Haploid is the quality of a cell or organism having a single set of chromosomes. Organisms that reproduce asexually are haploid. Sexually reproducing organisms are diploid (having two sets of chromosomes, one from each parent). In humans, only their egg and sperm cells are haploid.

Haploid refers to a cell or an organism that has only a single set of chromosomes. This is to be contrasted with diploid. "Di" means two, of course. So most animal cells and plant cells are diploid. Then they're diploid in part because they got one chromosome from their mother and one chromosome from their father, therefore making them diploid. A haploid cell only has one set of chromosomes, and most of the time that refers to the so-called sex cells, either eggs or sperm. And these are [a] critical transition from a diploid cell to a haploid cell to allow normal reproduction to occur, so that when these two haploid cells come together with a single set of genetic information--single chromosomes--they can come together into a so-called zygote made of when the egg cell and the sperm cell come together that then reconstitutes a diploid cell, which can then become a new individual.

A haplotype is a set of DNA variations, or polymorphisms, that tend to be inherited together. A haplotype can refer to a combination of alleles or to a set of single nucleotide polymorphisms (SNPs) found on the same chromosome. Information about haplotypes is being collected by the International HapMap Project and is used to investigate the influence of genes on disease.

A haplotype is in its most general sense referring to a set of DNA variations along a chromosome that tend to be inherited together because they're very close together. They get inherited together because they're not generally crossovers or recombinations between these markers or between these different polymorphisms because they are very, very close. So a haplotype can refer to a combination of alleles in a single gene, or it could be alleles across multiple genes. It could be single nucleotide polymorphisms that are not in a gene but are in-between genes. Basically, it just means that these are variations in the DNA that are so close together that they tend not to recombine, and therefore tend to be passed down through the generations together. And the International HapMap Project has given us a very excellent tool to detect these regions of haplotypes that are passed together and to use those in genetic studies.

Joan E. Bailey-Wilson, Ph.D.

Heterozygous refers to having inherited different forms of a particular gene from each parent. A heterozygous genotype stands in contrast to a homozygous genotype, where an individual inherits identical forms of a particular gene from each parent.

Heterozygous is a state of having inherited different forms of a particular gene from each one of your biological parents. Now, by different forms we generally mean that there are different portions of the gene where the sequence is different. They may be inconsequential portions of the gene, or they may in fact be pretty important portions of the gene. That doesn't really matter for our discussion today. The word "heterozygous" simply means that your biological mother and your biological father, when they contributed their copies of a particular gene to you, they did so in a way so that the DNA sequence is slightly different. It can be different at one point in the gene, or it can be different at dozens and dozens of different points in the gene. Now, a heterozygous genotype stands in contrast to a homozygous genotype. And in the case of a homozygous genotype, we're talking about a case where we've gotten identical forms of a particular gene from each biological parent. That is, if we were to read along the DNA sequence that mom gave you and the DNA sequence that dad gave you, we would find absolutely, positively no differences in that gene or in the region of the gene that we're concerned about. "Heterozygous" meaning different, "homozygous" meaning the same.

A histone is a protein that provides structural support to a chromosome. In order for very long DNA molecules to fit into the cell nucleus, they wrap around complexes of histone proteins, giving the chromosome a more compact shape. Some variants of histones are associated with the regulation of gene expression.

Histones are proteins that are critical in the packing of DNA into the cell and into chromatin and chromosomes. They're also very important for regulation of genes. We used to think that histones acted essentially as DNA suitcases to sort of hold the DNA, but it was very clear that histones are regulated and have a lot to do with when genes are turned on and turned off. You can think about them as a regulated suitcase that determines when the suitcase is opened and a gene gets out. So they turn out to have very important functions, not only structurally, but also in the regulation of gene function in expression.

Homologous recombination is a type of genetic recombination that occurs during meiosis (the formation of egg and sperm cells). Paired chromosomes from the male and female parent align so that similar DNA sequences from the paired chromosomes cross over each other. Crossing over results in a shuffling of genetic material and is an important cause of the genetic variation seen among offspring.

