Sex linkage
In X-linked recessive inheritance, a son born to a carrier mother and an unaffected father has a 50% chance of being affected, while a daughter has a 50% chance of being a carrier, however a fraction of carriers may display a milder (or even full) form of the condition due to a phenomenon known as skewed X-inactivation, in which the normal process of inactivating half of the female body's X chromosomes preferably targets a certain parent's X chromosome (the father's in this case).
In X-linked dominant inheritance, a son or daughter born to an affected mother and an unaffected father both have a 50% chance of being affected (though a few X-linked dominant conditions are embryonic lethal for the son, making them appear to only occur in females).
In classical genetics, a mating experiment called a reciprocal cross is performed to test if an animal's trait is sex-linked.
The exact pattern of inheritance varies, depending on whether the father or the mother has the trait of interest.
Their children would inherit the disorder as follows: In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents.
A few scholars have suggested discontinuing the use of the terms dominant and recessive when referring to X-linked inheritance, stating that the highly variable penetrance of X-linked traits in females as a result of mechanisms such as skewed X-inactivation or somatic mosaicism is difficult to reconcile with standard definitions of dominance and recessiveness.
[22] Examples: female sterility in Drosophila; and many polymorphic characters in insects, especially in relation to mimicry.
A disease or trait determined by a gene on the X chromosome demonstrates X-linked inheritance, which can be divided into dominant and recessive patterns.
The first X-linked genetic disorder described on paper was by John Dalton in 1794, then later in 1910, following Thomas Hunt Morgan's experiment, more about the sex-linked inheritance was understood.
In 1961, Mary Lyon proposed the hypothesis of random X-chromosome inactivation providing the fundamental for understanding the mechanism of X-linked inheritance.
Common X-linked genetic diseases include Red-green colour blindness, which affects an individual's ability to see red or green images; X-linked agammaglobulinemia, resulting in a deficiency of immunity; Duchenne Muscular Dystrophy, causing muscle weakness and immobility; Hemophilia A, leading to blood clotting deficiency.
X-linked recessive diseases are more frequently encountered than dominant ones and predominantly affect males, with Red-green colour blindness having the highest prevalence among all.
[citation needed] Examples include: Red-green colour blindness is a type of colour vision deficiency (CVD) caused by a mutation in X-linked genes, affecting cone cells responsible for absorbing red or green light.
In milder cases, those affected exhibit reduced sensitivity to red or green light, as a result of hybridisation of the genes,[27] shifting the response of one cone towards that of the other.
[26] In the more extreme conditions, there is a deletion or replacement of the respective coding genes,[28] resulting in the absence of L or M cones photopigments and thus losing the ability to differentiate between red or green light completely.
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder that impairs the body’s ability to produce antibodies, which are proteins protecting us from disease-causing antigens, resulting in severe bacterial infections.
Duchenne Muscular Dystrophy (DMD) is a severe neuromuscular disease causing progressive weakness and damage of muscle tissues,[32] leading to mobility loss and difficulties in daily activities.
[35] With the loss of the dystrophin complex, the muscle cells would no longer be protected and therefore result in progressive damage or degeneration.
Patients with mild haemophilia often do not experience heavy bleeding except for surgeries and significant trauma.
[37] Prenatal screening is offered to females during pregnancy, it involves both maternal blood tests and ultrasound to check for possible defect genes in developing fetus.
[38] The screening result only confirms a possibility of genetic disease, so parents would be prepared psychologically, or could consider the option of pregnancy termination.
A few drops of blood would be collected with a cotton paper from the heel of a newborn that is less than a week old,[39] samples would then be analysed for a variety of disorders.
