Overview: Locating Genes Along Chromosomes



Mendel’s “hereditary factors” were genes
Today we can show 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
Figure 15.1
CONCEPT 15.1: MENDELIAN
INHERITANCE HAS ITS PHYSICAL
BASIS IN THE BEHAVIOR OF
CHROMOSOMES
P Generation
Yellow-round
seeds (YYRR)
Mendel and Meiosis
Y
Y
Green-wrinkled
seeds (yyrr)
ry

R R
r
y
Meiosis
Fertilization
y
R Y
Gametes
r
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation
R
y
r
Y
R
r
Y
y
Meiosis
LAW OF SEGREGATION
The two alleles for each
gene separate during
gamete formation.
r
R
r
R
Y
y
LAW OF INDEPENDENT
ASSORTMENT Alleles of genes
on nonhomologous chromosomes
assort independently during
gamete formation.
Metaphase I
Y
y
1
1
R
r
Y
y
r
R
Y
y
Anaphase I
R
r
Y
y
r
R
Y
y
2
2
Gametes
R
R
1/
4
YR
F2 Generation
3
y
Y
Y
Fertilization recombines
the R and r alleles at
random.
Metaphase II
r
1/
4
Y
Y
y
r
r
r
1/
yr
4
y
y
R
R
1/
Yr
4
yR
An F1  F1 cross-fertilization
3
9
:3
:3
:1
Fertilization results in the
9:3:3:1 phenotypic ratio
in the F2 generation.
Mendel and Meiosis
P Generation
Yellow-round
seeds (YYRR)
Y
Y
R R
r

y
y
r
Meiosis
Fertilization
Gametes
R Y
y
r
Green-wrinkled
seeds (yyrr)
Figure 15.2b
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation
R
y
r
R
y
r
Y
Y
LAW OF INDEPENDENT
ASSORTMENT Alleles of
genes on nonhomologous
chromosomes assort
independently during gamete
formation.
Meiosis
LAW OF SEGREGATION
The two alleles for each
gene separate during
gamete formation.
r
R
Y
y
r
R
Metaphase I
y
Y
1
1
R
r
r
R
Y
y
Anaphase I
Y
y
r
R
2
y
Y
Y
R
R
1/
4
YR
r
1/
4
yr
y
Y
Y
Y
y
r
R
2
y
Y
Gametes
r
Metaphase
II
r
r
1/
4
Yr
y
y
R
R
1/
4
yR
Mendel and Meiosis
LAW OF INDEPENDENT
ASSORTMENT
LAW OF SEGREGATION
F2 Generation
3 Fertilization
recombines the
R and r alleles
at random.
An F1  F1 cross-fertilization
9
:3
:3
:1
3 Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
Morgan’s Experimental Evidence for Mendel
The first solid evidence associating a specific
gene with a specific chromosome came from
Thomas Hunt Morgan, an embryologist
 Morgan’s experiments with fruit flies provided
convincing evidence that chromosomes are the
location of Mendel’s heritable factors

Morgan’s Choice of Experimental Organism

Several characteristics make fruit flies a
convenient organism for genetic studies
◦ They produce many offspring
◦ A generation can be bred every two weeks
◦ They have only four pairs of chromosomes

Morgan noted  Traits alternative
wild type, or
to the wild type
normal,
are called mutant
phenotypes that phenotypes
were common in
the fly populations
Figure 15.4
EXPERIMENT
P
Generation
F1
Generation
All offspring
had red eyes.
RESULTS
The F2 generation showed the 3:1
red:white eye ratio, but only males
had white eyes
F2
Generation
CONCLUSION
P
Generation
X
X
w
X
Y
w
w
Eggs
F1
Generation
w
w
w
Sperm
w
w
w
Eggs
F2
Generation
The F1 generation all had red eyes
w
Sperm
w
w
w
w
w
w
w
Morgan determined that the
white-eyed mutant allele
must be located on the X
chromosome
EXPERIMENT
P
Generation
F1
Generation
RESULTS
F2
Generation
All offspring
had red eyes.
CONCLUSION
P
Generation
X
X
w
X
Y
w
w
Eggs
F1
Generation
Sperm
w
w
w
w
w
Eggs
F2
Generation
w
w
w
Sperm
w
w
w
w
w
w
In humans and some other animals, there is a chromosomal
basis of sex determination
CONCEPT 15.2: SEX-LINKED
GENES EXHIBIT UNIQUE
PATTERNS OF INHERITANCE
The Chromosomal Basis of Sex
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 codes
for a protein that directs the
development of male
anatomical features

