CHAPTER 4

SEX DETERMINATION AND

SEX LINKAGE
 LESSON LEARNING OUTCOME
UPON COMPLETION OF THIS LECTURE, STUDENT SHOUD BE ABLE TO

• Understand that Sex Is Determined by a

Number of Different Mechanisms
• Understand the Concept that Sex-Linked
Characteristics Are Determined by Genes on
the Sex Chromosomes.
• State and Explain the concept of Dosage
Compensation and the LYON HYPOTHESIS
• Describe how some phenotypes are
influenced by individual’s Sex
 Sex Determination
1. Mechanisms of sex determination
include:

a. Genotypic sex determination, in which sex is

governed by genotype.
b. Environmental sex determination, in which
sex is governed by internal and external
environmental conditions.
MONOECIOUS VS. DIOECIOUS
MONOECIOUS DIOECIOUS
In Greek that means "one house" so this In Greek that means "two houses" so this
means both sexes live in the same "house" means each sex lives in a different "house"
or individual. or individual.
Both male and female sex organs in the same Dioecious organisms come in two sexes,
individual. male and female.
Produce both male and female gametes - Each individual will produce only one type of
sperm and egg, respectively. gamete.

Example: Majority of plants (peas, maize, Example: Most animals (homo sapiens) and
etc.) and some animals (earthworms, hydra) some plants (such as, oak trees and date
palms)
Occasionally the word hermaphrodite is used
to mean the same thing
 SEX DETERMINATION
• In many animal species, chromosomes play a role in sex determination
• DIFFERENT MECHANISM OF SEX DETERMINATION IN ANIMALS: (a) X-Y system in
mammals, (b) X-O system in certain insects, (c) The Z-W system in birds, (d) The
haplo-diploid system in bees
THE X-Y SYSTEM
IN MAMMALS
• Humans have 46 chromosomes
– 44 autosomes
– 2 sex chromosomes
• Males contain one X and one Y chromosome
– They are termed heterogametic:
produce two kinds of gametes with
respect to sex chromosomes (X or Y)
• Females have two X chromosomes
– They are termed homogametic:
produce gametes with only one kind of
sex chromosome (X)
• The Y chromosome determines maleness
THE X-O SYSTEM IN
CERTAIN INSECTS
• In some insects,
– Males are XO and females are XX
• In other insects (fruit fly, for example)
– Males are XY and females are XX XO SYSTEM
O indicating
• The Y chromosome does NOT determines absence of a
maleness second sex
• Rather, it is the ratio between the X chromosome
chromosomes and the number of sets of
autosomes (X/A) determine sex!
• If a grasshopper has one X chromosome
and is diploid for the autosomes (2n), the
ratio is ½ or 0.5 MALE
– If X/A = 0.5, it becomes a male
– If X/A = 1.0, it becomes a female
 • The Y chromosome in
Drosophila plays no role in sex
Fruit fly (Drosophila melanogaster) determination.

• The sex of the fly is

determined by the ratio of X
chromosome to sets of
autosomes (X:A).

• In female Drosophila the ratio

is 1:1, there are two X
chromosomes and two copies
of each autosomes (ratio of X’s
to A’ was 1.0 or greater).

• In male Drosophila the ratio is

1:2, only one X chromosome
and two copies of each
autosomes (the ratio is 0.5 or
less).
Figure 1.0: Drosophila melanogaster
(fruit fly), an organism used extensively
in genetics experiments.

(a) Female (left) and male (right).

Top, adult flies; bottom, drawings of
ventral abdominal surface to show
differences in genitalia.

(b) Chromosomes of Drosophila

melanogaster diagrammed to show
their morphological differences.

A female (left) has four pairs of

chromosomes in her somatic cells,
including a pair of X chromosomes.

The only difference in the male is an XY

pair of sex chromosomes instead of
two X’s.
Figure 1.1 Inheritance pattern of X and Y chromosomes in organisms where the
female is XX and the male is XY. (a) Production of the F1 generation. (b) Production of
the F2 generation.
THE X-O SYSTEM
IN NEMATODE - MONOECIOUS

The small nematode, C. elegans, exhibits a

similar pattern, except that worms with two X
chromosomes are true hermaphrodites (with
male and female in the same individual),
while those with only one X chromosome are
true males.
 • The sex chromosomes are
THE Z-W SYSTEM designated Z and W to
distinguish them from the
IN BIRDS X and Y chromosomes of
mammals

In birds and some reptiles, as well as moths, the male

is homogametic (ZZ) and the female heterogametic
(ZW).

