Cancer is a disease in which some of the body’s cells grow uncontrollably. There are many different types of cancer, and each begins when a single cell acquires a genomic change (or mutation) that allows the cell to divide and multiply unchecked. Additional mutations can cause the cancer to spread to other sites. Such mutations can be caused by errors during DNA replication or result from DNA damage due to environmental exposures (such as tobacco smoke or the sun’s ultraviolet rays). In certain cases, mutations in cancer genes are inherited, which increases a person’s risk of developing cancer.

Cancer. Importantly, most mutations that occur in cancer genes don't actually lead to disease. Your body has an excellent system of DNA repair genes that actually remove most such mutations as they occur before they can be propagated.

Elaine A. Ostrander, Ph.D., Chief & NIH Distinguished Investigator, Cancer Genetics and Comparative Genomics Branch

A cancer-susceptibility gene is a gene that, when changed (or mutated), gives an individual an increased risk for developing cancer. Individuals who have inherited mutations in certain cancer-susceptibility genes have a lifetime risk of cancer that is significantly higher than the general population (e.g., BRCA1/BRCA2 ). Individuals in the high-risk category may benefit from more frequent cancer screens. There are also many gene variants associated with a small increase in risk. In some cases, environmental factors may also play a role.

Cancer Susceptibility Gene. One of the most interesting research questions in cancer susceptibility is why certain genes predispose to particular cancers. For instance, women with mutations in the BRCA1 or BRCA2 genes are at increased risk for cancers of the breast and ovary, but not for blood cancers like lymphoma or leukemia.

Elaine A. Ostrander, Ph.D., Chief & NIH Distinguished Investigator, Cancer Genetics and Comparative Genomics Branch

The term candidate gene refers to a gene that is believed to be related to a particular trait, such as a disease or a physical attribute. Because of its genomic location or its known function, the gene is suspected to play a role in that trait, thus making it a candidate for additional study.

Candidate Gene. The more you know about a trait the better job you can do selecting a candidate gene for further study. For instance, if you're studying the genetics of body size, genes that control bone growth, lipid processing, and insulin growth factors are all excellent candidate genes.

Elaine A. Ostrander, Ph.D., Chief & NIH Distinguished Investigator, Cancer Genetics and Comparative Genomics Branch

A carcinogen is a substance, organism or agent capable of causing cancer. Carcinogens may occur naturally in the environment (such as ultraviolet rays in sunlight and certain viruses) or may be generated by humans (such as automobile exhaust fumes and cigarette smoke). Most carcinogens work by interacting with a cell’s DNA to produce mutations.

Carcinogen. A carcinogen is any substance that can cause cancer. It's important to identify items that might be carcinogenic because we can then take specific measures to avoid or limit our exposure to them. The US Department of Health and Human Services National Toxicology Program, and the World Health Organization's International Agency for Research on Cancer both use evidence-based approaches to catalog substances that are known or reasonably anticipated to be human carcinogens. Both use evidence-based approaches to catalog substances that are known or are reasonably anticipated to be human carcinogens. To date, over 500 substances have been identified as definitive, probable, or possible carcinogens for humans. This includes items like asbestos, automobile exhaust, processed meat, or ultraviolet rays. I should stress that exposure to a carcinogen does not necessarily mean you will get cancer. A number of factors influence whether a person exposed to a carcinogen will ultimately develop cancer, including the amount and duration of the exposure, exposure to other environmental factors, and the individual's genetic background.

Carolyn M. Hutter, Ph.D., Director, Division of Genome Sciences

A carrier, as related to genetics, is an individual who “carries” and can pass on to its offspring a genomic variant (allele) associated with a disease (or trait) that is inherited in an autosomal recessive or sex-linked manner, and who does not show symptoms of that disease (or features of that trait). The carrier has inherited the variant allele from one parent and a normal allele from the other parent. Any offspring of carriers is at risk of inheriting a variant allele from their parents, which would result in that child having the disease (or trait).

Carrier. The key to understanding carrier in the genetic sense is that, even though we all have two copies of each gene, for some genes you can have only one working copy and essentially have no major medical issues. The challenge arises when you have a child with another person who is also a carrier for the same autosomal recessive disorder, and the child inherits both nonworking copies from each parent. There's a 25% chance of this happening with every pregnancy. Most often, people don't know that they are carriers. As a result, it's now possible to genetically screen prospective parents to determine whether they are carriers for any of the more commonly seen autosomal recessive disorders.

