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).