What Are Genotypes?

Genotypes are the specific genetic variants an organism carries at defined positions in its genome. The National Human Genome Research Institute defines a genotype as a scoring of the type of variant present at a given locus, written either with allele symbols such as BB, Bb, and bb or as the observed bases, such as CC, CT, and TT. Because most organisms of interest in genetics are diploid and carry two copies of each chromosome, a genotype at a biallelic site names the pair of alleles inherited from the two parents, and an individual is described as homozygous when the two match and heterozygous when they differ.

The term is used at two scales. It can refer to a single locus, as when a clinical laboratory reports the genotype of a variant associated with cystic fibrosis, or to the full set of variants an individual carries, which is how it is used in population genetics and quantitative genetics. The complementary concept is the phenotype, the set of observable traits, and the relationship between the two is mediated by gene expression, regulatory context, epistatic interaction between loci, and environment.

Genotype, Phenotype, and Inheritance

Classical genetics established the vocabulary. Alleles are described as dominant when one copy determines the phenotype and recessive when two copies are required, though most traits in humans are polygenic and follow no simple Mendelian pattern. Penetrance measures the fraction of individuals with a given genotype who express the associated trait, and expressivity measures how strongly they express it, both of which can be well below complete. Modern practice largely abandons single-gene reasoning for continuous traits and models the aggregate contribution of many loci, an approach that assumes small additive effects distributed across the genome.

Genotyping Technologies

Determining a genotype is a measurement problem, and the instrumentation has changed several times. Restriction fragment length polymorphism analysis and gel electrophoresis gave way to polymerase chain reaction assays with allele-specific probes, then to microarrays that interrogate hundreds of thousands to millions of single nucleotide polymorphisms on a single chip by hybridization and fluorescent readout. High-throughput sequencing now reads bases directly, with whole-genome sequencing giving complete coverage and targeted panels covering selected regions at higher depth. Variants discovered by these methods are deposited in reference resources including the NCBI dbSNP database. Nanopore and single-molecule real-time platforms extend the reach of genotyping to structural variants and repeat expansions that short reads resolve poorly.

Computational Analysis of Genotype Data

Raw instrument output becomes a genotype only after substantial computation. Base calling, alignment to a reference genome, and probabilistic variant calling each contribute uncertainty, and quality control removes samples and markers with excessive missingness or departures from Hardy-Weinberg equilibrium. Imputation uses haplotype reference panels to infer genotypes at sites that were not directly measured, which lets studies on different array platforms be combined. Genome-wide association studies then test each variant against a trait and correct for the resulting multiple comparisons, with results curated in the GWAS Catalog maintained by EMBL-EBI and NHGRI. Because a genotype is a permanent identifier that also discloses information about relatives, storage and sharing raise privacy questions that have driven work on secure multiparty computation and differential privacy for genomic data.

Applications

Genotype data has applications in a range of fields, including:

• Clinical diagnosis of inherited disease and carrier screening
• Pharmacogenomics, matching drug choice and dosing to metabolic variants
• Polygenic risk scoring for common complex diseases
• Plant and livestock breeding through genomic selection
• Forensic identification and kinship analysis
• Population genetics, ancestry inference, and conservation biology