Sex linked inheritance

1
 There are 23 pairs of chromosomes in human, out of which 22
pairs are autosomes and 1 pair is sex-chromosome.
 Characters linked to gene may be present on any chromosome.
However, sex chromosome consists the genes that is responsible to
determine sex in an organism. Such character is called sexual
character. While the character other than determining sex are called
non-sexual/ Vegetative characters.
 When the genes carrying non-sexual / vegetative characters are
inherited from one generation to other via sex chromosome, this
phenomenon is known as sex-linked inheritance. And such genes
are called sex-linked genes.
 For example., Colour blindness, haemophilia in human, eye colour
in Drosophila etc.
 There are two types of sex-chromosomes; X- chromosome and Y-
chromosome. Bina Wagle, IOST,PhD Scholar 2
 Males are heterogametic (having XY-
chromosome) while females are homogametic
(having XX-chromosome).
 The genes inherited via sex chromosome may be
linked with X or Y- chromosome.
Hence, depending on the location of the genes on
sex chromosome, sex-linked inheritance may be of
different types

Bina Wagle, IOST,PhD Scholar 3

 X-linked inheritance (Common): the genes located on x-
chromosome are responsible for the inheritance of some
somatic characters, such genes are called X-linked genes
and inheritance is called X-linked inheritance. E.g., Eye
colour in Drosophila, Colour blindness in Human,
Haemophilia (Bleeder disease) in human being.
 Y-linked inheritance ( Rare): when the genes located on Y-
chromosomes are inherited, it is known as Y-linked genes. And
inheritance is known as Y-linked inheritance.E.g. Hypertrichosis(hair
on Ear), Male infertility (Father to son) examples,(Mutations or
microdeletions in AZF region (Azoospermia factors) of Y chromosome lead to low
sperm count or azoospermia. Passed from father to son if fertile enough to
reproduce.)
 XY-linked inheritance: the genes for some characters are located on
both X and Y-chromosomes, such genes are called XY-linked genes
and phenomena is known as XY-linked inheritance. Eg, Xeroderma
pigmentosa (Skin cancer) Bina Wagle, IOST,PhD Scholar 4
 Characteristics of sex-linked genes
 A female can express recessive traits only if both the X-
chromosomes possesses that trait (homozygous). It is
because female has two X- chromosomes.
 A male has only one X-chromosome due to which traits
can be expressed even if it is in recessive form.
 A father can only transmit X-chromosome to his daughter
and Y-chromosome to his son. Hence, X-linked traits is
only passed to daughter while Y-linked traits to son.
 Since, a daughter receives one X-chromosome from her
father and same X-chromosome is passed on to her
children, thus, it is notable that grandchildren receive
same x-linked traits from grandfather via their mother.
This is called criss cross inheritance.
Bina Wagle, IOST,PhD Scholar 5
 Most of the sex-linked traits are recessive.
 Since, male has only one X-chromosome,
they are likely to have more sex-linked
disorders than female due to the lack of
corresponding allele.
 Heterozygous females are only carrier of
sex-liked traits.

Bina Wagle, IOST,PhD Scholar 6

 Criss cross inheritance
It is a phenomenon in which a parent passes the
traits to the grand child of same sex through the
offspring of opposite sex. E.g., father passes the
traits to grandson through his daughter while the
mother passes the traits to her grand-daughter
through her son.
Importance of criss cross inheritance
 Any traits showing criss cross inheritance is linked
with sex chromosome.
 It is useful in understanding the past, present and
future of sex-liked disorders.
 It also proves that genes are located on sex
chromosomes. Bina Wagle, IOST,PhD Scholar 7
• The genes which occur exclusively on the
X chromosome (mammals, Drosophila,
Melandrium, etc.) or on the analogous
Z chromosome (in birds and other species
with ZO or ZW mechanism of sex
determination) are called
X- or Z -linked genes.

**Why X-linked inheritance is common?

= Most genes for sex link traits are present
only on the X chromosome, which is larger,
the Y-chromosome is smaller (Very few
genes are located on Y chromosome).
Bina Wagle, IOST,PhD Scholar 8
• Because of their location in the sex
chromosomes, they are said to be “sex
linked traits”
• The genes which exclusively occur in
Y chromosome are called holandric
genes.
• The inheritance of X- or Z-linked and
holandric genes is called sex-linked
inheritance

Bina Wagle, IOST,PhD Scholar 9

• Male has XY chromosomes only, So ,if X
has defective gene, Disease appear.
• Female has XX chromosomes, So, if
both XX defective –Disease appear.
• Female are usually carrier, if X is
defective.
• Male are not carrier.

