Types of Mendelian Disorders in Humans and Examples

Mendelian disorders in humans are genetic conditions that follow Mendel’s laws of inheritance, resulting from mutations in a single gene. Common examples of Mendelian disorders are hemophilia, cystic fibrosis, thalassemia, etc. These disorders adhere to predictable patterns of transmission, either through autosomal dominant, autosomal recessive, or X-linked inheritance.

Understanding these Mendelian disorders in humans helps us understand the relationship between genes and phenotypes and guides medical research to promote health and prevent disease. In this article, we will study Mendelian Disorder, the Principles of Mendelian Disorders, and the examples of Mendelian Disorder in detail.

Mendelian Disorders

Mendelian disorders are also known as Mendelian diseases or monogenic disorders. They are genetic diseases caused by mutations in a single gene and follow Mendel’s laws of inheritance i.e., they are typically inherited in a predictable pattern based on the principles of dominance, recessive, or X-linked inheritance. They are typically categorised into five major groups based on their pattern of inheritance. These are Autosomal dominant disorders, Autosomal recessive disorders, Sex-linked dominant disorders, sex-linked recessive disorders and mitochondrial disorders.Some common examples of Mendelian disorders are haemophilia, phenylketonuria, etc.

Principles of Mendelian Disorders

Mendelian disorders follow Mendel’s laws of inheritance, which include the following principles:

• Law of Segregation: During gamete formation, the two alleles for a trait segregate from each other, so that each gamete carries only one allele for each gene. This means that each parent contributes one allele to their offspring.
• Law of Independent Assortment: Genes for different traits are inherited independently of each other. This means that the inheritance of one trait does not influence the inheritance of another trait, assuming the genes are located on different chromosomes or far apart on the same chromosome.
• Principle of Dominance: According to this principle, alleles of a gene can show equal or unequal dominance. In heterozygous individuals, the dominant allele always expresses itself. While for homozygous individuals if the recessive alleles are present, the phenotype will be expressed. However, if the genes are codominant, then both the traits will be expressed equally and an intermediate phenotype will be expressed.

Types of Mendelian Disorders

Depending on the pattern of inheritance, Mendelian disorders can be classified into five different types. These are:

• Autosomal Dominant Disorder: These disorders occur when a mutation occurs in a gene located on an autosomal chromosome. These traits are dominant and are expressed even if only one copy of the mutated gene is present on the loci.
• Autosomal Recessive Disorders: These disorders also occur when the mutation occurs in an autosomal gene. However, these are recessive disorders and are expressed in an individual only when two copies of mutated genes are present on the loci. Typically both parents are carriers of the mutated gene but do not show symptoms of the disorder.
• Sex-linked Dominant Disorders: These disorders are caused by mutations in genes located on the sex chromosomes (X and Y). If a dominant allele is present on the X chromosome, females are more likely to be affected than males because they have two X chromosomes.
• Sex-linked Recessive Disorder: These disorders are caused by mutations in genes located on the sex chromosomes (X and Y). Since males have only one X chromosome, they are more likely to be affected if they inherit a mutated X-linked recessive gene.
• Mitochondrial Disorders: These disorders are caused by mutations in the mitochondrial DNA, which is separate from the nuclear DNA and is inherited exclusively from the mother.

Examples of Mendelian Disorders in Humans

Sickle Cell Anaemia

Sickle cell anaemia is an autosomal recessisve disorder in which the red blood cells in blood turn out to be sickle shaped and lack the ability to carry sufficient amount of oxygen.

Sickle cell anaemia is caused due to a point mutation that occurs in the gene that codes for the beta-globin subunit of hemoglobin.

In this mutation single nucleotide substitution leads to the replacement of a glutamic acid residue in the 6th position of beta-globin chain with a valine residue. These abnormal chains lead to production of abnormal haemoglobins called S haemoglobins. These haemoglobin tend to stick together under low oxygen level and dehydration.

These abnormal haemoglobin molecules make the flexible RBCs rigid and attain shape of a sickle. These sickle shaped blood cells tend to get stuck in the blood vessels and hamper flow of oxygen to tissues. Thereby causing various symptoms like pain, dizziness, fatigue, etc.

Thalassemia

Thalassemia is also an autosomal recessive disorder. It is caused by mutations in HBB genes. Thalassemia are odf different types. Common types include alpha thalassemia and beta thalassemia. In Alpha thalassemia the alpha chain of hemoglobin is defective whereas in beta thalassemia the beta chain becomes defective.

Symptoms of thalassemia can vary widely depending on the type and severity of the condition. Common symptoms include fatigue, weakness, pale or yellowish skin, bone deformities, and slow growth.

Treatment for thalassemia typically involves managing symptoms and complications. This may include blood transfusions to replenish hemoglobin levels, iron chelation therapy to remove excess iron from the body, and, in severe cases, bone marrow transplantation, which can potentially cure the disorder by replacing the defective stem cells that produce abnormal blood cells.

Cystic Fibrosis

Cystic Fibrosis is an autosomal recessive disorder. It primarily affects the lungs and digestive system. It is caused by mutations in the CFTR gene, which is responsible for production of a protein called the cystic fibrosis transmembrane conductance regulator (CFTR).

A defective gene results in production of defective CFTR factor that ultimately causes the production of a thick and sticky mucus that clogs the airways and obstructs the pancreas.

Common symptoms include respiratory issues like chronic cough and lung infections, digestive problems like pancreatic insufficiency, and complications affecting other organs.

