Mapping is the process of making a representative diagram cataloging the genes and other features of a chromosome and showing their relative locations. Cytogenetic maps are made using photomicrographs of chromosomes stained to reveal structural variations. Genetic maps use the idea of linkage to estimate the relative locations of genes. Physical maps, made using recombinant DNA (rDNA) technology, show the actual physical locations of landmarks along a chromosome.

The process of establishing the spatial relationship of landmarks within DNA is called mapping. Such landmarks can be genes or regions that vary among individuals. Mapping can involve simply ordering such landmarks, or in some cases precisely determining the spacing between them. Cytogenetic maps give the order of stained chromosome bands. Genetic maps represent the positions of polymorphisms--regions where the DNA sequence differs among individuals. Physical maps depict the actual physical locations of landmarks along a stretch of DNA.

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

A marker is a DNA sequence with a known physical location on a chromosome. Markers can help link an inherited disease with the responsible genes. DNA segments close to each other on a chromosome tend to be inherited together. Markers are used to track the inheritance of a nearby gene that has not yet been identified but whose approximate location is known. The marker itself may be a part of a gene or may have no known function.

Genetic marker is a very simple concept. Think about it as a signpost. Think about DNA as one long road from one end to the other. And what one needs is mile markers or signposts along that road so that when one is traveling from one end of the road to the other, you know where you are. And those signposts, those markers, can come from a variety of sources. Usually, they come from the variations in DNA sequence. Sometimes they're single variations of DNA sequence referred to as a single nucleotide polymorphisms, or SNP markers. Sometimes they're known as microsatellites. There are a variety of types of genetic markers. But the important thing is that those markers serve as signposts, which help researchers relate a particular kind of trait or disease that they're trying to figure out the genetic basis of to a particular location in DNA. And so the change in DNA sequence may actually be in the disease gene itself that they're looking for, but more frequently it's just what it says: It's a marker of it, which could be upstream or downstream, but is not actually the disease gene one is looking for.

Christopher P. Austin, M.D.

A megabase (abbreviated Mb) is a unit of measurement used to help designate the length of DNA. One megabase is equal to 1 million bases. 

No, Megabase is not the name of a heavy metal rock band from the 1980s, as it may sound. A megabase is an extremely useful unit of measurement that can be helpful for understanding the scale of information contained in DNA. For example, researchers can track the ever-decreasing cost of DNA sequencing by calculating the “cost per megabase of DNA sequence.” In 2001, it cost about 5,292 dollars and 39 cents per megabase, which equaled about 95 million 263 thousand and 072 dollars per human genome. By 2021, it cost only 0.006 dollars per megabase, which equaled about $562 per human genome. What an enormous difference! This is due to incredible advances in technology and computational techniques, as well as knowledge gained from decades of sequencing human genomes.

Sarah A. Bates, M.S., M.A., Chief, Office of Communications

Meiosis is the formation of egg and sperm cells. In sexually reproducing organisms, body cells are diploid, meaning they contain two sets of chromosomes (one set from each parent). To maintain this state, the egg and sperm that unite during fertilization must be haploid, meaning they each contain a single set of chromosomes. During meiosis, diploid cells undergo DNA replication, followed by two rounds of cell division, producing four haploid sex cells.

Meiosis. What a funny word with so many vowels. Well, this is a really important part of human biology and the biology of many other organisms that go through sexual reproduction. Basically, here's the problem: You've got a certain number of chromosomes; we humans have 46. But a child who's going to get half of their inheritance from their mother and father, they can't get 46 from both of them--that would be 92. So there has to be a way to take those paired chromosomes and break them apart in order to make gametes; sperm and eggs. That's what meiosis is all about. It's taking that complete set and breaking it down to a so-called haploid set and also providing the opportunity for recombination to occur to sort of scramble the copies and produce new kinds of outcomes, which is critical for the diversity of a species. Meiosis is one of those things that's hard to really get your mind around. There's meiosis 1, there's meiosis 2...you have to learn where the recombination occurs, but it is a really exciting part of human biology.

Gregor Mendel was an Austrian monk who in the 19th century worked out the basic laws of inheritance, even before the term "gene" had been coined. In his monastery garden, Mendel performed thousands of crosses with garden peas. Mendel explained his results by describing two laws of inheritance that introduced the idea of dominant and recessive traits.

Gregor Mendel, the Austrian monk laboring away in his garden in what is now Czechoslovakia with his pea plants, worked in relative unknown obscurity. [But he] did publish his results in 1865, showing that in fact you could model the inheritance of certain characteristics, such as wrinkled or smooth, by simple mathematical principles. It took another 35 years for his work to be rediscovered, but it provides the real fundamentals of understanding the genetic basis of inheritance, namely dominant and recessive traits upon which we now build much of human genetics.