Neil A. Hanchard, M.B.B.S., D.Phil., Senior Investigator, Center for Precision Health Research

Carrier screening involves testing to see if a person “carries” a genetic variation (allele) associated with a specific disease or trait. A carrier has inherited a normal and a variant allele for a disease- or trait-associated gene, one from each parent. Most typically, carrier screening is performed to look for recessively inherited diseases when the suspected carrier has no symptoms of the disease, but that person’s offspring could have the disease if the other parent is a carrier of a harmful variant in the same gene.

Carrier screening. Carrier screening is often thought about around the time a person may have a child, such as when a person is considering becoming pregnant. The person, sometimes with their partner, undergoes carrier screening to see if there's a chance that their child could be affected by a genetic condition. There are also other times that carrier screening may be done. Carrier screening is a great reminder of the way in which genetics is truly a family affair. That is, it shows how genetic changes can be shared among relatives and can be passed from one generation to the next.

Benjamin Solomon, M.D., Clinical Director, Office of the Clinical Director

cDNA, copy DNA. If you get to spend a week in a genomics lab, it is very likely that you will hear about cDNA one way or another. That's how important this word is and for a good reason. Imagine that for one of your experiments, you need to make a protein and a lot of it. Let's say you want to create a more stable version of insulin, a diabetes drug. One way to do it is to get cells that make this protein, let's say pancreatic cells. These cells will contain a gene with instructions on how to make insulin. These cells can also transcribe this gene to temporarily store this information in the form of RNA. Using a special enzyme called traverse transcriptase, you can convert RNA back to DNA, but the resulting DNA will look a little different from the original gene. For example, it will be much shorter than the gene from where it came from. This is why scientists use another word, cDNA, copy or complementary DNA, to tell these versions apart. What you can do with the cDNA of insulin is very interesting. You can clean it up. You can make changes to the sequence. And using special molecular tools, special enzymes, you can insert it back into genome of another organism, for example, yeast. Yeast is very good at making lots of proteins. And if you insert cDNA of insulin into its genome in the right place and configuration, it can start making insulin for you. This is one way scientists can make and test new versions of insulin with properties that can be helpful in treating diabetes.

Cell-free DNA testing is a laboratory method that involves analyzing free (i.e., non-cellular) DNA contained within a biological sample, most often to look for genomic variants associated with a hereditary or genetic disorder. For example, prenatal cell-free DNA testing is a non-invasive method used during pregnancy that examines the fetal DNA that is naturally present in the maternal bloodstream. Cell-free DNA testing is also used for the detection and characterization of some cancers and to monitor cancer therapy.

Cell-free DNA testing. Cell-free DNA testing was something that really changed many areas of clinical medicine and continues to do so. It's still a very active area of research in terms of ways to look for different types of genetic changes and in different clinical areas. Cell-free DNA testing is a great example of how genetic discoveries translate to different fields of medicine, such as the way cell-free fetal DNA is used in obstetrics practice.

— Benjamin Solomon, M.D.
Clinical Director
Office of the Clinical Director

A centimorgan is a unit used to measure genetic linkage. One centimorgan equals a one percent chance that a marker on a chromosome will become separated from a second marker on the same chromosome due to crossing over in a single generation. It translates to approximately one million base pairs of DNA sequence in the human genome. The centimorgan is named after the American geneticist Thomas Hunt Morgan.

Centimorgan is named after an American geneticist named Thomas Hunt Morgan. He worked on fruit flies, and he defined the capacity of one part of a genome to separate from another in going from one generation to another. And that's important because in every generation chromosomes exchange pieces of information, and that's call recombination. And that's important for introducing genetic diversity into the population. And it was necessary to define a rate at which this happens, and so that's where this term centimorgan comes from. "Centi" means just one-hundredth of, and so if a "morgan" represents the total recombination where all markers of one part of a chromosome will become separated from all others, then a centimorgan is the length of DNA over which that happens only one out of a hundred times, or one percent of the time. So one percent recombination equals a centimorgan. It depends on individual genomes what the distance that a centimorgan represents, and in individual genomes is different from fruit flies and zebrafish and bananas and humans, but given the recombination rate in humans, it represents about a million base pairs in the human genome.

Christopher P. Austin, M.D.