W chromosome
determines femaleness
THE HAPLOID-DIPLOID SYSTEM
IN BEES In bees, the sex of a honeybee is
determined by whether the egg is
fertilized or not (parthenogenesis)
• Males are known as the
drones
– They are haploid
– Produced from unfertilized eggs
• Females include the worker
bees and queen bees
– They are diploid
– Produced from fertilized eggs
 SEX DETERMINATION BY
ENVIRONMENTAL FACTORS
1. Among some DIOECIOUS TAXA - Such as some
species of fish, alligators and sea turtles.
2. sex is determined not by genetics but by the
environment.
3. Concentrations of hormones or differences in
temperature will cause the developing embryo
to develop as either a male or a female.

Temperature-dependent sex determination in three reptile species: the

American alligator ( Alligator mississippiensis), the red-eared slider turtle
(Trachemys scripta elegans), and the alligator snapping turtle (Macroclemys
temminckii).
Crocodiles, Most Turtles and Some Lizards

• Due to incubation temperature of eggs

• 3 distinct patterns
– CASE 1: low temps – 100% female; high temps – 100% male
– CASE 2: opposite of above
– CASE 3: low and high temps – 100% female; intermediate temp
– 100% male
Environmental sex determination

eg. American alligator (Alligator mississippiensis)

- fertilized eggs are incubated at 33°C – 100% male

- a few degrees below 33°C – nearly all female
- above 33°C – 95% females
A Human Karyotype
• We have 46 chromosomes, or
23 pairs.

• 44 of them are called

autosomes and are numbered
1 through 22. Chromosome 1
is the longest, 22 is the
shortest.

• The other 2 chromosomes are

the sex chromosomes:
the X chromosome and the Y
chromosome.

• Males have and X and a Y;

females have 2 X’s: XY vs. XX.
SEX DETERMINATION
IN HUMAN
• The basic rule: if the Y
chromosome is present,
the person is male. If
absent, the person is
female.

• In meiosis, the X and Y

chromosomes separate
and go into different
sperm cells: ½ the sperm
carry the X and the other
half carry the Y.

• All eggs have one of the

mother’s X chromosomes,
so when they are
fertilized, ½ of the zygotes
are XX (female), and ½
are XY (male).
CHROMOSOME Y
DETERMINE MALENESS
• The Y chromosome has the main
sex-determining gene on it, called SRY
(sex-determining region Y) .

• SRY gene is located just outside the

pseudoautosomal region in the short
arm of the Y chromosome

• Testis- determining factor (TDF) is a

product of this SRY gene
• Pseudoautosomal regions (PARS) –
Regions on Y chromosome that share
homology with X chromosome.
• These regions synapse/located on ends
of Y chromosome.

• The human Y chromosome contains 86 genes,

which code for only 23 distinct proteins.
Traits that are inherited via the Y
chromosome are called holandric traits.
The process of SRY Gene

sex Testes Development

determination Testosterone Production

in MALE Androgen Receptor on Embryonic Tissues

Male Characteristics

1. SRY gene produced TDF. TDF induces the medulla of the embryonic gonads to
develop into testes
2. After the testes have formed, TESTOSTERONE secretions initiates the development
of male sexual characteristic
3. Testosterone is a hormone that binds to receptors in many kinds of cell
4. Once bound, the hormone-receptor complex transmit a signal to the nucleus
instructing the cell in how to differentiate
5. The concerted differentiation of many types of cells leads to the development of
distinctly male characteristics such as heavy musculature, beard, and deep voice
Sex
Determination in
Female
• In the absence of a Y
chromosome, NO SRY
gene NO TDF is
produced.

• The lack of TDF allows the

cortex of the embryonic
gonads to develop into
ovaries.

