Nanopore DNA sequencing is a laboratory technique for determining the exact sequence of nucleotides, or bases, in a DNA molecule. The sequence of the bases (often referred to by the first letters of their chemical names: A, T, C and G) encodes the biological information that cells use to develop and operate. Nanopore DNA sequencing involves reading the code of single DNA strands as they are threaded through extremely tiny pores (nanopores) embedded within a membrane. As the DNA moves through the pore, it creates signals that can be converted to read each base. This approach offers a low-cost, rapid process for studying long stretches of DNA.

Nanopore DNA Sequencing. Early techniques for sequencing DNA relied on breaking the genome into many tiny pieces, creating vast copies of those pieces, sequencing them, and then putting the resulting data back together with computers. Nanopore DNA sequencing, however, threads one DNA strand through a really tiny nanopore and then detects minuscule changes in electric current to determine the different nucleotides of DNA. A major advantage of nanopore DNA sequencing is the ability to produce ultra-long reads — much, much longer than that produced by earlier techniques. It also detects the nucleotides from a single DNA molecule rather than many. These advantages have helped scientists work out complex regions of the human genome.

Nanotechnology is the science of manipulating matter on the atomic and molecular scales to solve problems. Nanotechnology is a developing applied science that has the potential to make significant contributions to many fields, including engineering, computer science, and medicine.

Nanotechnology is an area of research and application of that research to make devices and products. It studies the properties of materials that are between one and 100 nanometers in size. So what's a nanometer? It's 10 to the minus-nine meters or .000000001 meters. That's one ten-thousandths the diameter of the human hair. Or another way to look at it is the DNA molecule is about two and a half nanometers in diameter. Nanotechnology's interesting because scientists observe unusual properties of materials at that size scale. The materials don't behave either like the atoms from which they're made or like the bulk material with which we are familiar. Examples of nanometer particles are gold, that instead of appearing the familiar color we call gold, appear red or blue or other colors depending on their exact size. And they also have different electrical properties from bulk gold that we use in jewelry or electronic devices. Or carbon nanotubes that are made of the same material as the graphite in your pencil lead that are incredibly strong, not brittle, and also have different electrical properties depending on how exactly the atoms come together. As biomedical scientists, we're interested in nanotechnology because we think we can use these new materials to make better devices to diagnose disease or to improve imaging agents that are used for MRI tests and even to deliver drugs more effectively.

Jeffery A. Schloss, Ph.D.

Newborn screening is a set of laboratory tests performed on newborn babies to detect a set of known genetic diseases. Typically, this testing is performed on a blood sample obtained from a heel prick when the baby is two or three days old. In the United States, newborn screening is mandatory for a defined set of genetic diseases, although the exact set differs from state to state. Newborn screening tests focus on conditions for which early diagnosis is important to treating or preventing disease.

Newborn genetic screening. Mandatory newborn screening programs are a classic public health success story. These programs save lives and prevent disability in thousands of infants every year by identifying certain conditions promptly after birth. Early detection of those conditions allows different kinds of treatments and interventions to be provided very early in a newborn's life when it can really make a difference in health outcomes and even help to prevent severe, irreversible disability. The reason why some states include different tests in their screening programs is complicated. A decision has to be made about what test to include based on which ones will bring about the best health outcomes for newborns. The decision-makers also have to consider the costs and feasibility of screening, diagnosis and treatment and weigh that against the potential health benefits of each test.

Non-coding DNA corresponds to the portions of an organism’s genome that do not code for amino acids, the building blocks of proteins. Some non-coding DNA sequences are known to serve functional roles, such as in the regulation of gene expression, while other areas of non-coding DNA have no known function.

Non-coding DNA. So I could talk about this one forever because it actually happened to be the part of the genome that I did most of my PhD work in. And there used to be an older and derogatory term called junk DNA, which, thankfully, doesn't get used these days much longer. So really, the thing to keep in mind here that human genome is a vast, vast expanse of nucleotides, 3.3 billion almost. And only a very, very small fraction of that, about 2% actually codes for what we know to be proteins. And so the question is, what really happens with the rest? Is it just there doing nothing? Or does it have a function? And for many years, particularly in the earlier stages of genomics as a field, people were not really sure that the non-coding parts of the genome have a purpose for being there. And now, or I would say over the last decade or so maybe, we are only just starting to realize that there are an immense number of ways in which what we think of as non-coding actually might just have a more subtle way of passing its information along. So it may not code in the classical protein-coding sense. But there is a ton of information crucial in many, many ways that is hidden in this part of the genome.

A nonsense mutation occurs in DNA when a sequence change gives rise to a stop codon rather than a codon specifying an amino acid. The presence of the new stop codon results in the production of a shortened protein that is likely non-functional.

A nonsense mutation, or its synonym, a stop mutation, is a change in DNA that causes a protein to terminate or end its translation earlier than expected. This is a common form of mutation in humans and in other animals that causes a shortened or nonfunctional protein to be expressed.

