Gen Bio II BIO102

1. Chapter 15
The Chromosomal
Basis of
Inheritance
Rob Swatski
Associate Professor of Biology
HACC – York Campus1

2. Overview: Genes and Chromosomes
We know Mendel’s “hereditary factors” are genes
We know genes are located on chromosomes in
specific regions (loci)
- Fluorescent “tagging”
2

3. Mitosis & meiosis were first described in the late 1800’s
The chromosome theory of inheritance:
- Mendelian genes have specific loci on chromosomes
- Chromosomes undergo segregation & independent
assortment
Chromosome behavior during meiosis accounts for
Mendel’s laws
3

4. P Generation
Gametes
Meiosis
Fertilization
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds (yyrr)
All F1 plants produce
yellow-round seeds (YyRr)
y
y
y
r
r
r
Y
Y
YR
RR

4

5. 0.5 mm
Meiosis
Metaphase I
Anaphase I
Metaphase II
Gametes
LAW OF SEGREGATION
The two alleles for each gene
separate during gamete
formation.
LAW OF INDEPENDENT
ASSORTMENT Alleles of genes
on nonhomologous
chromosomes assort
independently during gamete
formation.
1
4
yr 1 4 Yr1
4 YR
3 3
F1 Generation
1 4
yR
R
R
R
R
RR
R
R R R R
R
Y
Y
Y Y
Y
YY
Y
YY
YY
y
r r
rr
r r
rr
r r r r
y
y
y
y
y
y y
yyy
y
All F1 plants produce
yellow-round seeds (YyRr)
1
2 2
1
5

6. F2 Generation
3Fertilization
recombines the
R and r alleles
at random.
Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
An F1  F1 cross-fertilization
9 : 3 : 3 : 1
LAW OF SEGREGATION LAW OF INDEPENDENT
ASSORTMENT
3
6

7. Morgan’s Experimental Evidence
• The 1st solid evidence
associating a specific gene
with a specific chromosome
came from the
embryologist, Thomas Hunt
Morgan
• Morgan’s experiments with
fruit flies provided
convincing evidence that
Mendel’s heritable factors
are located on
chromosomes
7

8. 8
The “Fly Room” @ Columbia University

9. 9

10. 10
Drosophila melanogaster

11. Why Fruit Flies?
- Fast breeding rate & lots of offspring
- New generation produced every 2 weeks
- The have only 4 pairs of chromosomes
11

12. Wild type (normal) phenotypes were common in the fly populations
Traits alternative to the wild type are called mutant phenotypes
wild type mutant
12

13. Correlating Behavior of a Gene’s Alleles with
Behavior of a Chromosome Pair
In one mating experiment, Morgan crossed:
- male white eyes (mutant) with female red eyes (wild
type)
- The F1 generation all had red eyes
- The F2 generation showed the 3:1 red:white eye ratio,
but only males had white eyes
- The white-eyed mutant allele must be on the X
chromosome
Morgan’s finding supported the chromosome theory of
inheritance
13

14. All offspring
had red eyes.
P
Generation
F1
Generation
F2
Generation
RESULTS
EXPERIMENT
14

15. F2
Generation
P
Generation
Eggs
Eggs
Sperm
Sperm
X
w
CONCLUSION
X
X Y
w
w
w w
w
w
w w
w
w
w
w
w
w
w w
F1
Generation
15

16. The Chromosomal Basis of Sex
In humans & other mammals,
there are 2 varieties of sex
chromosomes:
- larger X chromosome
- smaller Y chromosome
Only the ends of Y chromosomes
are homologous with
corresponding regions of the
X chromosomes
The SRY gene on the Y
chromosome codes for the
development of testes
X
Y
16

17. (a) The X-Y system: females are XX and males are XY
44 +
XY
44 +
XX
Parents
44 +
XY
44 +
XX
22 +
X
22 +
X
22 +
Yor
or
Sperm Egg
+
Zygotes (offspring)
17

18. (b) The X-0 system (insects)
22 +
XX
22 +
X
(c) The Z-W system (birds, fishes, insects)
- Sex chromosomes are present in the egg (not sperm)
76 +
ZW
76 +
ZZ
X0
18

19. (d) The haplo-diploid system (bees & ants)
- No sex chromosomes
32
(Diploid)
16
(Haploid)
19

20. Inheritance of Sex-Linked Genes
Sex-linked gene: a gene that is located on either sex
chromosome
- in humans, this usually refers to x-linked genes,
which are genes located on the X chromosome
(there are few Y-linked genes)
- X chromosomes have genes for many characters,
most unrelated to sex
- contains 2000 genes
20

