellow-round Green-wrinkled seeds (YYRR) seeds (yyrr)
Figure 12.2a
P Generation
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds (yyrr) Y y r R R r Y y
Meiosis
Figure 12.2a The chromosomal basis of Mendel’s laws (part 1)
Fertilization R Y y r
Gametes 5

6.     All F1 plants produce yellow-round seeds (YyRr). F1 Generation
Figure 12.2b
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation R R y y r r Y Y
Meiosis
LAW OF INDEPENDENT
ASSORTMENT
Alleles of genes on
nonhomologous
chromosomes assort
independently.
LAW OF
SEGREGATION
The two alleles for
each gene separate. R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y
Metaphase II R r r R
Figure 12.2b The chromosomal basis of Mendel’s laws (part 2) 2 2 Y y Y y y Y Y Y Y y y y R R r r r r R R 1 4  YR 1 4  yr 1 4  Yr 1 4  yR 6

7. An F1  F1 cross-fertilization 3 Fertilization results in the 9:3:3:1
Figure 12.2c
LAW OF
SEGREGATION
LAW OF
INDEPENDENT
ASSORTMENT
F2 Generation 3
Fertilization
recombines the
R and r alleles
at random.
An F1  F1 cross-fertilization 3
Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation. 9
: 3
: 3
: 1
Figure 12.2c The chromosomal basis of Mendel’s laws (part 3) 7

8. Thomas Hunt Morgan
Provided first solid evidence associating a specific gene with a specific chromosome
Worked with fruit flies

9. Thomas Hunt Morgan
Used reciprocal crosses - 2 crosses where the trait of each sex is reversed
Example -
1- White eyed male X Red eyed female
2- White eyed female X Red eyed male
Red: wild type (most common) w+
White: mutant type w

10. White-eyed males show up in F2
Thomas Morgan X X
1/2 Y Y
recessive male
all red-
eyed F1
offspring
1/2
1/4 X X
1/4
1/4 X X
1/2
1/4 X X
1/2
gametes
White-eyed males show up in F2
generation
Fig. 12-9, p.193

11. Morgan’s cross showed all red eyes (w+) for the F1 generation
3:1 phenotypic ratio for the F2
BUT… only the males had white eyes

12. All females had red eyes, and half the males had red and half had white

13. Morgan showed that eye color must be linked to its sex

14. 12.2 Sex Linked Genes
In mammals:
XX – female
XY - male

15. The Y Chromosome Fewer than two dozen genes identified
SRY gene (sex-determining region of Y) is the master gene for male sex determination

16. The X Chromosome Carries more than 2,300 genes
Most for nonsexual traits
Genes on X chromosome can be expressed in both sexes
Gene on either sex chromosome is called a sex-linked gene

17. Fathers pass all of there X linked alleles to all of their daughters but none to their sons
Mothers pass all of there X linked alleles to both daughters and sons
If an X linked trait is recessive, a male will express the phenotype, a female will only express it if she is homozygous recessive

18. Symbols

19. Sperm Eggs (a) Sperm Sperm Eggs Eggs (b) (c) XNXN XnY Xn Y XN XNXn XNY
Figure 12.7
XNXN
XnY Xn Y
Sperm
Eggs XN
XNXn
XNY XN
XNXn
XNY
(a)
XNXn
XNY
XNXn
XnY
Figure 12.7 The transmission of X-linked recessive traits XN Y
Sperm Xn Y
Sperm
Eggs XN
XNXN
XNY
Eggs XN
XNXn
XNY Xn
XNXn
XnY Xn
XnXn
XnY
(b)
(c) 19

20. Some disorders caused by recessive alleles on the X chromosome in humans
Color blindness (mostly X-linked)
Duchenne muscular dystrophy
Hemophilia 20

21. Color Blindness
Fig , p.195

22. Color Blindness
Fig , p.195

23. Hemophilia
Fig , p.194

24. X Chromosome Inactivation
One X is inactivated in each cell of female mammals
(Paternal X in Marsupials, random in Placentals)
The inactive X condenses into a Barr body
Creates “mosaic” for X chromosomes
Governed by XIST gene
Dosage compensation theory - shutdown prevents “overdose” of gene products in females

26. X Chromosome Inactivation
Fig. 15-5, p.234

27. X chromosomes Allele for orange fur Early embryo: Allele for black fur
Figure 12.8
X chromosomes
Allele for
orange fur
Early embryo:
Allele for
black fur
Cell division and
X chromosome
inactivation
Two cell
populations
in adult cat:
Active X
Inactive X
Active X
Black fur
Orange fur
Figure 12.8 X inactivation and the tortoiseshell cat 27

28. Concept 12.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome
Genes located on the same chromosome are called linked genes
Degree of linkage varies with distance between loci 28

29. Crossover Frequency Proportional to the distance that separates genesB C D
Crossing over will disrupt linkage between A and B more often than C and D
In-text figure Page 178

30. Complete linkage: Off spring will all look like a parent, no recombination of genes (due to crossing over) occurs

31. Complete Linkage A B a b x Parents: A B a b AB ab F1 offspring:
All AaBb
meiosis, gamete formation
Equal ratios of two types of gametes: A B a b
Figure Page 178
50% AB
50% ab

32. Incomplete linkage: produces new combinations of the genes in the offspring
Due to crossing over of homologous chromosomes in between the linked genes
Demonstrates an exception to Mendal’s laws

33. Incomplete Linkage AC ac A C a c x Parents: A C a c F1 offspring:
All AaCc
meiosis, gamete formation A a A a
Unequal ratios of four types of gametes: C c c C
parental
genotypes
recombinant
genotypes
Figure Page 178

34.  When in sweet peas a cross is made between blue flower and long pollen (BBLL) with red flower and round pollen (bbll) in F1 expected blue flower and long pollen (BbLl) heterozygous condition is expressed.

