A pedigree is a genetic representation of a family tree that diagrams the inheritance of a trait or disease though several generations. The pedigree shows the relationships between family members and indicates which individuals express or silently carry the trait in question.

A pedigree is a representation of our family tree. It shows how individuals within a family are related to each other. We can also indicate which individuals have a particular trait or genetic condition. If we take a pedigree, which we usually try to include at least three generations, we might be able to determine how a particular trait is inherited. Using that information, we might be able to tell the chance that a given individual will have the trait themselves or could pass it on to their children. There are standard ways to draw pedigrees so that we can all look at a pedigree and understand it. We use squares to represent males and circles to represent females. We then can number our generations with roman numerals, so the top generation would be generation one, or Roman numeral I. Along this line, we'd indicate males and females. We would indicate marriages between individuals with a horizontal line connecting the two individuals. If an individual has a genetic trait, we would blacken those individuals in or shade them so that it would be understood that they had a particular trait. We would then draw a line, a vertical line, off the horizontal line where we would indicate any of their children that they had, and we would then indicate if any of their children were infected. And we can do this for as many generations as we have. It's important when we draw pedigree that we try to put in as much information as possible. So for example, if there have been children that died in early infancy or were stillborn, we also want to include those individuals. And those are typically shown as very small blackened-in symbols to indicate there was a loss of a child, either in pregnancy or early in life.

A peptide is one or more amino acids linked by chemical bonds. The term also refers to the type of chemical bond that joins the amino acids together. A series of linked amino acids is a polypeptide. The cell's proteins are made from one or more polypeptides.

The term "peptides" refers to a series of amino acids linked together. Amino acids are the basic unit that make proteins, and a short series of those--short chain of amino acids--is called a peptide. Peptides are then organized in more complex structures, which are called proteins. And proteins are the building blocks of a cell.

Pharmacogenomics is a branch of pharmacology concerned with using DNA and amino acid sequence data to inform drug development and testing. An important application of pharmacogenomics is correlating individual genetic variation with drug responses.

Pharmacogenomics is a combination of two fields and two different words: "pharmacology" and "genomics". So what that refers to is differences in different people's genomes, which result in differences in their pharmacology. Or in other words, the way they respond to a drug, because that is what pharmacology is. So pharmacogenomics is used in many ways. It's used most commonly to ask whether different people who have slightly different genomes, that is, the sequence of one gene or another, is different from one person or another. Is that going to influence their response to a drug, either in a positive way--that is, will one person get a therapeutic effect from a drug and the other person not--or in a bad way--that is, is one person going to get a side effect from a drug and the other one won't--as a result of that difference in the DNA sequence?

Christopher P. Austin, M.D.

A phenotype is an individual's observable traits, such as height, eye color, and blood type. The genetic contribution to the phenotype is called the genotype. Some traits are largely determined by the genotype, while other traits are largely determined by environmental factors.

"Phenotype" simply refers to an observable trait. "Pheno" simply means "observe" and comes from the same root as the word "phenomenon". And so it's an observable type of an organism, and it can refer to anything from a common trait, such as height or hair color, to presence or absence of a disease. Frequently, phenotypes are related and used--the term is used--to relate a difference in DNA sequence among individuals with a difference in trait, be it height or hair color, or disease, or what have you. But it's important to remember that phenotypes are equally, or even sometimes more greatly influenced by environmental effects than genetic effects. So a phenotype can be directly related to a genotype, but not necessarily. There's usually not a one-to-one correlation between a genotype and a phenotype. There are almost always environmental influences, such as what one eats, how much one exercises, how much one smokes, etc. All of those are environmental influences which will affect the phenotype as well.

A physical map of a chromosome or a genome that shows the physical locations of genes and other DNA sequences of interest. Physical maps are used to help scientists identify and isolate genes by positional cloning.

Physical maps of DNA reflect the location of landmarks across a chromosome. Such landmarks can correspond to functional parts of the DNA, such as genes, or just random non-functional sequences. At a minimum, physical maps depict the relative order of landmarks across a chromosome; more refined physical maps actually indicate the exact distances between adjacent landmarks. Nowadays, very precise physical maps can be constructed based on the actual sequence of a chromosome, which provides exact base pair distances between landmarks.

A plasmid is a small, often circular DNA molecule found in bacteria and other cells. Plasmids are separate from the bacterial chromosome and replicate independently of it. They generally carry only a small number of genes, notably some associated with antibiotic resistance. Plasmids may be passed between different bacterial cells.

