What does it mean to be heterozygous (having two different alleles of a gene)?

Understanding Heterozygosity in Genetics

Being heterozygous means having two different alleles (variants) of a gene, with one allele inherited from each parent. 1

Key Characteristics of Heterozygosity

Heterozygosity occurs when an individual inherits different versions of the same gene from their mother and father. This creates a genetic state that has several important features:

• Allelic Composition: A heterozygous individual has two different alleles at a particular genetic locus (e.g., A/G instead of A/A or G/G) 1
• Notation: Typically represented as having different letters or symbols for each allele (e.g., Aa, where "A" is one allele and "a" is another)
• Contrast with Homozygosity: Differs from homozygous individuals who have identical alleles at the same locus (either both dominant or both recessive) 1

Expression Patterns in Heterozygotes

The phenotypic expression in heterozygotes can follow several patterns:

1. Dominant Expression: When one allele is dominant, the heterozygote will express the dominant trait despite having one recessive allele
2. Intermediate Expression: Some heterozygotes show an intermediate phenotype between the two homozygous states
3. Molecular Heterosis: In some cases, heterozygotes may show significantly greater effects (positive heterosis) or lesser effects (negative heterosis) than either homozygous state 2

Clinical Significance

Heterozygosity has important implications for health and disease:

• Carrier Status: Heterozygotes for recessive disease mutations are typically carriers who don't manifest the full disease but can pass the mutation to offspring 3
• Compound Heterozygosity: When an individual has two different mutated alleles within the same gene, which can cause recessive diseases 4, 5
• Gene Expression Phenotypes: Heterozygous carriers of certain mutations may have distinct gene expression patterns that differ from non-carriers 3

Examples of Heterozygosity in Disease

• Bardet-Biedl Syndrome: Compound heterozygous mutations in the BBS1 gene can cause this condition, sometimes with milder presentations than homozygous mutations 5
• Nijmegen Breakage Syndrome: Carriers show distinct gene expression patterns despite not having the full syndrome 3

Practical Implications

Understanding heterozygosity is crucial for:

• Genetic counseling and risk assessment
• Interpreting genetic test results
• Understanding inheritance patterns of diseases
• Predicting disease risk in families

Heterozygosity represents the genetic diversity that exists within individuals and contributes significantly to the overall genetic architecture of complex human traits and diseases.