Affected Individual- An individual who has a particular trait or disease. The individual expresses the trait or has signs and symptoms of the disease, which is called the “phenotype”.
Allele- A version of a DNA sequence. Most inherited differences between individuals are the result of genetic differences at a specific location in the genome. These differences are called alleles. There may be many different alleles for the same location, but an individual inherits only two alleles, one from each parent, for any given genomic location.
Amino Acid- An amino acid is the molecule that serves as the building block for proteins. There are 20 different amino acids used in human proteins. A protein consists of one or more chains of amino acids (called polypeptides). The sequence of amino acids in a polypeptide is encoded in the DNA of a gene. Some amino acids can be synthesized in the body, but others (essential amino acids) cannot and must be obtained from a person’s diet.
Autosome- any chromosome that is not a sex chromosome.
Autosomal Recessive- One of the ways a genetic trait or a genetic condition can be inherited. Autosomal means that the disease gene is located on the numbered, or non-sex chromosomes (1-22). Recessive means that two copies of the mutated gene or region (one from each biological parent) are required to cause the disorder/disease. An example of an autosomal recessive disorder is cystic fibrosis.
Autosomal Dominant- One of the ways a genetic trait or a genetic condition can be inherited. Autosomal means that the disease gene is located on the numbered, or non-sex chromosomes (1-22). Dominant means that only one copy of the mutated gene or region (from a biological parent) is required to cause the disorder/disease. An example of an autosomal dominant disorder is Marfan syndrome.
Base Pair- Two complementary bases in a double-stranded nucleic acid molecule (DNA), consisting of a purine (adenine and guanine) in one strand linked by hydrogen bonds to a pyrimidine (cytosine and thymine) in the other. Cytosine always pairs with guanine, and adenine with thymine.
Base Sequence- The sequence of purines (adenine or guanine) and pyrimidines (cytosine and thymine) in DNA. The order of bases is represented as a string of As, Cs, Gs, and Ts.
Benign- A DNA variant that does not lead to known genetic conditions.
Biomarker- A biological molecule found in blood, other body fluids, or tissues that indicates a normal or abnormal process, or a condition or disease. A biomarker may be used to diagnose a disease or condition, or to see how well the body responds to a treatment. May also be called molecular marker or signature molecule.
Cancer- Cancer is a disease in which some of the body’s cells grow uncontrollably. There are many different types of cancer, and each begins when a single cell acquires a genomic change (or mutation) that allows the cell to divide and multiply unchecked. Additional mutations can cause the cancer to spread to other sites in the body. Cancer mutations are usually not inherited, but rather caused by errors during DNA replication or result from DNA damage due to environmental exposures (such as tobacco smoke or the sun’s ultraviolet rays). In certain cases, mutations in cancer genes can be inherited, which increases a person’s risk of developing cancer.
Carrier- A carrier is an individual who “carries” a genomic variant (allele) associated with a disease (or trait) in their DNA but does not show symptoms of that disease (or features of that trait). Carriers occur in autosomal recessive or X-linked recessive traits, where one normal allele is enough for normal function, even if an abnormal allele is also present. The carrier inherits the variant allele from one parent and a normal allele from the other parent. Offspring of parents who are both carriers are at risk of inheriting both variant alleles from their parents, which would result in that child being affected by the disease (or trait). For X-linked recessive disorders, females can be carriers, but males (having only one X chromosome) can only be affected or unaffected.
Cell Free DNA Testing- Cell-free DNA testing (cfDNA) is a laboratory method that examines free DNA, usually from dead or damaged cells, circulating in a body fluid (usually blood). This technique is used to look for genomic variants associated with a hereditary or genetic disorder. For example, prenatal cell-free DNA testing is a non-invasive method used during pregnancy that examines the fetal DNA that is naturally present in the maternal bloodstream. Cell-free DNA testing is also used for the detection and characterization of some cancers and to monitor cancer therapy.
CFTR Modulator- A class of drugs that act by improving production, intracellular processing, and/or function of the defective CFTR protein. Defected CFTR protein causes cystic fibrosis, an autosomal recessive disorder that affects the lungs, pancreas, and other organs.
Chromosomes- Threadlike structures made of protein and a single very long molecule of DNA that provides the genomic information in the cell. In plants and animals (including humans), chromosomes reside in the nucleus of each cell. Humans have 22 pairs of numbered chromosomes (autosomes) and one pair of sex chromosomes (XX or XY), for a total of 46. Chromosomes are large enough that some changes can be observed with a microscope.
