Genes are the blueprints within our bodies, carrying the instructions to build and maintain an organism. These instructions are stored in our DNA, dictating physical characteristics and cell function. While most of our genetic code is shared, small differences, known as gene variants, exist in these DNA sequences. These unique variations contribute to the distinct traits and characteristics that make each individual unique.
Understanding Gene Variants
Gene variants are differences in the order of DNA building blocks, or nucleotides, that make up our genes. These variations range in size from a single nucleotide change to much larger alterations involving thousands of these building blocks. The most common type is a single nucleotide variant (SNV), where one DNA base—adenine (A), guanine (G), cytosine (C), or thymine (T)—is replaced by another at a specific position in the genome. For example, an A might be swapped for a G.
Gene variants also include insertions or deletions, known as indels, which involve the addition of extra DNA segments or the removal of existing ones. These indels can be small, affecting a few nucleotides, or larger, encompassing several hundred. Another type is copy number variations (CNVs), where entire sections of DNA are duplicated or deleted, meaning an individual might have more or fewer copies of a particular gene or DNA region.
Larger-scale changes are categorized as structural variations, involving rearrangements of DNA. These can include inversions, where a segment of DNA is flipped, or translocations, where parts of chromosomes break off and reattach to a different chromosome. All these variations represent ways our genetic code can naturally differ among individuals and are a normal part of human genetic diversity.
How Gene Variants Occur
Gene variants arise through two processes: spontaneous changes in DNA or inheritance from parents. Spontaneous changes, known as mutations, occur during DNA replication when cells divide. Although our cells have repair mechanisms, occasional errors happen as DNA copies itself, leading to a new variant not present in the original DNA. These errors are random and infrequent.
Environmental factors can also induce spontaneous changes in DNA. Exposure to certain chemicals, such as those in cigarette smoke, or radiation, like ultraviolet (UV) light from the sun, can damage DNA and lead to alterations in its sequence. While many of these changes are repaired by the cell, some can persist and become permanent gene variants. Most spontaneous changes are harmless or corrected.
The second source of gene variants is inheritance. Children receive half their genetic material from each parent. This means variants in parents’ DNA can be passed to offspring. Each parent contributes one copy of each gene, leading to a unique combination of variants in the child. This blending of genetic material from both parents ensures every individual has a distinct set of gene variants, contributing to human genetic diversity.
How Gene Variants Influence Traits and Health
Gene variants can influence an individual by affecting the function of proteins, which are the molecular machines in cells. A change in a gene’s DNA sequence can alter the instructions for making a protein, potentially leading to a protein that functions differently, is produced in altered amounts, or is not made at all. These protein changes then ripple through cellular processes, influencing an individual’s biology.
These variations contribute to many observable traits, known as phenotypes. For instance, gene variants influence physical characteristics such as eye color, hair texture, and height. They also play a role in less obvious traits, like susceptibility to certain tastes or smells.
Gene variants are also relevant in pharmacogenomics, the study of how genes affect a person’s response to drugs. Variants in genes encoding drug-metabolizing enzymes, like the CYP2D6 enzyme, can influence how quickly a person breaks down certain medications, such as antidepressants or pain relievers. This can mean a standard drug dose might be too high for someone with a slower metabolizing variant, leading to adverse side effects, or too low for a fast metabolizer, rendering the medication ineffective.
Beyond drug response, gene variants can impact an individual’s susceptibility to various diseases. Some variants can increase the likelihood of developing conditions like heart disease, type 2 diabetes, or certain cancers. For example, specific variants in the BRCA1 and BRCA2 genes are linked to a higher lifetime risk of breast and ovarian cancers. Other variants can offer protective effects, such as the CCR5-delta32 variant, which provides resistance to HIV infection.
Not all gene variants are harmful. Many are neutral, having no effect on health or traits. Others can even be beneficial, providing an evolutionary advantage. An example is the sickle cell trait, caused by a single nucleotide variant in the hemoglobin gene, which, when present in one copy, offers protection against malaria where the disease is prevalent. The wide array of gene variants underscores the complexity and adaptability of the human genome.