The recessive mutant allele is present on the X chromosome. Some of the genes present on the X chromosome functionally resemble the genes present on the autosomes. The recessive traits manifest only in a homozygous state or in a double dose. A mutation of a gene present on the X chromosome expresses the phenotype in males. These males show hemizygosity for the gene mutation since they have only one X chromosome. The females show homozygosity for the gene mutation. Since the females have two X chromosomes, they have a copy of the gene mutation on each X chromosome. Carriers have only one copy of the mutant gene. Hence, they do not express the phenotype. A carrier female transmits the gene to the next generation. An affected male transmits the mutant gene to all his daughters who become carriers in the future.
Characteristics:
1. The X-linked recessive inheritance predominantly affects males since they consist of a single X chromosome with the affected or a mutated gene.
2. A homozygous female is rare in this case (mutant allele occurs mostly in the double dose).
3. Mostly, the unaffected carrier females transmit the mutant gene to their sons.
Consider a mating between a normal male and a carrier female. 25% of the females exhibit a normal phenotype, 25% of the males exhibit a normal phenotype, 25% of the females become carriers, and remaining 25% of the males exhibit a normal phenotype. Consider another mating example between the affected male and a normal female. In this case, an affected male will never transmit the disorder. 50% of the females will become carriers whereas 50% of the males will exhibit a normal phenotype.
Image 1: X-linked recessive inheritance (Affected father and unaffected mother)
Image 2: X-linked recessive inheritance (Unaffected father and carrier mother)
Disorders associated with X-linked recessive inheritance:
Duchenne muscular dystrophy (DMD):
It severely affects the muscles. This type of dystrophinopathy is predominant in males. DMD involves severe muscular weakness and wasting. An affected person shows an awkward structure of the shoulders and arms while walking. They have very weak belly muscles. These weak muscles lead to the sticking of the belly, thereby affecting the sitting position of the person. Individuals with DMD have weak thighs, weak muscles in the front leg, foot drop and bent knees. Children with DMD may walk on toes due to tight heel cord (contracture). The calf muscles get replaced by fat and the connective tissues. Most of them use a wheelchair since they show difficulty in walking. A gene known as DMD gene gets mutated. The DMD gene encodes a protein known as dystrophin. Different kinds of DMD gene mutations exist. They lead to a wide range of dystrophinopathies. The protein dystrophin mainly gets synthesized in the heart and the skeletal muscles. However, neurons also synthesize this protein in small amounts. Inheritance of DMD follows an X-linked recessive pattern of inheritance. Improper synthesis of dystrophin protein due to DMD gene mutation affects the muscles and the bones of the individual. In DMD, the dystrophin is almost not there. Hence, muscle cells become a deficit of this essential protein. Muscle cells start becoming weak and hence, they die. Patients with DMD also experience heart problems.
Mainly the X chromosome consists of the DMD gene. Hence, a mutated DMD gene mainly passes through the X chromosome. Males have only one X chromosome. Females have two X chromosomes. Each X chromosome has a single copy of the DMD gene. Males receive their X chromosome from the mother and Y chromosome from the father. Hence, the mutated gene passes on from the mother. Since females have two X chromosomes, so they get the disorder if both the X chromosomes have a mutated gene. If one X chromosome has a mutated gene, the females become carriers of DMD gene mutation. A man with DMD will pass on the trait to all his daughters. Since sons inherit Y chromosome, the father may not pass the trait to the son. Sometimes de novo mutations also occur in the family.
Hemophilia:
It belongs to a category of bleeding disorders. It lowers the body’s natural process of blood clotting. Individuals with hemophilia bleed for a very long time. Bleeding in these individuals not necessarily involve an accident or an injury. It may also happen spontaneously. Individuals suffering from hemophilia have blood in their urine and the stools. Their gums always bleed. They also have deep bruises, frequent nosebleeds, and joint pains.
There are two main types of hemophilia. Hemophilia A (classic hemophilia) results in factor VIII protein deficiency thereby affecting 1 in 4000 individuals. Hemophilia B (Christmas disease) arises due to factor IX protein deficiency and affects 1 in 20,000 individuals. Hemophilia occurs commonly in males than in females.
Genetics:
Hemophilia A arises due to changes in a gene known as F8 gene. A normal F8 gene provides instructions in making coagulation factor VIII protein. Hemophilia B arises due to changes in the F9 gene. It encodes coagulation factor IX. Both the proteins work together in the blood clotting process. A blood clot majorly plays a role in protecting the body from excessive blood loss. Without the factor VIII and factor IX proteins, the blood clotting process becomes inefficient.
The genes associated with hemophilia are present on the X chromosome. Males have one copy of X chromosome inherited from the mother. Hence, if the mother has a copy of a mutated gene on the X chromosomes, she becomes a carrier of the trait. Females have two X chromosomes. Hence, they either become carriers or express the trait fully.
Color blindness:
Color blindness (an X-linked recessive type of disorder) is responsible for lowering a person’s ability to see colors or differentiate color shades. These individuals face a problem in identifying colors and hence, get confused while performing tasks. Identifying traffic lights, selecting ripe fruits, and identifying next to similar colors becomes difficult for them. They become uncomfortable in bright environments. Such individuals have a problem in the development of the color sensing cones in the eye. Color blindness gets detected using the Ishihara test of determining various colors. There are many forms of color blindness such as red-green color blindness, blue-yellow color blindness, and total color blindness.
Genetics:
The X chromosomal genes such as OPN1LW, OPN1MW, and OPN1SW get mutated leading to color vision deficiency. A light-sensitive tissue consists of the color vision promoting proteins. It is present at the backside of the eye. The ophthalmic structures (consisting of rods and cones) transmit the signals from the eye to the brain. Rods provide vision in low light whereas cones provide vision in bright light. The above genes help in making opsins in the cones. Mutated genes result in color blindness or difficulty in visualizing specific spectrum of colors.
[1] Medical genetics, G.P. Pal
[2] Human Genetics, 3/e, Gangane
[3] Vogel and Motulsky's Human Genetics: Problems and Approaches, Friedrich Vogel, Gunter Vogel, Arno G. Motulsky
[4] Biology for the IB Diploma: Standard and Higher Level, Andrew Allott
[5] Principles of Medical Genetics, Thomas D. Gelehrter
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