Mendelian Disorders in Humans

A Mendelian disorder is a form of genetic disorder that develops as a result of alterations in one gene or abnormalities in the genome. A disorder like this can be seen from birth and discovered through family lineage and the genealogical record. These inherited disorders are extremely rare, affecting only one person in many thousands. Hereditary problems, on the other hand, can be acquired. Non-inheritable hereditary problems are caused, for the most part, by mutations or errors in the DNA, though inheritable hereditary disorders, on the other hand, usually occur in the germline cells. For example, the disease could be caused by an acquired hereditary disorder, a mutation caused by environmental factors, or something else entirely.

Some key points about Mendelian disorders:

•  Mendel’s examinations of pea plants in terms of inheritance patterns have provided a strong foundation for our understanding of single-gene diseases in humans. 
• A Mendelian disorder is caused by mutations in a single gene. 
• Mendelian disorders are caused by single-locus mutations. This might happen on the autosome or the sex chromosome. 
• Pedigree’s study of a family with a history of Mendelian disorder can be used to determine whether the trait is dominant or recessive, and the probability of its occurrence in future generations.

Types of Mendelian Disorders

The following are types of Mendelian disorders, as defined by Mendel’s laws of inheritance:

1. Autosomal dominant
2. Autosomal recessive
3. Sex-linked dominant
4. Sex-linked recessive

• Autosomal dominant

The mutant gene in an autosomal dominant disorder is a dominant gene on one of the autosomal chromosomes.

• Autosomal Recessive 

An autosomal recessive disorder requires the presence of two copies of a defective gene for the disease or characteristic to develop.

• Sex-linked dominant

Sex-linked dominant is a hereditary disorder, in which a trait or disorder can be passed down through families. the sex-linked dominant disease is caused by one abnormal gene on the X chromosome.

• Sex-linked recessive

In recessive inheritance, however, both matching genes must be defective for disease to occur. If only one of the two genes in a pair is defective, the disease is either not present or is minor. A carrier is someone who has one defective gene but no symptoms. Carriers can pass on defective genes to their children. 

Examples of Mendelian disorders in humans

There are some common examples of Mendelian genetic disorders, which are as follows:

1. Sickle cell anaemia
2. Muscular dystrophy
3. Cystic fibrosis
4. Thalassemia
5. Phenylketonuria
6. Colour blindness
7. Skeletal dysplasia
8. Haemophilia

Let us understand some of these disorders in more detail:

1. Sickle Cell Anaemia

• This is an autosomal recessive hereditary condition. 
• A sickle cell anaemic person normally inherits the defective gene from both carrier parents, according to the Mendelian law of inheritance.
• Sickle Cell Disease anaemia is induced by a shift in the location of the 6th amino acid in haemoglobin’s beta-globin chain. The amino acid Glutamate is replaced with Valine in this case.
• A physical change in the mutant haemoglobin molecule causes the transformation of a biconcave RBC into a Sickle Cell.
• Because of its deformed shape, this sickle-celled RBC has a reduced oxygen-carrying capacity than biconcave RBCs.

2. Phenylketonuria

• This is a hereditary autosomal recessive disorder.
• Phenylketonuria is an example of an inherited disorder in which the amino acid phenylalanine is not properly digested.
• The affected person lacks the enzyme that converts phenylalanine to tyrosine in this condition. As a result, phenylalanine accumulates in the body and is converted into several derivatives that cause mental retardation.

3. Thalassemia

• This is a genetic disorder in which the body does not produce enough haemoglobin. As a result, a large number of red blood cells are destroyed, resulting in anaemia in patients. Fatigue, weakness, and paleness are all symptoms of thalassemia.
• It is a recessive autosomal condition. Trait, minor, intermedia, and major thalassemia are the four forms of thalassemia determined on severity.
• Thalassemia causes facial bone deformations, swelling in the abdomen, and black urine, among other signs and effects.

4. Cystic fibrosis

• Cystic Fibrosis is a disease that affects the lungs.
• Cystic Fibrosis is an example of an autosomal recessive disorder.
• The respiratory and digestive systems are both affected by cystic fibrosis. Patients with this inherited disorder produce large amounts of mucus, which blocks the lungs and pancreas’ passageways.
• Cystic fibrosis patients have a life expectancy of fewer than ten years.

5. Huntington’s disease

Huntington’s disease is a well-known autosomal dominant single-gene disease; most people with a single copy of the mutant huntingtin gene (HTT) will develop the condition later in life. Autosomal dominant disorders typically affect people in their early years and prevent them from living through infancy or childhood, preventing them from reproducing and potentially passing the mutation on to their children. The late start of Huntington’s disease, on the other hand, implies that many people with the disease have already had children before they even realise they have the gene.

Conclusion

Mendelian disorders are passed down through families in a manner that reflects the inheritance of a single causative gene. Families with cystic fibrosis, Huntington’s disease, and fragile X syndrome show a wide range of inheritance patterns, which reflect the nature of the underlying gene and the causing genetic lesion.