Sex Linked Inheritance: Characteristics, Types and Disorders

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Sex Linked Inheritance – Sex Linkage in Drosophila and Man With Diagram

As the principle of inheritance given by Mendel, a parental organism may transmit a gene or factor for a character to any of its offspring. In different countries, experiments on other organisms were carried out to verify whether the principles are applicable to all types of organisms or not. On the basis of their experimental findings, they came to the conclusion that Mendel’s law of segregation is universally applicable. However, in the case of certain genes, the expression of features as well as inheritance of the same has some sex-specific mode, and certain characters are prone to be more expressed in males than in females. In such cases, when a male showing mutant features is crossed with a normal female, all the F, progeny appear to be normal. But if the female of this population is crossed with a normal male, all their female progeny appear to be normal. Still, half of their male progeny may express the mutation under consideration.

However, in a reciprocal cross when a mutant female is crossed with a normal male, though all the female progeny appear to be normal, all their male progeny show mutant features. The proper explanation for such a pattern of inheritance was first given by Morgan in 1910 and he discovered sex-linked inheritance in the case of Drosophila melanogaster. He observed a relationship between white and red-eye features with the X-chromosome of the fruit fly. Morgan observed a similar pattern of inheritance of the eye features as Wilson and others attended the inheritance of X-chromosome in XO and XX grasshoppers (Pronetor sp.). On the basis of this Morgan predicted that the genes determining the white or red eye feature of Drosophila is present on X-chromosomes. He was the pioneer to characterize the pattern of sex-linked inheritance.

Sex Linkage and Types

The presence of a gene on the X-chromosome is referred to as sex linkage. However, such a concept needs certain modifications. Actually, sex chromosomes are of two types viz. X-chromosome and Y-chromosome. Therefore, genes present on any of these two chromosomes should come under the purview of sex linkage. Genes present on the X-chromosome come under X-linkage and those present on the Y-chromosome come under Y-linkage. It has been found that a small portion on the terminal part of the Y chromosome is homologous with a part on the X chromosome and the genes present in this region follow the pattern of inheritance as found in the case of autosomal genes. For this reason, this linkage is called pseudo-autosomal linkage. Therefore, typical sex-linked inheritance will be observed for the genes present on the non-homologous part of the X and Y chromosomes. On this basis, sex linkage may be categorized into two types, namely X-linkage, and Y-linkage.

• X-linkage: Genes being present on X-chromosome come under the purview of X-linkage.
• Y-linkage: Genes present on the Y-chromosome come under the purview of Y-linkage. Y-linked genes show male-to-male inheritance and therefore, they are called holandric genes.

Sex Linkage in Drosophila Melanogaster

In 1910 suddenly Morgan obtained white-eyed flies in the population of normal-eyed flies. To know the nature of the newly obtained feature he crossed the red-eyed female with a white-eyed male. The flies produced in the next generation were found to be red-eyed, indicating that the red-eye feature is dominant over the white-eye feature. When F1 female and male flies were allowed to cross, he found that among 4252 flies 782 flies appeared to be white-eyed. Therefore, the flies in the F2 generation deviated significantly from the expected 3 red: 1 white. Not only that Morgan observed that all the white-eyed flies in the F2 generation were males and there was no female with white eye features. When he crossed F1 red females with white-eyed males, both red and white-eyed females were developed.

In explaining such a result Morgan pointed out that the genes determining the white eye feature in Drosophila were recessive to its normal allele capable of determining red eye feature. Not only that, these alleles for eye features were located on X-chromosome and Y-chromosome did not contain this gene. The female fly contained a pair of X-chromosomes and the male-only one. Therefore, the gene determining the white eye feature needed homozygous condition in females and for this reason, the heterozygous F1 female in mating with white-eyed males could produce 50% white-eyed females.

The F1 red-eyed female in its one X-chromosome carried the gene for the white eye feature and the other X-chromosome contained the normal allele. Hence the F1 female may be called a carrier of the white eye gene. The carrier female in F2 could produce white-eyed males. Therefore, the white eye male of the parental generation could transmit the character to the F2 males through the daughters. This indicates that there is a transmission of character from grand-father to grand-son through daughter and such an inheritance of character is observed in the case of X-linked recessive character. Morgan stated this pattern of inheritance of character as a criss-cross inheritance.

Sex-Linked Inheritance in Drosophila for a Dominant Gene:
The pattern of inheritance for a sex-linked recessive gene differs from that of a dominant gene. The normal eye shape in Drosophila is round, but due t,o mutation on the X chromosome the eye shape may turn into Bar shaped condition. In Bar condition, the reddish area of the eye is reduced with a decrease in the number of ocelli. The Bar eye mutation (B) is dominant in nature, while its normal allele (B+) is recessive to it. When a normal female is crossed with a Bar eyed male, all the F1 female progeny appear to be Bar eyed, but all males become normal. The cross between F1 male and female results in the F2 progeny where half of both male and female progeny appear to be Bar eyed.

Bar eye features in a fruit flies with different expressions:

A list of several mutations on X Chromosome and D.melanoguster:

Phenotypic Feature	Genic Notation	Dominant or Recessive	Location on X Chromosome
1. Yellow body	y	Recessive	0
2. White-eye	w	Recessive	1.5
3. Notch wing	N	Dominant	3
4. Cut wing	ct	Recessive	20
5. Vermilion wing	v	Recessive	33
6. Miniature wing	m	Recessive	36.1
7. Forked bristle	f	Recessive	56.1
8. Bar eye	B	Dominant	57

Y linkage:
Almost the whole of the Y chromosome in Drosophila is heterochromatic and the number of effective genes on this chromosome is significantly less than on the X chromosome. Though in Drosophila males, one X chromosome is always accompanied by one Y chromosome, male sex determination may occur without any difficulty in the absence of a Y chromosome. In the absence of a Y chromosome, the males become infertile. On the Y chromosome, there are four fertility-promoting genes that are inherited only from male to male. It is found that a small segment in the small arm of Y is homologous to a terminal portion of the X chromosome. At this region the gene for bobbed bristle (b) is present. This gene is considered to be incompletely sex-linked.

