Mendelian disorders are genetic diseases caused by mutations in a single gene following the inheritance patterns described by Gregor Mendel in his laws of inheritance. These disorders follow dominant, recessive, or sex-linked patterns, meaning they can be predicted based on family genetics.
Mendelian disorders affect individuals in different ways, ranging from mild symptoms to life-threatening conditions. This article explores the types of Mendelian inheritance, with real-world examples of disorders, their genetic basis, symptoms, and impact on affected individuals.
1. Autosomal Dominant Disorders
In autosomal dominant inheritance, a person only needs one copy of the mutated gene (from one parent) to develop the disorder. The affected gene is located on one of the non-sex chromosomes (autosomes).
Example: Huntington’s Disease
Genetic Basis
- Caused by a mutation in the HTT gene on chromosome 4.
- The mutation leads to abnormal repetition of the CAG sequence, producing a faulty huntingtin protein that damages brain cells.
Symptoms
- Develops in adulthood (usually between ages 30-50).
- Causes progressive brain degeneration, leading to movement disorders, cognitive decline, and psychiatric symptoms.
- Symptoms worsen over time, and there is no cure.
Real-World Impact
- If one parent has the disorder, each child has a 50% chance of inheriting it.
- Predictive genetic testing helps individuals plan for the future.
Example: Marfan Syndrome
Genetic Basis
- Caused by a mutation in the FBN1 gene on chromosome 15, which affects the protein fibrillin-1, crucial for connective tissue strength.
Symptoms
- Tall stature, long limbs, and flexible joints.
- Weakness in the aorta, increasing the risk of life-threatening heart problems.
- Vision problems due to lens dislocation.
Real-World Impact
- Affected individuals require regular heart monitoring and may undergo preventive surgeries.
- If a parent has the condition, there is a 50% chance of passing it to offspring.
2. Autosomal Recessive Disorders
In autosomal recessive inheritance, a person needs two copies of the mutated gene (one from each parent) to develop the disorder. Carriers (with one copy) usually do not show symptoms.
Example: Cystic Fibrosis (CF)
Genetic Basis
- Caused by mutations in the CFTR gene on chromosome 7, affecting chloride ion transport in cells.
Symptoms
- Thick mucus buildup in lungs → Leads to difficulty breathing, chronic lung infections, and lung damage.
- Digestive problems due to mucus blocking pancreatic enzymes.
Real-World Impact
- Common in Caucasian populations, affecting about 1 in 2,500 births.
- Treatments include lung therapies, enzyme supplements, and gene-targeted drugs.
Example: Sickle Cell Anemia
Genetic Basis
- Caused by a mutation in the HBB gene on chromosome 11, altering hemoglobin in red blood cells.
Symptoms
- Red blood cells become crescent-shaped, reducing oxygen transport.
- Severe pain episodes, anemia, and organ damage.
- Increased risk of stroke and infections.
Real-World Impact
- Common in African, Mediterranean, and Indian populations.
- Carriers (sickle cell trait) are resistant to malaria, providing a survival advantage in malaria-prone regions.
3. Sex-Linked Disorders (X-Linked Recessive)
Sex-linked disorders occur due to mutations in genes located on the X chromosome. Since males (XY) only have one X chromosome, they are more affected by X-linked recessive disorders, while females (XX) can be carriers.
Example: Hemophilia
Genetic Basis
- Caused by a mutation in genes coding for blood clotting factors VIII or IX.
Symptoms
- Excessive bleeding from minor cuts or internal bleeding from injuries.
- Can lead to joint damage and life-threatening blood loss.
Real-World Impact
- Historically known as the “Royal Disease”, affecting European royal families, including descendants of Queen Victoria.
- Treated with clotting factor replacement therapy.
Example: Duchenne Muscular Dystrophy (DMD)
Genetic Basis
- Caused by mutations in the DMD gene on the X chromosome, which produces dystrophin (a muscle protein).
Symptoms
- Progressive muscle weakness appearing in early childhood.
- Loss of mobility, often requiring wheelchairs by adolescence.
- Heart and lung failure in later stages.
Real-World Impact
- More common in males (1 in 3,500 male births).
- Ongoing research explores gene therapy as a future treatment.
4. Co-Dominant and Mitochondrial Disorders
Some Mendelian disorders follow non-traditional inheritance patterns, such as co-dominance (both alleles are expressed) and mitochondrial inheritance (genes inherited from the mother).
Example: Beta-Thalassemia (Co-Dominant Inheritance)
Genetic Basis
- Mutation in the HBB gene, reducing hemoglobin production.
Symptoms
- Mild anemia in carriers (Beta-Thalassemia Minor).
- Severe anemia in homozygous individuals (Beta-Thalassemia Major), requiring regular blood transfusions.
Real-World Impact
- More common in Mediterranean, Middle Eastern, and South Asian populations.
Example: Leber’s Hereditary Optic Neuropathy (LHON) (Mitochondrial Inheritance)
Genetic Basis
- Caused by mutations in mitochondrial DNA (passed only from the mother).
Symptoms
- Sudden vision loss in young adulthood due to optic nerve damage.
Real-World Impact
- Affects males more often than females, though both can inherit it from their mother.
Conclusion
Mendelian disorders follow predictable inheritance patterns based on dominant, recessive, and sex-linked traits. Each disorder results from a single-gene mutation, impacting an individual’s health in different ways.
By studying these disorders, scientists develop genetic screening, treatments, and preventive measures to improve patient outcomes. Understanding Mendelian inheritance also helps individuals and families make informed decisions about genetic risks and medical care.