Sex Linkage

Any gene located on the X chromosome (mammals, Drosophila, and others) or on the
analogous Z chromosome (in birds and other species with the ZO or ZW mechanism of
sex determination) is said to be sex-linked. The first sex-linked gene found in
Drosophila was the recessive white-eye mutation. Reciprocal crosses involving
autosomal traits yield comparable results. This is not true with sex-linked traits. When
white-eyed females are crossed with wild-type (red-eyed) males, all the male offspring
have white eyes like their mother and all the female offspring have red eyes like their
father

This crisscross method of inheritance is characteristic of sex-linked genes. This

peculiar type of inheritance is due to the fact that the Y chromosome carries no
alleles homologous to those at the white locus on the X chromosome. In fact, in most
organisms with the Y-type chromosome, the Y is virtually devoid of known genes.
Thus males carry only one allele for sex-linked traits. This one-allelic condition is
termed hemizygous in contrast to the homozygous or heterozygous possibilities in
the female.
VARIATIONS OF SEX LINKAGE
The sex chromosomes (X and Y) often are of unequal size, shape,
and/or staining qualities. The fact that they pair during meiosis is
indication that they contain at least some homologous segments.
Genes on the homologous segments are said to be incompletely
sex-linked or partially sex-linked and may recombine by crossing
over in both sexes just as do the gene loci on homologous
autosomes. Special crosses are required to demonstrate the
presence of such genes on the X chromosome, and few examples
are known. Genes on the non homologous segment of the X
chromosome are said to be completely sex- linked and exhibit
the peculiar mode of inheritance. In humans, a few genes are
known to reside in the non homologous portion of the Y
chromosome. In such cases, the trait would be expressed only in
males and would always be transmitted from father to son. Such
completely Y-linked genes are called holandric genes
The majority of genes are carried on autosomes, chromosomes that code for traits not directly involved in
determining the sex of the individual. There are 22 pairs of autosomes and 2 sex chromosomes (X and Y) for
each person. Females have two X chromosomes (XX) while males have one X and one Y (XY). The X chromosome
is as large as many of the autosomes, but the Y chromosome is about one-third of the size of the X chromosome
and is missing genes present on the X chromosome. The genes carried only on the X chromosome are called sex-
liked genes and do not produce female characteristics. Sex-linked genes have recessive alleles that cause
baldness, hemophilia, and color blindness. For a woman to express these phenotypes, she must have two
recessive alleles, one on each X chromosome. However, because the male only has one X chromosome and these
sex-linked genes are not present on the Y chromosome, the presence of only one recessive allele will give a male
the recessive phenotype. In sex-linked inheritance, the terms homozygous and heterozygous in the male do not
apply. It is interesting to note that with sex-linked inheritance, the father cannot pass the condition to his son. The
son can receive only a Y chromosome from his father and an X chromosome from his mother.
The transmission of body characters from parents to offsprings along with sex
is called sex linked inheritance
Examples:
1. Colour blindness
2. Haemophilia
3. Eye colour in Drosophila
4. Hypertrichosis
5. Ichthyosis hystrix

Types of sex linked inheritance

1. X-linked inheritance
2. Y- linked inheritance
3. XY- linked inheritance
4. Completely sex linked inheritance
5. Incompletely sex linked inheritance
 X-linked inheritance

Certain sex linked genes are located only on X chromosomes and

their alleles are absent in Y chromosome. These genes are called X-
linked genes; the characters are controlled by these genes are called
X-linked characters; and their mode of inheritance is called X-linked
inheritance Eg) colour blindness, Haemophilia, eye colour in
Drosophila etc
Y- linked inheritance
Certain sex linked genes are located only on Y chromosomes are called
Y – linked genes. The Y linked genes are confined male only hence
they are also called Holandric genes. The genes are transmitted
directly from father to son. their mode of inheritance is called Y-linked
inheritance Eg) Hypertrichosis, Ichthyosis hystrix etc
 XY- linked inheritance
Certain sex linked genes are located on X and Y chromosomes are called
XY – linked genes. their mode of inheritance is called XY-linked
inheritance
Eg) Xeroderma pigmentosum , Nephritis, Retinitis pigmentosa etc

Completely sex linked inheritance

The X and Y chromosome are not similar. The X
chromosome is large and straight. But the Y
chromosome is smaller and one end is curved. The
lower part of X chromosome is similar to that of Y
chromosome. These two parts are called
homologous region. They have the same type of
gene, The remaining parts of the X and Y
chromosome are not similar. So they are called non-
homologous region or differential regions. They do
not contain similar type of genes.
The genes located on non-homologous regions inherit together because crossing
over does not occur in these regions. So the genes located on non-homologous
regions are called completely sex linked gene and their inheritance is called
completely sex linked inheritance Eg) Haemophilia, colour blindness

