Pedigree Analysis and Probability in Genetic Inheritance

Pedigree Analysis in Genetics

Introduction to Pedigree Analysis

Pedigree analysis is a fundamental tool in genetics for tracing the inheritance patterns of traits and genetic disorders across generations. By examining family trees, geneticists can predict future offspring outcomes and determine the mode of inheritance for specific traits.

• Pedigree: A diagram representing family relationships and the transmission of inherited traits.

• Application: Used to identify inheritance patterns (dominant, recessive, autosomal, sex-linked) and predict genetic outcomes.

Probability Laws in Genetic Inheritance

Probability laws are essential for calculating the likelihood of genetic outcomes. Two main rules are applied:

• Multiplication Rule: Used for independent events (e.g., inheritance of genes on different chromosomes). Formula: $P(A ext{ and } B) = P(A) imes P(B)$

• Addition Rule: Used for mutually exclusive events (e.g., chance of being a boy or girl). Formula: $P(A ext{ or } B) = P(A) + P(B)$

Examples of Probability Application

• Multiplication Rule:

  • Probability of all boys in 3 births: $P( ext{BBB}) = rac{1}{2} imes rac{1}{2} imes rac{1}{2} = rac{1}{8}$

  • Probability of ABC phenotype in AaBbCc x AaBbCc cross: $P(ABC) = rac{3}{4} imes rac{3}{4} imes rac{3}{4} = rac{27}{64}$

• Addition Rule:

  • Probability of boy or girl in a birth: $P( ext{boy or girl}) = rac{1}{2} + rac{1}{2} = 1$

  • Probability of a gamete from a heterozygote (Aa): $P( ext{A or a}) = rac{1}{2} + rac{1}{2} = 1$

  • Probability of dominant phenotype in Aa x Aa: $P( ext{dominant phenotype}) = P( ext{AA}) + P( ext{Aa}) = rac{1}{4} + rac{1}{2} = rac{3}{4}$

Relationship Between Mendelian and Probability Laws

Probability Law	Mendelian Law Applied For	Type of Events Applied For
Multiplication law	Law of independent assortment	Independent events
Addition law	Law of segregation	Mutually exclusive events

Pedigree Symbols and Interpretation

Pedigree Key

• Square: Male

• Circle: Female

• Shaded: Affected individual

• Unshaded: Unaffected individual

• Horizontal line: Mating

• Vertical line: Offspring

Determining Dominant vs. Recessive Traits

• Recessive Trait: Unaffected parents can have affected children (e.g., attached earlobe).

• Dominant Trait: Affected parents can have unaffected children (e.g., widow's peak).

Human Genetic Disorders: Pedigree Analysis

Inheritance Mode Determination

Dominant vs. Recessive

• Recessive Disorders:

  • Two unaffected parents have affected children (conclusive evidence).

  • Disease often skips generations (supportive evidence).

• Dominant Disorders:

  • Two affected parents have unaffected children (conclusive evidence).

  • Disease appears in every generation (supportive evidence).

Autosomal vs. Sex-Linked

• Autosomal Disorders:

  • Equal representation in males and females.

  • Conclusive evidence: Unaffected parents have affected daughter (autosomal recessive); affected parents have healthy daughter (autosomal dominant).

• Sex-Linked Disorders:

  • Over-representation in one sex (usually males for X-linked recessive).

  • Conclusive evidence: Unaffected parents with X-linked recessive disorder cannot have affected daughters, only sons.

Pedigree Patterns for Major Inheritance Modes

• Autosomal Recessive: Both sexes involved, generations skipped.

• Autosomal Dominant: Both sexes involved, generations not skipped.

• X-linked Recessive: Trait is rare, skips generations, males more often affected, affected fathers do not pass to sons.

• X-linked Dominant: Trait appears in every generation, affected father only has affected daughters, not sons.

• Y-linked: Only males affected, father to son transmission, all sons inherit trait.

Summary Table: Inheritance Mode Determination from Human Pedigrees

Inheritance Mode	Conclusive Evidence	Suggestive Evidence
Autosomal dominant	Two affected parents have unaffected daughter	Disease appears every generation; equal in males and females
Autosomal recessive	Two unaffected parents have affected daughter	Disease skips generations; equal in males and females
X-linked dominant	Two affected parents have unaffected sons	All daughters affected; trait appears every generation
X-linked recessive	Two unaffected parents have affected sons	Males more affected; trait skips generations

Modes of Inheritance of Genetic Disorders

• Autosomal dominant

• Autosomal recessive

• X-linked dominant

• X-linked recessive

• Y-linked and mitochondrial inheritance (less common)

Inheritance Patterns and Probabilities

• Autosomal recessive: 25% chance offspring will have disorder if both parents are carriers.

• Autosomal dominant: 50% chance offspring will have disorder if one parent is affected.

• X-linked recessive: 50% of sons affected if mother is carrier; daughters are healthy.

• X-linked dominant: All daughters affected if father is affected; 50% of children affected if mother is affected.

Questions for Pedigree Analysis

• Does the trait skip generations?

• Does it appear in both sexes or predominantly one?

• Do two unaffected parents have an affected child?

• Do two affected parents have an unaffected child?

Additional info:

• Pedigree analysis is a key method for diagnosing and predicting genetic disorders in clinical genetics and research.

• Probability calculations are essential for genetic counseling and risk assessment.