Inheritance concepts, genotype–phenotype and the pedigree
The words geneticists use to link a genotype to what a person shows, and how a three-generation family tree reveals the pattern.
Key facts
- Genotype is the alleles at a locus; phenotype is what can be observed. Homozygous: two identical alleles; heterozygous: two different; hemizygous: one copy (X-linked genes in males); compound heterozygous: two different pathogenic alleles.
- Penetrance is the share of people with the genotype who show the disease; it can be incomplete or rise with age (Huntington disease, BRCA1/2).
- Expressivity is how severe the disease is in those affected; it varies widely within one family in neurofibromatosis type 1.
- Pleiotropy: one gene affects several organs (Marfan syndrome: eye, skeleton, aorta).
- Heterogeneity: many variants in one gene (allelic, as in CFTR), many genes for one phenotype (locus, as in hearing loss), or different disorders from one gene (phenotypic).
In detail
- Loss-of-function variants usually act recessively; when half the normal product is not enough (haploinsufficiency), loss of one copy is dominant.
- Gain-of-function variants (achondroplasia, Huntington disease) and dominant-negative variants, in which an abnormal protein spoils the normal one (collagen in osteogenesis imperfecta, fibrillin in Marfan), act dominantly.
- Pedigree symbols: squares for males, circles for females, filled shapes for affected people, an arrow for the proband, a double line for a consanguineous couple.
- A family history should cover three generations, ancestry, ages at diagnosis and death, pregnancy losses and consanguinity.
- A dominant disorder with unaffected parents suggests a new mutation, germline mosaicism, reduced penetrance or misattributed parentage.
- Also called
- Penetrance, expressivity and pleiotropy, Family history and pedigree drawing
Clinical notes
- Red flags for a hereditary condition: early onset, several affected relatives, bilateral or multiple tumours, rare tumours, consanguinity and repeated pregnancy losses.
- Genotype–phenotype correlation guides prognosis: in cystic fibrosis, some CFTR variants preserve pancreatic function.
Test yourself
Think of the answer, then tap the question to see it.
What is the difference between penetrance and expressivity?
Penetrance is whether a person with the genotype shows the disease at all; expressivity is how severe it is when present.
How does a dominant-negative variant act?
Its abnormal protein interferes with the normal protein from the other allele, so function falls below half.
What should a basic genetic family history include?
Three generations, ancestry, ages at diagnosis and death, pregnancy losses and any consanguinity.
Connections
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Pedigree (National Human Genome Research Institute (NHGRI), 2026); Mendelian Inheritance (National Human Genome Research Institute (NHGRI), 2026); What are reduced penetrance and variable expressivity?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Why is it important to know my family health history?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.