Northern blot is a laboratory technique used to detect a specific RNA sequence in a blood or tissue sample. The sample RNA molecules are separated by size using gel electrophoresis. The RNA fragments are transferred out of the gel to the surface of a membrane. The membrane is exposed to a DNA probe labeled with a radioactive or chemical tag. If the probe binds to the membrane, then the complementary RNA sequence is present in the sample.

Northern blot is used to analyze molecules of RNA. So typically you would isolate a population of RNA from some cell sample or tissue sample, and then you would electrophoretically allow the RNA to migrate down a gel. So you're going to have the smaller fragments at the bottom and the larger fragments at the top. Once you've finished what we call running the gel, you apply a membrane to the gel and transfer, either by a salt gradient or by electrophoretic transfer, the molecules, the RNA molecules, in the gel to a membrane, typically nitrocellulose. Having that on nitrocellulose is going to look mostly like a white piece of paper. Having that, you're going to be able to then interrogate the differences in the RNA samples. We can ask if some RNA is gone or not by marking that RNA and then finding its match on the northern blot membrane, or you can ask, does it change in size? You might expect a change in size if you had an alteration in RNA splicing. The term northern blot actually is a play on words from how people originally would analyze DNA. And a man named Edward Southern actually developed the protocol in which he would do a similar analysis, but you would allow DNA molecules to migrate on a gel and then transfer that a membrane. And that protocol was named after him, [and] his name is Southern. And so it seemed kind of like a nice play on words that if you were going to analyze a similar RNA molecule in a similar way that you would then name it northern blot. The "blot" of northern blot refers to the protocol itself where you have a gel and then you lay it, it's like a sandwich, you put the membrane you want to transfer it to on top and then you add a stack of absorbent material--we use paper towels--and it's as if you're blotting the DNA up to the top of your membrane for further analysis.

Stacie Loftus, Ph.D.

A nuclear membrane is a double membrane that encloses the cell nucleus. It serves to separate the chromosomes from the rest of the cell. The nuclear membrane includes an array of small holes or pores that permit the passage of certain materials, such as nucleic acids and proteins, between the nucleus and cytoplasm.

The nuclear membrane. When we divide the organisms that live on this planet, we make a distinction between those that have a nucleus, that are called eukaryotes, and those that don't have a nuclei, which we call prokaryotes. The nucleus contains all of the genetic material for a eukaryotic cell, but this genetic material needs to be protected. And it's protected by the nuclear membrane, which is a double membrane that encloses all the nuclear genetic material and all the other components of the nucleus. There are some small holes or pores that are in the nuclear membrane that allow the messenger RNA and the proteins to move between the nucleus and the cytoplasm. But the nuclear membrane is regulating what material should be in the nucleus in contrast to what material should be in the cytoplasm.

Julie A. Segre, Ph.D.

Nucleic acids are large biomolecules that play essential roles in all cells and viruses. A major function of nucleic acids involves the storage and expression of genomic information. Deoxyribonucleic acid, or DNA, encodes the information cells need to make proteins. A related type of nucleic acid, called ribonucleic acid (RNA), comes in different molecular forms that play multiple cellular roles, including protein synthesis. 

Believe it or not, there are many songs devoted to nucleic acids. Something about them inspires art. I won’t sing any of them, but I did first learn about nucleic acids through a song in chemistry class. Nucleic acids are made of nitrogen-containing bases, phosphate groups, and sugar molecules. Each type of nucleic acid has a distinctive structure and plays a different role in our cells. Researchers who first explored molecules inside the nucleus of cells found a peculiar compound that was not a protein or a lipid or a carbohydrate. It was new. The discovery of this molecule — nuclein, which upon further understanding became nucleic acid — set in motion the eventual discovery of DNA.

The nucleolus is a region found within the cell nucleus that is concerned with producing and assembling the cell's ribosomes. Following assembly, ribosomes are transported to the cell cytoplasm where they serve as the sites for protein synthesis.

Within the cell nucleus there's a very specific part called the nucleolus. This does not contain the chromosomes. What this contains is the machinery necessary to assemble the cell's ribosomal RNAs. Ribosomal RNAs then are transported through the nuclear pores into the cytoplasm where they become part of the ribosome, which is the protein machinery. These ribosomal RNAs guide the messenger RNAs through the ribosomes and help in the protein translation, but they themselves are RNA's that do not become proteins. They're non-coding RNAs that help the messenger RNAs to undergo the protein translation process. These RNAs, like the other messenger RNAs, are made in the nucleus, but ribosomal RNAs are made in the nucleolus which is a very specific part of the cell nucleus.

The nucleopore is one of a series of small holes found in the nuclear membrane. The nucleopore serves as a channel used for transporting nucleic acids and proteins into and out of the cell nucleus.