X
Y
Sex
Determination
Systems
Human males are XY
Human females are XX
Other organisms use
different systems!
44 
XY
44 
XX
Parents
22 
22 
X or Y
22 
X
Sperm
Egg
44 
XX
or
44 
XY
(a) The X-Y system Zygotes (offspring)
22 
XX
22 
X
76 
ZW
76 
ZZ
32
(Diploid)
16
(Haploid)
(b) The X-0 system
(c) The Z-W system
(d) The haplo-diploid system
Figure 15.6a
44 
XY
44 
XX
Parents
22 
X
Egg
22 
22 
or
X
Y
Sperm
44 
XX
or
44 
XY
Zygotes (offspring)
(a) The X-Y system
22 
XX
(b) The X-0 system
22 
X
Figure 15.6b
76 
ZW
76 
ZZ
32
16
(Diploid)
(Haploid)
(c) The Z-W system
(d) The haplo-diploid system
Sex-Linkage
A gene that is located on either sex
chromosome is called a sex-linked gene
 Genes on the Y = Y-linked genes; there are few
of these
 Genes on the X = X-linked genes

X-linked Inheritance
X chromosomes code for
many genes not related to
sex

Some disorders caused by recessive alleles on
the X chromosome in humans
◦ Color blindness (mostly X-linked)
◦ Duchenne muscular dystrophy
◦ Hemophilia
Transmitting X-linked genes: Colorblindness
XNXN
Sperm Xn
Sperm XN
Y
XNY
XNXn
Sperm Xn
Y
XnY
Y
Eggs XN
XNXn XNY
Eggs XN
XNXN XNY
Eggs XN
XNXn XNY
XN
XNXn XNY
Xn
XNXn XnY
Xn
XnXn XnY
(a)

XNXn
XnY
(b)
(c)
For a recessive X-linked trait to be expressed
◦ A female needs two copies of the allele (homozygous)
◦ A male needs only one copy of the allele (hemizygous)
 X-linked recessive disorders are much more common
in males than in females
X Inactivation in Female Mammals

In mammalian females, one 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

Female Mosaics:
X Inactivation
X chromosomes
Allele for
orange fur
Early embryo:
Allele for
black fur
Two cell
populations
in adult cat:
Cell division and
X chromosome
inactivation
Active X
Inactive X
Active X
Black fur
Orange fur
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
CONCEPT 15.3: LINKED
GENES TEND TO BE
INHERITED TOGETHER
BECAUSE OF LOCATION
Gene Linkage
Linked genes assort together
How Linkage Affects Inheritance
Morgan did other experiments with fruit flies
to see how linkage affects inheritance of two
characters
 Morgan crossed flies that differed in traits of
body color and wing size

Wild type
(gray body, normal wings)
Double mutant
(black body,
vestigial wings)
Figure 15.9-1
EXPERIMENT
P Generation (homozygous)
Wild type
(gray body, normal wings)
Double mutant
(black body,
vestigial wings)
b b vg vg
b b vg vg
Figure 15.9-2
EXPERIMENT
P Generation (homozygous)
Wild type
(gray body, normal wings)
Double mutant
(black body,
vestigial wings)
b b vg vg
b b vg vg
F1 dihybrid
(wild type)
b b vg vg
TESTCROSS
Double mutant
b b vg vg
Figure 15.9-3
EXPERIMENT
P Generation (homozygous)
Wild type
(gray body, normal wings)
Double mutant
(black body,
vestigial 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
Wild type
Black(gray-normal) vestigial
b vg
Grayvestigial
b vg
Blacknormal
b vg
Sperm
b b vg vg
b b vg vg
b b vg vg
b b vg vg
Figure 15.9-4
EXPERIMENT
P Generation (homozygous)
Wild type
(gray body, normal wings)
Double mutant
(black body,
vestigial 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
Wild type
Black(gray-normal) vestigial
b vg
Blacknormal
Grayvestigial
b vg
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
:
0
:
0
965
:
944
:
206
:
185
RESULTS
F1 dihybrid female
and homozygous
recessive male
in testcross
b+ vg+
b vg
b vg
b vg
b+ vg+
b vg
Most offspring
or
b vg

b vg
Morgan found body color and wing size are
usually inherited together in specific
combinations (parental phenotypes)
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