Bina Wagle, IOST,PhD Scholar 10

 Some sex-linked disorders
[Link] blindness in human being
[Link] colour in drosophila
[Link] (Royal Disease)

Bina Wagle, IOST,PhD Scholar 11

Heamophilia (Royal Disease)

• Defective clotting factor gene on

X chromosomes.
• Blood doesnot clot properly.
• Famous in the Royal families in
Europe. Victoria’s Queen

Bina Wagle, IOST,PhD Scholar 12

Colour Blindness in Human

• Defect in Red-Green vision gene on

X.
• Affected male cannot distinguished
red and green.
• Female needs two defective X to
show the disease, So it is rare in
them.
• CommonBinainWagle,
[Link],PhD Scholar 13
sex-linked genes can be classified into
following three types
• X-linked. is performed by those genes which are
localized in the nonhomologous sections of X-
chromosome, and that have no corresponding allele in
Y chromosome. The X-linked genes are commonly
known as sex-linked genes.
• Y-linked. is performed by those genes which are
localized in the non-homologous section of Y
chromosome, and that have no alleles in X-
chromosome. (Holandric genes )
• XY-linked. is performed by those genes which are
localized in homologous sections of X and Y
chromosomes

Bina Wagle, IOST,PhD Scholar 14

 Characteristics of Sex-linked
Inheritance
a. The pattern of inheritance of sex linked trait is criss-cross. It is the
transmission of a gene from mother to son or father to daughter. Those
patterns of inheritance are called crisscross inheritance or skip generation
inheritance, in which a character is inherited to the second generation
through the carrier of first generation. The father cannot pass a sex linked
allele to a son directly.
b. The mother can pass the allele of a trait to both daughter and son.

c. Only homozygous females can express a recessive trait, while heterozygous

female are carriers and do not express the trait.

d. Males express the trait immediately because of the absence of a

corresponding allele. This is the reason why males suffer from sex linked
disorders more than females.

e. Most of the sex linked traits are recessive. Some examples of sex linked traits
include Haemophilia or Bleeder’s disease, Daltinism or Colour blindness

Bina Wagle, IOST,PhD Scholar 15

 X-Linked X-Linked X-Linked
dominant recessive inheritance

Sex linked genes show the dominance recessive relationship only

in homogametic sex (e.g. female in humans) because it can
carry two alleles at the sex linked locus. So, female can be
homozygous or heterozygous.
• In the heterogametic sex (males in humans and females in
birds) do not show dominance recessive relationship because
the existence of only a single X or Z chromosome.
• The term hemizygous is used for X linked gene in males
as they carry only one allele with regard to sex linked trait
(In birds the female is hemizygous).

Bina Wagle, IOST,PhD Scholar 16

 Dominant X-linked genes
can be detected in human pedigrees (also in Drosophila) through
the following clues :
 It is more frequently found in the female than in the male of the
species.
 The affected males pass the condition on to all of their daughters
but to none of their sons
 Females usually pass the condition (defective phenotype) on to
one-half of their sons and daughters
 X-linked dominant gene fails to be transmitted to any son from a
mother which did not exhibit the trait itself.

Bina Wagle, IOST,PhD Scholar 17

XaXa XAY

XAXa xay

 P e d i g r e e c h a r t s h o w i n g h o w X - l i n k e d d o m i n a n t s a r e e x p r e s s e d in all t he
daughters of affected males

XaY

XAXa XaXa XAY XaY

Pedigree chart showing that females effected by a n X-Linked dominant

condition usually heterozygous a n d pass the condition to o n e - half of
their pro geny

Bina Wagle, IOST,PhD Scholar 18

• In humans, X-linked dominant conditions are
relatively rare. example is
• hypophosphatemia (XLH) - vitamin D-resistant
rickets).
• hereditary enamel hypoplasia (hypoplastic
amelogenesis imperfecta), in which tooth enamel
is abnormally thin so that teeth appear small and
wear rapidly down to the gums

Bina Wagle, IOST,PhD 19

 The X-linked recessive genes
• it show the following two more peculiar features
:criss-cross pattern of inheritance (i.e., in criss-cross
inheritance, a X-linked recessive gene is transmitted
from P1male parent (father) to F2 male progeny
(grandsons) through its F1 heterozygous females
(daughters), which are called carriers) and different
F1 and F2 results (ratios) in the reciprocal crosses.
• The X-linked recessives can be detected in human
pedigrees (also in Drosophila) through the
following:-