Nucleopore. Within the nuclear membrane of the cell there are small holes, or pores, that allow the very selective transport of nucleic acids and proteins into and out of the cell nucleus. The material found in the cell nucleus is distinct from the material found in the cytoplasm. And these nucleopores, which are of regulated size, allow for the very selective transport of nucleic acids and proteins into and out of the cell nucleus. We used to think that it was a regulated process of how nucleic acids such as mRNAs moved out of the cell nucleus, and recently we've become more aware that there also is a regulated process by which cells transport proteins and nucleic acids into the nucleus, so this is a dynamic process.

A nucleotide is the basic building block of nucleic acids (RNA and DNA). A nucleotide consists of a sugar molecule (either ribose in RNA or deoxyribose in DNA) attached to a phosphate group and a nitrogen-containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, the base uracil (U) takes the place of thymine. DNA and RNA molecules are polymers made up of long chains of nucleotides.

Nucleotide. It is the chains of these nucleotides that encode the information content in RNA and DNA.

Lawrence Brody, Ph.D., Director, Division of Genomics and Society

A nucleus is a membrane-bound organelle that contains the cell's chromosomes. Pores in the nuclear membrane allow for the passage of molecules in and out of the nucleus.

The nucleus is one of the most obvious parts of the cell when you look at a picture of the cell. It's in the middle of the cell, and the nucleus contains all of the cell's chromosomes, which encode the genetic material. So this is really an important part of the cell to protect. The nucleus has a membrane around it that keeps all the chromosomes inside and makes the distinction between the chromosomes being inside the nucleus and the other organelles and components of the cell staying outside. Sometimes things like RNA need to traffic between the nucleus and the cytoplasm, and so there are pores in this nuclear membrane that allow molecules to go in and out of the nucleus. It used to be thought that the nuclear membrane only allowed molecules to go out, but now it's realized that there is an active process also for bringing molecules into the nucleus.

An oncogene is a mutated gene that has the potential to cause cancer. Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division. Cancer can arise when a proto-oncogene is mutated, changing it into an oncogene and causing the cell to divide and multiply uncontrollably. Some oncogenes work like an accelerator pedal in a car, pushing a cell to divide again and again. Others work like a faulty brake in a car parked on a hill, also causing the cell to divide unchecked.

The name of oncogene suggests it is a gene that can cause cancer. Initially, oncogenes were identified in viruses, which could cause cancers in animals. Later, it was found that oncogenes can be mutated copies of certain normal cellular genes also called proto-oncogenes. Intact proto-oncogenes play important functions, regulating normal cellular growth, division, and apoptosis, which is the name for programmed or controlled cell death. Oncogenes or mutated copies of the proto-oncogenes may lead to uncontrolled cell growth and the escape from cell death, which may result in cancer development.

Paul P. Liu, M.D., Ph.D., Senior Investigator, Translational and Functional Genomics Branch

An open reading frame is a portion of a DNA molecule that, when translated into amino acids, contains no stop codons. The genetic code reads DNA sequences in groups of three base pairs, which means that a double-stranded DNA molecule can read in any of six possible reading frames--three in the forward direction and three in the reverse. A long open reading frame is likely part of a gene.

"Open reading frame" is a terrible term that we're stuck with. What it refers to is a frame of reference, and what is being read, "reading", is the RNA code, and it is being read by the ribosomes in order to make a protein. And "open" means that the road is open to keep reading, and the ribosome will be able to keep reading the RNA code and add another amino acid one after another. Now, DNA, though it is a monotonous repetition of As, Cs, Ts, and Gs, has a language, which is transcribed, of course, into RNA and then translated into a protein. And when it's translated into a protein, the mRNA is not read one letter at a time, but it's read three letters at a time. And those three letters are called a codon, and each of those codons, whether it's an AAA or UUU or an AUG, each of those codons is interpreted by the ribosome, the molecular machine, that's going to make the protein as a certain amino acid. So AUG codes for one amino acid, and UUU codes for another, and etc. So an open reading frame is the length of DNA, or RNA, which is transcribed into RNA, through which the ribosome can travel, adding one amino acid after another before it runs into a codon that doesn't code for any amino acid. And when that happens, it confuses the ribosome, and the ribosome stops. So you'll be pleased to hear that codons, which make that happen are called stop codons, and a stop codon ends an open reading frame. So an open reading frame is sometimes 300 amino acids long, and sometimes maybe it's 600, and sometimes it's longer. The longer an open reading frame is, the longer you get before you get to a stop codon, the more likely it is to be part of a gene which is coding for a protein. Now the finally confusing thing about an open reading frame is that because the codons are three nucleic acids long and DNA has two strands, the ribosome can read an RNA derived from one strand or another, and it can read it in 1-2-3s that are separated one from another so you can actually get three reading frames reading in one direction, three reading frames going in the other direction. So it's actually six different reading frames for every piece of DNA, which might give you an open reading frame.