• Ovaries secrete estrogen

and causes development
in the female pattern.
Male Egg with X sex chromosome Female
 Male Egg with X sex chromosome Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome
 Male Egg with X sex chromosome Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex
 Male Egg with X sex chromosome Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
and testes
 Male Egg with X sex chromosome Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
and testes

Testes secrete masculinizing

hormones, including No androgens secreted
testosterone, a potent androgen
 Male Egg with X sex chromosome Female

Fertilized by Fertilized by
Sperm with Y chromosome Sperm with X chromosome

Genetic
Embryo with XY sex chromosomes Embryo with XX sex chromosomes
sex

Sex-determining region of
No Y chromosome, so no
the Y chromosome (SRY)
Gonadal SRY. With no masculinizing
brings about development
sex influence, undifferentiated
of undifferentiated gonads
gonads develop into ovaries
into testes

Testes secrete masculinizing

hormones, including No androgens secreted
testosterone, a potent androgen

In presence of testicular With no masculinizing

hormones, undifferentiated hormones, undifferentiated
Phenotypic
reproductive tract and reproductive tract and
sex
external genitalia develop external genitalia develop
along male lines along female lines
SEX LINKAGE
Transmission of Genes Located on
Human Sex Chromosomes
• Genes that are found on one of the
two types of sex chromosomes but
not on both are termed sex-linked
– Indeed, sex-linked and X-linked
tend to be used synonymously

• Males have only one copy of the X

chromosome
– They are said to be hemizygous
for their X-linked genes
Transmission of Genes Located on
Human Sex Chromosomes
• The X and Y chromosomes also
Contains many
contain short regions of X-linked genes
homology at one end
– These promote the
necessary pairing of the
two chromosomes in
meiosis I of
spermatogenesis
Involved in
• The few genes found in this antibody
homologous region follow a production
pseudoautosomal pattern of
inheritance
Y-linked gene
– Their inheritance pattern is
Necessary for
the same as that of a gene
Follows a pseudoautosomal proper male
found on an autosome development
pattern of inheritance
 Sex linkage explained
• Thomas Hunt Morgan in The Fly
Room!
(Columbia University 1910)
• Fruit Flies (Drosophila melanogaster)
 Symbols for X-linked
Genes
• X and Y in genotype
• X-linked genes as
superscripts on X

• Example:
• Xw+ or X+ wild type
red-eyed fly
• Xw mutated
white-eyed fly
 Sex Linkage in HEMIZYGOTE
An organism
that carry only
Drosophila ONE COPY of a
gene
mutated gene
is X-linked!
1. Morgan (1910) found a mutant
white-eyed male fly, and used it in
a series of experiments that
showed a gene for eye color
located on the X chromosome.

2. First, he crossed the white-eyed

male with a wild-type (red-eyed)
female. All F1 flies had red eyes.
Therefore, the white-eyed trait is
recessive.

3. Next, F1 were interbred.

 Sex Linkage in
Drosophila
4. They produced an F2 with:
All of the
2,459 red-eyed females daughters,
1,011 red-eyed males but only
0 white-eyed females half of the
782 white-eyed males sons had
red eyes
5. The recessive number is too small to fit
Mendelian ratios.

6. Another peculiar segregation pattern in F2:

All of the F2 white-eyed flies were male.

This pattern suggested that the

inheritance of eye color was
linked to the sex chromosome
 Sex Linkage in Drosophila
Interpreting the Data
■ The first cross yielded NO white-eyed females in the F2
generation
■ These results indicate that the eye color alleles are

located on the X chromosome, BUT not on the Y!

■ Morgan also proposed that the white and the red

phenotypes were due to TWO different alleles, a

mutant allele denoted as w and a wild type allele
denoted w+

■ Genes that are physically located on the X chromosome

are called X-linked genes or X-linked alleles
A testcross between a white-eyed male 1. This cross produced
and a red-eyed female from F1 generation red-eyed males and
females, and white-eyed
males and females in
approximately equal
numbers.

2. Predicts a 1:1:1:1 ratio

3. The observed data are

129:132:88:86, which is a
ratio of 1.5:1.5:1:1.

4. Morgan concluded that

R (red eye color) and X
(a sex factor that is
present in two copies in
the female) are combined
and have never existed
apart.
QUESTION:

In Drosophila forked bristles (f) is an X-linked trait. Straight

bristles (F) is dominant. Vestigial wings (v) is autosomal
recessive, and its wild type allele (V) is dominant. A male
with straight bristles and homozygous for normal wings is
crossed to a vestigial winged female that is heterozygous
at the bristles locus. Show the genotypes and phenotypes
of their offspring.

