Genotype

A genotype is the genetic constitution of an organism or cell, considered either broadly or at particular locations in its genome. In practical genetics, the term commonly denotes the combination of alleles present at a specified genomic position, or locus—for example, $AA$, $Aa$, or $aa$. A genotype describes genetic information, whereas a phenotype describes an observable or measurable characteristic resulting from genetic and environmental influences. The distinction is fundamental to the study of inheritance and biological variation. (pmc.ncbi.nlm.nih.gov)

Scope and terminology

The meaning of genotype depends on the scale of the question. A single-locus genotype specifies the alleles at one location; a multilocus genotype specifies alleles at several locations. In a broader sense, an organism’s genotype refers to its overall genetic constitution. Consequently, two organisms described as having “the same genotype” in an experiment may match only at the loci being investigated, rather than throughout their genomes. (pmc.ncbi.nlm.nih.gov)

A locus need not correspond to an entire gene. It may be a single position in DNA, a segment containing a sequence difference, or another genomic marker. Genotypes can therefore be written using abstract allele symbols or explicit sequence information. At a position where the alternatives are the DNA bases C and T, for instance, the genotypes in a two-copy genome may be CC, CT, and TT. (genome.gov)

Genotype and genome are closely related but emphasize different things: genome identifies the complete genetic material, while genotype specifies its constitution, often in terms of differences relevant to a comparison. A genotype is not itself a statement about the effects of those differences. Some variants affect traits; others serve as markers without having an established functional effect. (genome.gov)

Allele combinations and notation

In diploid organisms, most nuclear loci occur in two copies, one on each member of a pair of homologous chromosomes. At such a locus:

• A homozygous genotype has two identical alleles, such as $AA$ or $aa$.
• A heterozygous genotype has two different alleles, such as $Aa$.

These descriptions apply to a particular locus: an individual can be homozygous at one location and heterozygous at another. Heterozygosity can also describe the extent of genetic variation across a collection of loci. (genome.gov)

Uppercase and lowercase letters often represent alleles with a dominant–recessive relationship in elementary examples. However, dominance is a relationship between alleles with respect to a specified phenotype, not a necessary feature of genotype notation. Sequence-based labels such as C/T do not imply dominance. Nor does a dominant allele necessarily become more frequent simply because it is dominant. (ncbi.nlm.nih.gov)

The familiar two-letter notation is not universal. Haploid genomes have one allele per locus, while polyploid genomes can have more than two. Deletions and duplications can also change the number of copies at a particular region. In these circumstances, an adequate genotype description may need to include allele dosage or copy number rather than only a pair of symbols. (ncbi.nlm.nih.gov)

Inheritance of genotypes

The classical explanation of genotype inheritance derives from the experiments of Gregor Mendel. During meiosis, the two alleles at a typical diploid locus segregate into different gametes. Fertilization brings together alleles from two gametes, producing the offspring’s genotype. (ncbi.nlm.nih.gov)

For an idealized cross between two heterozygotes, $Aa \times Aa$, each parent transmits $A$ or $a$ with probability $1/2$. The expected offspring probabilities are therefore

The expected genotypic ratio is $1:2:1$. If $A$ is completely dominant for the trait being measured, $AA$ and $Aa$ share the dominant phenotype, giving an expected phenotypic ratio of $3:1$. These are probability expectations across offspring, not a requirement that every group of four offspring contain precisely those proportions. (ncbi.nlm.nih.gov)

At multiple loci, inheritance depends on their chromosomal arrangement. Independent assortment applies to unlinked loci, whereas genetic linkage can cause nearby alleles to be inherited together. Chromosomal crossing-over can generate new combinations of linked alleles. (ncbi.nlm.nih.gov)

Genotype and phenotype

Genotype and phenotype are not interchangeable. Under complete dominance, different genotypes can produce the same measured phenotype. Conversely, organisms with the same genotype at a locus may differ in phenotype because of environmental influences or differences elsewhere in their genomes. Phenotype includes biochemical and physiological measurements as well as visible characteristics. (ncbi.nlm.nih.gov)

Several relationships illustrate why there is no universal one-to-one correspondence:

• Incomplete dominance: the heterozygote has a phenotype intermediate between those of the two homozygotes.
• Codominance: both alleles contribute distinguishable features to the heterozygote’s phenotype.
• Epistasis: the phenotypic effect associated with one gene is modified by one or more other genes.
• Environmental effects: conditions experienced by an organism influence the expression of its traits. (ncbi.nlm.nih.gov)

