Race is a social construct used to group people. Race was constructed as a hierarchal human-grouping system, generating racial classifications to identify, distinguish and marginalize some groups across nations, regions and the world. Race divides human populations into groups often based on physical appearance, social factors and cultural backgrounds.

Race is a political and social construct that is fluid. Racial categorization can change over time, place, and context. Race has been used historically to establish a social hierarchy, whereby individuals are treated differently resulting in racism. Genomic scientists are currently investigating the relationship between self-identified race and genetic ancestry. There is more genetic variation within self-identified racial groups than between them. I like Professor Audrey Smedley's definition. She states, “Race is a culturally structured systematic definition of a way of looking at perceiving and interpreting reality.”

Vence L. Bonham Jr., J.D., Acting Deputy Director

Recessive, as related to genetics, refers to the relationship between an observed trait and the two inherited versions of a gene related to that trait. Individuals inherit two versions of each gene, known as alleles, from each parent. In the case of a recessive trait, the alleles of the trait-causing gene are the same, and both (recessive) alleles must be present to express the trait. A recessive allele does not produce a trait at all when only one copy is present. This contrasts to a dominant trait, which requires that only one of the two alleles be present to express the trait.

Recessive Traits and Alleles. For most genes, except those on parts of the X-chromosome in men, we have two copies, one from our mother and one from our father. For any specific gene, one or both copies can have changes that result in the gene not working properly. For many genes, the body can tolerate a problem with one copy that is not working, but not both. In other words, as long as you have at least one working copy, you have enough for your cells to work normally. However, if both copies are damaged, the cell can't function normally. This may cause anything from a change in hair color to a difficult health problem. Recessive traits follow this pattern. Carriers have one gene copy with a problem, but have enough leftover function from the other copy for normal cell function. People with two altered genes are missing whatever cell function is associated with the gene. Dominant traits occur when either half of the normal gene function is not enough, or when the change to a single copy causes new damaging effects to the cell that the normal gene does not.

David Adams, M.D., Ph.D., Senior Clinician, Office of the Clinical Director

Recombinant DNA technology involves using enzymes and various laboratory techniques to manipulate and isolate DNA segments of interest. This method can be used to combine (or splice) DNA from different species or to create genes with new functions. The resulting copies are often referred to as recombinant DNA. Such work typically involves propagating the recombinant DNA in a bacterial or yeast cell, whose cellular machinery copies the engineered DNA along with its own.

Recombinant DNA Technology. Recombinant DNA technology is an extremely important research tool in biology. It allows scientists to manipulate DNA fragments in order to study them in the lab. It involves using a variety of laboratory methods to put a piece of DNA into a bacterial or yeast cell. Once in, the bacteria or yeast will copy the DNA along with its own. Recombinant DNA technology has been successfully applied to make important proteins used in the treatment of human diseases, such as insulin and growth hormone.

Kris A. Wetterstrand, M.S., Scientific Liaison to the Director for Extramural Activities, Office of the Director

A repressor is a protein that turns off the expression of one or more genes. The repressor protein works by binding to the gene's promoter region, preventing the production of messenger RNA (mRNA).

A repressor is a protein that has a negative effect on gene expression. So these usually are proteins that bind to DNA, and they either prevent the RNA transcription machinery from getting in there and transcribing that DNA, or they just slow it down. So repressors are present in cells where you don't want a particular gene expressed. So if the repressor cell recognizes a sequence in that gene, it will travel to there and keep that gene off in that cell. And this is how you prevent hemoglobin from being expressed in neurons, and how you would prevent liver enzymes from being expressed in red blood cells. Repressors are very difficult to study because it's much easier to study things that give you more of what you're looking for. But I think as we go along we're going to find they play as important a role in gene regulation as the activating proteins.

A restriction enzyme is a protein isolated from bacteria that cleaves DNA sequences at sequence-specific sites, producing DNA fragments with a known sequence at each end. The use of restriction enzymes is critical to certain laboratory methods, including recombinant DNA technology and genetic engineering.

Restriction enzyme. Restriction enzymes are incredibly cool, and there are at least three thousand of them. Each one of these enzymes cuts a specific DNA sequence and doesn't discriminate as to where the DNA comes from — bacteria, fungi, mouse, or human, snip, snip, snip.

Prabarna Ganguly, Ph.D., Chief Communications Officer, Nucleus Genomics

Restriction fragment length polymorphism (abbreviated RFLP) refers to differences (or variations) among people in their DNA sequences at sites recognized by restriction enzymes. Such variation results in different sized (or length) DNA fragments produced by digesting the DNA with a restriction enzyme. RFLPs can be used as genetic markers, which are often used to follow the inheritance of DNA through families.