ANSWER:
SEX-LINKED TRAITS IN
HUMANS
CHARACTERISTICS OF SEX-LINKED
RECESSIVE INHERITANCE
X-LINKED RECESSIVE INHERITANCE
• Involving RECESSIVE ALLELES on
the X chromosome
• Most affected individuals are
male!! - HEMIZYGOUS
• Affected males result from
mother who are affected
(homozygous recessive).
Because male get their X from
their mother.
• Affected females come from
affected fathers and affected or
carrier mothers.
• females express it only if they
get a copy from both parents.
X-LINKED RECESSIVE
INHERITANCE
1. With a carrier mother,
1
a) ⁄2 of her sons will show the
trait and
1
b) ⁄2 will be free of the allele.

2. A carrier female crossed with a

normal male will have
1
a) ⁄2 carrier daughters and
1
b) ⁄2 normal daughters.
3. Example: Hemophilia, Color
blindness
CHARACTERISTICS OF SEX-LINKED RECESSIVE
INHERITANCE
1. Affected fathers transmit the recessive allele to all
daughters (who are therefore carriers), and to none of
their sons.
JUSTIFICATION?
Affected fathers are HEMIZYGOUS! Their genotype is XhY. Every daughter
MUST receive X chromosome that carry the recessive allele from the father
and every son will inherit Y chromosome from the father.

2. Father-to-son transmission of X-linked alleles

generally does not occur.

JUSTIFICATION?
Every son will ONLY inherit Y chromosome from the father.
CHARACTERISTICS OF SEX-LINKED RECESSIVE
INHERITANCE

3. Many more males than females exhibit the trait.

JUSTIFICATION
MALES are HEMIZYGOUS! Their genotype is XhY. They only need ONE COPY
OF THE RECESSIVE allele to express the phenotype. Females need to be
homozygous recessive to express the phenotype.

4. All sons of affected (homozygous recessive) mothers

are expected to show the trait.

JUSTIFICATION
Because all sons will receive one X chromosome that carry the recessive
allele from the mother and Y chromosome from the father. Because they
are HEMIZYGOUS, they will be affected!
EXAMPLE OF X-LINKED RECESSIVE INHERITANCE
HEMOPHILIA
Figure 1.0: X-linked recessive inheritance (a) Painting of Queen
Victoria as a young woman. (b) Pedigree of Queen Victoria (III-2)
and her descendants, showing the inheritance of hemophilia.
QUEEN VICTORIA HAEMOPHILIA FAMILY LINEAGE
1. Queen Victoria of England was a
carrier of the gene for hemophilia.
2. She passed the harmful allele for this
X-linked trait on to one of her four
sons and at least two of her five
daughters.
3. Her son Leopold had the disease and
died at age 30, while her daughters
were only carriers.
4. As a result of marrying into other
European royal families, the
princesses Alice and Beatrice spread
hemophilia to Russia, Germany, and
Spain.
5. By the early 20th century, ten of
Victoria’s descendents had
hemophilia. All of them were men.
EXAMPLE OF X-LINKED
RECESSIVE INHERITANCE
DUCHENNE
MUSCULAR
DYSTROPHY

Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a

protein in the muscles).

MD is characterized by gradual irreversible wasting of skeletal muscle. It is an

X-linked trait most often passed on to sons by their mothers.

The most common form, begins to weaken the legs of boys by age 3 and
inevitably gets worse with each passing year.
Inheritance of Duchenne Muscular Dystrophy
EXAMPLE OF X-LINKED RECESSIVE INHERITANCE
RED GREEN COLOR-BLINDNESS

• For the condition to arise in females

requires the homozygous recessive
genotype and as the recessive allele
is relatively rare in the population
this is unlikely to occur.
• The heterozygous females are not
affected but are capable of passing
the recessive allele to their offspring.
They are termed carriers.
• Normal sight is dominant over red
green colour blindness.
• XB for normal sight allele
• Xb for colour blindness allele
Normal vision Red green color
blindness

Another form of red

green colorblindness
parents phenotype normal female colour blind male
genotype X BX B X bY

gametes XB XB Xb Y

Offsprings Male gametes

Female gametes Xb Y
XB XB Xb XBY
XB XB Xb XBY

Ratio: 100% normal sighted carrier female (XB Xb)

100% normal sighted male (XBY)
parents phenotype carrier female colour blind male
genotype X BX b X bY

gametes XB Xb Xb Y

Offspring Male gametes

Female gametes Xb Y
XB XB X b XB Y
Xb Xb X b Xb Y

Ratio: 50% normal sighted carrier female (XB Xb)

50% colour blind female (Xb Xb)
50% normal sighted male (XBY)
50% colour blind male (XbY)
Female carrier* mates with normal male
Sper *of x-linked
FxM m Recessive disease
X AX a X AY XA Y

XA
F M
X AX A X AY
normal normal
Egg
s
Xa
F M
X AX a X aY
carrier affected

• Half* her daughters will be carriers

• Half* her sons will be affected
*on average
CHARACTERISTICS OF SEX-LINKED
DOMINANT INHERITANCE
 X-LINKED DOMINANT INHERITANCE
Involving DOMINANT ALLELE on the X
chromosome

Only a few X-linked dominants are known.