A plasmid is a small circular DNA molecule found in bacteria and some other microscopic organisms. Plasmids are physically separate from chromosomal DNA and replicate independently. They typically have a small number of genes — notably, some associated with antibiotic resistance — and can be passed from one cell to another. Scientists use recombinant DNA methods to splice genes that they want to study into a plasmid. When the plasmid copies itself, it also makes copies of the inserted gene.

A point mutation is when a single base pair is altered. Point mutations can have one of three effects. First, the base substitution can be a silent mutation where the altered codon corresponds to the same amino acid. Second, the base substitution can be a missense mutation where the altered codon corresponds to a different amino acid. Or third, the base substitution can be a nonsense mutation where the altered codon corresponds to a stop signal.

Point mutations are a large category of mutations that describe a change in single nucleotide of DNA, such that that nucleotide is switched for another nucleotide, or that nucleotide is deleted, or a single nucleotide is inserted into the DNA that causes that DNA to be different from the normal or wild type gene sequence.

Leslie G. Biesecker, M.D.

Polydactyly is a condition in which a person has more than the normal number of fingers or toes. It can occur in association with other physical anomalies or intellectual impairment, or it may occur as an isolated birth defect. Polydactyly can either be inherited or it can arise sporadically in an individual.

Polydactyly. In my human genetics class in college, I mentioned to my lab partner that I had never met anyone with polydactyly, and he replied, “Yes, you have.” It turns out that he was born with an extra finger on each hand that had been surgically removed, which helps to explain why I wouldn't have noticed. His hands actually looked nothing like the different photographs of hands with polydactyly that we had studied in class which had illustrated a lot of different ways that it can manifest with the extra fingers in different locations.

A polygenic risk score (abbreviated PRS) uses genomic information alone to assess a person’s chances of having or developing a particular medical condition. A person’s PRS is a statistical calculation based on the presence or absence of multiple genomic variants, without taking environmental or other factors into account.

Polygenic risk score. We know the differences in how the spelling of a person's DNA or genomic variants interact with many other factors such as their health habits, the drugs they're taking, and the diseases they may develop. So polygenic risk scores, or PRS, are only one factor in predicting disease. Still, just because of the play of chance, there are some people who happen to have a large number of harmful variants that can put them at the top 1% or even the top 1/1,000 or 1/10,000 of risk. Such individuals may do better if they are tested more frequently for early signs of disease as with mammograms, for example, or if they adopt lifestyle changes early on to help prevent the disease entirely. As scientists learn more about using PRS, we may see such scores coming into wider use.

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

A polygenic trait is a characteristic, such as height or skin color, that is influenced by two or more genes. Because multiple genes are involved, polygenic traits do not follow the patterns of Mendelian inheritance. Many polygenic traits are also influenced by the environment and are called multifactorial.

Polygenic Trait. As we've gotten better at identifying regions of the human genome that are associated with disease and at analyzing complicated genomic data, we've learned that the genetic component of many of the most important health conditions of our time — cancer, heart disease, diabetes — are due to the effects of multiple genes. Hence, polygenic, or many genes. This has been a fascinating area of study, as scientists have begun to study these conditions and realized that the ways that we have of predicting risks for polygenic traits have tremendous potential for improving human health.

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

Polymerase chain reaction (abbreviated PCR) is a laboratory technique for rapidly producing (amplifying) millions to billions of copies of a specific segment of DNA, which can then be studied in greater detail. PCR involves using short synthetic DNA fragments called primers to select a segment of the genome to be amplified, and then multiple rounds of DNA synthesis to amplify that segment.

Polymerase chain reaction, PCR. So PCR dates back to the mid-1980s, which is more or less the time when the Human Genome Project was being considered and then started at the end of that decade. PCR has been really fundamental to so much of biology and biomedical research since then. Since we're at the Genome Institute, it's worth noting that it was a fundamental technology behind the early days of the Human Genome Project. And it has played an important role up till today. And it's going to continue to play one for a long time, I suspect, although you never know — there's always another groundbreaking technology.

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

Polymorphism, as related to genomics, refers to the presence of two or more variant forms of a specific DNA sequence that can occur among different individuals or populations. The most common type of polymorphism involves variation at a single nucleotide (also called a single-nucleotide polymorphism, or SNP). Other polymorphisms can be much larger, involving longer stretches of DNA.

Polymorphism. The term polymorphism means many forms. And I love it as an example of how genomics is a series of discoveries that lead to even more questions. When we started sequencing human genomes, we learned that humans are pretty identical, but we saw specific changes between people in one letter at a time, which we now call a single nucleotide polymorphism, or a SNP. When we knew what to look for, we saw that this type of variation was actually all over the genome and we could use it to look at all kinds of genetic questions. We then realized that humans also varied in much bigger chunks of their genome than we thought. So, for example, you might have two copies of an area that has 1 million nucleotides, but I might have four copies or no copies. Polymorphisms are one way that many forms of genomes can lead to many forms of humans.