Bina Wagle, IOST,PhD Scholar 20

i) The X-linked recessive phenotype is usually found more
frequently in the male than in the female.??This is because
an affected female can result only when both mother and
father bear the X-linked recessive allele (XAXa × XaY),
whereas an affected male can result when only the mother
carries the gene. Further, if the recessive X-linked gene is
very rare, almost all observed cases will occur in males.
(ii) Usually none of the offspring of an affected male will be
affected, but all his daughters will carry the gene in
masked heterozygous condition, so one half of their sons
(i.e., grandsons of F1 father) will be affected
(iii) None of the sons of an affected male will inherit the X-
linked recessive gene, so not only will they be free of the
defective phenotype; but they will not pass the gene along
to their offspring
Bina Wagle, IOST,PhD Scholar 21
XAXA XaY

XAY XAXa XAY

1 2

XaY XAY XAXa XAXA

Fig. Pedigree showing how X-linked recessive genes are expressed in males, then
carried unexpressed by females in the next generation, to be expressed in their
sons. II.3 and III.4 heterozygous or carrier females are not distinguished
phenotypically
Bina Wagle, IOST,PhD Scholar 22
Bina Wagle, IOST,PhD Scholar 23
 Example of Inheritance of X-Linked Recessive Genes

The crisscross inheritance of recessive X- linked genes can be well

understood by following classical examples in Drosophila, man,
moth and chikens etc.:
1. Inheritance of X-Linked Gene for Eye Colour in Drosophila
In Drosophila, the gene for white eye color is X-linked and recessive
to another X-linked ,dominant gene for red-eye color. It is
discovered by Morgan in 1910.
Following crosses between white eyed and red eyed Drosophila will
make clear the characteristic criss-cross inheritance of gene for
white eyed color in it :

Bina Wagle, IOST,PhD Scholar 24

(a) Red eyed female × White eyed male If a wild red eyed female
Drosophila is crossed with a mutant white eyed male Drosophila, all the F1
individuals irrespective of their sex have red eyes
P XRXR X XrY
F1 XRX r , XRY
Red eyed female , Red eyed male

• When the red eyed male and red eyed female individuals of F1 are intercrossed,
XRXr X XRY

XRXR, XRY , XRXr , XrY

Red eyed female, red eyed male, Red eyed female, white eyed male
3 red : 1white eyed
• the F2 progeny is found to include an exclusively red eyed female population and a
male population with 50 per cent red eyed individuals and 50 per cent white eyed
individuals. Thus, F2 generation includes red eyed and white eyed individuals in the
ratio of 3: 1.
Bina Wagle, IOST,PhD Scholar 25
(b) White eyed female × Red eyed male. When a white eyed female
Drosophila is crossed with a red eyed male Drosophila, all the female individuals in the F1
generation are red eyed
XrXr x XRY
XRXr , XrY
Red eyed female , white eyed male

• When these red eyed female individuals and white eyed male individuals of F1 are
intercrossed,
XRXr x XrY
XRXr , XRY, XrXr, XrY
Red eyed female , Red eyed male , white eyed female , white eyed male
• the female population of F2 generation is found to include 50 per cent red eyed and 50
per cent white eyed flies. Similarly, the male population of F2 includes 50 per cent, red
eyed and 50 per cent white eyed flies.
The results of these experiments, thus, are clearly indicating that the trait located on a
sex chromosome alternates the sex from one generation to the next generation, i.e, the
trait of white eyes transfers from P1 father to F1 daughter and from F1 daughter to F2
son. Bina Wagle, IOST,PhD Scholar 26
Inheritance of X-Linked Recessive Genes in Humans

In human beings more than 150 confirmed or highly probable X-

linked traits are known; most of these are recessives. Certain
well known examples
 red- green colour blindness or daltonism,
 haemophilia
 Duchenne’s muscular dystrophy.
 G6PD deficiency - deficiency of enzyme glucose-6 phosphate
dehydrogenase ,in erythrocytes causing haemolytic anaemia
during allergy reaction of persons for the drugs such as
sulphonamides or for the broad bean (Vicia faba), called favism;
 night blindness
 white frontal patch of hair.

Bina Wagle, IOST,PhD Scholar 27

 Colour blindness
a dominant X- linked gene is necessary for the formation of the colour sensitive
cells, the cones, in the retina of eye. According to trichromatic theory of colour
vision, there are three different types of cones, each with its characteristic pigment
that react most strongly to red, green and violet light. The recessive form of this
gene (i.e., presence of recessive X-linked allele for colour blindness) is incapable of
producing the colour sensitive cones and the homozygous recessive females (Xc Xc)
and hemizygous recessive males (Xc Y) are unable to distinguish between these two
colours.
• The frequency of colour blind women is much less than colour blind man?
(i) Marriage between colour-blind man and normal vision woman.
When colour-blind man marries with a normal vision woman, then they will
produce normal vision male and female individuals in F1. The marriage
between a F1 normal vision woman and normal vision male will produce in F2
two normal vision female, one normal vision male and one colour-blind male