21. X-linked genes follow specific patterns of inheritance
For a recessive sex-linked trait to be expressed:
- A female needs 2 copies of the allele (XnXn) =
homozygous
- A male needs only 1 copy of the allele (XnY) =
hemizygous
Sex-linked recessive disorders are much more common
in males than in females – why?
21

22. (a) (b) (c)
XN
XN Xn
Y XN
Xn
  XN
Y XN
Xn
 Xn
Y
YXn
SpermYXN
SpermYXn
Sperm
XN
Xn
Eggs XN
XN
XN
Xn
XN
Y
XN
Y
Eggs XN
Xn
XN
XN
Xn
XN
XN
Y
Xn
Y
Eggs XN
Xn
XN
Xn
Xn
Xn
XN
Y
Xn
Y
Transmission of Sex-Linked Recessive Traits
22

23. Sex-linked recessive disorders in humans include:
- Color blindness
- Duchenne muscular dystrophy
- Hemophilia
23

24. X-inactivation in Female Mammals
In female mammals, 1 of the two X chromosomes in
each cell is randomly inactivated during embryonic
development
- the inactive X condenses into a Barr body
If a female is heterozygous for a particular gene
located on the X chromosome, she will be a mosaic
for that character
24

25. X chromosomes
Early embryo:
Allele for
orange fur
Allele for
black fur
Cell division &
X chromosome
inactivation
2 cell
populations
in adult cat:
Active X
Active X
Inactive X
Black fur Orange fur
25
Tortoiseshell cat

26. Linked genes: located near each other on the same
chromosome
- Linked genes are usually inherited together
26

27. How Linkage Affects Inheritance
Morgan experimented with fruit flies to see how
linkage affects the inheritance of 2 characters
He crossed flies that differed in:
- body color & wing size
27

28. P Generation (homozygous)
Wild type
(gray body, normal wings)
F1 dihybrid
(wild type)
Testcross
offspring
TESTCROSS
b b vg vg
b b vg vg
b b vg vg
b b vg vg
Double mutant
(black body,
vestigial wings)
Double mutant
Eggs
Sperm
EXPERIMENT
RESULTS
PREDICTED RATIOS
Wild type
(gray-normal)
Black-
vestigial
Gray-
vestigial
Black-
normal
b vg b vg b vg b vg
b b vg vg b b vg vg b b vg vg b b vg vg
965 944 206 185
1
1
1
1
1
0
1
0
If genes are located on different chromosomes:
If genes are located on the same chromosome and
parental alleles are always inherited together:
:
:
:
:
:
:
:
:
:
b vg
28

29. Conclusion:
body color & wing size are usually inherited together in
specific combinations
(parental phenotypes)
These genes do not assort independently & Morgan
reasoned that they were on the same chromosome
29

30. Most offspring
(F2)
F1 dihybrid female
& homozygous
recessive male
in testcross
or
b+ vg+
b vg
b+ vg+
b vg
b vg
b vg
b vg
b vg
Results: a much higher % of parental phenotypes than would
be expected by independent assortment 30

31. However, non-parental phenotypes were also
produced
Understanding this result involves exploring
genetic recombination
- the production of offspring with combinations
of traits different from either parent
Both findings of Mendel & Morgan relate to the
chromosomal basis of recombination
31

32. Recombination of Unlinked Genes:
Independent Assortment of Chromosomes
Mendel observed that combinations of traits in some
offspring differ from either parent
- Parental types: offspring with a phenotype matching 1
of the parental phenotypes
- Recombinant types (recombinants): offspring with
non-parental phenotypes (new combinations of traits)
A 50% frequency of recombination is observed for any 2
genes on different chromosomes
32

33. YyRr
Gametes from green-
wrinkled homozygous
recessive parent (yyrr)
Gametes from yellow-round
heterozygous parent (YyRr)
Parental-
type
offspring
Recombinant
Offspring (50%)
yr
yyrr Yyrr yyRr
YR yr Yr yR
33

34. Recombination of Linked Genes: Crossing Over
Morgan discovered that genes can be linked, but the
linkage was incomplete (as shown by the appearance
of recombinant phenotypes)
Morgan proposed that some process must sometimes
break the physical connection between genes on the
same chromosome
= the crossing over of homologous chromosomes
during meiosis
34

