Genes, Variants and Gene Expression

What a gene is

The National Human Genome Research Institute (NHGRI) describes a gene as the basic unit of inheritance, passed from parents to offspring. [1] Most genes code for proteins, and humans have approximately 20,000 protein-coding genes. [2] MedlinePlus Genetics adds that many genes do not code for proteins and instead help control other genes. [3] Genes are made of DNA, and the full set of DNA instructions in a cell is the genome. [4] For the wider field, see Genomics Explained.

Evidence label used on this page: established means described in the same way by national health or genome bodies. Other labels are explained in How We Label Evidence in Specialty Topics.

Variants: differences in the DNA

A gene variant is a permanent change in the DNA sequence that makes up a gene. [5] The older word "mutation" is still common, but MedlinePlus notes that "variant" is considered more accurate because changes in DNA do not always cause disease. [5]

• Inherited (germline) variants come from a parent and are present in virtually every cell.
• Non-inherited (somatic) variants arise during life in certain cells and cannot be passed to the next generation. [6]

People are far more alike than different. The DNA of any two people is 99.9% identical, and the small difference carries variation that contributes to differences in health and traits together with environment. [7] Forms of a gene or DNA location that differ between people are called alleles, and a person inherits two, one from each parent. [8] NHGRI estimates that an individual genome has roughly 4 to 5 million variants. [9]

Most variants do not cause disease

MedlinePlus states that only a small percentage of variants cause genetic disorders, and most have no impact on health or development. [10] When a variant is linked with a condition, laboratories classify it using a standard five-term scale: pathogenic, likely pathogenic, uncertain significance, likely benign and benign. [11] A result of "uncertain significance" means the evidence does not yet say either way. It is not a warning, and it is not a clearance. Read more in Variant Interpretation and Variants of Uncertain Significance.

Gene expression: what "turned on" means

NHGRI defines gene expression as the process by which the information in a gene is turned into a function, mostly through making RNA molecules that code for proteins or serve other roles. [12] It is regulated carefully and changes substantially across conditions and cell types. [13] This is why a muscle cell and a skin cell, with the same DNA, behave differently.

Two cautions follow from this:

1. Expression is not the same as the amount of protein. A review of the evidence found that transcript levels by themselves are not sufficient to predict protein levels in many scenarios. [14]
2. Expression is not the same as health. A change in how active a gene is, measured in cells or blood, is a laboratory signal. It is not a clinical outcome. See Biomarkers vs Clinical Outcomes.

The phrase "turning genes on or off" is a simplification. For more, see Why "Turning Genes On or Off" Is Often an Oversimplification.

Why one gene rarely tells the whole story

Single-gene conditions such as cystic fibrosis exist, but common problems such as heart disease, type 2 diabetes and obesity have no single genetic cause. They are influenced by multiple genes together with lifestyle and environment. [15] A claim that a single gene "explains" a common condition, or that a supplement "supports" a gene, should be treated as a marketing claim unless a human study measured a clinical outcome. See Claim Check: "Changes Gene Expression" Means Treats Disease.

Where individual gene records live

This guide explains concepts. Records for individual genes and variants belong in the Research Library, which is the place to look up a specific gene.