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

2. Overview: Locating Genes Along Chromosomes
Mendel’s “hereditary factors” were genes
Today we know that genes are located on chromosomes
The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene
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3. Mitosis and meiosis were first described in the late 1800s
The chromosome theory of inheritance states:
Mendelian genes have specific loci (positions) on chromosomes
Chromosomes undergo segregation and independent assortment
The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

4. Fig. 15-2 Figure 15.2 The chromosomal basis of Mendel’s laws
P Generation
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds ( yyrr) Y y  r Y R R r y
Meiosis
Fertilization R Y y r
Gametes
All F1 plants produce
yellow-round seeds (YyRr)
F1 Generation R R y y r r Y Y
LAW OF SEGREGATION
The two alleles for each gene
separate during gamete
formation.
Meiosis
LAW OF INDEPENDENT
ASSORTMENT Alleles of genes
on nonhomologous
chromosomes assort
independently during gamete
formation. R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y
Figure 15.2 The chromosomal basis of Mendel’s laws R r
Metaphase II r R 2 2 Y y Y y y Y Y y Y Y y y
Gametes R R r r r r R R
1/4 YR
1/4 yr
1/4 Yr
1/4 yR
F2 Generation
An F1  F1 cross-fertilization 3 3 9
: 3
: 3
: 1

5. Morgan worked with fruit flies
Concept 12.1: Morgan showed that Mendelian inheritance has its physical basis in the behavior of chromosomes: scientific inquiry
Several researchers proposed in the early 1900s that genes are located on chromosomes
Thomas Hunt Morgan
Provided convincing evidence that chromosomes are the location of Mendel’s heritable factors
Morgan worked with fruit flies
Because they breed at a high rate
A new generation can be bred every two weeks
They have only four pairs of chromosomes

6. Morgan’s Experimental Evidence: Scientific Inquiry
Morgan first observed and noted
Wild type: or normal, phenotypes that were common in the fly populations
Mutant phenotypes: Traits alternative to the wild type
Wild
Mutant

7. In one experiment Morgan mated male flies with white eyes (mutant) with female flies with 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 F2 generation showed a typical Mendelian
3:1 ratio of red eyes to white eyes. However, no females displayed the
white-eye trait; they all had red eyes. Half the males had white eyes,
and half had red eyes.
Morgan then bred an F1 red-eyed female to an F1 red-eyed male to
produce the F2 generation.
RESULTS P
Generation F1 X F2
Morgan mated a wild-type (red-eyed) female
with a mutant white-eyed male. The F1 offspring all had red eyes.
EXPERIMENT
Morgan determined that the white-eye mutant allele must be located on the X chromosome

8. Morgan’s Experimental Evidence
CONCLUSION
Since all F1 offspring had red eyes, the mutant
white-eye trait (w) must be recessive to the wild-type red-eye trait (w+).
Since the recessive trait—white eyes—was expressed only in males in
the F2 generation, Morgan hypothesized that the eye-color gene is
located on the X chromosome and that there is no corresponding locus
on the Y chromosome, as diagrammed here. P
Generation F1 F2
Ova
(eggs)
Sperm X Y W W+

9. Concept 12.2: Sex-linked genes exhibit unique patterns of inheritance
The behavior of the members of the pair of sex chromosomes can be correlated with the behavior of the two alleles of the eye-color gene white
Humans and other mammals have two types of sex chromosomes: a larger X chromosome and a smaller Y chromosome
Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome
The SRY gene on the Y chromosome is required for the developments of testes
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10. 44  XY 44  XX Parents 22  X 22  X 22  or Sperm Egg 44  XX 44 
Figure 12.6
44  XY
44  XX
Parents
22  X
22  X
22  Y or
Sperm
Egg
Figure 12.6 The mammalian X-Y chromosomal system of sex determination
44  XX
44  XY or
Zygotes (offspring)
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11. Inheritance of X-Linked Genes
The sex chromosomes have genes for many characters unrelated to sex
Sex-linked gene: a gene located on either sex chromosome follow specific patterns of inheritance
Some recessive alleles found on the X chromosome in humans cause certain types of disorders
Color blindness
Duchenne muscular dystrophy
Hemophilia