35. Testcross
parents
Replication
of chromo-
somes
Gray body, normal wings
(F1 dihybrid)
Black body, vestigial wings
(double mutant)
Replication
of chromo-
somes
b+ vg+
b+ vg+
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b+ vg+
b+ vg
b vg+
b vg
Recombinant
chromosomes
Meiosis I and II
Meiosis I
Meiosis II
Eggs Sperm
b+ vg+
b vg b+ vg b vgb vg+
Crossing-
over
35

36. 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+
Spermb vg
Parental-type offspring Recombinant offspring
(206 + 185 = 391)
b vg
b+ vg b vg+
b vg+
Recombination
frequency
=
391 recombinants
2,300 total offspring
 100 = 17%
Eggs
Recombinant
chromosomes
36

37. Recombinant chromosomes bring alleles together in
new combinations in gametes
Random fertilization further increases the number of
variant combinations that can be produced
This abundance of genetic variation is the raw material
upon which natural selection works
New Combinations of Alleles: Variation for
Normal Selection
37

38. Genetic Maps
Alfred Sturtevant, one of Morgan’s students,
constructed a genetic map: an ordered list of loci
along a particular chromosome
Sturtevant predicted that:
the farther apart 2 genes are, the higher the
probability that a crossover will occur between them
& therefore the higher the recombination frequency
38

39. Linkage Maps
Genetic map of a chromosome based on
recombination frequencies
Distances between genes expressed as map units:
1 map unit (centimorgan)
= 1% recombination frequency
Map units indicate relative distance & order, not
precise locations of genes
39

40. RESULTS
Recombination
frequencies
Chromosome
9% 9.5%
17%
b cn vg
40

41. Genes that are far apart on the same chromosome
can have a recombination frequency near 50%
Such genes are physically linked, but genetically
unlinked, & behave as if found on different
chromosomes
41

42. Sturtevant used recombination frequencies to make
linkage maps of fruit fly genes
Using methods like chromosomal banding, geneticists
can develop cytogenetic maps of chromosomes
- Indicate positions of genes with respect to
chromosomal features
42

43. Mutant phenotypes
Short
aristae
Black
body
Cinnabar
eyes
Vestigial
wings
Brown
eyes
Red
eyes
Normal
wings
Red
eyes
Gray
body
Long aristae
(appendages
on head)
Wild-type phenotypes
0 48.5 57.5 67.0 104.5
A partial linkage map of a Drosophila chromosome 43

44. Large-scale chromosomal alterations often lead to
spontaneous abortions (miscarriages) or cause a
variety of developmental disorders
Plants tolerate such genetic changes better than
animals do
Alteration of Chromosome Number or
Structure Cause Some Genetic
Disorders
44

45. Abnormal Chromosome Number
Nondisjunction: pairs of homologous chromosomes do
not separate normally during meiosis
- As a result, one gamete receives 2 of the same type
of chromosome & another gamete receives no copy
45

46. Meiosis I
Nondisjunction
of homologous chromosomes
(a) Nondisjunction of homologous
chromosomes in meiosis I
(b) Nondisjunction of sister
chromatids in meiosis II
Meiosis II
Nondisjunction of
sister chromatids
Gametes
Number of chromosomes
n + 1 n + 1 n + 1n – 1 n – 1 n – 1 n n
46
Normal

47. Aneuploidy: results from the fertilization of gametes
in which nondisjunction occurred
- offspring have an abnormal number of a particular
chromosome
Monosomic zygote: has only 1 copy of a particular
chromosome (ex: Turner Syndrome – females
have 1 X chromosome); most others lethal
Trisomic zygote: has 3 copies of a particular
chromosome (ex: Trisomy 21 – Down Syndrome)
47

48. Polyploidy: organism has more than 2 complete
sets of chromosomes
- Common in plants, but not animals (in some
flatworms & leeches)
- Polyploids are more normal in appearance than
aneuploids
- Triploidy (3n): 3 sets of chromosomes
(Ex: seedless watermelons)
- Tetraploidy (4n): 4 sets of chromosomes
(Ex: cotton, salmon)
48

49. Alterations of Chromosome Structure
Breakage of a chromosome can lead to 4 types of
changes in structure:
- Deletion: removes a chromosomal segment
- Duplication: repeats a segment
- Inversion: reverses the orientation of a segment
within a chromosome
- Translocation: moves a segment from 1
chromosome to another non-homologous
chromosome
49

50. (a) Deletion
(b) Duplication
(c) Inversion
(d) Translocation
A deletion removes a chromosomal segment.
A duplication repeats a segment.
An inversion reverses a segment within a
chromosome.
A translocation moves a segment from one
chromosome to a non-homologous chromosome.
A B C D E F G H
A B C E F G H
A B C D E F G H
A B C D E F G HB C
A B C D E F G H
A D C B E F G H
A B C D E F G H M N O P Q R
GM N O C HFED A B P Q R
50