Incompletely sex linked inheritance

The genes located on homologous regions of sex
chromosomes do not inherit together because crossing over
may occur in these regions. So these genes are called
Incompletely sex linked genes and their inheritance is called
incompletely sex linked inheritance Eg) Retinitis pigmentosa,
Nephritis
The X-linked genes exhibit following characteristic patterns of
inheritance :
1.The differential region of each chromosome (i.e., X) contain genes
that have no counterparts on the other kind of sex chromosome.
These genes, whether dominant or recessive, show their effects in the
male phenotype. Genes in the differential regions are called
hemizygous (“half-zygous”) in the males.
2. The X-linked recessive genes 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 P1 male
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.
Inheritance of X-Linked Gene for Eye Colour in
Drosophila
In Drosophila, the gene for white eye colour is X-linked and
recessive to another X-linked, dominant gene for red-eye
colour. 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 colour in it :
1.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 (Fig). When the red eyed male and
red eyed female individuals of F1 are intercrossed, 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, F 2
generation includes red eyed and white eyed individuals in
the ratio of 3: 1.
(2) Haemophilia. Haemophilia 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
haemophillia lacks in normal clotting substance (thromboplastin) in
blood so minor injuries cause continuous bleeding and ultimate death of
the person due to haemorrhages. This hereditary disease was reported
by John Cotto of Philadelphia in 1803 in man. Recently, two types of X-
linked haemophilia have been recognized :
(a) Haemophilia A. It is characterized by lack of antihaemophilic globulin (Factor
VIII). About four fifths of the cases of haemophilic are of this type.
(b) Haemophilia B. It is also called “christmas disease” after the family in
which it was first described in detail. Haemophilia B results from a defect in
plasma thromboplastic component (factor IX). This is milder form of haemophilia.
Woodliff and Jackson in 1966 have found the occurrence of both types of
haemophilia in an unusual family, both segregating independently; therefore, they
concluded that the two loci (i.e. haemophilia A and haemophilia B) were far apart
on the X chromosome (i.e. , having a distance of more than 40 map units between
them. Haemophilia is well known in the royal families of Europe, where it is
traceable to Queen Victoria of England, who must have been heterozygous
(carrier). No haemophiliac is known in her ancestry; hence, it is concluded that
her haemophilia allele arose from a mutant gamete. Since it is caused by
recessive X-linked gene, a lady may carry the disease (i.e., she is carrier but
nonsufferer and would transmit it to 50 per cent of her sons, even if the father is
normal
(3) Colour blindness. In human beings, 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 (X c Xc)and
hemizygous recessive males (Xc Y) are unable to distinguish between these two colours
(Wilson, 1911). The frequency of colour blind women is much less than colour blind man.
Detailed studies indicate that there are two closely linked gene loci each with several multiple
alleles controlling the colour blind trait. Lack of the colorable pigment in the retinal cones
results in an inability to discriminate green colours. This defect is known as deuteranopia or
deutan colour blindness. It affects about 8 per cent of human males but only about 0.7 per
cent of females. The deutan or green colour blindness is first to be described in literature and
is most commonly encountered sex-linked trait in human beings. Likewise, lack of
erythrolable pigment which is necessary for discrimination in red end of the spectrum
results in protanopia or protan colour-blindness.
This abnormality is much less common than the
deutan type, occurring in only about 2 per cent of
males and in only 4 women out of 10,000. It is also
caused by an X-linked recessive gene present quite
close to the deuteranopia locus. Still other forms of
colour blindness, some X-linked and some autosomal,
are also known in humans The inheritance of colour
blindness can be studied in the following two types of
marriages :
Marriage between colour-blind man and normal
visioned woman. When colour-blind man marries
with a normal visioned woman, then they will produce
normal visioned male and female individuals in F1.
The marriage between a F1 normal visioned woman
and normal visioned male will produce in F2 two
normal visioned female, one normal visioned male
and one colour-blind male
 NON-DISJUNCTION
The failure of homologs (at meiosis) or sister chromatids (at mitosis) to separate properly to
opposite poles is called non-disjunction. The sex chromosomes pass through the phenomenon of
nondisjunction and present various interesting situations. The non-disjunction may be of following
types:

1. Primary Non-disjunction
The phenomenon of primry non-disjunction was discovered by C.B. Bridges (1916) during his
classical matings of Drosophila melanogaster. Let us consider one of his classical crosses as
follows: The gene for wild type red eyes (+) is carried by the X chromosome; a recessive allele (v)
produces vermilion eyes in homozygous females (XvXv) and in all males (XvY). Normally vermillion-
eyed females mated to red-eyed males produce only red-eyed daughters and vermilion eyed sons