Bina Wagle, IOST,PhD Scholar 28

 Normal female Colour-blind male

Parent : X+ X+ X Xc Y

Gametes : (X+) (Xc) (Y)

F1: ½ X+Xc : ½ X+Y

(ii) Marriage between a carrier female and a normal male produces the
carrier female x Normal male
P2 X+Xc X+Y
G2 X+, XC X+, Y
F2 X+X+, X+Y, X+XC, XCY
Normal female Normal male carrier female Colour-blind male
Bina Wagle, IOST,PhD Scholar 29
Bina Wagle, IOST,PhD Scholar 30
 Hemophilia
is the most serious and notorious disease which is more common in men than women.
This is also known as bleeder’s disease. The person which contains the recessive gene for
hemophilia lacks in normal clotting substance (thromboplastin) in blood so minor injuries
cause continuous bleeding and ultimate death of the person due to hemorrhages. This
hereditary disease was reported by John Cotto of Philadelphia in 1803 in man.
(a) Hemophilia A. It is characterized by lack of anti hemophilic globulin (Factor VIII).
About four fifths of the cases of hemophilic are of this type.
(b) Hemophilia B. It is also called “christmas disease” after the family in which it was first
described in detail. Hemophilia B results from a defect in plasma thromboplastic
component (factor IX). This is milder form of hemophilia.
Parents : X+Xh × X+Y
Normal mother(carrier) Normal father
Gametes: (X+) (Xh) (X+) (Y)
Progeny : X +X + , X+Xh , X+Y , XhY
Normal daughter, Normal (carrier), Normal , Hemophilic
Bina Wagle, IOST,PhD Scholar 31
B. INHERITANCE OF Y-LINKED GENES
Genes in the non-homologous region of the Y chromosome pass
directly from male to male.
 In man, the Y-linked or holandric genes are transmitted directly
from father to son Having hairy ears was once thought to be a Y-
linked trait in humans, but that hypothesis has been discredited.
 It has often been said that little is known about genes that may
be Y-linked. This is no longer true. As of the year 2012, about
three dozen genes were known to be Y-linked including:
 ASMTY (which stands for acetyl serotonin methyltransferase)
 TSPY (testis-specific protein)
 Y-Chromosome deletions are a frequent genetic cause of male
infertility. In some males a small deletion in the DAZ gene
(deleted in azoosprmia) on the Y chromosome cause azoospermia

Bina Wagle, IOST,PhD Scholar 32

• SEX-INFLUENCED GENES
are autosomal genes those whose dominance is influenced by the sex of the
bearer. Thus, male and female individuals may be similar for a particular trait but
give different phenotypic expressions of the same trait..
Example :
1- In man the baldness may occur due to disease, radiation or thyroid defects
but in some families balldness is found to be inherited trait. In such inherited
baldness the hairs gradually become thin on head top, leaving ultimately a fringe
of hair low on the head and commonly known as pattern baldness. The gene B
for baldness is found to be dominant in males and recessive in females. In
heterozygous condition it expresses itself only in the presence of male hormones
(in male sex):
Genotype Phenotypes

Men women
BB Bald Bald
Bb Bald Non-bald
bb Non- Non-bald
bald

2- In sheep, the genes for the development of horns is dominant in males and
recessive in female.
Bina Wagle, IOST,PhD Scholar 33
SEX-LIMITED GENES
Sex-limited genes are autosomal genes whose phenotypic expression is
determined by the presence or absence of one of the sex hormones. Their
phenotypic effect is limited to one sex or other. In other words, the penetrance
of a sex-limited gene in one sex remain zero.
Sex-limited genes are responsible for sexual dimorphism, which is a phenotypic
(directly observable) difference between males and females of the same species.
These differences can be reflected in size, color, behavior ,Example
1. The bulls have genes for milk production which they transmit to their
daughters, but they or their sons are unable to express this trait. The production
of milk is, therefore, limited to variable expression only in the female sex.
2. Beard development in human beings is a sex limited trait as men normally
have beards, whereas women normally do not. Likewise, the genes for male
voice, body hair and physique are autosomal in human beings, but they are
expressed only in the presence of androgens which are absent in females.
3. In chicken the recessive gene (h) for cock feathering is male sex-limited (i.e., it
is penetrant only in male environment)

Bina Wagle, IOST,PhD Scholar 34

Genotype Phenotypes
male female
HH Hen feathering Hen-feathering

Hh Hen feathering Hen-feathering

hh Cock feathering Hen-feathering

Bina Wagle, IOST,PhD Scholar 35