RFLPs have been very useful to use as markers for following a genomic DNA, either from human or other animals. What is it, though? So basically, if you follow the sequence of DNA, particular sites, a series of four to eight nucleic acids, results in a restriction site where an enzyme from bacteria can actually bind and cleave that DNA. So why is that useful? Well, we can take advantage of this fact to actually look for differences between people if they have that restriction enzyme site or not. So a single base difference between two people could result in either the presence or absence of that restriction site. So then, if you isolate that piece of DNA surrounding that site from two people, from one of them it will be cut by the enzyme and the other one it won't. And that results in a polymorphism, or difference between those two people. We typically see these, or we monitor these, by isolating the DNA, cutting it with that bacterial restriction enzyme, and running it on a gel using electrophoresis. In one person, without the enzyme site you'll see one band, and the person that has the enzyme site, you'll see two bands, representing the two cleaved products. So these differences in nucleic acid sequences and restriction enzyme binding sites just mean that there's a difference in the sequence between those two people. That sequence difference doesn't necessarily mean that there's a disease associated with it. It's a polymorphism that we could use to follow the inheritance of DNA.

Shurjo K. Sen, Ph.D., Program Director, Division of Genome Sciences

A retrovirus is a virus that uses RNA as its genetic material. When a retrovirus infects a cell, it makes a DNA copy of its genome that is inserted into the DNA of the host cell. There are a variety of different retroviruses that cause human diseases such as some forms of cancer and AIDS.

Ribonucleic acid, or RNA. I often think of RNA as being the less well-known cousin of DNA, particularly for people outside the field of biology or genomics. But really, when you think about it, RNA, in so many ways, is the actual functional form of nucleic acids that really the body uses to do the business of, you know, constructing cells or responding to immune challenges, of carrying amino acids from one part of the cell to the other, that quite often I feel that RNA doesn't get the respect it deserves. So what I think we can share is that the different forms of RNA -- mRNA, tRNA, rRNA -- each in their own way have absolutely fundamental functions without which the biology of the genome could not be translated into practice. And I guess the most obvious one here might be mRNAs, because these are the transcribed forms of genes, the form in which a gene gets read by the cell. But really, I would encourage everyone to learn about the unique roles that tRNAs and rRNAs have as well, because each of these fits into the puzzle of life in a wonderfully unique way.

Shurjo K. Sen, Ph.D., Program Director, Division of Genome Sciences

Ribonucleic acid (abbreviated RNA) is a nucleic acid present in all living cells that has structural similarities to DNA. Unlike DNA, however, RNA is most often single-stranded. An RNA molecule has a backbone made of alternating phosphate groups and the sugar ribose, rather than the deoxyribose found in DNA. Attached to each sugar is one of four bases: adenine (A), uracil (U), cytosine (C) or guanine (G). Different types of RNA exist in cells: messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA). In addition, some RNAs are involved in regulating gene expression. Certain viruses use RNA as their genomic material.

RNA, or ribonucleic acid, is a nucleic acid that is similar in structure to DNA but different in subtle ways. The cell uses RNA for a number of different tasks, one of which is called messenger RNA, or mRNA. And that is the nucleic acid information molecule that transfers information from the genome into proteins by translation. Another form of RNA is tRNA, or transfer RNA, and these are non-protein encoding RNA molecules that physically carry amino acids to the translation site that allows them to be assembled into chains of proteins in the process of translation.

Leslie G. Biesecker, M.D.

A ribosome is an intercellular structure made of both RNA and protein, and it is the site of protein synthesis in the cell. The ribosome reads the messenger RNA (mRNA) sequence and translates that genetic code into a specified string of amino acids, which grow into long chains that fold to form proteins.

Ribosome. A ribosome is the cellular machinery responsible for making proteins. There are many ribosomes in each cell, each made up of two subunits. These two subunits lock around the messenger RNA and then travel along the length of the messenger RNA molecule reading each three-letter codon. The ribosome serves as a docking station for the transfer RNA that matches the sequence of bases on the messenger RNA. Each three-letter codon on the messenger RNA pairs with the matching anticodon on a specific transfer RNA, and that specific RNA allows for the addition of a specific amino acid on the end of the growing protein chain. The ribosome then breaks up after the completion of the protein.

Risk, as related to genetics, refers to the probability that an individual will be affected by a particular heritable or genetic disorder. Both a person’s genome and environmental exposures can influence risk. An individual’s risk may be higher because they inherit a genetic variant (or allele) in one gene or a combination of many variants in different genes that increases susceptibility to or overtly causes a disorder. Other individuals may be at higher risk because they have been exposed to one or more environmental factors that promote the development of a certain disorder.

