A person’s genome is composed of approximately three billion DNA “letters,” known as bases, and a single nucleotide variant (SNV) is a change in just one of these letters. This alteration is analogous to a single typographical error in a book and is the most frequent type of genetic variation among humans.
These variations are a source of human diversity. While many SNVs have no discernible effect, others can influence traits, predispose individuals to health conditions, or cause disease. Understanding these single-letter changes is a focus of modern genetics and medicine.
Formation and Classification of SNVs
SNVs are classified based on their origin. Germline variants are inherited from a parent and are present in the DNA of every cell. These variants are passed down through generations, contributing to the genetic makeup of a family line.
Somatic variants are not inherited but are acquired during an individual’s life. These changes can arise from errors when a cell divides or from exposure to environmental factors like radiation. Somatic SNVs are confined to a specific subset of cells, such as a tumor, and are not passed on to offspring.
SNVs are also classified by their effect on protein-coding genes. A silent variant is a substitution where the change in the DNA letter does not alter the resulting amino acid. This is possible because the genetic code has redundancy, with multiple three-letter DNA sequences, or codons, specifying the same amino acid.
A missense variant is a substitution that leads to a different amino acid in the protein sequence, which can alter the protein’s structure and function. A nonsense variant transforms a codon that specifies an amino acid into a “stop” signal. This premature termination results in a shortened and usually non-functional protein.
The Role of SNVs in Health and Disease
Certain SNVs are directly linked to disease. A classic example is sickle cell anemia, which is caused by a single missense variant in the HBB gene. This one-letter change results in an altered hemoglobin protein, causing red blood cells to deform into a sickle shape and leading to numerous health problems.
Nonsense variants are often associated with genetic disorders. For instance, many cases of cystic fibrosis are caused by SNVs that introduce a premature stop codon in the CFTR gene. The resulting non-functional protein disrupts the balance of salt and water in cells, leading to the disease’s characteristic thick mucus.
Somatic SNVs play a role in the development of cancer. As cells accumulate these variants throughout a person’s life, changes in genes that regulate cell growth can lead to uncontrolled proliferation. The accumulation of multiple somatic SNVs in specific genes can drive the progression from a normal cell to a malignant tumor.
Methods for Detecting SNVs
The primary method for identifying SNVs is DNA sequencing, which determines the precise order of the A, C, G, and T bases in a DNA strand. By comparing an individual’s sequenced DNA to a standardized reference genome, researchers can pinpoint the locations of these variants.
Next-Generation Sequencing (NGS) is a high-throughput approach that allows for the rapid and simultaneous sequencing of millions of DNA fragments. This capability makes it possible to sequence a person’s entire genome or specific regions of interest in a cost-effective and time-efficient manner.
The process of NGS involves breaking the genome into smaller pieces, sequencing these fragments, and using computational tools to reassemble them. The individual’s sequence is then aligned against the reference sequence. Any single-base mismatches that are consistently identified represent the SNVs unique to that person.
Applications in Personalized Medicine and Ancestry
One practical application of SNV data is in pharmacogenomics, which studies how a person’s genetic makeup affects their response to drugs. This information helps doctors select the most effective medication and dosage for an individual, minimizing adverse side effects. For example, specific SNVs can predict how a patient will metabolize a certain anesthetic or chemotherapy agent.
In personalized medicine, identifying the specific somatic SNVs within a tumor can guide the use of targeted therapies. These drugs are designed to attack cancer cells that have particular genetic variants, leaving healthy cells largely unharmed. This approach allows treatment plans to be tailored to the individual patient.
Beyond medicine, patterns of shared SNVs provide a tool for tracing human history and ancestry. Population geneticists analyze these variants across different groups to reconstruct ancient migration routes and understand how human populations have evolved. Commercial genetic testing companies use this principle, comparing a customer’s SNVs to a reference database to identify their ancestral origins.