Chromosome Rearrangement- A chromosomal rearrangement means that pieces of chromosomes are missing, duplicated (there are extra copies), or moved around.
Copy Number Variations (CNV)- Copy number variations (abbreviated CNV) are differences between individuals in the number of copies of a segment of DNA. Most DNA in the human genome exists in two copies (though there are many exceptions). The individual variants may be short or include thousands to millions of bases (even whole chromosomes). These structural differences may be due to duplications, deletions or other changes, and may or may not contain genes.
Cytogeneticist- A geneticist who specializes in the study of chromosomes and their structure and function within the cell. In the laboratory, cytogeneticists most commonly use techniques like karyotyping, FISH, and microarrays which look at chromosome structure.
DNA- Deoxyribonucleic acid (abbreviated DNA) is the molecule that carries genetic information for the development and functioning of an organism. DNA is made of two linked strands that wind around each other to resemble a twisted ladder — a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), cytosine (C), guanine (G) or thymine (T). These bases can occur in any order, and form a “four-letter code" for biological information, such as the instructions for making a protein or an RNA molecule.
The two strands of DNA are connected across the two strands by chemical bonds between the bases: adenine bonds with thymine, and cytosine bonds with guanine. This is why DNA length is often measured in “base pairs”. 
Deletion- is a type of change or variation that involves the loss of one or more nucleotides from a segment of DNA. A deletion can involve the loss of any number of nucleotides, from a single nucleotide to an entire piece of a chromosome.
De novo mutation - A genetic alteration that is present for the first time in an individual as a result of a variant (or mutation) in the egg or sperm of one of the parents or in the fertilized egg itself. This variant will not be present in earlier generations but could potentially be inherited by the individual’s children.
Diagnostic Testing - are tests administered by medical professionals to identify with high accuracy the presence or absence of illness/disorder in patients. Diagnostic genetic testing may identify or confirm the diagnosis of a genetic condition. This testing may be done before birth, or any time during a person's life to help determine the cause and course of a disorder as well as the choice(s) of treatment(s).
DNA Methylation- A chemical reaction in the cell in which a small molecule called a methyl group gets added to DNA. The addition of methyl groups can alter how DNA is structured or functions in the cell. For example, methylation of the DNA sequence of a gene may turn the gene off so it does not make a protein.
DNA Sequencing- The process of determining the order of bases in DNA. Sequencing is done by various methods and laboratory techniques to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The sequence of the DNA can then be compared to known references to determine if a mutation or variant is present.
Duplication- Refers to a type of change or variation in which one or more copies of a DNA segment is produced. Duplications can be as small as a single base to a large chromosomal region. Duplications occur in all organisms. For example, they are especially prominent in plants, although they can also cause genetic diseases in humans. Duplications have been an important mechanism in the evolution of the genomes of humans and other organisms.
Electrophoresis- A laboratory technique used to separate DNA, RNA or protein molecules based on their size and electrical charge. An electric current is used to move the molecules through a gel. The gel allows smaller molecules to move faster than larger molecules. To determine the size of the molecules in a sample, standards of known sizes are separated on the same gel and then compared to the sample.
Epigenetics- The study of changes in DNA that do not involve alterations to the underlying DNA sequence. Epigenetic changes arise during normal development and aging and in response to behavior (e.g. diet and exercise) and environment. Certain epigenetic changes may be passed from one generation to the next.
Environmental Factors- Exposures to substances (such as pesticides or industrial waste) where we live or work, behaviors (such as smoking or poor diet) that can increase an individual’s risk of disease or stressful situations (such as racism). These exposures can increase an individual’s risk of genetic damage or disease.
Exome- An exome is the sequence of all the exons in a genome, which are the protein-coding regions. In humans, the exome comprises about 1.5% of the genome.
Family History- A family history, is a record of the diseases and health conditions of an individual and that person’s biological family members, both living and deceased. A family history can help determine whether someone has an increased genetic risk of having or developing certain diseases, disorders or conditions. It is often analyzed by drawing a pedigree (a family tree) that illustrates the relationships among individuals.