12. XNXN XnY XNXn XNY XNXn XnY Sperm Xn Y Sperm XN Y Sperm Xn Y Eggs XN
Figure 15.7
XNXN
XnY
XNXn
XNY
XNXn
XnY
Sperm Xn Y
Sperm XN Y
Sperm Xn Y
Eggs XN
XNXn
XNY
Eggs XN
XNXN
XNY
Eggs XN
XNXn
XNY XN
XNXn
XNY Xn
XNXn
XnY Xn
XnXn
XnY
Figure 15.7 The transmission of X-linked recessive traits.
(a)
(b)
(c)

13. X inactivation in Female Mammals
In mammalian females
One of the two X chromosomes in each cell is randomly inactivated during embryonic development (becomes Barr body)
Affects allele expression in different cells
For example tortoiseshell calico cats
If a female is heterozygous for a particular gene located on the X chromosome
She will be a mosaic for that character

14. 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
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15. Concept 12.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome
Each chromosome has hundreds or thousands of genes (except the Y chromosome)
Genes located on the same chromosome that tend to be inherited together are called linked genes
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16. How Linkage Affects Inheritance
Morgan did other experiments with fruit flies
To see how linkage affects the inheritance of two different characters
Morgan crossed flies that differed in traits of two different characters
Wings: normal (wild) vs. vestigial (mutant)
Body color: gray (wild) vs. black (mutant)

17. How Linkage Affects Inheritance
Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes)
He reasoned that since these genes did not assort independently, they were on the same chromosome
However, nonparental phenotypes were also produced
Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent
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18. Wild type (gray-normal)
Figure
EXPERIMENT
P Generation (homozygous)
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)
b b vg vg
b b vg vg
F1 dihybrid (wild type)
Double mutant
TESTCROSS
b b vg vg
b b vg vg
Testcross offspring
Eggs
b vg
b vg
b vg
b vg
Wild type (gray-normal)
Black- vestigial
Gray- vestigial
Black- normal
b vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?
Sperm
b b vg vg
b b vg vg
b b vg vg
b b vg vg
PREDICTED RATIOS
If genes are located on different chromosomes: 1 : 1 : 1 : 1
If genes are located on the same chromosome and parental alleles are always inherited together: 1 : 1 : :
RESULTS
965 :
944 :
206 :
185

19. Genetic Recombination and Linkage
Morgan determined that
Genes that are close together on the same chromosome are linked and do not assort independently
Unlinked genes are either on separate chromosomes or are far apart on the same chromosome and assort independently
Parents
in testcross
b+ vg+
b vg
b+ vg+
b vg
b vg
Most
offspring X or

20. Recombination of Unlinked Genes: Independent Assortment of Chromosomes
Recombinant offspring: are those that show new combinations of the parental traits
When 50% of all offspring are recombinants
Geneticists say that there is a 50% frequency of recombination
Gametes from green-
wrinkled homozygous
recessive parent (yyrr)
Gametes from yellow-round
heterozygous parent (YyRr)
Parental-
type offspring
Recombinant
offspring
YyRr
yyrr
Yyrr
yyRr YR yr Yr yR

21. Recombination of Linked Genes: Crossing Over
Morgan discovered that genes can be linked
But due to the appearance of recombinant phenotypes, the linkage appeared incomplete
Morgan proposed that
Some process must occasionally break the physical connection between genes on the same chromosome
Crossing over of homologous chromosomes was the mechanism