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

Mendelian inheritance refers to patterns of inheritance that are characteristic of organisms that reproduce sexually. The Austrian monk Gregor Mendel performed thousands of crosses with garden peas at his monastery during the middle of the 19th century. Mendel explained his results by describing two laws of inheritance that introduced the idea of dominant and recessive genes.

Mendelian inheritance refers to the kind of inheritance you can understand more simply as the consequence of a single gene. So in human genetics, for instance, when you look at a condition like Huntington's disease, and you see that it follows this pattern where an affected person who passes that to a child, the child has a 50 percent chance of being infected... That's dominant Mendelian inheritance. Hemophilia, where you see a condition where the female seems to be unaffected but there's X-linked inheritance, that's also Mendelian. Or cystic fibrosis, where it's autosomal recessive, you can model that also by Mendel's rules of the consequence of a single gene.

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

Messenger RNA (mRNA) is a single-stranded RNA molecule that is complementary to one of the DNA strands of a gene. The mRNA is an RNA version of the gene that leaves the cell nucleus and moves to the cytoplasm where proteins are made. During protein synthesis, an organelle called a ribosome moves along the mRNA, reads its base sequence, and uses the genetic code to translate each three-base triplet, or codon, into its corresponding amino acid.

Messenger RNAs, also known as mRNA, are one of the types of RNA that are found in the cell. This particular one, like most RNAs, are made in the nucleus and then exported to the cytoplasm where the translation machinery, the machinery that actually makes proteins, binds to these mRNA molecules and reads the code on the mRNA to make a specific protein. So in general, one gene, the DNA for one gene, can be transcribed into an mRNA molecule that will end up making one specific protein.

Lawrence C. Brody, Ph.D.

Metagenomics is the study of a collection of genetic material (genomes) from a mixed community of organisms. Metagenomics usually refers to the study of microbial communities.

"Metagenomics" is the two words "meta" and "genomics". So genomics is obtaining the DNA sequence, but meta implies that we're doing it of many organisms together. And metagenomics is usually used when we are studying microbial communities where we can't separate one microbe from another. Like there may be two bacteria that grow together, and so when you take the DNA sequence, you're getting the DNA sequence of two bacteria together. Now, as an example of this, you can imagine that I could go in and take the DNA sequence of a person who lives in New York City. But if I were to come in and take the DNA from everyone who lives in New York City and sequence it together, that would be the equivalent of what we're doing when were sequencing the DNA of all of the bacteria that live in one place on your skin or your intestine together. So we're not just looking at one organism, we're looking at the DNA sequence of all of the organisms together. Because we could imagine sequencing the DNA of an individual in New York, but imagine if our technology was limited and we couldn't separate these people in New York. If we need to take the DNA sequence of every person in New York together, and then later we try to figure out which DNA belonged to which person, that's often what we are doing when we're studying bacterial and fungal communities together.

— Julie A. Segre, Ph.D.

Metaphase is a stage during the process of cell division (mitosis or meiosis). Usually, individual chromosomes cannot be observed in the cell nucleus. However, during metaphase of mitosis or meiosis the chromosomes condense and become distinguishable as they align in the center of the dividing cell. Metaphase chromosomes are used during the karyotyping procedure that is used to look for chromosomal abnormalities.

Metaphase is a stage in the cell cycle where all the genetic material is condensing into chromosomes. These chromosomes then become visible. During this stage, the nucleus disappears and the chromosomes appear in the cytoplasm of the cell. During this stage in human cells, the chromosomes then become visible under the microscope. As metaphase continues, the cells partition into the two daughter cells. Cells in metaphase are used in medical research to measure whether all of the chromosomes are present and whether or not they are all intact. This process of looking at chromosomes under the microscope is called karyotyping.

Methylation is a chemical modification of DNA and other molecules that may be retained as cells divide to make more cells. When found in DNA, methylation can alter gene expression. In this process, chemical tags called methyl groups attach to a particular location within DNA where they turn a gene on or off, thereby regulating the production of proteins that the gene encodes.

Methylation. Methylation is also used to identify different types of genomes. So for different bacteria, they methylate different sequences. Some bacteria will methylate the sequence GAATTC and that's how they recognize their own DNA versus foreign invading DNA. This methylation is also at the heart of how restriction enzymes are produced in a bacterial cell that don't then chop up that own cell's DNA but are used to recognize foreign DNA. That may be too complicated but that's what I think is interesting about methylation. It was really important for us for making YAC libraries. That's just my own little 2 cents.