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

Population genomics is the large-scale application of genomic technologies to study populations of individuals. For example, population genomics research can be used to study human ancestry, migrations and health.

Population Genomics. Basically, population genomics allows scientists to understand how groups are related over time. It also allows scientists to understand our ancestral backgrounds and how that ancestral background has been shaped over time, in terms of the environment that our ancestors have lived their lives.

Charles N. Rotimi, Ph.D.

Positional cloning is a laboratory technique used to locate the position of a disease-associated gene along the chromosome. This approach works even when little or no information is available about the biochemical basis of the disease. Positional cloning is used in conjunction with linkage analysis. It involves the isolation of partially overlapping DNA segments that progress along the chromosome toward a candidate gene.

Positional cloning is a term derived from the late 1980s which basically was to be contrasted to functional cloning, so probably we should define both. Functional cloning was finding a gene by understanding something about what its function is. So the hemophilia gene was identified by knowing there was a problem with a blood clotting factor and then figuring out what gene must have coded for that, and isolating or cloning that gene. But for most diseases, we don't have enough information to guess what the function was, so positional cloning, which came into being as a need of trying to identify the cause of things like cystic fibrosis, was a way of identifying the gene by its position in the genome. Various jokes were made about this. Some people said, oh, positional cloning is a sort of thing where you have to get into a certain position in order to do the work, or if you succeed at it you're guaranteed a position in the university. Not true. Basically, it's the position in the genome that you're trying to zero in on by a series of steps that go from a larger view to narrower view to finally zeroing in on the single base pair that's gone awry. And in many instances that's what you're looking for.

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

Precision medicine (generally considered analogous to personalized medicine or individualized medicine) is an innovative approach that uses information about an individual’s genomic, environmental and lifestyle information to guide decisions related to their medical management. The goal of precision medicine is to provide more a precise approach for the prevention, diagnosis and treatment of disease.

Precision medicine. Precision medicine or precision healthcare is medical care that takes advantage of large data sets of individuals such as their genome or their entire electronic health record to tailor their healthcare to their unique attributes. It is common sense that no two individuals are the same, and so they should not get the same healthcare. Precision healthcare embodies that simple idea.

Leslie G. Biesecker, M.D., Director & NIH Distinguished Investigator, Center for Precision Health Research

A primer, as related to genomics, is a short single-stranded DNA fragment used in certain laboratory techniques, such as the polymerase chain reaction (PCR). In the PCR method, a pair of primers hybridizes with the sample DNA and defines the region that will be amplified, resulting in millions and millions of copies in a very short timeframe. Primers are also used in DNA sequencing and other experimental processes.

Primer. If you spend the weekend in a genomics lab, it is very likely you will hear about primers. That is how important primers are, and for a good reason. Primers are short stretches of DNA that target unique sequences and help identify a unique part of genome — let's say, a gene. Primers are usually 18 to 25 nucleotides long. They can be synthesized in a special lab, and are used in many different ways. For example, you can make multiple new copies of DNA from a template. You can introduce useful changes to the template DNA, where you can use them to analyze DNA by telling different versions of different copies.

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

A proband is an individual who is affected by a genetic condition or who is concerned they are at risk. Usually, the proband is the first person in a family who brings the concern of a genetic disorder to the attention of healthcare professionals.

Proband. When genetics professionals like genetic counselors talk with families or individuals with genetic conditions or risk factors, one important goal may be tracing the condition back through generations of a person's family. Even though the proband might be the first person in the family to seek medical attention, evidence of the condition might be present in many previous generations of the family.

Julie C. Sapp, Sc.M., C.G.C., Genetic Counselor, Precision Genomics Section

A promoter is a sequence of DNA needed to turn a gene on or off. The process of transcription is initiated at the promoter. Usually found near the beginning of a gene, the promoter has a binding site for the enzyme used to make a messenger RNA (mRNA) molecule.

The promoter region is the sequence typically referred to that's right upstream or right next to where a gene is about to be transcribed. It's the region where certain regulatory elements will bind; these are proteins that will bind to help RNA get transcribed. Now, "promoter", the term "promoter", can actually be a little bit of a nebulous term because it's not very exact. There are specific sequences that are generally found within a promoter region, but sometimes people refer to even extended promoter region that might include sequences that are farther upstream of the gene that might help enhance or repress the particular gene that's about to be transcribed in certain cell types. In general, if you think of the promoter as that piece of DNA that's just upstream of the transcription start site of a gene, that's pretty much what we refer to as promoters.