Genetic notation follows a deceptively simple core principle: gene symbols are italicized, and the proteins they encode are not. That single rule, applied consistently, prevents the most common errors in scientific manuscripts. But the details branch quickly depending on the organism, the type of genetic change, and whether you are describing a chromosome, a single nucleotide swap, or an entire genome’s worth of ploidy. What follows is a practical walk-through of the conventions that govern how genotypes are written across biology and medicine, starting with the rules that apply most broadly and moving into the organism-specific and context-specific systems you are most likely to encounter.
Italics Separate the Gene From Its Product
The single most universal rule in genetic notation is typographic: when you are referring to the gene itself (the stretch of DNA), you italicize the symbol. When you are referring to the protein that gene encodes, you write the same symbol in regular (roman) type. This distinction matters because a gene and its protein are different molecular entities that behave differently, and readers need to know which one you mean. A manuscript that switches between the two without signaling the difference through formatting will confuse reviewers and, eventually, anyone trying to replicate the work.1San Francisco Edit. How to Write Genotypes: Core Rules for Genetic Notation
This convention holds across virtually every organism-specific nomenclature system. Whether you are writing about a human gene, a mouse gene, a bacterial gene, or a plant gene, the italics-versus-roman distinction is in effect. It is the one formatting habit worth building into muscle memory before learning any of the organism-specific quirks.
Human Gene Symbols Are All Uppercase
For human genes, the HUGO Gene Nomenclature Committee (HGNC) sets the standard. Approved human gene symbols are short, italicized, uppercase alphanumeric strings. The protein product uses the same name but in normal roman font, typically with only the first letter capitalized. So the gene is written as BRCA1 (italicized, all caps), while the protein it produces is written as BRCA1 or Brca1 in roman type, depending on the journal’s style.2Nature Genetics (via Europe PMC). Guidelines for human gene nomenclature
The HGNC guidelines also specify that symbols should ideally describe the gene or its function, should be unique, and should not be offensive or easily misinterpreted. That last point is not merely a courtesy. Over the years, several gene names have been revised because their original names created confusion in clinical contexts or were considered inappropriate for use in patient-facing reports. If you are writing a manuscript or a database entry, always check the current HGNC-approved symbol rather than relying on whatever name a gene was given when it was first characterized.
Mouse, Rat, and Other Rodent Genes Follow Different Capitalization
One of the most frequent formatting mistakes in papers that study both human and rodent systems is applying the same capitalization rules to both. Human gene symbols are all uppercase. Rodent gene symbols use lowercase letters with only the first letter capitalized. So the human gene is TNFA, while the mouse ortholog is Tnfa. Both are italicized, but the capitalization pattern differs.1San Francisco Edit. How to Write Genotypes: Core Rules for Genetic Notation
The International Committee on Standardized Genetic Nomenclature for Mice maintains these conventions, and they extend to strain names, alleles, and transgenes as well. For mouse strains and genes, proper nomenclature is considered essential for data interpretation, archiving, and cross-study comparison. When nomenclature is used inconsistently, it becomes harder to search databases, compare results across labs, and perform meta-analyses. That might sound abstract, but in practice it means that a paper using non-standard gene symbols may be functionally invisible to other researchers searching for the same gene under its official name.3PubMed Central. Commentary: mouse genetic nomenclature. Standardization of strain, gene, and protein symbols
Bacterial Gene Notation
The conventions for bacteria trace back to a 1966 proposal that established a system still recognizable today. Bacterial gene symbols consist of three italicized lowercase letters, often derived from the function or the pathway involved. For example, his refers to genes in the histidine biosynthesis pathway. Different loci within that pathway are distinguished by appending an uppercase letter and sometimes a number, so hisA1 identifies a specific allele at a specific locus.4Oxford Academic (Genetics). A proposal for a uniform nomenclature in bacterial genetics
Phenotypic designations in bacteria use the same three-letter abbreviation but in roman type with the first letter capitalized, followed by a superscript plus or minus sign to indicate whether the organism displays the wild-type or mutant phenotype. So His+ means the bacterium can synthesize histidine normally, and His− means it cannot. This gene-versus-phenotype formatting mirrors the broader italics-versus-roman rule but adds the superscript shorthand, which is specific to microbial genetics.
Wild-Type Alleles and the Plus Sign
Across many systems, the wild-type allele is marked with a superscript plus sign appended to the gene symbol. In fission yeast, for instance, the wild-type allele of a gene is written as the gene symbol followed by a plus sign, such as ase1+. This notation becomes compulsory in certain contexts, particularly when writing diploid genotypes where you need to distinguish a wild-type copy from a mutant copy on the homologous chromosome, or when indicating that a wild-type allele is still present at a locus that also carries an insertion.5PubMed Central. Revised fission yeast gene and allele nomenclature guidelines for machine readability
In Drosophila, the convention is slightly different: a superscript plus is used on the gene symbol to denote the wild-type allele, but the placement and style details vary by journal. The underlying idea is the same, though. The plus sign is a universal shorthand for “the version found in nature, before any mutation was introduced.” If you are writing a genotype for any model organism and want to specify that an allele is wild-type, the plus sign is almost always the correct way to do it.