Cystic fibrosis has no cure but early diagnosis and comprehensive care, including medications, airway clearance techniques, nutritional support, and pulmonary rehabilitation, can help manage symptoms, slow disease progression, and improve quality of life for individuals with CF.

Phenylketonuria

Phenylketonuria is also an autosomal recessive disorder caused by mutation in PAH gene located on chromosome 12. The defective PAH gene does not produce phenylalanine hydrolases that metabolise phenylalanine. Therefore, phenyalanine start accumulating in blood and tissues.

Without treatment, PKU can lead to intellectual disability, developmental delays, seizures, behavioral problems, and other neurological complications.

The primary treatment for PKU is a lifelong low-phenylalanine diet, which restricts the intake of high-protein foods and includes specially formulated medical foods low in phenylalanine. In some cases, supplemental medication may also be used to help lower phenylalanine levels in the blood.

Huntington’s Disease

Huntington’s Disease is a neurodegenerative disorder caused by mutation of HTT gene located on chromosome 4. It is a dominant autosomal disorder.

Huntington’s disease is characterized by a progressive decline in motor control, cognitive function, and psychiatric symptoms. Symptoms typically appear in adulthood, usually between the ages of 30 and 50, but they can sometimes develop earlier or later in life.

There is no cure for Huntington’s disease, and treatment focuses on managing symptoms and providing supportive care. Medications can help alleviate some symptoms, while therapy and support groups can assist in coping with the challenges of the disease.

Haemophilia

Haemophilia is a X-linked recessive disorder. It is caused by mutations in genes responsible for producing clotting factors, essential proteins involved in the blood clotting process.

Symptoms of hemophilia can vary depending on the severity of the clotting factor deficiency. Common symptoms include:

• Prolonged bleeding after injuries or surgeries
• Frequent nosebleeds
• Easy bruising
• Joint pain and swelling due to bleeding into the joints (hemarthrosis)
• Excessive bleeding from minor cuts or dental procedures

Haemophilia is categorised in two types : Haemophilia A and Haemophilia B. Haemophilia A occurs with mutation in F8 gene of X-chromosome whereas Haemophilia B occurs with mutation in F9 gene of X-chromosome.

Haemophilia may occur due to spontaneous mutation in F8 or F9 gene and in such case it can be termed as sporadic haemophilia.

Treatment for hemophilia typically involves replacing the deficient clotting factor through intravenous infusion of clotting factor concentrates.

Colour Blindness

Colour blindness is a X-linked recessive disorder. It is characterised by the lack of ability in recognising certain colors. The most common types of color blindness are red-green color blindness and blue-yellow color blindness.

Color blindness is typically diagnosed through specialized tests, such as the Ishihara color test, which uses color plates to detect deficiencies in color perception.

There is no cure for color blindness. Individuals with this condition can learn to adapt to their color vision deficiency. This may involve using color vision aids, such as specialized lenses or apps, and making lifestyle adjustments to accommodate for difficulties with color perception.

Conclusion

Mendelian disorders in humans follow a typical inheritance pattern that can be classified as dominant inheritance and recessive inheritance. These disorders do not have cures as they are all caused by genetic mutations. However, all of the Mendelian genetic disorders can be managed and controlled through early diagnosis and supportive care. Some of these disorders prove to be lethal and patients do not live long with these disorders. While some of these disorders are highly manageable and patients suffering them can live a happy life with certain restrictions.

FAQs on Mendelian Disorders in Humans

What are Mendelian disorders?

Mendelian disorders are genetic conditions caused by mutations in a single gene. They are typically inherited in a predictable pattern according to Mendel’s laws of inheritance. Examples include cystic fibrosis, sickle cell disease, and Huntington’s disease.

What are the 3 Major Genetic Disorders?

The 3 major genetic disorders are single-gene disorder, chromosomal disorder, and complex gene disorder.

How Many Types of Mendelian Disorders are there?

There are five types of Mendelian Disorders.

Is Turner Syndrome a Mendelian Disorder?

No, Turner syndrome is not a Mendelian disorder. It is a chromosomal disorder caused by the complete or partial absence of one of the X chromosomes in females.

What is Maternal Inheritance?

Maternal inheritance refers to the transmission of genetic traits exclusively through the maternal lineage. This occurs when certain genes, typically located in the mitochondria.

What Disorder is also Known as Royal Disease?

The disorder commonly known as the “Royal disease” is hemophilia, specifically hemophilia B (also known as factor IX deficiency). It earned this nickname because it was prevalent among the descendants of Queen Victoria of England.

What are the Common Mendelian Diseases?

Some common examples of Mendelian diseases are cystic fibrosis, sickle cell disease, hemophilia, Huntington’s disease, phenylketonuria (PKU), Marfan syndrome, familial hypercholesterolemia, and cystinuria.

Name one Autosomal Recessive Genetic Disorder.

Cystic Fibrosis is an example of recessive genetic disorder.

Name one Example of an X-linked Recessive.

Haemophilia is an example of X-linked recessive.

What is the Difference Between Mendelian and Non-Mendelian Disorders?

Mendelian disorders arise from mutations in single genes following predictable inheritance patterns, while non-Mendelian disorders result from complex interactions between multiple genes and environmental factors.

What are Mendelian Disorders Give Two Examples?

Mendelian disorders are genetic conditions caused by mutations in single genes, following Mendel’s laws of inheritance. Examples include cystic fibrosis and sickle cell anemia.