A CLOSER LOOK AT MENDELIAN DISORDERS

Mendelian disorders are genetic conditions that follow the principles of Mendel’s laws of inheritance. These principles state that traits are inherited in a predictable manner and that each parent contributes one allele (a version of a gene) to their offspring. The postulates of Mendelian disorders are as follows:

1. The law of segregation: Each parent contributes one allele to their offspring, and these alleles segregate from each other during gamete formation. This means that each child inherits one allele from each parent, resulting in a unique combination of alleles.

2. The law of independent assortment: Alleles for different genes are sorted independently of each other during gamete formation. This means that the presence of one allele does not affect the probability of another allele being present.

3. The law of dominance: One allele can be dominant over another allele, meaning that the dominant allele will be expressed in the phenotype even if the other allele is present.

4. The law of recessiveness: An allele that is recessive will not be expressed in the phenotype if a dominant allele is present.

5. The law of penetrance: The expression of a trait is determined by both the alleles that an individual possesses and the environment in which they live.

6. The law of complete penetrance: If an individual has the necessary alleles for a particular trait, they will always express that trait.

7. The law of variable expression: The expression of a trait can vary among individuals who have the same alleles, even if they are homozygous (have two copies of the same allele).

8. The law of heritability: The expression of a trait is influenced by both genetic and environmental factors.

9. The law of pleiotropy: A single gene can influence multiple traits.

10. The law of polygenicity: Multiple genes contribute to the expression of a trait.

These postulates provide a framework for understanding the inheritance of Mendelian disorders, such as sickle cell anemia, cystic fibrosis, and Huntington’s disease. By studying the patterns of inheritance of these disorders, scientists can gain insights into the underlying genetic causes and develop new treatments and therapies.

 

Inheritance patterns in genetic disorders

Inheritance patterns in genetic disorders can be categorized into three main types: autosomal dominant disorders, autosomal recessive disorders, and X-linked disorders. These patterns determine how the disorder is passed down from one generation to the next.

1. Autosomal Dominant Disorders:
Autosomal dominant disorders are caused by a mutation in a single gene on one of the non-sex chromosomes (autosomes). In this inheritance pattern, an affected individual has a 50% chance of passing the disorder on to each of their offspring. Both males and females can be affected by autosomal dominant disorders.

The inheritance of autosomal dominant disorders follows a specific pattern. If one parent carries the mutated gene, there is a 50% chance that each child will inherit the disorder.

Examples of autosomal dominant disorders include Huntington’s disease, Marfan syndrome, neurofibromatosis type 1, and familial hypercholesterolemia. These disorders often exhibit variable expressivity, meaning that the severity of symptoms can vary among affected individuals.

2. Autosomal Recessive Disorders:
Autosomal recessive disorders occur when an individual inherits two copies of a mutated gene, one from each parent. The parents themselves are typically unaffected carriers of the disorder, meaning they carry one copy of the mutated gene but do not show symptoms. In this inheritance pattern, both males and females have an equal chance of being affected.

The inheritance of autosomal recessive disorders follows a specific pattern. If both parents are carriers (heterozygous), there is a 25% chance that each child will inherit two copies of the mutated gene and be affected by the disorder. There is also a 50% chance that each child will be a carrier like their parents, and a 25% chance that they will neither be affected nor carriers.

Examples of autosomal recessive disorders include cystic fibrosis, sickle cell anemia, Tay-Sachs disease, and phenylketonuria (PKU). These disorders often show a higher prevalence in populations with a history of consanguineous marriages (marriages between close relatives).

3. X-Linked Disorders:
X-linked disorders are caused by mutations in genes located on the X chromosome. Since males have one X chromosome and females have two, the inheritance pattern of X-linked disorders differs between males and females.

The inheritance of X-linked disorders follows a specific pattern. If a male inherits the mutated gene on his single X chromosome, he will be affected by the disorder. However, if a female inherits the mutated gene on one of her two X chromosomes, she will typically be an unaffected carrier.

Females can be affected by X-linked disorders if they inherit the mutated gene from both parents. This is relatively rare since the affected father would pass the mutated gene to his daughters but not his sons. Males, on the other hand, cannot pass an X-linked disorder to their sons but will always pass it to their daughters.

Examples of X-linked disorders include Duchenne muscular dystrophy, hemophilia A and B, and color blindness.

In summary, autosomal dominant disorders are caused by a mutation in a single gene on one of the non-sex chromosomes and follow a 50% chance of inheritance from an affected parent. Autosomal recessive disorders occur when an individual inherits two copies of a mutated gene and follow a 25% chance of inheritance from carrier parents. X-linked disorders are caused by mutations on the X chromosome and have different inheritance patterns for males and females.

 

Examples of autosomal and X-linked disorders explained 

Here are some examples of autosomal and X-linked disorders, along with explanations of each:

A) Autosomal Disorders:

1. Sickle Cell Anemia: This is a genetic disorder that affects hemoglobin production in the body. It is caused by a point mutation in the HBB gene, which codes for the beta-globin subunit of hemoglobin. The mutation results in the production of abnormal hemoglobin, leading to red blood cells that are sickle-shaped and prone to rupture. Sickle cell anemia is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.

2. Cystic Fibrosis: This is a genetic disorder that affects the respiratory and digestive systems. It is caused by a deletion of three nucleotides in the CFTR gene, which codes for the cystic fibrosis transmembrane conductance regulator protein. This protein regulates the movement of chloride ions in and out of cells, and the deletion leads to the production of thick, sticky mucus that can clog airways and digestive passages. Cystic fibrosis is an autosomal recessive disorder.

3. Huntington’s Disease: This is a neurodegenerative disorder that causes progressive damage to the brain, leading to cognitive decline, motor dysfunction, and psychiatric symptoms. It is caused by an expansion of a CAG repeat in the Huntingtin gene, leading to a toxic protein that causes brain cell death. Huntington’s disease is an autosomal dominant disorder, meaning that an individual only needs to inherit one copy of the mutated gene to develop the condition.

 

B) X-Linked Disorders:

1. Hemophilia A: This is a genetic disorder that affects blood clotting. It is caused by a mutation in the F8 gene, which codes for the coagulation factor VIII. The mutation leads to a deficiency of factor VIII, which is necessary for blood clotting. Hemophilia A is an X-linked recessive disorder, meaning that an individual must inherit one copy of the mutated gene (from their mother) to develop the condition.

2. Duchenne Muscular Dystrophy: This is a genetic disorder that affects muscle strength and function. It is caused by a mutation in the DMD gene, which codes for the dystrophin protein. The mutation leads to a deficiency of dystrophin, which is necessary for muscle strength and function. Duchenne muscular dystrophy is an X-linked recessive disorder.

3. Turner Syndrome: This is a genetic disorder that affects females and is caused by a missing or partially deleted X chromosome. It can result in a range of symptoms, including short stature, infertility, and heart and kidney problems. Turner syndrome is an X-linked recessive disorder.