Learning Objective: At the end of this lesson, the learner will be able to define key genetic terms, understand patterns of inheritance, and recognize clinical examples relevant to USMLE Step 1.
High-Yield Genetic Terms
| Term | Definition | Example / Notes |
|---|---|---|
| Codominance | Both alleles contribute to the phenotype of the heterozygote | Blood groups A, B, AB; α1-antitrypsin deficiency; HLA groups |
| Variable expressivity | The same genotype produces variable phenotypes | NF1 patients may have differing severity |
| Incomplete penetrance | Not all individuals with a pathogenic variant express the disease | BRCA1 mutations do not always cause cancer |
| Pleiotropy | One gene affects multiple phenotypes | Cystic fibrosis → lungs, pancreas, male infertility |
| Anticipation | Disease onset occurs earlier or is more severe in succeeding generations | Trinucleotide repeat diseases (Huntington’s disease) |
| Loss of heterozygosity | Both alleles of a tumor suppressor gene must be inactivated for cancer | Retinoblastoma, Lynch syndrome, Li-Fraumeni syndrome |
| Epistasis | One gene affects the phenotypic expression of another | Albinism, alopecia |
| Aneuploidy | An abnormal number of chromosomes due to nondisjunction | Down syndrome (trisomy 21), Turner syndrome (45, XO) |
| Dominant negative mutation | Mutant protein interferes with normal protein function | p53 mutation blocks wild-type p53 |
| Linkage disequilibrium | Certain alleles are inherited together more often than expected | HLA gene, CFTR gene |
| Mosaicism | Presence of genetically distinct cell lines | McCune-Albright syndrome; somatic vs germline mosaicism |
| Locus heterogeneity | Mutations at different loci cause the same disease | Albinism, retinitis pigmentosa |
| Allelic heterogeneity | Different mutations in the same gene cause the same disease | β-thalassemia |
| Heteroplasmy | Both normal and mutated mitochondrial DNA in one individual | Leber hereditary optic neuropathy |
| Uniparental disomy (UPD) | Both chromosomes are inherited from one parent | Prader-Willi, Angelman syndromes; heterodisomy = meiosis I error, isodisomy = meiosis II/postzygotic duplication |
High-Yield Tips
- Codominance → both alleles visible in the phenotype.
- Incomplete penetrance → genotype ≠ phenotype.
- Pleiotropy → one gene, multiple systems affected.
- Anticipation → trinucleotide repeat expansion.
- Mosaicism → explains variable phenotype; can be somatic or germline.
- UPD → can reveal recessive disorders unexpectedly.