22. Animation: Crossing Over
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23. Recombination of Linked Genes: Crossing Over
Linked genes exhibit recombination frequencies less than 50%
Figure 15.6
Testcross
parents
Gray body,
normal wings
(F1 dihybrid) b+
vg+ b vg
Replication of
chromosomes
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
Meiosis II: Segregation
of chromatids produces
recombinant gametes
with the new allele 
Recombinant
chromosome
b+vg+
b   vg
b+ vg
b vg+
b vg
Sperm
Meiosis I and II:
Even if crossing over
occurs, no new allele
combinations are
produced.
Ova
Gametes
offspring
b+  vg+
b   vg
b+   vg
b   vg+
965
Wild type
(gray-normal)
b  vg
b  vg+
944
Black-
vestigial
206
Gray-
185
normal
Recombination
frequency =
391 recombinants
2,300 total offspring
100 = 17%
Parental-type offspring
Recombinant offspring
Black body, vestigial wings (double mutant)

24. Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry
Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome
Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

25. Recombination frequencies
A linkage map is a genetic map of a chromosome based on recombination frequencies
Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency
Map units indicate relative distance and order, not precise locations of genes
Chromosome
Recombination frequencies 9%
9.5%
17% b cn vg

26. Cytogenetic maps indicate the positions of genes with respect to chromosomal features
Mutant phenotypes
Short
aristae
Maroon
eyes
Black body
Cinnabar
Vestigial
wings
Down-
curved
16.5
48.5
104.5
Long
(appendages
on head)
Red
Gray
body
Normal
Wild-type phenotypes
Brown
57.5
67.0
75.5
Figure A partial genetic (linkage) map of a Drosophila chromosome.

27. Nondisjunction of sister chromatids in meiosis II
Concept 12.4: Alterations of chromosome number or structure cause some genetic disorders
Large-scale chromosomal alterations often lead to spontaneous abortions or cause a variety of developmental disorders
Non-disjunction → aneuploidy
Meiosis I
Nondisjunction
Meiosis II
Gametes
n + 1
n  1
n – 1
n –1 n
Number of chromosomes
Nondisjunction of homologous
chromosomes in meiosis I
Nondisjunction of sister
chromatids in meiosis II
(a)
(b)
Pairs of homologous chromosomes do not separate normally during meiosis
Gametes contain two copies or no copies of a particular chromosome

28. Abnormal Chromosome Number
Aneuploidy
Results from the fertilization of gametes in which nondisjunction occurred
Is a condition in which offspring have an abnormal number of a particular chromosome
Trisomic: zygote has three copies of a particular chromosome
Monosomic: zygote has only one copy of a particular chromosome
Polyploidy: a condition in which there are more than two complete sets of chromosomes in an organism
More common in plants than animals

29. Alterations of Chromosome Structure
(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 nonhomologous chromosome. A B C D E F G H M N O P Q R
Breakage of a chromosome can lead to four types of changes in chromosome structure

30. Human Disorders Due to Chromosomal Alterations
Alterations of chromosome number and structure are associated with a number of serious human disorders
Down syndrome
Is usually the result of an extra chromosome 21, trisomy 21
Figure 15.15

31. 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
About one in every 1,000 males is born with an extra Y chromosome (XYY) and does not exhibit any defined syndrome
Females with trisomy X (XXX) have no unusual physical features except being slightly taller than average
Monosomy X, called Turner syndrome, produces X0 females, who are sterile
It is the only known viable monosomy in humans

32. Disorders Caused by Structurally Altered Chromosomes
Cri du chat is a disorder caused by a deletion in a chromosome (mentally retarded and typically die in infancy)
Certain cancers are caused by translocations of chromosomes (e.g. chronic myeloginous lukemia)
Normal chromosome 9
Reciprocal
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Translocated chromosome 22

33. You should now be able to:
Explain the chromosomal theory of inheritance and its discovery
Explain why sex-linked diseases are more common in human males than females
Distinguish between sex-linked genes and linked genes
Explain how meiosis accounts for recombinant phenotypes
Explain how linkage maps are constructed

34. Explain how nondisjunction can lead to aneuploidy
Define trisomy, triploidy, and polyploidy
Distinguish among deletions, duplications, inversions, and translocations