L29 2025 - Pedigrees

Page 2: Family Pedigree Overview

Family Structure Diagram

• Mexico family structure outlines familial relationships and health issues.

• Members include:

  • Grandparents: Father (60's, colon cancer), Mother (70's, breast cancer diagnosed at 68)

  • Uncles and Aunts with various health issues (high cholesterol and blood pressure)

  • Siblings and cousins with age differences and health conditions described.

• Notable conditions include heart attacks and clubfoot noted in family relationships.

Page 3: Understanding Pedigrees

Definition and Key Features

• Pedigrees: Diagrams of family relationships, representing modes of inheritance (MOI).

• Key Symbols:

  • Symbols = People

  • Lines = Genetic Relationships

    • Horizontal Lines = Mating

    • Vertical Lines = Offspring

  • Shading = Trait of Interest

  • Circles XX = Females; Squares XY = Males

  • Diagonal line denotes a deceased individual.

  • shading = trait of interest

Page 4: Genetic Disorders

BRCA2 Deficiency

• BRCA2 as a genetic mutation reference; additional details or images listed under Creative Commons License indicating its importance in genetic studies.

Page 5: Sex Chromosome vs. Autosome Traits

Gene Location Importance in Inheritance

• Pedigrees assist in identifying if a trait's gene resides on an autosome or a sex chromosome.

Page 6: Implications of Gene Positioning

Understanding Inheritance Patterns

1. Autosomal Traits: Passed from parents to offspring independent of sex chromosomes.

2. X-Linked Traits: Almost exclusively inherited via the X chromosome affecting individuals' sex determination (XX or XY).

• Knowledge of inheritance types influences couples' reproductive decisions.

Page 7: Four Possible Modes of Inheritance (MOI)

1. Autosomal Recessive: Examples Cystic Fibrosis and Sickle Cell Anemia.

2. Autosomal Dominant: Example is Retinoblastoma.

3. X-Linked Recessive: Example is Duchenne Muscular Dystrophy.

4. X-Linked Dominant: Example is Rett Syndrome.

Page 8: Complexity of Inheritance

Evaluating Pedigree Complexity

• Understanding that there are no shortcuts to determine which MOI applies, and some pedigrees may display multiple MOI.

Page 9: Pedigree Labeling Techniques

• Freedom to choose labelling methods for pedigrees, with the necessity of including a legend for clarity.

• Allelic Representation:

  • Autosomal = A⁺A⁺, A⁺A^-, A^-A^-

  • X-Linked = X^A+X^A+, X^A+X^A-, X^A-X^A-, X^A+Y, X^A-Y

Page 10: Dominant Trait Legend

Understanding Dominant Traits in Pedigrees

Male:

• Normal: A-A-

• Affected: A+A+ or A+A-

Female:

• Normal: XA-XA- or XA-Y

• Affected: XA+XA+ or XA+XA- or XA+Y

Page 11: Recessive Trait Legend

Understanding Recessive Traits in Pedigrees

Male:

• Normal: A+A+ or A+A-

• Affected: A-A-

Female:

• Normal: XA+XA+ or XA+XA- or XA+Y

• Affected: XA-XA- or XA-Y

Page 12: Key Takeaways from Pedigree Analysis

• Parents are not assumed to be true-breeding strains, always investigate homozygosity.

• Autosomal Dominant traits require individuals to be labeled distinctly: homozygous dominant vs. heterozygous.

Page 13: Understand Obligatory Heterozygosity

• Distinguishing between normal (A-A-) and affected (A+A+) or (A+A-) individuals.

• Critical to label individuals correctly for accurate pedigree analysis.

Page 14: Pedigrees as Data Representation

• Recognition that pedigrees are often small and do not provide full 1:1 or 1:2:1 ratios.

Page 15: Dominant vs. Recessive Traits

Visual Representation

• Autosomal Dominant Trait: Normal: A-A-, Affected: A+A+ or A+A-.

• Autosomal Recessive Trait: Normal: A+A+ or A+A-, Affected: A-A-.

Page 16: X-Linked vs. Autosomal Traits

Identification Strategies

• Identification of inheritance types through definitions/examples of X-Linked Dominance and Autosomal Dominance.

Page 17: Male-Male Transmission

Identifying Autosomal Inheritance

• Male to male transmission supports an autosomal trait; identifies the importance of understanding inheritance modes.

Page 18: Practice Exercise

Trial Dominant Inheritance Scenario

• Understanding contributions to traits based on pedigree analysis, further reinforcing MOI practice.

Page 19: Importance of Comprehensive Data

Generational Analysis

• Importance of collecting data from multiple generations to accurately determine MOI from pedigrees.

Page 20: Pedigree Analysis Exercise

Exclusion Methods for X-Linked Inheritance

• Analyze pedigree data to exclude possible inheritance types based on male to male transmission.

Page 21: Mixing Modes of Inheritance

Key Reminders

• Avoid mixing alleles from different inheritance modes: either autosomal or X-linked, but not both.

Page 22: Simplicity in Analysis

Recessive Hypothesis Evaluation

• Consider statistical likelihood of recessive traits across generations; review clues in exam questions for dominance or recessive indications.

• Look at question text for clues:

  • Is the disease present in every generation?

  • Is the family outbred?

    • suggests dominance

  • Is the family inbred?

  • Are generations skipped? (data missing)

    • suggests recessive

Page 23: Understanding Inbreeding

Review of Genetic Relationships

• Discussion on inbreeding and its relation to genetic diseases; focus on the family members involved and their potential genetic links.

Page 24: Inbreeding Analysis

• Key questions to determine inheritance type and mode based on family relations and genetic conditions noted in pedigree analysis.

Page 25: Genetic Disease Inquiry

Autosomal vs. X-Linked Enquiry

• Thought exercise regarding dominant and recessive classifications for diseases within pedigree contexts.

Page 26: Confirmation on X-Linked Traits

• Analyze unaffected members of the pedigree to rule in or rule out X-linked inheritance hypotheses based on the traits present.

Page 27: Autosomal Confirmation

Critical Analysis

• Evaluating potential for an autosomal recessive disease based on observed family member traits in the pedigree.

Page 28: Exploring Albinism

Mode of Inheritance Practice

• Exercises to explore albinism through all four modes of inheritance presented earlier in the course slide.

Page 29: Closing Remarks

University of Glasgow

• Invitation for questions and discussion regarding the intricacies of genetic inheritance.