What Allele Letters Represent
Allele letters are standardized nomenclature designations that identify specific genetic variants at a given gene locus, typically consisting of the gene name followed by an asterisk (*) and a combination of numbers and letters that uniquely specify the particular sequence variation. 1
Core Definition and Structure
An allele represents one of two versions of a DNA sequence that an individual inherits (one maternal, one paternal) for any genomic location. 2 The letter and number combinations following the gene name serve as unique identifiers for each distinct genetic variant.
Standard Nomenclature Format
The established format follows this pattern: 1
- Gene symbol (e.g., CYP2D6, HLA-DRB1, DMPK)
- Asterisk (*) separator
- Number specifying the key mutation
- Letter (when applicable) specifying additional mutations within that variant group
For example, in HLA-DRB1*15:01, the "15" indicates the primary allele group and "01" specifies the particular subtype within that group. 2
Clinical Context: Allele Categories
Normal vs. Variant Alleles
In diseases like myotonic dystrophy type 1 (DM1), alleles are categorized by functional significance rather than arbitrary letters: 2
- Normal alleles: 5-34 CTG repeats (stable, non-pathologic)
- Variable alleles: 35-49 repeats (unstable but asymptomatic in the carrier; risk for expansion in offspring)
- Fully-variable alleles: ≥50 repeats (unstable and disease-causing)
Pedigree Documentation Standards
When recording alleles on family pedigrees, standardized guidelines recommend: 2
- Placing mutation information in parentheses below the individual's symbol
- Writing the affected allele first for repetitive sequences
- Documenting specific mutations when known (e.g., E+(ΔF508) for cystic fibrosis)
Functional Significance
Allelic variants commonly affect gene expression levels, not just protein structure. Studies demonstrate that 54% of heterozygous genes show preferential expression of one allele, with some showing greater than fourfold differences between alleles. 3 This allele-specific expression variation contributes substantially to human phenotypic diversity beyond simple amino acid changes. 4
Important Caveats
- The same allele designation system applies across different gene families, but the specific numbering schemes may vary by gene 1, 5
- Allele letters/numbers do not inherently indicate severity—clinical correlation requires understanding the specific mutation's functional impact 2
- For complex genes like HLA, amino acid positions (not just allele numbers) often provide more clinically relevant information for disease association studies 2