Mendelian Disorders: Definition, Types, Development, Examples, Facts

Mendelian disorders are genetic conditions that are caused due to mutations in a single gene and follow inheritance patterns described by Gregor Mendel. They are caused by inheriting genes based on the laws of inheritance postulated by Mendel. These disorders depend upon the type of mutation and location of the gene. They follow autosomal dominant, autosomal recessive, or X- linked. The study of Mendelian genetics helps to predict the possibility of such disorders in future generations and explain how specific genes are passed from one generation to next.

This Story also Contains

1. What are Mendelian Disorders?
2. Types of Mendelian Disorders
3. Examples of Mendelian Disorders
4. Recommended Video on Mendelian Disorders
5. MCQs in Mendelian Disorders

One of the key tools used in understanding and tracking Mendelian disorders is pedigree analysis. This method examines family histories to trace the genetic disorder and find carriers and affected individuals. The study of Mendelian genetics not only for early diagnosis but also to prevent the recurrence of such disorders in future generations. It helps in genetic counselling and plan the treatment accordingly.

What are Mendelian Disorders?

Mendelian disorders are genetic disorders that are caused by mutations in a single gene. These disorders follow a clear inheritance pattern—autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive, according to the principles of Gregor Mendel. They are passed from one generation to another depending on how the genes are inherited.

These disorders can seriously affect the health and quality of life of a person. Understanding their nature is beneficial for diagnosis, genetic counselling, and the development of targeted treatments. The study of these rare conditions has provided key insights into genes and heredity.

The father of modern genetics, Gregor Mendel, discovered the basic rules of heredity through his experiments with pea plants in the 19th century. He demonstrated that traits were passed as distinct units now called genes. He gave Mendel’s laws of segregation and Mendel’s law of independent assortment. His work was ignored at the time but it later gained recognition. It has now become the foundation for modern genetics and hereditary diseases.

Types of Mendelian Disorders

Mendelian disorders are classified based on how the mutated gene is inherited from one generation to the next. These inheritance patterns help to predict the likelihood of a disorder. Each type follows specific rules established through Mendel’s laws of inheritance. These disorders can be categorized into:

Autosomal Dominant Disorders

These are genetic disorders caused by mutation in a single allele of a gene. The genes are located on one of the autosomes. Affected individuals need only one copy of the mutated gene to express the disorder. There is a 50% probability that the disorder will be passed on to progeny by the patient.

Examples:

• Huntington's Disease: A neurodegenerative disorder causing progressive motor dysfunction, cognitive impairment, and psychiatric disturbances, typically appearing in mid-adulthood.

• Marfan Syndrome: A systemic connective tissue disorder that affects the heart, eyes, blood vessels, and skeleton, leading to cardiovascular complications. It is caused by mutations affecting the fibrillin-1 protein.

Autosomal Recessive Disorders

These disorders occur when an individual has two copies of a mutated gene, one from each parent. Individuals with only one mutated allele are carriers and are asymptomatic but they can pass the gene to offspring.

Examples:

• Cystic Fibrosis: An autosomal recessive disorder affecting the digestive and respiratory system due to mutations in the CFTR gene.

• Sickle Cell Anemia: An autosomal genetic disorder whereby the erythrocytes are in a sickle-shape. It causes anemia, pain, and many other serious complications.

X-Linked Dominant Disorders

X-linked dominant disorders arise from mutations in genes located on the X chromosome. They are expressed when just one copy of the mutated gene is present. These disorders affect both males and females, though the extent and frequency depend upon the composition of X chromosome.

Examples:

• Rett Syndrome: A neurodevelopmental disorder mostly seen in females, characterized by normal early growth followed by the loss of motor skills and speech.

• Fragile X Syndrome: A genetic condition leading to intellectual disability, behavioral challenges, and distinctive physical features.

X-Linked Recessive Disorders

X-linked recessive disorders are due to a mutation on the X chromosome. Males are more affected because they have only one X chromosome. Females have two X chromosomes, and are generally carriers unless they inherit two copies of the mutated gene.

Examples:

• Hemophilia: This disorder is caused by an inability of blood to clot, resulting in continuous and excessive bleeding from the injured site.

• Duchenne Muscular Dystrophy: It causes progressive degeneration and weakness of muscle.

Examples of Mendelian Disorders

Mendelian disorders show predictable patterns. They can be classified based on the modes of inheritance. These disorders show early in life and can affect various organs. They help to understand gene interaction and how to provide treatment to the patients. The examples are described below:

Sickle Cell Anaemia

• Sickle cell anemia affects haemoglobin and makes erythrocytes rigid, sickle-shaped.

• These abnormal cells obstruct blood flow, causing anemia and pain, which are termed sickle cell crises and possible organ damage.

• Patients are more prone to infection due to spleen damage.

• Additional complications such as stroke, acute chest syndrome, and pulmonary hypertension.

• Management includes pain relief, blood transfusions, and drugs like hydroxyurea.

Muscular Dystrophy

• These are a group of genetic disorders that result in muscle weakness and degeneration.

• Duchenne Muscular Dystrophy (DMD) is the most severe form and mostly affects the boys in their early childhood.

• Characterised by progressive muscle wasting, loss of walking ability, later respiratory and cardiac complications.

• Treatment includes physical therapy, steroids, and supportive care to maintain function.

