A gene is the basic physical and functional unit of heredity. Genes are made up of DNA. Some genes act as instructions to make molecules called proteins. However, many genes do not code for proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. An international research effort called the Human Genome Project, which worked to determine the sequence of the human genome and identify the genes that it contains, estimated that humans have between 20,000 and 25,000 genes.

Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.

Scientists keep track of genes by giving them unique names. Because gene names can be long, genes are also assigned symbols, which are short combinations of letters (and sometimes numbers) that represent an abbreviated version of the gene name. For example, a gene on chromosome 7 that has been associated with cystic fibrosis is called the cystic fibrosis transmembrane conductance regulator; its symbol is CFTR.

Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs.

Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function. Amino acids are coded by combinations of three DNA building blocks (nucleotides), determined by the sequence of genes.

Proteins can be described according to their large range of functions in the body, listed in alphabetical order:

Most genes contain the information needed to make functional molecules called proteins. (A few genes produce regulatory molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression.

During the process of transcription, the information stored in a gene's DNA is passed to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of building blocks called nucleotides, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm.

Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which "reads" the sequence of mRNA nucleotides. Each sequence of three nucleotides, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three nucleotides that does not code for an amino acid).

The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.”

Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood.

Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.

Epigenetics is the study of how cells control gene activity without changing the DNA sequence."Epi-" means on or above in Greek, and "epigenetic" describes factors beyond the genetic code. Epigenetic changes are modifications to DNA that regulate whether genes are turned on or off. These modifications are attached to DNA and do not change the sequence of DNA building blocks. Within the complete set of DNA in a cell (genome), all of the modifications that regulate the activity (expression) of the genes is known as the epigenome.

Because epigenetic changes help determine whether genes are turned on or off, they influence the production of proteins in cells. This regulation helps ensure that each cell produces only proteins that are necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Patterns of epigenetic modification vary among individuals, in different tissues within an individual, and even in different cells within a tissue. Environmental influences, such as a person’s diet and exposure to pollutants, can impact the epigenome. Epigenetic modifications can be maintained from cell to cell as cells divide and, in some cases, can be inherited through the generations.

A common type of epigenetic modification is called DNA methylation. DNA methylation involves the attachment of small chemical groups called methyl groups (each consisting of one carbon atom and three hydrogen atoms) to DNA building blocks. When methyl groups are present on a gene, that gene is turned off or silenced, and no protein is produced from that gene.

Another common epigenetic change is histone modification. Histones are structural proteins in the cell nucleus. DNA wraps around histones, giving chromosomes their shape. Histones can be modified by the addition or removal of chemical groups, such as methyl groups or acetyl groups (each consisting of two carbon, three hydrogen, and one oxygen atoms). The chemical groups influence how tightly the DNA is wrapped around histones, which affects whether a gene can be turned on or off.

Errors in the epigenetic process, such as modification of the wrong gene or failure to add a chemical group to a particular gene or histone, can lead to abnormal gene activity or inactivity. Altered gene activity, including that caused by epigenetic errors, is a common cause of genetic disorders. Conditions such as cancers, metabolic disorders, and degenerative disorders have been found to be related to epigenetic errors.

Scientists continue to explore the relationship between the genome and the chemical compounds that modify it. In particular, they are studying the effects that epigenetic modifications and errors have on gene function, protein production, and human health.

There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells.

Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by certain genes. When mitosis is not regulated correctly, health problems such as cancer can result.

The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of gene shuffling while the cells are dividing.

A variety of genes are involved in the control of cell growth and division. The cell replicates itself in an organized, step-by-step fashion known as the cell cycle. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cell cycle has checkpoints (also called restriction points), which allow certain genes to check for problems and halt the cycle for repairs if something goes wrong.

If a cell has an error in its DNA that cannot be repaired, it may undergo self-destruction (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells that no longer work or that it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues.

Disruption of normal regulation of the cell cycle can lead to diseases such as cancer. When the cell cycle proceeds without control, cells can divide without order and accumulate genetic errors that can lead to a cancerous tumor.

Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, which is a precise description of a gene's position on a chromosome. The molecular location is based on the sequence of DNA building blocks (nucleotides) that make up the chromosome.

Cytogenetic location

Geneticists use a standardized way of describing a gene's cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome:

17q12

It can also be written as a range of bands, if less is known about the exact location:

17q12-q21

The combination of numbers and letters provide a gene's “address” on a chromosome. This address is made up of several parts:

• The chromosome on which the gene can be found. The first number or letter used to describe a gene's location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.

• The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene's address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.

• The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.

Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene's cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm, or the very end, of chromosome 14.

Molecular location

The Human Genome Project, an international research effort completed in 2003, determined the sequence of nucleotides for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of nucleotides. It describes the gene’s precise position on a chromosome and indicates the size of the gene. Knowing the molecular location also allows researchers to determine exactly how far a gene is from other genes on the same chromosome.

Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address.

What are genes?

Genes are segments of DNA that contain instructions for building the molecules that make the body work. Most of the molecules are proteins. Parents pass their genes to their offspring.

What is a genome?

A genome is all of the genetic material in an organism. It is made of DNA (or RNA in some viruses) and includes genes and other elements that control the activity of those genes.

Does everybody have the same genome?

The human genome is mostly the same in all people. But there are variations across the genome. This genetic variation accounts for about 0.001 percent of each person's DNA and contributes to differences in appearance and health. People who are closely related have more similar DNA.

Some of the variations between individuals result from epigenetic changes. These changes arise from chemical tags that attach to DNA and affect how cells read DNA’s instructions. Epigenetic changes can be inherited.

Is genetic variation related to health and disease?

Many differences in DNA have no effect on health or disease risk. But some do. Because parents pass their genes on to their offspring, some diseases tend to cluster in families, similar to other inherited traits.

Genetic variations can influence how people respond to certain medicines, as well.

What does it mean to have a genetic risk?

Having a genetic risk means that a person has inherited the tendency to develop a certain illness. It does not mean that he or she will definitely develop the illness. Rather, it means there is a higher chance of developing it than if he or she did not have the risk.

What can a genetic test reveal?

A genetic test can identify genetic variations that studies have linked to the risk of developing a specific disease or of passing a disease gene on to descendants. A genetic test can also indicate how a person might respond to certain medicines.

Why does genetic research sometimes involve specific population groups?

Population groups often include people with the same ancestry and therefore very similar genomes. Plus, populations may share diets, environments and other characteristics that influence health. These genetic and environmental similarities make it easier for scientists to spot rare differences in a population group that could be related to health or disease. Such studies also can help explain why some medical conditions are more common in certain population groups.

Can researchers study someone's genes without permission?

Scientists who conduct research with people follow strict rules. Among other things, they must obtain signed consent from participants. And before collecting blood, cheek swabs or other samples that contain DNA, researchers must tell participants the purpose of the study, how they will use the samples, and whether and for how long they will store the samples.

Why do scientists study the genes of other organisms?

All living things evolved from a common ancestor. Therefore, humans, animals and other organisms share many of the same genes, and the molecules made from them function in similar ways. For example, the human and mouse genomes are about 85 percent the same. Two-thirds of human genes known to be involved in cancer have counterparts in the fruit fly.

Researchers have found many genes that have been preserved in multiple organisms for millions of years. They can study these preserved genes and compare the genomes of different species to find similarities and differences that improve their understanding of how human genes function and are controlled. This helps researchers develop new strategies to treat and prevent human disease. Scientists also study the genes of bacteria, viruses and fungi to find ways to prevent or treat infection. Increasingly, these studies are helping them understand how microbes on and in the body affect human health, sometimes in beneficial ways.