35. However, test cross between blue and long (BbLl) and double recessive (bbll) gave blue long (43.7%), red round (43.7%), blue round (6.3%) and red long (6.3%). The parent combinations are 87.4% are due to linkage in genes on two homologous chromosomes, while in case of new combinations (12.6%) the genes get separated due to breaking of chromosomes at the time of crossing over in prophase-I of meiosis. New combinations in the progeny appeared due to incomplete linkage 

36. Morgan provided evidence with crossing fruit flies
See page 237

37. b vg b vg F1 dihybrid female and homozygous recessive male
Figure 12.UN01
b vg
b vg
F1 dihybrid female
and homozygous
recessive male
in testcross
b vg
b vg
b vg
b vg
Figure 12.UN01 In-text figure, testcross, p. 234
Most offspring or
b vg
b vg 37

38. F1 dihybrid testcross b vg+ b vg Wild-type F1 dihybrid (gray body,
Figure 12.10b
F1 dihybrid testcross
b vg+
b vg
Wild-type F1
dihybrid
(gray body,
normal wings)
Homozygous
recessive
(black body,
vestigial wings)
b vg
b vg
b vg+
b vg
b vg+
b vg
b vg
b vg
b vg
b vg
Meiosis I
b vg+
Meiosis I and II
b vg
b vg
Figure 12.10b Chromosomal basis for recombination of linked genes (part 2: testcross)
b vg
Recombinant
chromosomes
Meiosis II
b+ vg+
b vg
b+ vg
b vg+
b vg
Eggs
Sperm 38

39. Parental-type offspring Recombinant offspring
Figure 12.10c
Recombinant
chromosomes
b vg+
b vg
b vg
b vg
Eggs
Testcross
offspring
965
Wild type
(gray-normal)
944
Black-
vestigial
206
Gray-
vestigial
185
Black-
normal
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Figure 12.10c Chromosomal basis for recombination of linked genes (part 3: testcross offspring)
Sperm
Parental-type offspring
Recombinant offspring
Recombination
frequency
391 recombinants 
  17%
2,300 total offspring 39

40. A linkage map - genetic map of chromosome based on recombination frequencies
Distances expressed as map units; one map unit represents a 1% recombination frequency 40

41. Results Recombination frequencies 9% 9.5% Chromosome 17% b cn vg
Figure 12.11
Results
Recombination
frequencies 9%
9.5%
Chromosome
17%
Figure Research method: constructing a linkage map b cn vg 41

42. Abnormal Chromosome Number
nondisjunction, pairs of homologous chromosomes do not separate during meiosis
result, - one gamete carries extra chromosome, and another gamete receives none
Video: Nondisjunction 42

43. Nondisjunction of homo- logous chromosomes in meiosis I (b)
Figure
Meiosis I
Nondisjunction
Meiosis II
Non-
disjunction
Gametes
Figure Meiotic nondisjunction (step 3)
n  1
n  1
n − 1
n − 1
n  1
n − 1 n n
Number of chromosomes
(a)
Nondisjunction of homo-
logous chromosomes in
meiosis I
(b)
Nondisjunction of sister
chromatids in meiosis II 43

44. Aneuploidy results from fertilization of gametes in which nondisjunction occurred
Offspring with this condition have an abnormal number of a particular chromosome 44

45. A monosomic zygote has only 1 copy of a particular chromosome
A trisomic zygote has three copies of a particular chromosome 45

46. Alterations of Chromosome Structure
Breakage of a chromosome can lead to four types of changes in chromosome structure:
Deletion removes a chromosomal segment
Duplication repeats a segment
Inversion reverses orientation of a segment within a chromosome
Translocation moves a segment from one chromosome to another 46

47. (a) Deletion A deletion removes a chromosomal segment. (b) Duplication
Figure 12.14a
(a) Deletion
A deletion removes a
chromosomal segment.
(b) Duplication
Figure 12.14a Alterations of chromosome structure (part 1: deletion and duplication)
A duplication repeats
a segment. 47

48. An inversion reverses a segment within a chromosome.
Figure 12.14b
(c) Inversion
An inversion reverses a segment
within a chromosome.
(d) Translocation
Figure 12.14b Alterations of chromosome structure (part 2: inversion and translocation)
A translocation moves a segment
from one chromosome to a
nonhomologous chromosome. 48

49. Down Syndrome (Trisomy 21)
Down syndrome is an aneuploid condition that results from three copies of chromosome 21
It affects about one out of every 700 children born in the United States
The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained 49

50. Figure 12.15
Figure Down syndrome 50

51. Down Syndrome
Fig , p.199

52. Aneuploidy of Sex Chromosomes
Nondisjunction of sex chromosomes produces a variety of aneuploid conditions
Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals
Females with trisomy X (XXX) have no unusual physical features except being slightly taller than average 52

53. It is the only known viable monosomy in humans
Monosomy X, called Turner syndrome, produces X0 females, who are sterile
It is the only known viable monosomy in humans 53

54. Disorders Caused by Structurally Altered Chromosomes
The syndrome cri du chat (“cry of the cat”) results from a specific deletion in chromosome 5
A child born with this syndrome is mentally disabled and has a catlike cry; individuals usually die in infancy or early childhood 54

55. Deletion
Cri-du-chat
Fig , p.196

56. Disorders Caused by Structurally Altered Chromosomes
Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes 56