Central Dogma. The fundamental theory of central dogma was developed by Francis Crick in 1958. His version was a bit more global and included the notion that information does not flow from proteins to nucleic acids. Scientists have since discovered several exceptions to the theory. On particularly notable example is that of prions. Prions are infectious proteins which replicate without going through DNA or RNA intermediates. Prions are responsible for the rare but devastating neurologic disease, Creutzfeldt-Jakob, which is a uniformly lethal disease that causes degeneration of the nervous system.

Elaine A. Ostrander, Ph.D.

Chief & NIH Distinguished Investigator

Cancer Genetics and Comparative Genomics Branch

A centromere is a constricted region of a chromosome that separates it into a short arm (p) and a long arm (q). During cell division, the chromosomes first replicate so that each daughter cell receives a complete set of chromosomes. Following DNA replication, the chromosome consists of two identical structures called sister chromatids, which are joined at the centromere.

The centromere is a very specific part of the chromosome. When you look at the chromosomes, there's a part that is not always right in the middle, but it's somewhere between one-third and two-thirds of the way down the chromosome. It's called the centromere. That's the part where the cell's chromosomes are constricted, and they're a little bit tighter, and it almost looks like a little ball in the middle of two sticks. The centromere is what separates the chromosome into what we call, for human chromosomes, the P and Q arm. And these P and Q arms are a part of what we use when we do cytogenetics to say how many chromosomes are present in a cell and what chromosome number they are. That's based on the banding pattern of the cell, but a lot of that is based on how big the P arm is relative to the Q arm. So it's always an important consideration for us to know where the centromere is. That's visually how we use it for some genetic tests, but it's also important that the centromere has a very important function during cell division. During cell division, this is the place where the chromosomes, when they're undergoing replication, that they're held together so that the chromosomes don't lose their sister chromatid during the cell division process.

A chromatid is one of two identical halves of a replicated chromosome. During cell division, the chromosomes first replicate so that each daughter cell receives a complete set of chromosomes. Following DNA replication, the chromosome consists of two identical structures called sister chromatids, which are joined at the centromere.

So what's a chromatid? Well, during DNA division, when a cell divides, it needs to take its DNA and duplicate it and then transfer half of it to one cell and half to the other cell. Well, DNA's arranged in chromosomes, as you know, so what happens is, as a chromosome replicates, or makes a copy of itself, it's arranged as two chromosomes next to each other, called chromatids. Then during mitosis, when the DNA is transferred to the two daughter cells, one of each of those chromatids is transferred to each of the two cells. So a chromatid is one copy of a chromosome after DNA replication.

Chromatin is a substance within a chromosome consisting of DNA and protein. The DNA carries the cell's genetic instructions. The major proteins in chromatin are histones, which help package the DNA in a compact form that fits in the cell nucleus. Changes in chromatin structure are associated with DNA replication and gene expression.

Chromatin is the material that makes up a chromosome that consists of DNA and protein. The major proteins in chromatin are proteins called histones. They act as packaging elements for the DNA. The reason that chromatin is important is that it's a pretty good packing trick to get all the DNA inside a cell. If one took the DNA inside of one cell and stretched it out end to end, it would be about a yard long. Each cell is about a hundredth of a millimeter across, so it's pretty good packing job for the yard of DNA within something that is a hundredth of a millimeter in diameter. And the chromatin does that by wrapping and re-wrapping the DNA in a very tight coil. And that arrangement is called chromatin.

Christopher P. Austin, M.D.

A chromosome is an organized package of DNA found in the nucleus of the cell. Different organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes--22 pairs of numbered chromosomes, called autosomes, and one pair of sex chromosomes, X and Y. Each parent contributes one chromosome to each pair so that offspring get half of their chromosomes from their mother and half from their father.

A chromosome is the structure housing DNA in a cell. Chromosomes are structurally quite sophisticated, containing elements necessary for processes such as replication and segregation. Each species has a characteristic set of chromosomes with respect to number and organization. For example, humans have 23 pairs of chromosomes--22 pairs of numbered chromosomes called autosomes, 1 through 22, and one pair of sex chromosomes, X and Y. Each parent contributes one chromosome of each pair to an offspring.

Eric D. Green, M.D., Ph.D.

Cloning is the process of making identical copies of an organism, cell, or DNA sequence. Molecular cloning is a process by which scientists amplify a desired DNA sequence. The target sequence is isolated, inserted into another DNA molecule (known as a vector), and introduced into a suitable host cell. Then, each time the host cell divides, it replicates the foreign DNA sequence along with its own DNA. Cloning also can refer to asexual reproduction.