Genetic Recombination and Linkage
Offspring with a
phenotype matching one
of the parental phenotypes
are called parental types
 Offspring with nonparental
phenotypes are called
recombinant types, or
recombinants
 A 50% frequency of
recombination is observed
for any two genes on
different chromosomes

Parental vs. Recombinant Phenotypes
Gametes from yellow-round
dihybrid parent (YyRr)
Gametes from greenwrinkled homozygous
recessive parent (yyrr)
YR
yr
Yr
yR
YyRr
yyrr
Yyrr
yyRr
yr
Parentaltype
offspring
Recombinant
offspring
Recombination of Linked Genes: Crossing Over
Morgan discovered that
genes can be linked, but
the linkage was
incomplete, because
some recombinant
phenotypes were
observed
 Some process must
occasionally break the
physical connection
between genes on the
same chromosome

Crossing Over
and
Recombination
Black body, vestigial wings
(double mutant)
Gray body, normal wings
(F1 dihybrid)
Testcross
parents
b vg
b vg
b vg
b vg
Replication
of chromosomes
Meiosis I
Replication
of chromosomes
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Meiosis I and II
Recombinant chromosomes
bring alleles together in new
combinations in gametes
b vg
b vg
Recombinant
chromosomes
bvg
Genetic variation drives
evolution!
b vg
Meiosis II
b vg
b vg
b vg
944
Blackvestigial
206
Grayvestigial
185
Blacknormal
Eggs
Testcross
offspring
965
Wild type
(gray-normal)
b vg
b vg
b vg
b vg
b
b vg
b vg
b vg
Parental-type offspring
b vg
vg
Recombinant offspring
391 recombinants
Recombination

 100  17%
frequency
2,300 total offspring
Sperm
Mapping Distance Between Genes Using Recombination Data
Recombination
frequencies
9%
Chromosome
1 map unit = 1%
recombination
frequency
9.5%
17%
b
cn
vg
A linkage map is a genetic map of a chromosome based on
recombination frequencies
The farther apart two genes are, the higher the probability crossover
will occur and therefore the higher the recombination frequency
Distances between genes can be expressed as map units.
Genes that are far apart on the same chromosome
can have a recombination frequency near 50%
 Such genes are physically linked, but genetically
unlinked, and behave as if found on different
chromosomes

Genetic Linkage Map: Cytogenic Mapping
Mutant phenotypes
Short
aristae
0
Long aristae
(appendages
on head)
Black
body
Cinnabar Vestigial
eyes
wings
48.5 57.5
Gray
body
Red
eyes
Brown
eyes
67.0
104.5
Normal
wings
Red
eyes
Wild-type phenotypes
Large-scale chromosomal alterations in humans and other
mammals often lead to spontaneous abortions
(miscarriages) or cause a variety of developmental
disorders
Plants tolerate such genetic changes better than animals do
Concept 15.4: Alterations of
chromosome number or
structure cause some genetic
disorders
Chromosomal Changes and Disorders
Abnormal
Chromosome
Number
Alteration of
Chromosome
Structure
Abnormal
Chromosome
Number
Meiosis I
Nondisjunction
In nondisjunction, pairs of homologous chromosomes do not
separate normally during meiosis
Abnormal
Chromosome
Number
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
As a result, one gamete receives two of the same type of
chromosome, and another gamete receives no copy
Abnormal
Chromosome
Number
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n1 n1 n1 n1
n1 n1
n
n
Number of chromosomes
(a) Nondisjunction of homologous chromosomes in
meiosis I
(b) Nondisjunction of sister
chromatids in meiosis II
Aneuploidy


The fertilization of
gametes in which
nondisjunction
occurred
Offspring with this
condition have an
abnormal number of
a particular
chromosome
A monosomic zygote has only one copy of
a particular chromosome
 A trisomic zygote has three copies of a
particular chromosome

Polyploidy: More than 2 Sets of Chromosomes
◦ Triploidy (3n) is three sets of chromosomes
◦ Tetraploidy (4n) is four sets of chromosomes
Polyploidy is common in plants, but not
animals
 Polyploids are more normal in appearance
than aneuploids

Triploidy (3n)
Hexaploidy (6n)
Octoploidy (8n)
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
Alterations of Chromosome Structure
(a) Deletion
A B C D E
F G H
A deletion removes a chromosomal segment.
A B C E
F G H
(b) Duplication
A B C D E
F G H
A duplication repeats a segment.
A B C B C D E
F G H
Alterations of Chromosome Structure
(c) Inversion
A B C D E
F G H
An inversion reverses a segment within a
chromosome.
A D C B E
F G H
(d) Translocation
A B C D E
F G H
M N O P Q
R
A translocation moves a segment from one
chromosome to a nonhomologous chromosome.
M N O C D E
F G H
A B P Q
R
Human Disorders Due to
Chromosomal Alterations
Most mammalian aneuploidy are lethal but some
survive to birth and beyond
 These surviving individuals have a set of symptoms,
or syndrome.