Scientific racism. Scientific racism is a historical pattern of ideologies that generate pseudo-scientific racist beliefs. That perpetually influences racial bias and discrimination in science and research. Leading scientists across scientific institutions in the 19th and early 20th centuries were proponents of such ideologies. By the mid-20th century, pseudo-scientific racist beliefs were widely disproven. However, evidence shows that scientific racism persists in science and research.

Scientific racism. Scientific racism is an organized system of misusing science to promote false scientific beliefs in which dominant racial and ethnic groups are perceived as being superior. Scientific racism unfortunately continues to exist, and we must continually monitor science to avoid scientific racism.

Vence L. Bonham Jr., J.D., Acting Deputy Director

A secondary genomic finding refers to a genomic variant, found through the analysis of a person’s genome, that is of potential medical value yet is unrelated to the initial reason for examining the person’s genome. In certain cases, a secondary genomic finding might offer clinicians the chance to identify a previously unrecognized risk for disease that could change the medical management of that patient and potentially prevent or more effectively treat the disease.

Secondary genomic finding. Secondary findings are in a way an added bonus for having a person's genome examined for some disease or symptom they may be having. It's sort of like finding a spot on a chest x-ray done for some other reason in time to identify and remove an early cancer or finding an unusually low blood count in a test looking for signs of an infection. About 1 in 25 people who have their genome analyzed will have a variant that suggests doctors should change something about their care, such as looking more carefully for a cancer or heart condition or inserting a specialized kind of pacemaker to prevent sudden death. Sometimes secondary findings are things people would prefer not to know about, such as risk of a disease that has no treatment, so they should understand the chances of such findings before their genome is examined.

Teri Manolio, M.D., Ph.D., Director, Division of Genomic Medicine

A sex chromosome is a type of chromosome involved in sex determination. Humans and most other mammals have two sex chromosomes, X and Y, that in combination determine the sex of an individual. Females have two X chromosomes in their cells, while males have one X and one Y.

Sex linked is a trait in which a gene is located on a sex chromosome. In humans, the term generally refers to traits that are influenced by genes on the X chromosome. This is because the X chromosome is large and contains many more genes than the smaller Y chromosome. In a sex-linked disease, it is usually males who are affected because they have a single copy of X chromosome that carries the mutation. In females, the effect of the mutation may be masked by the second healthy copy of the X chromosome.

Sex linked... These are traits that are found on either one of the chromosomes that determine sex, or the sex chromosomes. And in humans this is the X or the Y chromosomes. And so some of the more familiar sex-linked traits are hemophilia, red-green color blindness, congenital night blindness, some high blood pressure genes, Duchenne muscular dystrophy, and also Fragile X syndrome. So what's also very interesting is that you can imagine that for individuals who are XY or males, having these different mutations on the genes, on the X chromosome, is particularly problematic, because unlike females, there are not two X chromosomes that give you the potential of carrying a normal gene on the X chromosome. Which is why in many cases you'll see that males are more often afflicted with these sex-linked disorders.

Shotgun sequencing is a laboratory technique for determining the DNA sequence of an organism’s genome. The method involves randomly breaking up the genome into small DNA fragments that are sequenced individually. A computer program looks for overlaps in the DNA sequences, using them to reassemble the fragments in their correct order to reconstitute the genome.

Imagine taking a page in a book, making hundreds of copies of it, taking those copies and putting them in a paper shredder that magically creates strips of paper that contain various bits and pieces of the original sentences on the starting page. Then imagine reading each of those strips containing the bits and pieces of the sentences, looking for overlapping words and phrases, and eventually being able to reconstruct the entire text on the starting page by having read enough of those shreds of paper. In essence, that is shotgun DNA sequencing. Instead of a page of a book, a scientist starts with a piece of clone DNA or even an entire genome. The DNA is broken apart and many many many many many sequence reads are generated from the DNA pieces. All of those data are analyzed by a computer program that looks for overlapping stretches of sequence and eventually puts that DNA puzzle back together.

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

A single nucleotide polymorphism (abbreviated SNP, pronounced snip) is a genomic variant at a single base position in the DNA. Scientists study if and how SNPs in a genome influence health, disease, drug response and other traits.

