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Genetic Polymorphism

For medical students2 min readUpdated 2026-10-10

Genetic polymorphism refers to the presence of minor, non-lethal variations in DNA sequence resulting from mutations. These variations preserve normal organismal function throughout ontogeny while leading to structural protein variants, shaping each individual's unique profile.

LocalizationFound in both exonic and intronic DNA sequences

Individual limitNo more than 2 variants of any protein per person

Population scaleHundreds of variants for a single protein (e.g., >600 for hemoglobin HbA)

Molecular Nature and Allelic Variants

The phenomenon is based on allelic variants of genes. These are forms of a gene that occupy strictly homologous loci on chromosomes. The main feature of allelic variants is that they encode proteins with very similar spatial structures and identical functions. Essentially, such proteins represent polymorphic isoforms of a single protein.

At the molecular level, polymorphism represents minor deviations in the nucleotide sequence of DNA. Importantly, such mutations are fully compatible with normal function and development of the organism at all stages of ontogeny.

Types of Genetic Polymorphism

Changes in genetic material can affect both coding regions (exons) and non-coding regions (introns). There are two main types of such changes:

Qualitative polymorphism — caused by point substitutions of nucleotides in the DNA chain.
Quantitative polymorphism — associated with variation in the number of nucleotide repeats, which can vary significantly in length.

Biochemical Individuality and Variability

Genetic polymorphism serves as the fundamental basis for ethnic and individual genome differences. The scale of this phenomenon differs drastically at the level of a single person versus an entire population:

In an individual, genetic variability is strictly limited: a maximum of two different variants can be present for any given protein.
In the human population, the number of such variants can be enormous. A classic example is hemoglobin HbA, for which over 600 genetically distinct groups have been described.

Because protein polymorphism is so vast, biochemical individuality is formed. The genomes of all people on the planet are unique with specific differences. The only exception to this rule is identical twins, whose genomes are completely identical.

Frequently asked questions

What laboratory methods are used to detect genetic polymorphism?

Modern molecular genetic DNA analysis technologies are used in laboratory practice to detect genetic polymorphism. The main tools include:

Polymerase Chain Reaction (PCR) — allows direct identification of genes and multi-amplification of specific regions.
Restriction Fragment Length Polymorphism (RFLP) — analysis of changes in DNA fragment sizes after treatment with restriction endonucleases.
Sequencing — direct determination of the nucleotide sequence of genes.
Allele-specific probes — detection of mutations using molecular probes.
Direct detection — direct identification of mutant genes.

Give examples of multifactorial diseases associated with genetic polymorphism.

Genetic polymorphism is noted as a component of genetic predisposition in a number of multifactorial diseases and disease groups. Examples include:

Crohn's disease — exact etiology is unknown; it is a multifactorial disease with about 100 associated genetic polymorphisms described.
Essential hypertension — a multifactorial disease with polygenic hereditary predisposition; polymorphisms of genes determining RAAS activity, sympathetic reactivity, renal sodium transport, endothelial function, and vascular wall structure are inherited.
Autoimmune diseases — considered multifactorial; genetic predisposition is linked to specific HLA antigens and cytokine gene polymorphisms.
Rheumatoid arthritis — GWAS identified over 100 single nucleotide polymorphisms associated with RA risk and progression; the major genetic risk factor is carriage of HLA-DR01/04.

What is the role of enzyme genetic polymorphism in drug pharmacokinetics?

Genetic polymorphism of drug-metabolizing enzymes, especially cytochrome P450 enzymes, leads to differences in amino acid sequences, altered enzyme specificity/activity, and individual drug responses.

For CYP2D6, sources describe marked interindividual variability in the metabolism of nebivolol; metoprolol is also metabolized by CYP2D6, and its metabolic rate is individual.

Metabolism Type	Confirmed Pharmacokinetic and Clinical Features
Extensive (fast) metabolizers	High enzyme activity; for nebivolol — intensive presystemic metabolism, low bioavailability (~12%), T1/2 approx. 10 hours.
Poor metabolizers	For nebivolol — nearly complete bioavailability (~96%), T1/2 30–50 hours, significantly lower cardioselectivity. For metoprolol in poor metabolizers, the risk of side effects is approximately 5-fold higher.

Sources also note that DPYD gene variants are associated with pyrimidine analog toxicity (5-fluorouracil, capecitabine), and UGT1A1 polymorphism with irinotecan class drug toxicity.

What are allelic protein variants?

They are polymorphic isoforms of the same protein encoded by genes occupying strictly homologous loci on chromosomes.

What is the difference between qualitative and quantitative polymorphism?

Qualitative polymorphism arises from the substitution of individual nucleotides in the DNA sequence. Quantitative polymorphism manifests as variation in the number of nucleotide repeats of differing lengths.

Which individuals have completely identical genomes?

Due to tremendous genetic polymorphism, the genomes of all people are distinct and unique. The only exception is identical twins.

Go deeper

Mutational process as the basis for ethnic and individual differences
Exonic and intronic DNA sequences in polymorphism
The role of polymorphism in normal human ontogeny
Multiple variants of hemoglobin HbA in the population