For complex traits, genotype information can help explain variation without providing a complete prediction of an individual outcome. Many genomic variants may contribute, and their effects occur within environmental and biological contexts. A statistical association between a genotype and a trait also does not, by itself, establish that the measured variant is causal: the variant may instead mark a nearby causal region. (genome.gov)

Haplotypes and phase

A haplotype is a group of variants located along a single chromosome that tend to be inherited together. A multilocus genotype identifies the alleles present but does not necessarily identify which alleles lie on the same chromosome. That additional arrangement is called phase. (genome.gov)

For example, an individual heterozygous at two loci has the multilocus genotype $AaBb$. Its two chromosome copies could carry the haplotypes $AB$ and $ab$, or instead $Ab$ and $aB$. The allele inventory is identical, but the phase differs. This distinction matters when following linked variants through inheritance. (genome.gov)

The Variant Call Format encodes allele identities numerically. In its genotype field, 0 denotes the reference allele and 1 the first listed alternative allele. Thus, 0/1 represents an unphased heterozygous genotype, while 0|1 indicates a phased genotype. “Reference” is a sequence-comparison label, not a designation of biological superiority, dominance, or ancestral status. (samtools.github.io)

Determining genotypes

Genotyping is the process of determining the alleles present in a sample. Methods include targeted assays, DNA microarrays, and DNA sequencing. Arrays generally interrogate a predefined collection of variants, whereas sequencing reads DNA bases from selected regions or across a genome and supports computational identification of variants and allele combinations. (genome.gov)

A genotype call is an inference from experimental data. It is distinct from the underlying biological genotype and may be uncertain or incorrect. Sequencing errors, inadequate coverage, technical bias, and difficulty interpreting particular regions can affect calls. Data formats consequently provide fields for information such as read depth, genotype quality, and genotype likelihoods. Missing genotype data are not equivalent to a confirmed reference genotype. (genome.gov)

The sampled tissue can also matter. In mosaicism, one individual contains populations of cells with different genomes. Describing an individual as having a single genotype may therefore be insufficient for a mosaic variant; interpretation must account for the cellular populations represented in the sample. (genome.gov)

Genotypes in populations and research

Population genetics distinguishes allele frequencies from genotype frequencies. At a two-allele diploid locus, let $p$ be the frequency of $A$ and $q$ the frequency of $a$, with $p+q=1$. Under the assumptions of Hardy–Weinberg equilibrium, expected genotype frequencies are

These proportions describe a population model rather than the inheritance probabilities of one specified parental cross. Departures from the model can reflect population structure, nonrandom mating, or other biological and technical factors. (ncbi.nlm.nih.gov)

Genotype data support linkage mapping, comparisons of genetic variation, and genome-wide association studies. Association studies compare genomic markers across many individuals to identify variants associated with measured traits or diseases. Such findings identify regions for further investigation; they do not necessarily identify the causal variant or fully explain the associated phenotype. (genome.gov)

Historical development

The Danish plant physiologist Wilhelm Johannsen introduced the terms genotype, phenotype, and gene in his 1909 book Elemente der exakten Erblichkeitslehre. His conceptual distinction grew from experiments with beans, published in 1903, which separated stable hereditary differences from variation in observable characteristics within pure lines. (pmc.ncbi.nlm.nih.gov)

Johannsen’s genotype was an underlying hereditary constitution, not a DNA sequence: the molecular nature of genes was not yet known. Later developments in chromosome theory and molecular genetics gave the concept increasingly specific physical interpretations. Modern usage retains the distinction between hereditary constitution and observable traits while frequently using genotype in the narrower, operational sense of an allele combination at specified genomic locations. (pmc.ncbi.nlm.nih.gov)

References

1. Genotypegenome.gov
2. Phenotypegenome.gov
3. Heterozygousgenome.gov
4. The holist tradition in twentieth century genetics. Wilhelm Johannsen's genotype conceptpmc.ncbi.nlm.nih.gov
5. Heredity, Genes, and DNAncbi.nlm.nih.gov
6. Genetics: Inheritance Patternsncbi.nlm.nih.gov
7. Mapping Genomesncbi.nlm.nih.gov
8. Epistasisgenome.gov
9. Haplotypegenome.gov
10. The VCF specificationsamtools.github.io
11. Genotyping and DNA Sequencing Methodsgenome.gov
12. Mosaicismgenome.gov