Julie Segre, Ph.D., Chief and NIH Distinguished Investigator Translational and Functional Genomics Branch

Microarray technology is a developing technology used to study the expression of many genes at once. It involves placing thousands of gene sequences in known locations on a glass slide called a gene chip. A sample containing DNA or RNA is placed in contact with the gene chip. Complementary base pairing between the sample and the gene sequences on the chip produces light that is measured. Areas on the chip producing light identify genes that are expressed in the sample.

Microarrays are a technology that basically miniaturize processes that have been used in molecular genetics laboratories for years. They allow detection of DNA or RNA molecules by hybridizing or sticking to target DNA molecules or RNA molecules on a glass slide, with detection of that adherent DNA or RNA molecule by various labels or dyes that allow them to be seen under a microscope.

A microbiome is all of the genetic material found within an individual microbe such as a bacterium, fungal cell, or virus. It also may refer to the collection of genetic material found in a community of microbes that live together.

Microbiome. Microbes are the small organisms that we can just barely see under a microscope, like bacteria, fungi, viruses... And these microbes live everywhere. They live in the soil, they live in the water, and they live in and on our body. The microbiome is a new term that refers to all of the genetic material found in an individual microbe such as one of these bacteria or fungi or viruses. So if we think about the entire DNA sequence of a microbe, that is the microbiome.

Microsatellite sequences are repetitive DNA sequences usually several base pairs in length. Microsatellite sequences are composed of non-coding DNA and are not parts of genes. They are used as genetic markers to follow the inheritance of genes in families.

A microsatellite. These are little bits of DNA in our genome that are very simple in the sense that they're only made up of two or three combinations of letters, like CACACA or GATGATGAT. And it turns out that these little repetitive sequences within our genome vary very quickly between different people. And so it's very easy [for] these microsatellite repetitive sequences to try and so-call fingerprint DNA with a particular human being.

Elliott Margulies, Ph.D.

A missense mutation is when the change of a single base pair causes the substitution of a different amino acid in the resulting protein. This amino acid substitution may have no effect, or it may render the protein nonfunctional.

A missense mutation is a mistake in the DNA which results in the wrong amino acid being incorporated into a protein because of change, that single DNA sequence change, results in a different amino acid codon which the ribosome recognizes. Changes in amino acid can be very important in the function of a protein. But sometimes they make no difference at all, or very little difference. Sometimes missense mutations cause amino acids to be incorporated, which make the protein more effective in doing its job. More frequently, it causes the protein to be less effective in doing its job. But this is really the grist of evolution, when missense mutations happen, and therefore small changes, frequently small changes in proteins, happen, and it happens to be that it improves the function of a protein. That will sometimes give the organism that has it a competitive advantage over its colleagues and be maintained in the population.

Christopher P. Austin, M.D.

Mitochondrial DNA is the small circular chromosome found inside mitochondria. The mitochondria are organelles found in cells that are the sites of energy production. The mitochondria, and thus mitochondrial DNA, are passed from mother to offspring.

Inside the mitochondrion is a certain type of DNA. That's different in a way from the DNA that's in the nucleus. This DNA is small and circular. It has only 16,500 or so base pairs in it. And it encodes different proteins that are specific for the mitochondrial. Now, remember those pathways that are within the mitochondrion for producing energy. Some of the enzymes in those pathways, and some of the proteins that are needed to function in those pathways, are produced by the mitochondrial DNA. The mitochondrial DNA is critically important for many of the pathways that produce energy within the mitochondria. And if there's a defect in some of those mitochondrial DNA bases, that is to say a mutation, you will have a mitochondrial disease, which will involve the inability to produce sufficient energy in things like the muscle and the brain, and the kidney. Mitochondrial DNA, unlike nuclear DNA, is inherited from the mother, while nuclear DNA is inherited from both parents. So this is very helpful sometimes in determining how a person has a certain disorder in the family. Sometimes a disease will be inherited through the mother's line, as opposed to both parents. You can tell from a pedigree or a group of family history whether or not this is a mitochondrial disease because of that.

William Gahl, M.D., Ph.D.

Mitosis is a cellular process that replicates chromosomes and produces two identical nuclei in preparation for cell division. Generally, mitosis is immediately followed by the equal division of the cell nuclei and other cell contents into two daughter cells.

We all started as one cell. That's pretty hard to imagine, but that's true. And now there's about a hundred trillion cells in each of our bodies, and they each have to carry the complete DNA instruction set. So that means when cells divide, a process has to occur of copying all of that. And that is mitosis, where each chromosome has to be turned into a pair, and then they have to split apart properly so that each of the daughter cells gets a complete set.