Have you ever wondered why, when you look at a large family that has maybe 10 children, they all look related one to another? That is, you could all pick out that they were all members of the Brewster family, but yet it's pretty easy to distinguish one child from another. They look similar, but they also look different. And the reason for that is the term "homologous recombination". This is a type of genetic recombination that occurs during the formation of the egg and the sperm cells, and you'll recall formation of egg and sperm cells is called meiosis. During meiosis, what happens is that paired chromosomes from the male and the female parent align so that similar DNA sequences from the paired chromosomes have an opportunity to flip-flop, or to cross over one another. That crossing over results in the shuffling of genetic material, much as the very gentle shuffling of a deck of cards would do. And it's important because it's one of the sources of genetic variation that we see among offspring of parents.

Homozygous is a genetic condition where an individual inherits the same alleles for a particular gene from both parents.

Homozygous describes the genetic condition or the genetic state where an individual has inherited the same DNA sequence for a particular gene from both their biological mother and their biological father. It's often used in the context of disease. We talk about a situation where an individual has inherited a mutant allele or an error in DNA sequence from their mother and they have inherited the identical mutant allele from their father. We would then say that individual is homozygous for that mutation. They have two identical copies of the deleterious version of that gene and, as a result, they are then going to be predisposed to the genetic condition the gene codes for.

The Human Genome Project was an international project that mapped and sequenced the entire human genome. Completed in April 2003, data from the project are freely available to researchers and others interested in genetics and human health.

The Human Genome Project was announced in 1990. It was an international effort, but the United States was in a very strong leadership position. And it had this audacious goal of reading out all letters of the human DNA code by 2005. To the great relief of those of us involved in it, and I think the joy of the general public, we finished that project in 2003, more than two years ahead of schedule, and under budget, and produced all of this data in the public domain where, for all time, people can be working on understanding how it works and applying it for medical benefit.

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

A human genome reference sequence is an accepted representation of the human genome sequence that is used by researchers as a standard for comparison to DNA sequences generated in their studies. The scientists responsible for assembling and updating such reference sequences aim to provide the highest-quality, best possible consensus representations of the sequence and structural diversity found in the human genome among populations. The genome reference sequence provides a general framework and is not the DNA sequence of a single person.

At the completion of the Human Genome Project back in 2003, scientists achieved a major milestone – a DNA sequence that covered 99 percent of the human genome's gene-containing regions and was of 99.99 percent accurate. This set of data, as intended, was a “reference” for the human genome, not representing one single person over the whole genome, but a collection of different – albeit anonymous – people. It was an example of a human genome off which scientists could base research studies or compare other human genomes. Since then, researchers have worked to fill the gaps an improve the inaccuracies in the human genome sequence. They have also worked tremendously hard to represent places in the genome where humans are different. The Human Genome Reference Sequence is not an example of one human but represents many different varieties of human genomes.

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

Huntington's disease is an inherited disease characterized by the progressive loss of brain and muscle function. Symptoms usually begin during middle age. The disease is inherited as an autosomal dominant trait, meaning that a single mutated copy of the responsible gene is sufficient to cause the disease.

Huntington's disease is the classic example of what we call autosomal dominant condition, where an affected individual has one abnormal copy and one normal copy of the gene, and therefore their child has a 50 percent chance of inheriting it. This is a tragic and frustrating condition which comes on in mid-life with a progressive neurological deterioration that extends over more than a decade in many cases, and for which at the present time we don't have adequate therapy, but that is a very high priority for the medical research enterprise. The disease clearly at the present time causes all kinds of havoc in the families that are affected by it. And perhaps the most famous person affected by Huntington's disease was Woody Guthrie.

Hybridization is the process of combining two complementary single-stranded DNA or RNA molecules and allowing them to form a single double-stranded molecule through base pairing. In a reversal of this process, a double-stranded DNA (or RNA, or DNA/RNA) molecule can be heated to break the base pairing and separate the two strands. Hybridization is a part of many important laboratory techniques such as polymerase chain reaction and Southern blotting.

