Pedigrees

Learning Objectives

Determine the classification of alleles in pedigree charts as recessive, dominant, X-linked recessive, or X-linked dominant.

Pre-Class Review

True/False Statements:
- Two genes located on the same chromosome will most likely be inherited together? .
- If one gene is located on Chromosome 3 and another is located on Chromosome 4, it is likely they will be inherited together since chromosome 3 and 4 are close together? .
X-linked Recessive Traits:
- a. Females as Carriers: Females often serve as carriers because they possess two X chromosomes.
- b. Expression in Females: Females can only express this trait if both X chromosomes carry the allele for the condition.
- c. Male Expression: Males have only one X chromosome; if their X chromosome is affected, they will have the trait.
- d. Hallmarks of Inheritance:
  - i. Males are primarily affected by X-linked recessive traits.
  - ii. Females are typically unaffected but can be carriers.
  - iii. Conditions demonstrating this pattern include color blindness and hemophilia.
X-linked Dominant Traits:
- a. Only one affected X chromosome is needed for an individual to display the condition.
- b. Inheritance from Father: Males, having only one X chromosome, will pass the affected X chromosome to all daughters, meaning all daughters will inherit the trait, while none of the sons will inherit it.
- c. Maternal Inheritance: If a mother is affected, the ratio of affected offspring is approximately 50/50 based on gender, indicating that if an offspring inherits the affected X, they will display the trait regardless of being male or female.
- d. Conditions with X-linked Dominant Pattern: Examples include hypophosphatemic rickets, Rett syndrome, and Alport syndrome.
Genotype Questions:
- XLA is a recessive disorder where the body cannot produce immune cells (B cells). The responsible gene (gene A) is located on the X chromosome.
- Genotype Question: What is the genotype for a female with XLA?
  - a. $X^AY$
  - b. $X^AX^a$
  - c. $X^AX^A$
  - d. $X^aX^a$
  - e. $X^aY$
- Parental Genotypes for Problem 4: Based on the background, possible parental genotypes include:
  - a. $X^AX^A$ and $X^aY$
  - b. $X^AX^A$ and $X^AY$
  - c. $X^AX^a$ and $X^AY$
  - d. $X^AX^a$ and $X^aY$
  - e. $X^aX^a$ and $X^AY$.

Reading Pedigrees

Definition of Pedigrees:
- a. Family Tree Analogy: Pedigrees resemble family trees in structure, both showing multiple generations of a family.
- b. Labeling: Both types of diagrams label parents and their offspring.
- c. Analytical Nature of Pedigrees: Pedigrees are more analytical and track how alleles are passed from one generation to the next.
Drawing and Interpreting Pedigrees:
- a. Sex Annotation: When creating pedigrees, sex is distinguished by different shapes; typically, diamonds symbolize hypothetical future offspring.
- b. Affected Individuals: Individuals expressing the trait are represented by filled shapes.
- c. Unaffected Individuals: Individuals not displaying the trait are shown with unfilled or lighter shapes.
Labeling Generations and Individuals:
- a. Generations are labeled with Roman numerals (I, II, III, etc.).
- b. Individuals are labeled with Arabic numerals (1, 2, 3, 4, etc.).
- c. If asked about a particular individual in a pedigree, the notation is typically used, e.g., the male (II, 2) mates with an affected female.
- d. Probability Calculation: What is the probability that they have an affected child?
Steps for Solving Pedigree Problems:
- a. Frequency of Trait: Examine how common the trait is. Dominant traits are generally observed more frequently than recessive traits (however, not always).
- b. Generational Presence: Determine if the trait manifests in every generation, focusing primarily on parent-offspring relationships. Traits appearing in each generation may indicate dominance.
- c. Skip Generations: Investigate if two unaffected parents can have an affected child; such occurrences often indicate recessive traits.
- d. Gender Distribution in Affected Individuals:
  - i. X-linked recessive traits tend to be more prevalent in males.
  - ii. Females can exhibit X-recessive traits, but this is rare since they require two affected X chromosomes.
  - iii. X-linked dominant traits suggest affected fathers result in all affected daughters.
  - iv. X-linked dominant traits from affected mothers have equal proportions of affected sons and daughters.
- e. Mitochondrial Inheritance: Determine if a trait follows only one family line; mitochondrial conditions are inherited from the mother only, as fathers cannot pass on mitochondrial traits.
- f. Punnett Square Ratios: Utilize knowledge of Punnett square ratios, bearing in mind that these are guidelines and not absolute rules.

Examples of Inheritance Patterns

Example 1 - Analyzing the Inheritance Pattern:
- a. Breakdown: Examine whether the pattern is common, if it appears across generations, whether two unaffected parents have an affected child.
- b. Determine the expected inheritance pattern from observations.
Example 2 Analysis:
- a. It’s common and appears in every generation.
- b. Check if two affected parents can have a non-affected child.
- c. Decide if the trait is sex-linked and determine the inheritance pattern.
Example 3 Assessment:
- a. Examine if the trait is common and determine if it appears in every generation.
- b. Check for affected offspring from unaffected parents and assess if the trait is sex-linked to determine inheritance.
Example 4 Review:
- a. Determine commonality.
- b. Check for skipped generations.
- c. Analyze unaffected parents having an affected child.
- d. Determine whether it involves X-linked inheritance.
Example 5 Review:
- a. Identify whether both trees exhibit the same pattern.
- b. Check commonality.
- c. Determine if generational skipping occurs.
- d. Assess if the trait is sex-linked.
X-Dominant Implications:
- a. Affected fathers will have affected daughters.
- b. Affected mothers will have a 50/50 ratio of affected children.