Explain pedigree analysis to illustrate hereditary disease with suitable examples.

Understanding Pedigree Analysis

Pedigree analysis is essentially a family tree that tracks the presence or absence of a particular phenotype (observable characteristic) to determine the mode of inheritance of a genetic trait. It’s based on the principle that traits are passed down through generations according to specific patterns dictated by the underlying genes.

Symbols Used in Pedigree Charts

Standardized symbols are used to represent individuals and their relationships in a pedigree chart:

• Square: Represents a male
• Circle: Represents a female
• Shaded Symbol: Indicates an individual affected by the trait
• Unshaded Symbol: Indicates an individual not affected by the trait
• Horizontal Line: Represents a mating or marriage
• Vertical Line: Connects parents to their offspring
• Roman Numerals: Indicate generations
• Arabic Numerals: Identify individuals within a generation
• Half-Shaded Symbol: Indicates a carrier (heterozygous) for a recessive trait

Modes of Inheritance and Examples

1. Autosomal Dominant Inheritance

In autosomal dominant inheritance, only one copy of the mutated gene is sufficient to cause the disease. Affected individuals usually have at least one affected parent. The trait appears in every generation.

Example: Huntington’s Disease – This neurodegenerative disorder is caused by a dominant allele of the HTT gene. If one parent has Huntington’s disease (Hh), there is a 50% chance their child will inherit the disease. The disease typically manifests in adulthood, making early diagnosis challenging.

2. Autosomal Recessive Inheritance

In autosomal recessive inheritance, two copies of the mutated gene are required for the disease to manifest. Affected individuals usually have unaffected parents who are carriers. The trait often skips generations.

Example: Cystic Fibrosis (CF) – CF is caused by mutations in the CFTR gene. Both parents must be carriers (Cc) for a child to be affected (cc). There is a 25% chance of an affected child, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. According to the Cystic Fibrosis Foundation, approximately 30,000 people in the United States are living with CF (as of 2023).

3. X-Linked Recessive Inheritance

In X-linked recessive inheritance, the mutated gene is located on the X chromosome. Males are more frequently affected because they have only one X chromosome. Females must inherit two copies of the mutated gene to be affected, making them typically carriers.

Example: Hemophilia A – This bleeding disorder is caused by a mutation in the F8 gene on the X chromosome. A carrier mother (X^HX^h) has a 50% chance of passing the mutated gene to her son (X^hY), who will be affected. Her daughter has a 50% chance of being a carrier (X^HX^h).

4. X-Linked Dominant Inheritance

In X-linked dominant inheritance, a single copy of the mutated gene on the X chromosome is sufficient to cause the disease. Affected males pass the trait to all their daughters but none of their sons. Affected females have a 50% chance of passing the trait to each child, regardless of sex.

Example: Fragile X Syndrome – While complex, Fragile X syndrome often exhibits X-linked dominant inheritance. It is caused by a mutation in the FMR1 gene. Affected females may have milder symptoms than affected males.

Analyzing Pedigrees to Determine Inheritance Patterns

Several clues help determine the mode of inheritance:

• If the trait appears in every generation, it’s likely dominant.
• If the trait skips generations, it’s likely recessive.
• If more males are affected, it suggests X-linked inheritance.
• If affected individuals have unaffected parents, it suggests recessive inheritance.