1-3-Pedigrees

Beyond Mendel's Laws

Pedigrees

Exceptions to Mendelian Genetics

  • Co-dominance vs. Incomplete Dominance vs. Penetrance

    • Definitions:

    • Co-dominance: No allele masks the expression of another; both traits fully manifest in the phenotype.

    • Incomplete Dominance: The dominant allele does not completely mask the recessive allele, resulting in an intermediate phenotype.

    • Penetrance: Phenotypic variability among individuals or populations, assessing whether a gene's expression leads to visible traits.

    • Comparison with Expressivity: While penetrance refers to the proportion of individuals expressing a trait, expressivity measures the degree of expression among those who do.

    • Mechanisms behind variability can differ, but the intensity of traits ranges from low to high.

Pedigree Analysis

Inheritance Patterns: Exceptions to Mendelian Rules

  • Imprinting: Different expression of genes depending on the parent (maternal vs. paternal).

    • Example: Non-imprinted gene A from the father versus imprinted gene B from the mother.

  • Mitochondrial Inheritance:

    • Maternal inheritance where mtDNA with mutations is passed down exclusively via the mother.

    • Paternal contributions to mtDNA are typically eliminated post-fertilization. Thus, mitochondrial diseases are inherited through the maternal lineage.

Analyzing Human Pedigrees

Simple Inheritance Analysis

  • Determine if a trait shows dominant or recessive patterns.

  • Assess genetic risk for:

    1. Pregnancy outcomes

    2. Adult-onset disorders

    3. Future offspring

Key Points of Inheritance

  • Genes are transmitted across generations; traits follow defined inheritance rules:

    • Dominant, recessive, and X-linked inheritance.

Patterns of Inheritance

  • Types of Inheritance:

    • Autosomal Dominant

    • Autosomal Recessive

    • X-linked (both recessive and dominant)

    • Imprinting effects based on parental origin.

    • Mitochondrial inheritance not linked to nuclear chromosomes.

Pedigree Symbols

  • Male: square

  • Female: circle

  • Parents’ to children's connection:

    • Roman numerals (I, II, III, etc.) indicate generations.

    • Arabic numbers (1, 2, 3, etc.) indicate birth order within generations (firstborn boy, girl, etc.).

  • Symbols definition:

    • Deceased individuals marked appropriately.

    • Unknown sex represented uniquely.

Proband and Pedigree Notation

  • Proband: Individual of focus in the pedigree, denoted by an arrow with the letter 'P'.

Types of Inheritance Patterns Detected in Pedigrees

  • Autosomal Dominant Traits:

    1. Visible in each generation.

    2. Equal incidence in males and females.

    3. Affected parents may have unaffected children.

    4. AA genotype usually affects individuals more severely.

Examples of Autosomal Dominant Genetic Disorders:

  • Achondroplasia: Dwarfism linked to growth anomalies.

  • Brachydactyly: Characterized by malformed hands with shortened fingers.

  • Familial Hypercholesterolemia: High cholesterol levels leading to cardiovascular issues.

  • Marfan Syndrome: Connective tissue disorder risking aortic aneurysm.

  • Porphyria: Inability to process porphyrin, leading to neurological disturbances (hallucinations).

Autosomal Recessive Traits

  • Key Characteristics:

    1. Can skip generations.

    2. Affects males and females equally.

    3. Unaffected parents may have affected offspring.

    4. All children from affected parents are also affected.

  • Risk Calculation: 25% risk of affected child if both parents are heterozygous (Aa).

Examples of Autosomal Recessive Genetic Disorders:

  • Cystic Fibrosis (CF): Excess mucus affecting glands and lungs.

  • Phenylketonuria (PKU): Accumulation of phenylalanine leading to cognitive impairments.

  • Sickle Cell Anemia (SCA): Abnormal blood hemoglobin causing vessel blockage.

  • Xeroderma Pigmentosum (XP): Lack of DNA repair enzymes leading to skin cancer susceptibility.

  • Tay-Sachs Disease (TSD): Fatal ailment due to defective metabolism in nerve cells.

Sex-Linked Traits

  • Genes located on the X chromosome (X-linked) and Y chromosome (Y-linked).

    • For X-linked traits:

      • Females can be homozygous (XX) or heterozygous (XX*).

      • Males are hemizygous (XY) and lack a second X for comparison.

Pedigree Examples for X-Linked Inheritance

  • For males, affected traits often follow maternal lineage, with half of daughters possibly becoming carriers.

Examples of X-Linked Recessive Genetic Disorders:

  • Red-green Colorblindness: Inability to perceive green and red hues.

  • Hemophilia A: Impairment in blood clotting.

  • Lesch-Nyhan Syndrome: Lack of HGPRT protein causes severe impairment and self-harm tendencies.

  • Muscular Dystrophy: A progressive muscle-wasting condition.

X-Linked Dominant Inheritance

  • Traits originating from a father affect all daughters prominently.

Mitochondrial Inheritance

  • Traits pass exclusively down the maternal line; fathers can be affected but do not transmit them to offspring.

Complex Inheritance Patterns

  • Considerations include:

    • Potential variable expressivity.

    • Gene-environment interactions.

    • New mutations.