DNA is usually found in the form of a double-stranded molecule. These two strands bind to one another in a complementary fashion by a process called hybridization. DNA naturally, when it is replicated, the new strand hybridizes to the old strand. In the laboratory we can take advantage of hybridization by generating nucleic acid probes which we can use to screen for the presence or absence of certain DNA molecules or RNA molecules in the cell.

Identical twins are also known as monozygotic twins. They result from the fertilization of a single egg that splits in two. Identical twins share all of their genes and are always of the same sex. In contrast, fraternal, or dizygotic, twins result from the fertilization of two separate eggs during the same pregnancy. They share half of their genes, just like any other siblings. Fraternal twins can be of the same or different sexes.

Identical twins are also called monozygotic twins. They result from the fertilization of a single egg with a single sperm. And as those cells divide and multiply, at some point very early in embryonic growth they split into two individuals. So that you can imagine that the genetic material in these two identical twins is identical to each other, hence the name. The contrast to this would be fraternal twins, which are twins born at the same time. However, they are actually the result of fertilization of two different eggs, and thus can be different genders and look different, and have different characteristics. What's becoming increasingly clear is even though we call identical twins identical, and we think of their genetic material as being identical, we need to be reminded that there are environmental influences that may change, actually, the characteristics of identical twins, reminding us, as we already know, that even though identical twins come from the same genetic material, in characteristics they may actually have differences as well.

In situ hybridization is a laboratory technique in which a single-stranded DNA or RNA sequence called a probe is allowed to form complementary base pairs with DNA or RNA present in a tissue or chromosome sample. The probe has a chemical or radioactive label attached to it so that its binding can be observed.

In situ hybridization. "In situ" is a Latin term for "in place", and then it's used in this context for detecting either RNA or DNA in the situation of the actual animal or the cells. It's a laboratory technique where it uses a probe, and this probe is usually made with DNA or RNA. It's single-stranded and it has some sort of moiety that you can detect either chemically or radioactively, and then that single-stranded is hybridized, and that's where the hybridization part comes in. You mix this probe in with your tissue sample, and you look for the single-stranded to bind in situ to the expressed mRNA or the DNA that you're looking for. You wash away the unbound probe, and then you look for where that gene is being expressed or where that piece of DNA is in the cell. This is a way of detecting things in sort of three-dimensional space, which is often very important for scientists to know where things are expressed both in terms of time and space.

Shawn Burgess, Ph.D.

An inherited trait is one that is genetically determined. Inherited traits are passed from parent to offspring according to the rules of Mendelian genetics. Most traits are not strictly determined by genes, but rather are influenced by both genes and environment.

"Inherited" is a word we use to describe traits that are passed by genetics from parents to child. It is often confused with the word "familial", which sometimes people use to mean the same thing. But it's important to recall that familial traits can be either acquired or inherited and can be caused by shared environment. When geneticists use the word "inherited", it's limited to the vertical transmission of traits attributable to genes.

Leslie G. Biesecker, M.D.

Insertion is a type of mutation involving the addition of genetic material. An insertion mutation can be small, involving a single extra DNA base pair, or large, involving a piece of a chromosome.

Insertion really means that something has been stuck in there. And again, as a geneticist, when we think of an insertion, we think of a piece of DNA, and that can be small or large, being stuck in at a place where it really doesn't belong. So an insertion of just one base pair could lead to something that we call a frameshift. It shifts the reading of the three-base pair code and by that can throw off the entire protein, and by that can lead, for example, to a birth defect. Insertion can be larger, that, for example, there is an insertion of three base pairs, and then it will not throw off the frame, or it will not lead to a frameshift, and potentially is less harmful than having the insertion of just one base pair. And of course you can have an insertion of huge pieces of DNA. They can be so large that you could actually see it on the chromosome analysis, where all of the smaller insertions you would see only by sequencing the stretch of DNA.