Sex-Linked Inheritance in Man

The pattern of inheritance of sex-linked genes in men is identical to the pattern found in Drosophila. Inheritance of many sex-linked genes in men has been observed and several such characteristics may be discussed in the following section.

1. Colour Blindness
In the general sense, colorblindness means a disability to recognize colour. Red-green colorblindness in man comes under the purview of sex linkage and the genes responsible for determination of this feature are present on the X chromosome. In the human population, about 8% of individuals suffer from this genetic defect.

Color blindness may be of two types, namely protanopia, and deuteranopia. In protanopia, the affected person fails to recognize the red colour. On the other hand, in the case of deuteranopia, the affected person suffers from not recognizing the green colour. Because the gene for colorblindness is X linked and recessive, the male can express the defect in hemizygous condition. The females can only express the feature in homozygous conditions. For this reason, the males in the population suffer more from this genetic defect than the female.

Problem:
Colour blindness in men is a sex-linked character. Suppose one color-blind woman marries one normal man. What will be the expected feature in their progeny?
Solution:

Result: In this case, all the female progeny would be normal and the male progeny would be colour-blind.

Problem:
If a carrier female for the gene for color-blindness marries an ordinary man, what will be the character of the progeny?
Solution:

Result: All the female progeny would be normal but half of the male progeny would be colour-blind.

Problem:
If a carrier female marries a colour-blind male, what would be the expected phenotypes of the progeny?
Solution:

Result: Half of the male and female progeny would be affected by color blindness.

2. Haemophilia
Haemophilia is a bleeding disorder in men in which the affected individual fails to show clotting of blood in case of damage of blood vessels due to some external injury. The disorder may be developed due to a deficiency of the clotting factor in the affected individual and therefore, the individual having hemophilia due to continuous bleeding may die. This defect has been found to occur due to a recessive mutation of a gene located on the X chromosome of man and therefore, it is an X-linked recessive genetic defect in man. Because of sex linkage, the defect is found to be more expressed in males in the population and females appear as carriers for the defect.

A carrier female may transmit the disease to half of her male progeny in the next generation. Because of such a bleeding disorder, the affected male normally dies at an early age. The Royal family of England was affected by this disease and the mutation probably appeared first in Queen Victoria. From the Queen, the defective gene was transmitted to many of her descendants subsequently and many affected males died of the disease. The Queen of Czar Nicholas II of Russia was a descendant of Queen Victoria and she was the carrier of this defective X-linked gene. She transmitted the gene to her only son Alex who was affected by haemophilia.

Haemophilia may be of two types namely haemophilia A and haemophilia B. In both situations, blood fails to coagulate due to the absence of clotting factors. In the case of haemophilia A clotting factor VIII is absent and in the case of haemophilia B clotting factor IX is absent. Out of these two types of haemophilia, type A haemophilia is more common in the human population. Out of 10000 men, 1 is found to be affected by this type of haemophilia.

The two major forms of haemophilia occur much more commonly in males than in females. Haemophilia A is the most common type of condition; 1 in 4,000 to 1 in 5,000 males worldwide are born with this disorder. Haemophilia B occurs in approximately 1 in 20,000 newborn males worldwide.

Some X-Linked Disorders in Man:

Name of the Disorder	Disease & Symptoms	Cause
1. Fabry’s Disease	Heart & Kidney Defects, Early Death	Deficiency of Galactosidase A
2. Haemophilia A	Bleeder’s Disorder: failure of blood clotting	Deficiency of clotting factor VIII
3. Haemophilia B	Christmas Disease: failure of clotting of blood	Deficiency of clotting factor IX
4. Muscular Dystrophy	Progressive life-shortening disorder, weakness	Muscle Degradation
5. Hunter Syndrome	Mucopolysaccharide storage disease: short stature, claw-like fingers, coarse facial features, slow mental retardation, and deafness	Deficiency of iduronate sulfatase enzyme
6. Ichthyosis	Scaly dry skin	Deficiency of steroid sulfatase enzyme

Holandric Gene:
Though mainly sex-linked gene refers to the gene located on the X-chromosome; there are two types of sex chromosomes namely X and Y. Hence the gene present on the Y chromosome also will come under the purview of sex linkage and there are certain characteristics in man those may be inherited along with the Y chromosome. Because the Y chromosome is limited to only human males, these characteristics, principally remain co fined to the male individual, and concerning such cha acter a transmission from male to male may only be o served. These types of genes showing expression only in males are called holandric genes. Hypertrichosis in which hair is developed on the pinna in the males is due to one holandric gene. Another gene responsible for male sex determination in men is SRY and this is an example of the holandric gene in men.

Problem:
Predict the result of a marriage between a carrier female of haemophilia gene and a normal male.
Solution:

Result: 50% of male and female progeny appear normal 50% of female progeny will be carriers and 50% of the male progeny becomes haemophilic.

Problem:
If a carrier female marries a hemophilic male what will be the result from the mating?
Solution:

Result: 50% Son will be normal. 50% of sons will be haemophilic, 50% of daughters will be carriers, and 50% of daughters will be haemophilic.