Examples include:

1.Hereditary enamel hypoplasia (faulty and

discolored tooth enamel).
2.Webbing to the tips of the toes.

Patterns of inheritance are the same as

X-linked recessives, except that
heterozygous females show the trait
(although often in a milder form).
CHARACTERISTICS OF SEX-LINKED DOMINANT
INHERITANCE

1. The trait is never passed from father to son.

JUSTIFICATION
Every son will ONLY inherit Y chromosome from the father which
doesn’t carry the dominant allele

2. All daughters of an affected male and a normal female are

affected. All sons of an affected male and a normal female
are normal.
JUSTIFICATION
Affected male will PASS one X-linked mutated dominant allele to the
daughter. Since the allele is dominant the daughter will be affected!

Every son will ONLY inherit Y chromosome from the father which
doesn’t carry the dominant allele.
CHARACTERISTICS OF SEX-LINKED DOMINANT
INHERITANCE

3. Males are usually more severely affected than females. The

trait may be lethal in males.
JUSTIFICATION
Because males are HEMIZYGOUS.

4. In the general population, females are more likely to be

affected than males, even if the disease is not lethal in
males.
JUSTIFICATION
FEMALES will always receive X chromosome from each of the parent. So
the chances of the females to receive the mutated dominant allele is
higher compare to males.
parents phenotype affected female normal male
genotype X BX b X bY

gametes XB Xb Xb Y

Offspring Male gametes

Female gametes Xb Y
XB XB X b XB Y
Xb Xb X b Xb Y

Matings of affected females(heterozygous)

Ratio: 50% affected female (XB Xb) and normal males produce 50% the sons
50% normal female (Xb Xb)
affected and 50% the daughters affected.
50% affected male (XBY)
50% normal male (XbY)
 X-linked dominant disease
Affected male mates with normal female
Sper
FxM m
X aX a X AY XA Y

Xa
F M
X aX A X aY
affected normal
Egg
s
Xa
F M
X aX A X aY
affected normal

• All his daughters will be affected

• None of his sons will be affected
 X-linked dominant disease
Affected female mates with normal male
Sper
FxM m
X AX a X aY Xa Y Work this out
for yourself

XA

Egg
s
Xa

• _______of her daughters will be _______

• _______of her sons will be ____________
EPIGENETIC INHERITANCE

Modification that occurs to a nuclear

gene or chromosome that alters gene
expression but is not permanent over
the course of many generation – do not
involve changes to the underlying DNA
sequence.
DOSAGE COMPENSATION COMPENSATE
=
EQUALIZATIO
• Gene dosage very important in mammalian N
species (not so true for plants)

– Correct number of chromosomes REMEMBER?

– Correct ratio of chromosomes/genes TRISOMY-13
TRISOMY 18
– Most abnormal karyotypes involving
autosomes lethal at early stage of
development
GENE DOSAGE
varies between
• How can sex chromosome variation (XX vs. XY) sexes in
mammals,
be tolerated—intended? because
– By DOSAGE COMPENSATION! females have
two copies of X
while males
have ONE only!
DOSAGE COMPENSATION
• Shouldn’t XX females produce twice the amount of X-linked gene
products as XY males?
• No, because XX females “compensate” by inactivating one of their X
chromosomes to make a single “dosage” of X-linked genes.

DEFINITION OF
DOSAGE COMPENSATION?

Hermann Muller, 1932

Dosage compensation refers to the phenomenon that the level of expression
of many genes on the sex chromosomes is similar in both sexes even
though males and females have a different complement of sex chromosomes.
WHAT IS THE MECHANISM OF
DOSAGE COMPENSATION?
EARLY IN DEVELOPMENT, gene
expression from the X chromosome
must be EQUALIZED to avoid death!
LYON HYPOTHESIS
In 1961, British geneticist, Mary F. Lyon published what has become known as Lyon Hypothesis.
She proposed that dosage compensation in mammals occurs by:
THE INACTIVATION of a SINGLE X CHROMOSOME in FEMALES

1. All but one X chromosome is inactivated in each somatic

(nonreproductive) cell. This inactivation occurs only when
there are at least TWO X chromosomes present.

