Pedigree Analysis

Mendelian Genetics Overview

Introduction to Pedigrees

• Analyze human pedigrees (family trees) to understand inheritance patterns of various traits.

Traits of Medical Interest

• Focus on several types of inheritance:

  • Autosomal Dominant

  • Autosomal Recessive

  • X-Linked Dominant

  • X-Linked Recessive

  • Cytoplasmically Inherited (Mitochondrial Genome)

Understanding Pedigree Symbols

Basic Pedigree Symbols

• Symbols used to represent individuals and relationships:

  • Male: Square

  • Female: Circle

  • Carrier Individuals: Half-filled symbols

  • Affected Individuals: Filled symbols

  • Death: Diagonal line through the symbol

  • Mating: Horizontal line between symbols

  • Twinning Symbol: Specific notation for dizygotic (fraternal twins) and monozygotic (identical twins).

Proband

• The first individual in a pedigree to seek genetic counseling or treatment (identified as the proband).

• Example: In a pedigree, proband could be Child 2 in Generation II.

Autosomal Recessive Traits

Characteristics

• Caused by mutations in genes on non-sex chromosomes (autosomes 1-22).

• Key Features:

  • No affected individuals in some generations.

  • Affected children can have unaffected parents.

  • Equal likelihood of being affected in males and females.

  • Requires two copies of mutated alleles to express the trait (loss of function).

Examples of Autosomal Recessive Traits

• Albinism

• Beta-Thalassemia

• Cystic Fibrosis

• PKU (Phenylketonuria)

• Sickle Cell Disease

• Tay-Sachs Disease

Inbreeding and Autosomal Recessive Traits

• Parents share a common ancestor, which may introduce recessive alleles into the population.

• Rare medically relevant recessive alleles in the population may cause conditions in offspring.

Autosomal Dominant Traits

Characteristics

• Caused by mutations in genes on autosomes.

• Key Features:

  • Affected individuals present in each generation.

  • Affected children usually have an affected parent.

  • Trait transmitted equally to males and females.

  • Requires one or two copies of the mutated allele to express trait.

Examples of Autosomal Dominant Traits

• Achondroplasia

• Huntington’s Disease

• Marfan Syndrome

• Li-Fraumeni Syndrome (increases risk of various cancers due to mutations in TP53 gene).

X-Linked Recessive Traits

Characteristics

• Caused by mutations in genes on the X chromosome.

• Key Features:

  • Some generations may be unaffected.

  • Affected individuals are typically male.

  • Affected males can have carrier daughters but their sons are generally unaffected unless their mother is a carrier.

  • 50% chance of having affected male children from carrier mothers.

Examples of X-Linked Recessive Traits

• Hemophilia A & B

• Duchenne Muscular Dystrophy

• Red-Green Color Blindness

X-Linked Dominant Traits

Characteristics

• Caused by mutations in genes on the X chromosome.

• Key Features:

  • Affected individuals appear in every generation.

  • Affected children have at least one affected parent.

  • Affected males typically have all affected daughters and no affected sons.

Examples of X-Linked Dominant Traits

• Hypertrichosis

• Fragile X Syndrome

• Vitamin D-Resistant Rickets

Cytoplasmic Inheritance

Characteristics

• Traits inherited through mitochondrial DNA, primarily from the mother.

• Key Features:

  • Affected mother leads to all affected children.

  • Affected father leads to all unaffected children.

Examples of Cytoplasmically Inherited Traits

• Mitochondrial Encephalopathy

• Myoclonic Epilepsy With Ragged Red Fibers (MERRF)

• Leber Hereditary Optic Neuropathy (LHON)

Analyzing Pedigrees

• Skills learned can be applied to analyze pedigrees for different inheritance types:

  • autosomal recessive,

  • X-linked recessive,

  • autosomal dominant,

  • X-linked dominant,

  • cytoplasmic inheritance.

Study Guide Questions

• Understand genetic inheritance patterns in pedigrees:

  • Autosomal Recessive Genetic Disorder

  • Autosomal Dominant Genetic Disorder

  • X-Linked Recessive Genetic Disorder

  • X-Linked Dominant Genetic Disorder

  • Cytoplasmically Inherited Genetic Disorder (related to mitochondrial genome).