Down Syndrome (Trisomy 21)
Down syndrome is an aneuploid condition that
results from three copies of chromosome 21
 It affects about 1in 700 children born in the US
 The frequency of Down syndrome increases with
the age of the mother

Aneuploidy of Sex Chromosomes
Syndrome
Genotype
Occurrence
Symptoms
Klinefelter
Syndrome
XXY
1/500 ~ 1/1000
XYY Syndrome
XYY
1/1000
• Normal sexual
development
• Taller than average
• Increased aggression
Turner Syndrome
(Monosomy X)
XO
1/2500
• Only viable
monosomy in
humans
• Sex organs do not
develop; sterile
Trisomy X
XXX
1/1000
• Learning disabled
• Fertile
• Slightly taller
• Underdeveloped
testes
• Male is sterile
• Some secondary
female
characteristics
Turner’s Syndrome
Klinefelter Syndrome
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
retarded and has a catlike
cry; individuals usually die
in infancy or early
childhood

CML: Chronic
Myelogenous Leukemia
CML caused by
translocations of
chromosomes
Normal chromosome 9
Normal chromosome 22
Reciprocal
translocation
Translocated chromosome 9
Translocated chromosome 22
(Philadelphia chromosome)
Concept 15.5: Some inheritance patterns are
exceptions to standard Mendelian inheritance



There are two normal exceptions to
Mendelian genetics
One exception involves genes located in the
nucleus, and the other exception involves
genes located outside the nucleus
In both cases, the sex of the parent
contributing an allele is a factor in the
pattern of inheritance
Genomic Imprinting
For a few mammalian traits, the phenotype
depends on which parent passed along the
alleles for those traits
 Such variation in phenotype is called
genomic imprinting
 Genomic imprinting involves the silencing of
certain genes that are “stamped” with an
imprint during gamete production

Figure 15.17
Paternal
chromosome
Maternal
chromosome
Normal Igf2 allele
is expressed.
Normal Igf2 allele
is not expressed.
Normal-sized mouse
(wild type)
(a) Homozygote
Mutant Igf2 allele
inherited from mother
Mutant Igf2 allele
inherited from father
Normal-sized mouse (wild type)
Dwarf mouse (mutant)
Normal Igf2 allele
is expressed.
Mutant Igf2 allele
is expressed.
Mutant Igf2 allele
is not expressed.
(b) Heterozygotes
Normal Igf2 allele
is not expressed.
It appears that imprinting is the result of the
methylation (addition of —CH3) of cysteine
nucleotides
 Genomic imprinting is thought to affect only a
small fraction of mammalian genes
 Most imprinted genes are critical for
embryonic development

Inheritance of Organelle Genes
Extranuclear genes (or cytoplasmic genes) are
found in organelles in the cytoplasm
 Mitochondria, chloroplasts, and 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 of extranuclear genes came
from studies on the inheritance of yellow or
white patches on leaves of an otherwise green
plant

Figure 15.18

Some defects in mitochondrial genes prevent
cells from making enough ATP and result in
diseases that affect the muscular and nervous
systems
◦ For example, mitochondrial myopathy and
Leber’s hereditary optic neuropathy
Figure 15.UN03
Sperm
P generation
gametes
D
C
B
A
c
b
a
d
E
F
e
f
The alleles of unlinked
genes are either on
separate chromosomes
(such as d and e)
or so far apart on the
same chromosome
(c and f) that they
assort independently.
This F1 cell has 2n  6 chromosomes and is heterozygous for all
six genes shown (AaBbCcDdEeFf).
Red  maternal; blue  paternal.
A
Each chromosome has
hundreds or thousands
of genes. Four (A, B, C,
F) are shown on this one.
Egg
F
D
e
C
B
d
E
c ba
f
Genes on the same chromosome whose alleles are so
close together that they do
not assort independently
(such as a, b, and c) are said
to be genetically linked.
Figure 15.UN04
Figure 15.UN05
Figure 15.UN06