Cloning is a word we use to describe a molecular process of making millions or billions of copies of a single molecule. It's different from the uses of the terms "cellular cloning" or "organism cloning" that are used in the reproductive genetics universe. We use molecular cloning to amplify, or make many copies of, genes or proteins or other micro molecules that amplifies the signal and allows us to study these molecules in a laboratory.

Leslie G. Biesecker, M.D.

Codominance is a relationship between two versions of a gene. Individuals receive one version of a gene, called an allele, from each parent. If the alleles are different, the dominant allele usually will be expressed, while the effect of the other allele, called recessive, is masked. In codominance, however, neither allele is recessive and the phenotypes of both alleles are expressed.

Codominance means that neither allele can mask the expression of the other allele. An example in humans would be the ABO blood group, where alleles A and alleles B are both expressed. So if an individual inherits allele A from their mother and allele B from their father, they have blood type AB.

Suzanne Hart, Ph.D.

A codon is a trinucleotide sequence of DNA or RNA that corresponds to a specific amino acid. The genetic code describes the relationship between the sequence of DNA bases (A, C, G, and T) in a gene and the corresponding protein sequence that it encodes. The cell reads the sequence of the gene in groups of three bases. There are 64 different codons: 61 specify amino acids while the remaining three are used as stop signals.

Codon is the name we give a stretch of the three nucleotides, you know, one of A, C, G, or T, three of which in a row, that code for a specific amino acid, and so the genetic code is made up of units called codons where you have three nucleotides that code for a specific amino acid next to another three nucleotides, another three nucleotides, and another three nucleotides. And the cellular machinery, again the ribosome, that comes through and reads that genetic code, plugs in the correct amino acid that corresponds to each of the triplet code that's in the codon.

A complex disease is caused by the interaction of multiple genes and environmental factors. Complex diseases are also called multifactorial. Examples of complex diseases include cancer and heart disease.

In a way, it's sort of funny that any disease would be called not complex, so this is one of those terms that initially seems a little odd, but in our own parlance--and geneticists have their own way of thinking about things--complex disease really is supposed to conjure up in your mind that this is not a simple Mendelian single-gene disorder. It's messier than that. A complex disease would have many genes involved, often significant environmental contributions involved. You might also say it's polygenic, another word that says multiple genes contributing. We're talking about diseases like diabetes, or the common cancers, or heart disease, where you don't expect it's going to be as simple as one glitch in the genome causing the condition.

Francis S. Collins, M.D., Ph.D.

Congenital conditions are those present from birth. Birth defects are described as being congenital. They can be caused by a genetic mutation, an unfavorable environment in the uterus, or a combination of both factors.

So congenital is something that's really present at birth. And when we talk about congenital, some people think it's just because it's present at birth that it has to mean that it's genetics, but that's not necessarily the case. Many birth defects that are seen at birth can be genetics, but then there are lots of other reasons of having something wrong at birth of the baby, and that could be due to medications, due to things the mother took during the pregnancy that then resulted in the baby having problems that could be seen at birth.

Maximilian Muenke, M.D.

A contig--from the word "contiguous"--is a series of overlapping DNA sequences used to make a physical map that reconstructs the original DNA sequence of a chromosome or a region of a chromosome. A contig can also refer to one of the DNA sequences used in making such a map.

A chromosome is a very long molecule of DNA. And it is very hard to study it at once, so what researchers do is they break it into smaller pieces and they sequence each one of those individual pieces first, and then they attempt to put it together to reconstruct the original chromosome sequence. A contig is the physical map, which results from putting together several little overlapping bits of DNA into a longer sequence. The contig is the physical map resulting from taking small pieces of DNA that overlap and putting them together into a longer sequence.

A copy number variation (CNV) is when the number of copies of a particular gene varies from one individual to the next. Following the completion of the Human Genome Project, it became apparent that the genome experiences gains and losses of genetic material. The extent to which copy number variation contributes to human disease is not yet known. It has long been recognized that some cancers are associated with elevated copy numbers of particular genes.

Copy number variation is a type of structural variation where you have a stretch of DNA, which is duplicated in some people, and sometimes even triplicated or quadruplicated. And so when you look at that chromosomal region, you will see a variation in the number of copies in normal people. Sometimes those copy number variants include genes, maybe several genes, which may mean that this person has four copies of that gene instead of the usual two, and somebody else has three, and somebody else has five. Interesting, we didn't really expect to see so much of that. It's now turning out to be pretty common, and in some instances, if those genes are involved in functions that are sensitive to the dosage, you might then see a consequence in terms of a disease risk.