51. Human Disorders Due to
Chromosomal Alterations
Some types of aneuploidy have higher survival rates,
resulting in individuals surviving to birth & beyond
These survivors have a set of symptoms (syndrome)
characteristic of the type of aneuploidy
51

52. Down Syndrome (Trisomy 21)
Aneuploidy due to 3 copies of
chromosome 21
- affects 1 out of every 700-1000
US children
- most common chromosomal
abnormality in humans
- frequency increases with
mother’s age (40+ years)
- due to nondisjunction in Meiosis I
- diagnosed via prenatal screening
52

53. 53
- Short stature
- Heart defects
- Developmental delays
- Sexually underdeveloped or sterile
- Mild/moderate intellectual disability
- 50-60 year life expectancy
Down Syndrome
(Trisomy 21)

54. Aneuploidy of Sex Chromosomes
Due to nondisjunction of sex chromosomes
Klinefelter syndrome: results from an extra X
chromosome in a male, producing XXY individuals
(the extra X chromosome is inactivated)
Monosomy X (Turner syndrome): produces sterile X0
females
- the only known viable monosomy in humans
- reproductive organs don’t mature
54

55. Klinefelter Syndrome
(47, XXY) 55
- 1 in 500-1000 births
- Hypogonadism
- Sterility
- Some have no
symptoms
- Lots of variations

56. Turner Syndrome
(X0) 56
- 1 in 2500 births
- Short stature
- Webbed necks
- Ovaries non-
functional
- Sterility
- Heart disease
- Hypothyroidism

57. 57
Turner Syndrome: webbed neck

58. Disorders Caused by Structurally Altered
Chromosomes
Cri du chat syndrome: due to a
specific deletion at the end of
chromosome 5 (deletions
often cause severe problems)
- 1 in 50,000 births
- mental retardation, catlike cry
- small head with unusual facial
features
- individuals usually die in
infancy or early childhood 58
partial
monosomy

59. Disorders Caused by Structurally Altered
Chromosomes
Certain cancers are caused by translocations of
chromosomes
- Chronic myelogenous leukemia (CML)
59
- Abnormal WBC’s accumulate
in blood during mitosis of
myeloid stem cells in red
bone marrow
- Cause unknown
- Diagnosed in mid-60’s
- Higher survival rates
- Treated with tyrosine kinase
inhibitors (TKI’s)

60. Normal chromosome 9
Normal chromosome 22
Reciprocal translocation
Translocated chromosome 9
Translocated chromosome 22 – much shorter
(Philadelphia chromosome): gene activated that causes
uncontrolled mitosis in CML patients 60

61. There are 2 normal exceptions to Mendelian genetics
1. One involves genes located inside the nucleus
(genomic imprinting)
2. The other involves genes located outside the nucleus
(extranuclear genes)
In both cases, the sex of the parent contributing an
allele is a factor in the pattern of inheritance
61

62. Genomic Imprinting
For a few mammalian developmental traits,
phenotype depends on which parent passed along
those alleles
- this phenotype variation is called genomic
imprinting
- involves the silencing of certain genes that are
“stamped” with an imprint during gamete
production
- due to the methylation (addition of –CH3) of
cysteine (C) nucleotides of DNA
62

63. Normal Igf2 allele
is expressed
Paternal
chromosome
Maternal
chromosome
(a) Homozygote
Wild-type mouse
(normal size)
Normal Igf2 allele
is not expressed
Genomic imprinting of the mouse Igf2 gene 63

64. Mutant Igf2 allele
inherited from mother
Mutant Igf2 allele
inherited from father
Normal size mouse
(wild type)
Dwarf mouse
(mutant)
Normal Igf2 allele
is expressed
Mutant Igf2 allele
is expressed
Mutant Igf2 allele
is not expressed
Normal Igf2 allele
is not expressed
(b) Heterozygotes
64

65. Inheritance of Organelle Genes
Extranuclear (cytoplasmic) genes: found in organelles
in the cytoplasm
- mitochondria, chloroplasts, & other plant plastids
carry small circular DNA molecules
- extranuclear genes are inherited maternally because
the zygote’s cytoplasm comes from the egg
- the first evidence came from studies on the
inheritance of yellow or white patches on leaves of
an otherwise green plant
65

66. 66

67. Some defects in mitochondrial genes prevent normal
ATP synthesis
- result in diseases that affect the muscular & nervous
systems
- Mitochondrial myopathy
67

68. 68