Genetic variations represent the differences in DNA sequences among individuals. These variations contribute to the unique characteristics that make each person distinct, from physical appearance to susceptibility to certain conditions. Among genetic changes, single nucleotide variants, often called SNVs, are a common form. Understanding SNVs provides insight into individual differences and their influence on health.
What Are Single Nucleotide Variants
Single nucleotide variants involve a change in a single DNA building block, a nucleotide, at a specific position within the genome. DNA is composed of four nucleotide bases: adenine (A), guanine (G), cytosine (C), and thymine (T). An SNV occurs when one base is replaced by another, for example, a G might be swapped for a T. This single base pair alteration distinguishes SNVs from larger genetic changes.
SNVs are the most frequently observed type of genetic variation in the human genome. Millions of these small differences are scattered across an individual’s DNA. While other genetic variations include insertions (extra DNA bases added) or deletions (bases removed), SNVs specifically refer to these single-point changes.
How Single Nucleotide Variants Form
Single nucleotide variants primarily arise during DNA replication. When cells divide, their DNA must be copied, and sometimes the molecular machinery makes mistakes. An incorrect nucleotide might be incorporated into the new DNA strand, such as an A being paired with a C instead of a T. These replication errors can lead to a permanent change if not corrected.
Environmental factors also contribute to SNV formation. Exposure to mutagens, agents that can alter DNA, can induce these single-base changes. For instance, ultraviolet (UV) radiation from sunlight can cause DNA damage, leading to T bases converting to C bases. Similarly, chemicals in cigarette smoke or industrial pollutants can directly modify DNA nucleotides, resulting in substitutions.
The human body possesses DNA repair mechanisms designed to correct these errors. Enzymes scan DNA for mismatches and lesions, attempting to restore the original sequence. However, these repair systems are not always perfect, and some changes can escape detection. When a DNA alteration persists and is passed on, it becomes a stable single nucleotide variant.
The Diverse Effects of Single Nucleotide Variants
The impact of single nucleotide variants on gene function and protein production varies widely depending on their location and the specific base change. When an SNV occurs within a protein-coding region, it can lead to different outcomes for the resulting protein.
A “silent” or synonymous SNV changes a single nucleotide but does not alter the protein’s amino acid sequence. This occurs because the genetic code is redundant; multiple three-nucleotide codons can specify the same amino acid.
A “missense” SNV results in a change in the protein’s amino acid sequence. For example, a base change might cause a codon that originally coded for valine to now code for alanine. This alteration can affect protein function, sometimes minimally if the new amino acid is similar or the change is in a non-functional part. However, a missense SNV can significantly impair protein function if it affects a region critical for its structure or activity.
A “nonsense” SNV introduces a premature “stop” signal, leading to early termination of protein synthesis. The resulting protein is often truncated and non-functional. SNVs can also occur in non-coding DNA regions, such as regulatory sequences that control gene expression. These variants can influence gene expression levels, affect messenger RNA processing, or alter other cellular processes without directly changing a protein’s amino acid sequence.
Single Nucleotide Variants and Human Health
Single nucleotide variants play a role in human health, influencing both disease susceptibility and individual characteristics. Specific SNVs are directly responsible for many monogenic genetic diseases, conditions caused by a change in a single gene. For example, a single nucleotide change in the HBB gene leads to sickle cell anemia. Similarly, certain SNVs in the CFTR gene are associated with cystic fibrosis.
SNVs also contribute to the predisposition for complex diseases, influenced by multiple genes and environmental factors. Conditions like heart disease, type 2 diabetes, and certain cancers are often linked to several SNVs, each contributing a small risk. The collective presence of these variants, along with lifestyle and environmental exposures, can increase an individual’s likelihood of developing these common disorders.
The influence of SNVs extends to an individual’s response to medications, a field known as pharmacogenomics. Specific SNVs can affect how a person metabolizes or reacts to certain drugs, determining drug efficacy or the likelihood of adverse side effects. For instance, variations in genes encoding drug-metabolizing enzymes can lead to different dosing requirements for medications like warfarin. Beyond disease, SNVs also contribute to normal variations in physical traits, such as eye color, hair texture, and height.
Identifying SNVs has become a cornerstone of personalized medicine and genetic testing. Analyzing an individual’s SNV profile can aid in diagnosing genetic conditions, provide insights into disease progression, and guide treatment strategies tailored to a patient’s unique genetic makeup. This information helps healthcare providers make more informed decisions, potentially optimizing therapy and improving patient outcomes.