Maximilian Muenke, M.D.

Intergenic regions are the stretches of DNA located between genes. In humans, intergenic regions are non-protein-coding and comprise a large majority of the genome. Some intergenic DNA is known to regulate the expression of nearby genes.

Intergenic Regions. Intergenic regions are the DNA regions between the coding genes. They comprise a very large portion of our DNA. They're important because they can actually be involved in regulating how a specific gene functions.

Ellen Sidransky, M.D., Chief and Senior Investigator, Medical Genetics Branch

An intron is a portion of a gene that does not code for amino acids. In the cells of plants and animals, most gene sequences are broken up by one or more introns. The parts of the gene sequence that are expressed in the protein are called exons, because they are expressed, while the parts of the gene sequence that are not expressed in the protein are called introns, because they come in between the exons.

Introns are very large chunks of RNA within a messenger RNA molecule that interfere with the code of the exons. And these introns get removed from the RNA molecule to leave a string of exons attached to each other so that the appropriate amino acids can be encoded for.

An inversion in a chromosome occurs when a segment breaks off and reattaches within the same chromosome, but in reverse orientation. DNA may or may not be lost in the process.

Inversion. An inversion occurs when part of your chromosome breaks off and then reattaches, but sometimes pieces along the edges are lost. Think of it as though you are reading the newspaper. Sometimes an internal page can get reversed. All the information is still there, but when you go to read the page, it doesn't make any sense. Therefore, having an inversion is an important complication.

Ellen Sidransky, M.D., Chief and Senior Investigator, Medical Genetics Branch

A karyotype is an individual's collection of chromosomes. The term also refers to a laboratory technique that produces an image of an individual's chromosomes. The karyotype is used to look for abnormal numbers or structures of chromosomes.

When I hear the word "karyotype", I think about a picture of chromosomes. When somebody has their blood studied to look at how many chromosomes they have and whether the chromosomes are complete, we come up with a picture in which we can line up all the chromosomes and count them. That way we can tell whether or not somebody has all the proper number of chromosomes, which is 46, and that way we can look at the X and the Y chromosomes and determine if it's a female or male. Somebody might order a chromosome study and look at a karyotype if they were worried that a child might have an extra or missing bit of chromosome material. So one of the most common things we can see on karyotyping is an extra Chromosome 21, which is associated with Down syndrome. We also get karyotypes when pregnant women choose to have testing on their unborn fetus, and the karyotype allows the providers to look at and count the chromosomes to determine whether or not the child is affected by having an extra chromosome.

A kilobase (abbreviated kb) is a unit of measurement used to help designate the length of DNA or RNA. One kilobase is equal to 1,000 bases.

Kilobase. It can be useful to think of a kilobase in the similar way we think of computer kilobytes. We hear of kilobytes when we describe computer memory. It simply refers to how much information a memory chip can store. When I was growing up memory chips and computers were measured in hundreds of kilobytes. Well, that's not a lot by today's standards. And that is a useful analogy, because in biology we tend to use kilobases when we describe the size of single gene or DNA. In contrast, when we describe genomes, the collection of all genes in an organism and its non coding DNA, we need to use a much larger unit, such as gigabase. In a similar way, we started using gigabytes to describe much larger memory chips and modern computers.

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

A knockout typically refers to an organism that has been genetically engineered to lack one or more specific genes. Scientists create knockouts (often in mice) so that they can study the impact of the missing genes and learn something about the genes' function.

Knockout does not refer to boxing, at least in this context. But it is a similar concept that what one is doing is inactivating a gene instead of inactivating your partner in boxing. This can be done in a variety of ways. Either one can insert a stop codon in the midst of a gene that one wants to eliminate the function of. Because, as we know, genes which have stock codons in the middle of them, when they occur naturally, they're frequently referred to as disease gene mutations, and they do that because they eliminate the function of the gene. So one can do this experimentally too, and when we do it experimentally on purpose--that's called a knockout. If one really wants to be extreme, one can knock out a gene by taking out the entire gene. One can go in and cut it at one end, cut it at the other, and take out the entire gene. That's the most extreme knockout. Then in that case, you're knocking the boxer out of the ring, so there's no possibility that he's going to come back. In the case of an induced stop mutation, it's a little bit like knocking out the boxer. It's likely he's not going to get up again, but it's always possible that he might. So you take a little bit of a chance. It's a little easier than knocking him out of the ring, but there's still a bit of a chance that your knockout may be incomplete.