Cystic Fibrosis

• A disorder that causes thick, sticky mucus to build up in the lungs and digestive system.

• This leads to severe respiratory issues like frequent lung infections, and difficulty breathing.

• Causes insufficiency of pancreatic enzyme due to the inability to activate these enzymes, leading to malnutrition and poor growth.

• It can also lead to diabetes mellitus, liver disease, and male infertility.

• Managed through airway clearance techniques, enzyme replacement, and medications such as CFTR modulators.

Thalassemia

• A genetic disorder that affects hemoglobin production, leading to anaemia.

• Symptoms include fatigue, weakness, and pale or yellowish skin.

• The severe forms, like beta-thalassemia major, require regular transfusion.

• The complications can also include iron overload, bone deforming, and spleen enlargement.

• Treatments range from blood transfusions and iron chelation therapy, in some cases, bone marrow transplantation.

Phenylketonuria (PKU)

• Phenylketonuria is a metabolic disorder caused by the lack of enzyme phenylalanine hydroxylase, which breaks down phenylalanine.

• If not treated, the phenylalanine continues to build up, causing damage to the human brain and hence leading to intellectual disability and developmental delay.

• The symptoms are musty odour, seizures, and behavioural problems.

• Diagnosis by newborn screening.

• Treatment includes a strict diet with low phenylalanine levels and special medical supplements.

Colour Blindness

• A genetic condition that impairs the ability of a person to see certain colours or differentiate between them, mostly red and green.

• Caused by mutations in genes for colour vision located on the X chromosome, hence more common in males.

• Usually mild and does not cause major disability but affects daily activities.

• Coping strategies and tools available e.g. colour corrective lenses. No cure is available.

Skeletal Dysplasia

• A group of disorders that affect the growth of bone, resulting in stunted growth with defects in skeletal muscles.

• Conditions like achondroplasia and osteogenesis imperfecta fall under this category.

• Symptoms include disproportionate limb length, joint problems, and spinal problems. It can also result in respiratory problems and many more. Complications, such as hearing loss and dental problems.

• Cured by orthopaedic surgery, physical therapy, and supportive care.

Haemophilia

• A genetic bleeding disorder where the blood does not clot and suffers from excessive bleeding from minor wounds.

• The common forms are haemophilia A and haemophilia B, due to a deficiency of clotting factor VIII and clotting factor IX, respectively.

• This can lead to prolonged, spontaneous bleeding into joints and muscles with pain and disability.

• Treated by regular infusion of clotting factor and preventive measures to reduce bleeding.

Recommended Video on Mendelian Disorders

MCQs in Mendelian Disorders

Q1. Directions: In the following questions, a statement of Assertion (A) is followed by a statement of reason (R).

Assertion: Human males are Homozygous for X- linked characters.

Reason: Human male carry only one X chromosome.

1. If both assertion and reason are true and reason is the correct explanation of assertion

2. If both assertion and reason are true but reason is not the correct explanation of assertion

3. If assertion is true but reason is false

4. If both assertion and reason are false

Correct Answer: 1) If both assertion and reason are true and the reason is the correct explanation of the assertion

Explanation:

Haemophilia -This is a sex-linked recessive disease, which shows transmission from unaffected carrier females to some of the male progeny. In this, a simple cut will result in non-stop bleeding and no blood clotting will take place. Hemizygon condition is when chromosomes are not present, although the child is diploid. In humans, males 44+xy condition is found in cells hence all the genes present on the x and y chromosomes are in hemizygous condition.

Hence, the correct answer is Option (1) If both assertion and reason are true and the reason is the correct explanation of the assertion.

Q2. A person with sickle cell anaemia is

1. more prone to malaria

2. more prone to typhoid

3. less prone to malaria

4. less prone to typhoid

Correct answer: 3) less prone to malaria

Explanation:

Patients suffering from sickle cell anemia demonstrate a distinct kind of immunity against malaria due to the abnormally shaped RBCs. Since the parasite will find less favour in sickle-shaped RBCs, severe infection would occur less often. This protection is confirmed through multiple clinical research works, mainly from malaria-prone areas where this sickle cell trait has occurred as an intrinsic mechanism for defending against malaria.

Hence the correct answer is Option (3) less prone to malaria.

Q3. Select the correct match

1. Haemophilia-Y linked

2. Phenylketonuria- Autosomal dominant trait

3. Sickle cell anaemia- Autosomal recessive trait chromosome 11

4. Thalassemia- X linked

Correct answer: 3) Sickle cell anaemia- Autosomal recessive trait chromosome 11.

Explanation:

Sickle cell anemia is an autosomal recessive genetic disorder located on chromosome 11, caused by a mutation in the gene encoding hemoglobin. This mutation leads to the production of abnormal hemoglobin, known as hemoglobin S, which causes red blood cells to adopt a sickle shape. These abnormally shaped cells are less flexible and can get stuck in small blood vessels, disrupting blood flow and leading to symptoms like anemia, pain crises, and other serious health complications. Individuals must inherit two copies of the sickle cell gene (one from each parent) to express the disease.

Hence, the correct answer is option (3) Sickle cell anaemia- Autosomal recessive trait chromosome 11.

Also Read:

• MCQs on Human Genetic Disorders

• Gene Interaction
  

• Molecular Basis of Inheritance