2. This inactivation of X chromosome is random

for each cell.
LYON HYPOTHESIS cont.

3. Once inactivation of X occurs in an embryonic cell, the same X

chromosome will be inactivated in all cells that descend from
that embryonic cell INACTIVATION IS PERMANENT!

4. Inactivation of X chromosome occurs early in

embryonic development (about 16 days after
conception).
5. Either the maternal or paternal of X
chromosome can be inactivated

6. Inactivation of second X equalizes the

activity of X linked genes in males and
females
Dosage Compensation Mechanism
for X-Linked Genes in Mammals
• In mammals, female somatic cell nuclei contain
a Barr body (highly condensed chromatin)
while male nuclei do not (Figure 1).

• The Lyon hypothesis explains the phenomenon:

a. A Barr body is a condensed and (mostly)

inactivated X chromosome. (Murray Barr &
Ewart Bertram).
b. Lyonization of one chromosome leaves ONE
transcriptionally active X, equalizing gene dose
between the sexes.
(Figure 1) Inactivation of one of the two X chromosomes in females so that the
normal state for a cell is to have two active sets of autosomes and only one active X
chromosome. The other X chromosome is condensed and inactive and is visible as a
dark staining "Barr body" pushed against the nuclear membrane.
OCCURRENCE of BARR BODIES in various
human karyotypes
1. Lyonization allows extra sex
chromosomes to be tolerated
well. No such mechanism
exists for autosomes, and so
an extra autosome is usually
lethal.
2. During inactivation, the
chromosomal DNA becomes
highly compacted so that
most of the genes on the
inactivated X chromosome
cannot be expressed.
3. The number of Barr bodies is
the number of X
chromosomes minus one.
X chromosome inactivation occurs during the 1. In any one female cell the inactivated X
first few days of embryonic life chromosome may be either the paternal
(Xp) or maternal (Xm).

2. Which one is inactivated is a matter of

chance but once that X has been
inactivated in that cell, all that nucleus'
descendants (clones through mitosis) will
have the same inactive X chromosome.

3. X inactivation is randomly determined

but once it happens it's permanent.

4. Each cell's descendants contribute to the

overall body of the organism. Because
some cells have inactivated paternal Xs
and others have inactivated maternal Xs,
the embryo and the organism it becomes
is a mixture of two types of cells -
expressing different alleles.

5. We call such an organism, made of two

different cell "types", a MOSAIC
 Females Are Mosaics for X-Linked Genes
1. An X is randomly chosen in each cell for
inactivation early in development (in humans,
day 16 post-fertilization).

2. Descendants of that cell will have the

same X inactivated, making female
mammals genetic mosaics. Examples
are:

i. Calico cats, in which differing

descendant cells produce patches of
different color on the animal.
ii. Women heterozygous for an X-linked
allele responsible for sweat glands, who
have a mosaic of normal skin and patches
lacking sweat glands (anhidrotic ectodermal
displasia).
 GENOTYPES PHENOTYPES
Female XO X O Orange fur
cats
Calico cat (patches of black
? and orange fur)

XB X B Black fur
Male XO Y Orange fur
cats
XB Y Black fur
Genotype X BY X OY X BX B X OX O X BX O
Females Are Mosaics for X-Linked Genes
• Some cells express
the maternal X and
others express the
paternal X

• Cats heterozygous
for orange and
black gene must
carry two X
chromosomes Calico cats are always female
Anhidrotic ectodermal dysplasia
• X-linked recessive disorder in humans characterized by small/lack teeth,
no sweat glands and sparse body hair.

• It affects males and is inherited through female carriers.

• Female carriers – the irregular patches of skin lacking sweat glands

arose from skin precursor cells that inactivated the X chromosome with
the normal allele.

• Each cell’s descendants contribute to the

overall body of the organism.