Writing Genotypes for Polyploid Organisms
Diploid organisms carry two copies of each gene, so a genotype is written as two allele symbols. In introductory genetics, you see the familiar format: AA, Aa, or aa. But many agriculturally important plants are polyploid, carrying three, four, or even six copies of each chromosome. This means genotypes have more allele slots to fill, and the notation has to accommodate that.
In triploid organisms, a single locus can have genotypes like AAA, AAa, Aaa, or aaa. Tetraploids add another tier: AAAA, AAAa, AAaa, Aaaa, and aaaa. In practice, researchers working with triploid loquats, for example, identified all four possible triploid genotypes at a flesh-color locus, and four of the five possible tetraploid genotypes in tetraploid plants (the fully homozygous recessive aaaa was absent).6PubMed Central. Genotyping of polyploid plants using quantitative PCR: application in the breeding of white-fleshed triploid loquats (Eriobotrya japonica)
The notation itself is straightforward: you list the allele symbol once for each copy present. What gets complicated is distinguishing dosage. An AAAa tetraploid has three dominant alleles and one recessive; an AAaa has two of each. These dosage differences can produce measurably different phenotypes, which is why the notation needs to track each copy rather than simply indicating “at least one dominant allele present.”
Describing Sequence Variants With HGVS Notation
When you need to describe a specific mutation at the DNA or protein level, the standard is the nomenclature maintained by the Human Genome Variation Society (now curated at the Sequence Variant Nomenclature website). This system, which has been widely adopted as an international standard, provides a way to write precisely where in a sequence a change occurred and what type of change it was.7PubMed. HGVS Recommendations for the Description of Sequence Variants: 2016 Update
HGVS notation uses a prefix to indicate the reference sequence type: “c.” for coding DNA, “g.” for genomic DNA, “m.” for mitochondrial DNA, “r.” for RNA, and “p.” for protein. After the prefix comes the position number, then a shorthand for what happened. A substitution at position 76 in the coding sequence from adenine to thymine, for instance, would be written as c.76A>T. A deletion might look like c.76delA, and an insertion would be specified with the flanking positions and the inserted bases.
The system was first proposed around 2000 and has been updated periodically to remove inconsistencies and tighten definitions so that variant descriptions can be processed automatically by software. If you are submitting variants to a database or writing a clinical report, HGVS notation is usually required. Many journals will not accept free-text descriptions of mutations when a standardized HGVS string exists.
Chromosome-Level Notation and the ISCN System
At a larger scale than individual genes or variants, chromosome rearrangements and karyotypes are described using the International System for Human Cytogenomic Nomenclature, commonly known as ISCN. This system provides standard rules for numbering human chromosomes and describing rearrangements like translocations, deletions, inversions, and duplications at the chromosomal level. It covers banding patterns at different resolution levels and is the standard for reporting clinical karyotypes.8PubMed. ISCN rules for listing chromosomal rearrangements
A normal female karyotype is written as 46,XX and a normal male as 46,XY. Structural abnormalities are added using standard abbreviations: “del” for deletion, “dup” for duplication, “inv” for inversion, “t” for translocation, and so on. The most recent revision, ISCN 2024, introduced a new abbreviation “U” to represent cases where the sex chromosome complement is undisclosed, written as 46,U. This applies in prenatal settings or when a clinician specifically requests that the sex chromosomes not be reported. The revision also clarified the distinction between “der” (for derivative chromosomes arising de novo or from meiotic malsegregation) and “rec” (for recombinant chromosomes arising from meiotic crossing over), and added rules for complex insertions involving more than two chromosomes.9Cytogenetic and Genome Research. ISCN 2024: Summary of Revisions and New Nomenclature
If you work in clinical cytogenetics or encounter karyotype reports in a medical context, ISCN notation is what you will see. It is separate from HGVS (which operates at the sequence level) and from gene-symbol conventions (which name individual genes). Think of it as the notation layer that describes the architecture of entire chromosomes.
Mitochondrial DNA Has Its Own Reference Frame
Mitochondrial genomes are small, circular, and maternally inherited, and they have their own numbering system for positions. Variants in mitochondrial DNA (mtDNA) are described using the same HGVS-style notation but with the “m.” prefix to indicate the mitochondrial reference sequence. The position numbers correspond to the revised Cambridge Reference Sequence, which is the standard reference for human mtDNA.
Mitochondrial disorders affect roughly one in 4,300 people, and describing mutations in mtDNA requires precise nucleotide numbering to communicate exactly where a change has occurred.10Journal of the American Association of Nurse Practitioners. Unraveling the Genome: Understanding the nomenclature of mitochondrial DNA mutations through examples of two specific disease entities Because mitochondria have their own genetic code with slight differences from the nuclear code, a protein-level description of a mitochondrial variant uses the mitochondrial codon table, not the standard one. This is a detail that trips up even experienced geneticists when they are writing up results for the first time.
