U01.01.045 Genetic terms

Understanding genetic terminology is crucial for mastering genetics concepts for USMLE Step 1. Below, we provide a detailed explanation of key genetic terms, definitions, and examples organized in tables for easy review.

Key Genetic Terms

1. Codominance

Definition: Both alleles contribute equally to the phenotype of the heterozygote.
Examples:
- Blood groups (A, B, AB).
- α1-antitrypsin deficiency.
- HLA groups.

2. Variable Expressivity

Definition: Patients with the same genotype show varying phenotypes.
Examples:
- Neurofibromatosis type 1 (NF1) presents with differing disease severities in patients.

3. Incomplete Penetrance

Definition: Not all individuals with a mutant genotype exhibit the mutant phenotype.
Formula:
% penetrance × probability of inheriting genotype = risk of expressing phenotype.
Examples:
- BRCA1 mutations may not always lead to breast or ovarian cancer.

4. Pleiotropy

Definition: A single gene influences multiple phenotypic traits.
Examples:
- Phenylketonuria (PKU) manifests as light skin, intellectual disability, and musty body odor.

5. Anticipation

Definition: Increased disease severity or earlier onset in successive generations.
Examples:
- Trinucleotide repeat disorders such as Huntington disease.

6. Loss of Heterozygosity

Definition: For tumor suppressor genes, both alleles must be inactivated for cancer to develop.
Examples:
- Retinoblastoma and the “two-hit hypothesis.”
- Lynch syndrome (HNPCC).
- Li-Fraumeni syndrome.

Additional Genetic Terms

Term	Definition	Example
Dominant Negative Mutation	A nonfunctional altered protein produced by a heterozygote prevents normal gene function.	Mutated p53 protein binds DNA and blocks nonmutated p53.
Linkage Disequilibrium	Tendency for certain alleles at linked loci to occur together more/less often than expected.	Observed in population-level studies, varies between populations.
Mosaicism	Presence of genetically distinct cell lines in an individual.	Somatic (e.g., McCune-Albright syndrome) or gonadal mosaicism.
Locus Heterogeneity	Mutations at different loci producing a similar phenotype.	Albinism.
Allelic Heterogeneity	Different mutations in the same locus producing the same phenotype.	β-thalassemia.
Heteroplasmy	Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial diseases.	mtDNA passed from mother to offspring (e.g., mitochondrial myopathies).
Uniparental Disomy	Inheritance of two chromosomes from one parent.	Prader-Willi and Angelman syndromes.

Points to Remember

Codominance: Think of blood types for straightforward examples.
Anticipation: Always associate with trinucleotide repeats.
Loss of Heterozygosity: Critical for tumor suppressor gene-related cancers.
Mosaicism: Distinguish somatic from gonadal presentations.
Uniparental Disomy: Key for understanding rare chromosomal disorders.

Bibliography

First Aid for the USMLE Step 1.
Genetics Review in Medical Education Resources.
Online MedEd USMLE Prep Materials.

This concise format with headings, subheadings, and tables will help students better grasp the concepts and efficiently review them for the exam.

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