• Some cells have inactivated paternal Xs and

others have inactivated maternal Xs

• The embryo and the organism becomes a

mixture of two types of cells - expressing
different alleles - MOSAIC
Dosage Compensation Mechanism for X-Linked
Genes in Drosophila melanogaster
THE HYPERACTIVATION of a SINGLE X CHROMOSOME in MALES

• In Drosophila, dosage compensation of

X-linked genes is achieved by an increase in
the activity of these genes in males.
• This phenomenon, called
HYPERACTIVATION, involves a complex of
different proteins that binds to many sites
on the X chromosome in males and triggers
a doubling of gene activity.
• When this protein complex does not bind, as
is the case in females, hyperactivation of
X-linked genes does not occur.
• In this way, total X-linked gene activity in
males and females is approximately
equalized.
SOME TRAITS ARE INFLUENCED
BY THE SEX OF THE INDIVIDUAL
SEX LIMITED AND
SEX INFLUENCED TRAITS
• There are two inheritance patterns expressed differently in the 2
sexes, but not controlled by alleles on sex chromosomes.

SEX LIMITED TRAITS SEX INFLUENCED TRAITS

Traits expressed in only ONE Traits appear in BOTH sexes but
sex, although the genes are occur in one sex more than the
present in both sexes. other.

Examples: in women, breast Example: Pattern or premature

and ovary formation and the baldness in human beings.
sperm production in men.
SEX LIMITED TRAITS
• Sex-limited traits appear in one sex but
not the other. Examples include:

i. Milk production in dairy cattle, where

both sexes have milk genes, but only
females express them.
ii. Horn formation in some sheep species,
where only males express the genes used
to produce horns.
iii. Facial hair distribution in humans.
 SEX INFLUENCED TRAITS
• Sex-influenced traits appear in both sexes, but the
sexes show either a difference in frequency of
occurrence or an altered relationship between
genotype and phenotype. Human examples
include:
1. Pattern baldness
2. Clubfoot (2;1).
SEX INFLUENCED TRAITS
EXAMPLE PATTERN OF BALDNESS
• Pattern baldness, controlled by an autosomal gene that is
dominant in males and recessive in females.
• A man needs only one allele (B) for the baldness trait to be
expressed, while a bald woman must be homozygous for the
trait (BB).
• This gene shows variable expressivity in:
(a) Age of onset.
(b) Site of baldness (crown or forehead).
(c) Degree of hair loss.

• The pattern baldness gene interacts with the individual’s

hormonal environment, and with other genes involved in hair
production.
• Since a bald woman must inherit the baldness trait from her mother and
father, it is less common in females. In addition, the trait typically results
in women with thinning hair rather than completely bald. The gene is
readily passed from mother to son because he will inherit one set of her
chromosomes.
• If B is the allele for baldness and b is the allele for normal hair, a bald
man can be heterozygous (Bb) or homozygous bald (BB). A man with
normal hair must be homozygous normal (bb).
• A normal woman can be homozygous normal (bb) or heterozygous (Bb).
A woman who has thinning hair and a receding hairline in later life must
be homozygous bald (BB).

Sex Baldness Normal Hair

Male BB, Bb bb

Female BB Bb, bb
• The sex-influenced nature of pattern baldness is related to
the production of the male sex hormone testosterone.

• The gene that affects pattern baldness encodes an enzyme

called 5-α-reductase which converts testosterone to 5-
α-dihydrotestosterone (DHT).

• DHT binds to cellular receptors and affects the expression of

many genes including those in the cells of the scalp.

• The allele that causes pattern baldness results in an

overexpression of this enzyme and has greater phenotypic
impact in males because mature males make more
testosterone than females.
Pattern baldness in the
Adams family line
(a) John Adams (father)
(b) John Quincy Adams
(son) (c) Charles Francis
Adams (grandson) (d)
Henry Adams
(great-grandson)

Brooker, chapter 4, page 83-84

Practice Problems
• If two individuals heterozygous for the pattern baldness allele have children,
what proportion of males will lose their hair? What proportion of females will
lose their hair?
Example of inheritance pattern
involving baldness
Bb X Bb

Gamete B b

B BB Bb
Bald male Bald male
Bald female Nonbald female
b Bb bb
Bald male Nonbald male
Nonbald female Nonbald female
• Rheumatoid arthritis occurs more often
in females than males due to the presence
of estrogen. A heterozygous woman
marries a heterozygous male. RR would
cause the condition in both sexes. A
homozygous recessive, rr genotype would
prevent the disorder in both sexes.

Q: Give the genotype and phenotype of their

children.
THE END