Pedigree Symbols and Evolving Standards
Genotype information often appears in the context of pedigrees, the family-tree diagrams used in clinical genetics to track inheritance patterns. Pedigree notation has its own standardized symbol set: squares for males, circles for females, filled symbols for affected individuals, half-filled for carriers, and so on. Recent updates to these standards have focused on sex and gender inclusivity, modifying how carrier status is depicted and introducing ways to represent individuals whose sex or gender identity does not fit the traditional binary symbol set.11PubMed. Standardized pedigree nomenclature update centered on sex and gender inclusivity: A practice resource of the National Society of Genetic Counselors
When genotypes are annotated on a pedigree, the allele symbols are typically written beneath or beside each individual’s symbol. The formatting rules described above still apply: italics for gene symbols, proper capitalization for the species, and standard allele notation. But pedigrees add a visual layer where the relationships between individuals carry information about inheritance mode. If a pedigree shows carrier status using a half-filled symbol and the genotype is written as, say, Aa, both the symbol and the text need to be consistent with each other and with the legend that accompanies the figure.
Database Formats Versus Manuscript Formats
There is a gap between how genotypes are written in a manuscript and how they are stored in a database. In a paper, you use italics, superscripts, and carefully formatted symbols. In a database or a computational pipeline, you need plain-text formats that machines can parse. The Variant Call Format (VCF), for example, is a widely used plain-text format for storing DNA polymorphism data including single nucleotide changes, insertions, deletions, and structural variants. VCF files are typically compressed and indexed so that software can quickly retrieve variants from specific genomic positions.12PubMed Central. The variant call format and VCFtools
This means that the same genotype might appear as BRCA1 c.68_69delAG in a manuscript, as a VCF record with chromosome, position, reference allele, and alternate allele fields in a database, and as NM_007294.4:c.68_69del in an HGVS-compliant clinical report. These are not contradictory; they are the same information expressed in different notation systems for different audiences. Knowing which format to use in which context is part of getting genotype notation right. A journal manuscript should use HGVS and standard gene symbols. A bioinformatics pipeline should use VCF. A clinical report should use both HGVS and ISCN as appropriate.
Mistakes That Derail Manuscripts
Certain errors come up again and again in submitted manuscripts and can delay or derail peer review. The most common ones are worth flagging explicitly:
- Dropping italics: Writing a gene symbol in roman type makes it look like you are referring to the protein. Many word processors strip italics during copy-paste, so check formatting after every transfer between documents.
- Wrong capitalization across species: Applying human-style all-caps to a mouse gene, or using mouse-style mixed case for a human gene. If your paper involves both species, double-check every gene symbol against the correct species convention.
- Invented or outdated symbols: Gene names change. A symbol that was standard five years ago may have been retired and replaced. Always verify the current approved symbol through the relevant nomenclature authority (HGNC for humans, MGI for mice, and so on).
- Free-text mutation descriptions: Writing “a deletion in exon 3” when a precise HGVS string exists. Journals increasingly require standardized variant notation, and free-text descriptions are ambiguous.
- Confusing genotype and phenotype notation in bacteria: Writing His+ in italics (which would mean a gene, not a phenotype) or writing his in roman type without italics (which strips the gene-level meaning).
These mistakes are not trivial stylistic preferences. Notation errors can make results ambiguous, make database entries unsearchable, and in clinical contexts, lead to misidentification of a patient’s variant. Journals and databases enforce these standards for a reason, and reviewers are trained to catch violations.
When Notation Systems Collide
Real-world genetics papers frequently need to use multiple notation systems in a single manuscript. A paper on a chromosomal translocation that disrupts a specific gene might include an ISCN karyotype string, an HGVS variant description, and a standard gene symbol, all in the same results section. Getting comfortable with the boundaries between these systems prevents confusion.
ISCN operates at the chromosome level: it tells you the total chromosome count, the sex chromosome complement, and any large-scale rearrangements. HGVS operates at the sequence level: it tells you exactly which nucleotide or amino acid changed at which position. Gene-symbol conventions operate at the naming level: they tell you which gene is being discussed and, through formatting, whether you mean the DNA element or the protein product. These three layers are complementary, not interchangeable. A clinical report for a patient with a balanced translocation that disrupts a tumor suppressor gene might read something like: karyotype 46,XX,t(11;22)(q23;q11.2), with disruption of MLL at the genomic level described as a specific HGVS variant. Each notation system handles its own layer of the description.
The fission yeast nomenclature community recently revised its guidelines specifically to improve machine readability, ensuring that gene and allele symbols can be parsed automatically by databases and text-mining tools.5PubMed Central. Revised fission yeast gene and allele nomenclature guidelines for machine readability That trend toward machine-parseable notation is spreading across organisms. It means the stakes for getting notation right are rising: a misformatted symbol is not just confusing to a human reader but invisible to the algorithms that index and connect genetic data across studies.