Single nucleotide polymorphism, or SNP. If you are reading a news story where it says, for example, scientists find the genetic contributors to diabetes or some other condition or trait, you're probably reading about SNPS. A SNP is a one-letter place where your genome varies from another genome sequence. Thanks to the Human Genome Project, we have found that these single letter changes in our genetic code are placed all across our genomes. We can see that the patterns vary between people and even between populations. If we want to identify genetic contributors to a common complex disease like diabetes, we can group together thousands of people who have diabetes and compare their SNP patterns to thousands of people who do not have diabetes. With enough people in our study, we can use the SNPs as markers to see that certain areas of the genome appear to be the same in people who have diabetes, and that tells us where we should look in more detail for a genetic cause.

Chris Gunter, Ph.D., Associate Investigator, Social and Behavioral Research Branch

Somatic cells are the cells in the body other than sperm and egg cells (which are called germ cells). In humans, somatic cells are diploid, meaning they contain two sets of chromosomes, one inherited from each parent. DNA mutations in somatic cells can affect an individual, but they cannot be passed on to their offspring.

Somatic cells. All organisms that are alive are made of one or more cells that are called somatic cells. In humans, somatic cells are diploid, meaning they contain two sets of chromosomes, one set inherited from each parent. Somatic mutations can impact the individual carrying the mutation, but cannot be passed on and have no effect on the offspring.

Belen Hurle, Ph.D., Former Associate Investigator, Division of Intramural Research

Southern blotting is a laboratory technique used to detect a specific DNA sequence in a blood or tissue sample. A restriction enzyme is used to cut a sample of DNA into fragments that are separated using gel electrophoresis. The DNA 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 probe sequence is present in the sample.

A Southern blot is a way to analyze DNA molecules. The protocol was developed by Edward Southern. And if you were going to perform a Southern blot, you would first want to separate DNA based upon size in a gel along an electric field... And so your larger fragments, again, at the top; your smaller fragments are going to be at the bottom. When you're done running your gel, you then transfer that to a membrane. So it's like making a sandwich: gel, membrane on top, stack of paper towels. And what you're looking for is, you're going to allow a solution to pass through the gel, up to the membrane, and it's going to be a soft gradient that pushes it through.

A stop codon is a sequence of three nucleotides (a trinucleotide) in DNA or messenger RNA (mRNA) that signals a halt to protein synthesis in the cell. There are 64 different trinucleotide codons: 61 specify amino acids and 3 are stop codons (i.e., UAA, UAG and UGA).

Stop codon. A stop codon is to protein synthesis what a period is to a sentence. Since a protein isn't infinitely long, biology created an incredibly clever way to say, “Stop! You've reached the end of this protein.”

Prabarna Ganguly, Ph.D., Chief Communications Officer, Nucleus Genomics

Substitution, as related to genomics, is a type of mutation in which one nucleotide is replaced by a different nucleotide. The term can also refer to the replacement of one amino acid in a protein with a different amino acid.

Substitution. It's always fascinated me how tiny changes in one's genome, like a simple substitution, can have such profound effects on human health. Changing a single nucleotide will change the amino acid sequence, which can impact how the protein it forms will look and act. Most of these small changes don't have a meaningful impact on human health or appearance, but we're quickly learning how to find the ones that are important. Knowing how small genetic changes work can then help us to discover new treatments for diseases. The differences between people's appearance comes from these seemingly miniscule changes in our genetic code, which I think should remind us that all humans share nearly all of our genetic material.

Benjamin E. Berkman, J.D., M.P.H., Deputy Director, NHGRI Bioethics Core

Susceptibility, as related to genetics, refers to the state of being predisposed to, or sensitive to, developing a certain disease. An individual’s disease susceptibility is influenced by a combination of genetic and environmental factors.

Susceptibility. On the most fundamental level, susceptibility helps communicate the risk of developing a disease. This risk emerges at the intersection of our genetic makeup and our environment. On the one hand, unique differences in DNA can increase or decrease our risk of developing a disease. On the other hand, our environment also matters. The quality of food, the air we breathe, the water we drink, can also increase or decrease the chance of developing a disease. Disease's susceptibility then helps combine these two elements of risk into one concept.

Oleg A. Shchelochkov, M.D., Director, Medical Genetics and Genomic Medicine Training Program

A syndrome, as related to genetics, is a group of traits or conditions that tend to occur together and characterize a recognizable disease. Some syndromes have a genetic cause.

Syndrome. Syndrome is a collection of distinctive features that tend to manifest in groups of individuals with the same disease. For example, Marfan syndrome shows features in three bodily systems: in the skeleton, in the heart, and in the eyes. Not everyone with Marfan syndrome will show the same exact set of features, but they will tend to cluster in these three areas. Other examples of well-known genetic syndromes are Down syndrome, Klinefelter syndrome, and fragile X syndrome.

Lucia Hindorff, Ph.D., M.P.H., Lead Extramural Training Program Director, Training, Diversity, and Health Equity Office