TEMPLATE
Autosomal Dominant Pedigree
In autosomal dominant inheritance, a single copy of the changed allele is enough for the trait to appear. Typical clues on a pedigree: the trait appears in every generation, and an affected parent has roughly a 50% chance of passing it to each child, regardless of sex. This example is fictional and simplified — real inheritance can be influenced by many other factors.
Inheritance pattern & biological mechanism
Autosomal dominant (AD) inheritance occurs when a single altered copy of a gene located on a non-sex chromosome (autosome) is sufficient to cause the phenotypic condition. Because the gene is autosomal, transmission occurs with equal frequency in males and females. The quintessential hallmark on a pedigree is vertical transmission across consecutive generations without skipping.
Key transmission rules
- An affected individual almost always has at least one affected parent (unless the condition arose via a de novo mutation).
- An affected heterozygote (Aa) partnered with an unaffected person (aa) has a 50% (1 in 2) probability of transmitting the altered allele to each pregnancy, regardless of the child’s sex.
- Unaffected family members (aa) do not harbor the mutated allele and cannot transmit the condition to their descendants.
- Male-to-male transmission occurs and rules out X-linked inheritance.
Representative real-world conditions
Huntington Disease
HTT gene (CAG trinucleotide repeat expansion)
Progressive neurodegenerative disorder characterized by chorea and cognitive decline, typically manifesting in mid-adulthood.
Marfan Syndrome
FBN1 gene (fibrillin-1)
Connective tissue disorder affecting ocular, skeletal, and cardiovascular systems, particularly predisposing to aortic root dilation.
Achondroplasia
FGFR3 gene
Common cause of disproportionate short stature; roughly 80% of cases arise from de novo mutations, but affected parents transmit dominantly.
Familial Adenomatous Polyposis (FAP)
APC gene
Development of hundreds to thousands of precancerous adenomatous colon polyps beginning in adolescence.
How to analyze this chart
- 1
Generation I: Father Arthur (I-1) is affected with genotype Aa; mother Beatrice (I-2) is unaffected (aa).
- 2
Generation II: Arthur transmits the trait to his son Charles (II-1, affected Aa) and daughter Edward (II-3, unaffected aa). Charles partners with unaffected Fiona (II-2).
- 3
Generation III: Charles (II-1) transmits the trait to daughter Grace (III-1, designated as proband) and Ivy (III-3), while son Henry (III-2) is unaffected (aa).
- 4
The vertical cascade from I-1 to II-1 to III-1 and III-3 demonstrates classic 50% phenotypic penetrance in both sexes.
Diagnostic checklist: confirming vs ruling out
Confirming clues
- ✓ Vertical pattern: condition appears in every generation without skipping.
- ✓ Both males and females are affected in roughly equal numbers.
- ✓ Direct father-to-son transmission is present, confirming autosomal rather than X-linked locus.
- ✓ Roughly 50% of the offspring of affected individuals express the phenotype.
Caveats & ruling out
- ⚠ If two unaffected parents produce multiple affected offspring, autosomal dominant is excluded (indicates recessive inheritance or germline mosaicism).
- ⚠ If an affected father only has affected daughters and never affected sons, consider X-linked dominant.
Frequently asked questions
Can an autosomal dominant condition ever skip a generation?
True skipping does not occur genetically, but apparent skipping can happen due to reduced penetrance (carrying the mutation without expressing symptoms) or variable expressivity (symptoms so mild they go unnoticed).
What are the risks if both parents are affected with an autosomal dominant trait?
If both parents are heterozygotes (Aa × Aa), each child has a 50% chance of being heterozygous affected (Aa), a 25% chance of being unaffected (aa), and a 25% chance of being homozygous affected (AA), which for many conditions is lethal in utero.
How does a de novo mutation look on an autosomal dominant chart?
A de novo mutation appears as a single affected individual whose parents and ancestors are completely unaffected. Once present, that individual has a 50% risk of passing it to each of their children.