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 variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).

A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)

A gene variant is a permanent change in the DNA sequence that makes up a gene. This type of genetic change used to be known as a gene mutation, but because changes in DNA do not always cause disease, it is thought that gene variant is a more accurate term. Variants can affect one or more DNA building blocks (nucleotides) in a gene.

Gene variants can be inherited from a parent or occur during a person’s lifetime:

• Inherited (or hereditary) variants are passed from parent to child and are present throughout a person’s life in virtually every cell in the body. These variants are also called germline variants because they are present in the parent’s egg or sperm cells, which are also called germ cells. When an egg and a sperm cell unite, the resulting fertilized egg cell contains DNA from both parents. Any variants that are present in that DNA will be present in the cells of the child that grows from the fertilized egg.
• Non-inherited variants occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. Because non-inherited variants typically occur in somatic cells (cells other than sperm and egg cells), they are often referred to as somatic variants. These variants cannot be passed to the next generation. Non-inherited variants can be caused by environmental factors such as ultraviolet radiation from the sun or can occur if an error is made as DNA copies itself during cell division.

Some genetic changes are described as new (de novo) variants; these variants are recognized in a child but not in either parent. In some cases, the variant occurs in a parent’s egg or sperm cell but is not present in any of their other cells. In other cases, the variant occurs in the fertilized egg shortly after the egg and sperm cells unite. (It is often impossible to tell exactly when a de novo variant happened.) As the fertilized egg divides, each resulting cell in the growing embryo will have the variant. De novo variants are one explanation for genetic disorders in which an affected child has a variant in every cell in the body, but the parents do not, and there is no family history of the disorder.

Variants acquired during development can lead to a situation called mosaicism, in which a set of cells in the body has a different genetic makeup than others. In mosaicism, the genetic change is not present in a parent’s egg or sperm cells, or in the fertilized egg, but happens later, anytime from embryonic development through adulthood. As cells grow and divide, cells that arise from the cell with the altered gene will have the variant, while other cells will not. When a proportion of somatic cells have a gene variant and others do not, it is called somatic mosaicism. Depending on the variant and how many cells are affected, somatic mosaicism may or may not cause health problems. When a proportion of egg or sperm cells have a variant and others do not, it is called germline mosaicism. In this situation, an unaffected parent can pass a genetic condition to their child.

Most variants do not lead to development of disease, and those that do are uncommon in the general population. Some variants occur often enough in the population to be considered common genetic variation. Several such variants are responsible for differences between people such as eye color, hair color, and blood type. Although many of these common variations in the DNA have no negative effects on a person’s health, some may influence the risk of developing certain disorders.

The gene is the basic physical unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify traits. Genes are arranged, one after another, on structures called chromosomes. A chromosome contains a single, long DNA molecule, only a portion of which corresponds to a single gene. Humans have approximately 20,000 genes arranged on their chromosomes.

A gene could be as short as a few hundred base pairs or as long as many thousands. The BRCA1 and BRCA2 genes, for instance, are very long and huge. The beta-globin gene, on the other hand, is only a few hundred of these nucleotides. A gene, in a common way of thinking about it, is a packet of information coding generally for a protein. Of course, [in] DNA, the gene doesn't do the work. It's the protein that's produced from that that carries out the function. It's gotten [a] little messy in that one gene doesn't just make one protein. Oftentimes, because of alternative splicing, one gene can produce multiple proteins. And of course there are genes that don't even make proteins at all. They make RNAs that have some other functional role. And some people have begun to question whether the term "gene" is useful because it's gotten so complicated. Not to worry, it is still a very useful term. Geneticists wouldn't know how to have a conversation without using the word.

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

Double helix is the description of the structure of a DNA molecule. A DNA molecule consists of two strands that wind around each other like a twisted ladder. Each strand has a backbone made of alternating groups of sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), cytosine (C), guanine (G), or thymine (T). The two strands are held together by bonds between the bases, adenine forming a base pair with thymine, and cytosine forming a base pair with guanine.

A double helix has become the icon for many, many kinds of discussions about where science has been and where it's going. This really is an amazing structure. You can't stare at the double helix for very long without having a sense of awe about the elegance of this information molecule DNA, with its double helical form basically being the way in which all living forms are connected to each other, because they all use this same structure for conveying that information. Of course, this is Watson and Crick's incredible realization back in 1953, but it will stand in history as probably one of the most significant scientific moments of all time.

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

A mutation is a change in a DNA sequence. Mutations can result from DNA copying mistakes made during cell division, exposure to ionizing radiation, exposure to chemicals called mutagens, or infection by viruses. Germ line mutations occur in the eggs and sperm and can be passed on to offspring, while somatic mutations occur in body cells and are not passed on.

Mutation has been the source of many Hollywood movies, but it's really a simple process of a mistake made in a DNA sequence as it's being copied. Some of that's just the background noise that DNA copying is not perfect, and we should be glad of that or evolution couldn't operate. But mutation can also be induced by things like radiation or carcinogens in a way that can increase the risk of cancers or birth defects. But it's pretty simple; it's basically an induced misspelling of the DNA sequence. That's a mutation.

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

An allele is one of two or more versions of DNA sequence (a single base or a segment of bases) at a given genomic location. An individual inherits two alleles, one from each parent, for any given genomic location where such variation exists. If the two alleles are the same, the individual is homozygous for that allele. If the alleles are different, the individual is heterozygous.

"Allele" is the word that we use to describe the alternative form or versions of a gene. People inherit one allele for each autosomal gene from each parent, and we tend to lump the alleles into categories. Typically, we call them either normal or wild-type alleles, or abnormal, or mutant alleles.

A carrier, as related to genetics, is an individual who “carries” and can pass on to its offspring a genomic variant (allele) associated with a disease (or trait) that is inherited in an autosomal recessive or sex-linked manner, and who does not show symptoms of that disease (or features of that trait). The carrier has inherited the variant allele from one parent and a normal allele from the other parent. Any offspring of carriers is at risk of inheriting a variant allele from their parents, which would result in that child having the disease (or trait).

Carrier. The key to understanding carrier in the genetic sense is that, even though we all have two copies of each gene, for some genes you can have only one working copy and essentially have no major medical issues. The challenge arises when you have a child with another person who is also a carrier for the same autosomal recessive disorder, and the child inherits both nonworking copies from each parent. There's a 25% chance of this happening with every pregnancy. Most often, people don't know that they are carriers. As a result, it's now possible to genetically screen prospective parents to determine whether they are carriers for any of the more commonly seen autosomal recessive disorders.

Neil A. Hanchard, M.B.B.S., D.Phil., Senior Investigator, Center for Precision Health Research