Crosses of this type, however, in rare cases produce unexpected vermilion-eyed daughters and
red-eyed sons with a frequency of one per 2,000 to 3,000 offspring. Bridges speculated that these
unusual progeny are due to a failure of the X chromosomes in an XX female to disjoin during
meiosis I of oogenesis. This phenomenon was termed primary disjunction by Bridges and this
event tends to produce three types of eggs: the majority of eggs with normal single X chromosome
and a small number of eggs with their two X chromosomes or no X at all. These eggs on normal
fertilization produce the following results :
The metafemales (AA XXX) are weak
and seldom live beyond the pupal stage;
the AAOY individual die in the egg stage.
Note that the AA XXY female indicate
that the presence of a Y chromosome
does not determine maleness itself,
though males without it (AAXO) are
sterile. From these results three facts
became established :
1. In Drosophila sex determination
occurs according to genetic balance
theory of Bridges.
2. In Drosophila, Y chromosome contains
genes for the spermatogenesis.
3. It provides strong support to
chromosome theroy of inheritance (i.e.,
Mendelian factors or genes are carried on
the chromosomes).
2. Secondary Non-disjunction
In next cross, Bridges mated the exceptional vermilion-eyed
females (AAXvXvY) that arose as a result of primary non-
disjunction to normal red-eyed males (AAX+Y). The progeny
of this cross included 96 per cent female with red eyes and
only 4 percent females had vermilion eyes indicating that
there was 4 per cent secondary non-disjunction (Fig). Thus,
primary non-disjunction may occur in either XX females or XY
males. In the former it leads to the production of XX and O
eggs. Occurrence in the first meiotic division of males
produces XY and O sperms. When such non-disjunction takes
place during the second meiotic division then XX, andXY and
O sperms result. Secondary non-disjunction, on the other
hand, occurs in XXY females, where it gives rise to XX, XY, X
and Y eggs (Fig. 12.19). As the term non-disjunction implies,
these aberrant gametes are produced only as a result of
failure of the sex chromosomes to disjoin after synapsis; they
are not physically attached. Similar results were obtained by
Bridges (1916) from the cross of red eyed male and white
eyed female Drosophila.
In Man the following syndromes are produced by non-disjunction.
Klinefelter’s syndrome(22AA+XXY=47)
Turner’s syndrome(22AA+X=45)
Down’s syndrome(21AA+A+XX=47)
 Gynandromorphs
Concepts of sex determination as developed for Drosophila are verified by the
occasional occurrence of gyandromorphs which are individuals in which part of the
body expressed male characters, whereas other parts express female characters. In a
way, gynandromorphs represent one kind of mosaic or an organism made up of
tissues of male and female genotypes. For example, a bilateral gynandromorph of
Drosophila is male on one side (right or left) and female on the other. It results due to
the loss of an X-chromosome in a particular cell during development, i.e., when the
laggered X chromosome fails to be incorporated in a daughter nucleus and is lost
forever. If this event happens during first cleavage (or mitotic division) of the zygote,
then one of the two blastomeres will have AAXX chromosomal complement and the
other will have AAXO. The portion of the body developing from AAXX blastomere will
be normal female and the portion developing from the AAXO blastomere will be male.
The cytological examination of gynandromorphs suggested that Y chromosome does
not play any role in the determination of sex in Drosophila.
There are 3 type of gynanders;
1.Bilateral gynanders: these have
male trait on one lateral side of the
body and female traits on the
otherlateral side Eg) Drosophila
2.Antero posterior gynanders: they
have features of one sex on anterior
half and those of the other sex on the
posterior half of the body Eg) Beetles
3.Sex piebalds
These are gynanders having a mixture
of male and female tissues in the
body.
Gynanders is produced in two ways
1. Loss of X chromosome

A gynander begins its development

with 2n(A)+XX chromosomes. But in the
cporse of cell division and X gets lost from
one of the products of cell division. So one
daughter cell possess 2n(A)+ XX
chromosome and other 2n(A)+X. In case,
this should happen during first zygotic
division two blastomeres with unequal
number of X chrpmosomes are formed. The
blastomere with 2n(A)+XX chromosomes
develops into female half, while the second
blastomere with 2n(A)+X chromosomes
produces male half
2. Binucleated Egg

This mechanism was explained by

Goldschmidt in silkworm moth. In silk worm,
females are XY and males are XX. During
oogenesis, X and Y chromosomes normally
separate, one passing into egg and the other
into polar body.
Sometimes both the nucleus are present in
the egg and a binucleate egg (XX and XY) is
produced. The binucleate egg may be
fertilized by two sperms, each fertilizing one
egg nucleus. After fertilization and cleavage,
one blastomere (XX) develops into male parts
and the other blastomere (XY) develops into
female parts.
 SEX-INFLUENCED TRAITS
The genes governing sex-influenced traits may reside on any of the
autosomes or on the homologous portions of the sex chromosomes. The
expression of dominance or recessiveness by the alleles of sex-
influenced loci is reversed in males and females due, in large part, to the
difference in the internal environment provided by the sex hormones.
Thus examples of sex-influenced traits are most readily found in the
higher animals with well-developed endocrine systems.
 SEX-LIMITED TRAITS
Some autosomal genes may only come to expression in one of the sexes
either because of differences in the internal hormonal environment or
because of anatomical dissimilarities. For example, we know that bulls
have many genes for milk production that they may 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 in only the
female sex. When the penetrance of a gene in one sex is zero, the trait
will be sex-limited.
Thank You