Francis S. Collins, M.D., Ph.D.

CRISPR (short for “clustered regularly interspaced short palindromic repeats”) is a technology that research scientists use to selectively modify the DNA of living organisms. CRISPR was adapted for use in the laboratory from naturally occurring genome editing systems found in bacteria.

CRISPR. When I first learned about CRISPR about a decade ago, the technology and the future possibilities were just amazing. A few years after that, I had the joy of meeting Dr. Jennifer Doudna at a small meeting at NHGRI, and we knew at that time that we were talking to a future Nobel Prize winner and, indeed, she got that very recently. This class of enzymes from bacteria has many, many uses, and I thought I'd pick one just for its timeliness. It provided the simple method for detection of COVID ribonucleic acid -- or RNA -- without making copies up front or performing gene amplification, or sometimes called PCR. And that's just a nice impactful example of so many places that this discovery has been important.

— Mike Smith, Ph.D.
Former Program Director, Genome Technology Program
Division of Genome Sciences

Crossing over is the swapping of genetic material that occurs in the germ line. During the formation of egg and sperm cells, also known as meiosis, paired chromosomes from each parent align so that similar DNA sequences from the paired chromosomes cross over one another. Crossing over results in a shuffling of genetic material and is an important cause of the genetic variation seen among offspring.

Crossing over is a biological occurrence that happens during meiosis when the paired homologs, or chromosomes of the same type, are lined up. In meiosis, they're lined up on the meiotic plates, [as they're] sometimes called, and those paired chromosomes then have to have some biological mechanism that sort of keeps them together. And it turns out that there are these things called chiasmata, which are actually where strands of the duplicated homologous chromosomes break and recombine with the same strand of the other homolog. So if you have two Chromosome 1s lined up, one strand of one Chromosome 1 will break and it will reanneal with a similar breakage on the other Chromosome 1. So that then the new chromosome that will happen will have part of, say, the maternal Chromosome 1 and the paternal Chromosome 1, where maternal and paternal means where that person got their Chromosomes 1s from, their one or their two. Therefore, the child that's formed out of one of those Chromosome 1s now has a piece of his or her grandmother's Chromosome 1 and a piece of his or her grandfather's Chromosome 1. And it's this crossing over that lets recombination across generations of genetic material happen, and it also allows us to use that information to find the locations of genes.

Cystic fibrosis is a hereditary disease characterized by faulty digestion, breathing problems, respiratory infections from mucus buildup, and the loss of salt in sweat. The disease is caused by mutations in a single gene and is inherited as an autosomal recessive trait, meaning that an affected individual inherits two mutated copies of the gene. In the past, cystic fibrosis was almost always fatal in childhood. Today, however, patients commonly live to be 30 years or older.

Cystic fibrosis of the pancreas was the original description of this disease because it affects the pancreas and the lungs, although it's the lungs that are the cause of the most major concerns these days. The pancreas problems, which were the cause of the original label, are actually well treated by enzyme replacement. And we've done much better in the treatment of the disease, so the average survival is now in the mid-30s. But after the gene was discovered in 1989, a gene called CFTR, many people had hopes that that would lead immediately to a cure. That was probably unrealistic. But happily, now some two decades later, there is real promise of drug treatment based upon an understanding of how the gene works, and maybe in the future this will be a disease for the history books.

Francis S. Collins, M.D., Ph.D.

Cytogenetics is the branch of genetics that studies the structure of DNA within the cell nucleus. This DNA is condensed during cell division and form chromosomes. The cytogenetic studies the number and morphology of chromosomes. Using chromosome banding techniques (classical cytogenetics) or hybridization fluorescently labeled probes (molecular cytogenetics). The number and morphology of chromosomes in a cell of a particular species are always constant, in most cells of the body (with the exception of reproductive cells and others such as the liver). This is a characteristic of each specie, in humans such as the number of chromosomes is 46.

Cytogenetics is the term we use to discuss looking at the genetic material through a microscope. Traditionally this was done with a light microscope and looking at chromosomes. In fact, chromosomes were visible to those using microscopes even before we knew that they were made of DNA. In modern times we can use advanced cytogenetics techniques such as fluorescence in situ hybridization (FISH) to look at the genetic material in the cell through a light microscope but at much higher resolution.

Amalia S. Dutra, Ph.D.