Linkage is the close association of genes or other DNA sequences on the same chromosome. The closer two genes are to each other on the chromosome, the greater the probability that they will be inherited together.

Linkage is referring to the close co-location of genes or of DNA variations to each other on the chromosomes. And these co-localizations are close enough that one can use genetic tools to find them being transmitted within families together. And the closer genes are to each other on a chromosome, the better chance you have to detect this linkage, because they are then more likely to be transmitted from grandparents, to parents, to children together, because there's less likely to be recombinations at meiosis between these genes. And so two genes that tend to be transmitted together we say are linked to each other.

Joan E. Bailey-Wilson, Ph.D.

A locus is the specific physical location of a gene or other DNA sequence on a chromosome, like a genetic street address. The plural of locus is "loci".

"Locus" is a term that we use to tell us where on a chromosome a specific gene is. So it's really the physical location of a gene or of a DNA polymorphism on a chromosome. And it's sort of like a street address for people. And one of the things that we think about when we're thinking about genes and chromosomes is we may think of the chromosome as a country, and then a region of a chromosome would maybe be the city, and then we'll get down to a very specific area, which is the locus, and that would be equivalent to, say, a person's street address. And that's the street address of that gene. An important thing to remember is that the plural of "locus" is "loci", not "locuses".

Joan E. Bailey-Wilson, Ph.D.

LOD stands for "logarithm of the odds." In genetics, the LOD score is a statistical estimate of whether two genes, or a gene and a disease gene, are likely to be located near each other on a chromosome and are therefore likely to be inherited. A LOD score of 3 or higher is generally understood to mean that two genes are located close to each other on the chromosome. In terms of significance, a LOD score of 3 means the odds are a thousand to one that the two genes are linked, and therefore inherited together.

LOD score is actually an acronym for "log of the odds," LOD. LOD score actually refers to a numerical result when estimating whether two genes, or a gene and a disease, are linked to one another. LOD scores are most often used to describe the data one gets out of family studies where you are looking at large families and an inheritance of traits or diseases within the families. So you can have the gene of interest unlinked to your disease and have a very low LOD score. In a family where the gene and a particular disease are segregating or being inherited together the odds of those being linked can actually be quite great and that would be a large LOD score. For example, in a pedigree to prove that a gene is linked to a condition we usually say that the LOD score has to be above 3. 3 is translated roughly into about 1,000-to-one odds that this gene really is linked to this disease as opposed to the alternative hypothesis which is unlinked. So therefore the higher the LOD score the more likely the two things you are following, usually a disease and a gene or a marker, actually are truly linked in the family.

Lawrence C. Brody, Ph.D.

LOH (short for “loss of heterozygosity”) refers to a type of mutation that results in the loss of one copy of a segment of DNA (typically containing a gene or group of genes). For most parts of the genome, human cells have two copies of any genomic segment — one from each parent — so in the case of LOH, only one copy would still be present.

Loss of heterozygosity, LOH. Loss of heterozygosity, LOH, is defined as the loss of one parent's contribution to the cell. It is a common form of allelic imbalance by which heterozygous somatic cells become homozygous because one of the two alleles gets lost. This form of chromosome instability is sufficient to provide selective growth, a major cause of tumorigenesis. LOH can be caused by degradation, deletion, due to an imbalance rearrangement, gene conversion, mitotic recombination, or loss of a whole chromosome [inaudible].

Amalia Dutra, Ph.D., Director, Cytogenetics and Microscopy Core