Fluorescence in situ hybridization (FISH)- A laboratory method used to detect and locate a specific DNA sequence on a chromosome. For this method, chromosomes from an individual are affixed to a glass slide and a small piece of DNA tagged with a fluorescent dye (called a probe) is added to the slide. The probe binds to its matching sequence on the chromosome (s). With the use of a special microscope, the chromosomes and the probe can be seen. Check out the inherited disorders webpage to learn more.
Gene- The gene is a sequence of DNA and is considered the basic unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify physical and biological traits. Most genes code for proteins, which have specific functions within the cell or body. Humans have approximately 20,000 protein-coding genes. DNA codes for protein using four distinct nucleotides, which are represented as letters (A, C, T, and G, see DNA).
Genome- The entire set of DNA instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes located in the cell’s nucleus. Human cells also contain a small mitochondrial genome that is located in the mitochondria in cells. Together, these genomes contain all the information needed for an individual to develop and function.
Genotype- The entire genetic makeup of an individual. It is often applied more narrowly to a variant present within a specific gene or location in the DNA. It can be represented by symbols. For example, BB, Bb, bb could be used to represent a given variant in a gene. Genotypes can also be represented by the actual DNA sequence at a specific location, such as CC, CT, TT. DNA sequencing and other methods can be used to determine the genotypes at millions of locations in a genome in a single experiment. Some genotypes contribute to an individual’s observable traits, called the phenotype.
Genetic code- Refers to the instructions contained in a gene that tell a cell how to make a specific protein. Each gene’s code uses the four nucleotide bases of DNA: adenine (A), cytosine (C), guanine (G) and thymine (T) — in various ways to spell out three-letter “codons” that specify which amino acid is needed at each position within a protein.
Genomic Imprinting- A process by which only one copy of a gene or DNA region in an individual is functional, while the other copy is turned off. The suppression/activation of an imprinted DNA region depends on whether the region was inherited from the mother or the father. For example, if the maternal copy of the gene is imprinted, then in that individual, the gene inherited from the mother is turned off and the only active/functional copy would be the one inherited from the father.
Genetic testing- The use of a laboratory test to examine an individual’s DNA and/or RNA for variations, typically performed in the context of medical care, ancestry studies or forensics. In a medical setting, the results of a genetic test can be used to confirm or rule out a suspected genetic disease. Results may also be used to determine the likelihood of parents passing on a genetic mutation to their offspring. Genetic testing may be performed prenatally or after birth. Genetic testing is also used to study the DNA and/or RNA of tumors in cancer.
Germ Cells- Reproductive cells of the body. Germ cells are egg cells in females and sperm cells in males.
Germ Line- The cells that form eggs in females and sperm in males. Germline cells contain the genetic information that is passed down from one generation to the next.
Heteroplasmy– two or more mitochondrial DNA types in an individual. This could also describe two different variants at a single position in the mitochondrial DNA within a cell.
Heterozygous- Inherited different versions (alleles) of a genomic marker from each biological parent. Thus, an individual who is heterozygous for a genomic marker has two different versions of that marker. By contrast, an individual who is homozygous for a marker has two identical versions of that marker.
Homozygous- refers to having inherited the same versions (alleles) of a genomic marker from each biological parent. Thus, an individual who is homozygous for a genomic marker has two identical versions of that marker. By contrast, an individual who is heterozygous for a marker has two different versions of that marker.
Inherited- Refers to a trait or variants encoded in DNA that are passed from a biological parent to their child. Types of inheritance include autosomal dominant, autosomal recessive and sex-linked.
Inherited Condition- Disorder caused in whole or in part by a change in the DNA sequence that is different than the sequence observed in unaffected individuals. Genetic disorders can be caused by a mutation in one gene, in multiple genes, by a combination of gene mutations and environmental factors, or by damage to chromosomes.
Insertion- A type of change/variation that involves the addition of one or more base pairs into a segment of DNA. An insertion can involve the addition of any number of base pairs, from a single nucleotide to a piece of a chromosome.
Intron- A segment of a DNA that is within a gene but does not code for a protein.
Karyotype- An individual’s complete set of chromosomes. The term also refers to a laboratory-produced image of a person’s chromosomes isolated from an individual cell and arranged in numerical order. A karyotype may be used to look for abnormalities in chromosome number or structure.
Karotyping- The process of creating a karyotype which a laboratory performs to see an individual's complete set of chromosomes.
Laboratory developed testing procedures (LDPs, also referred to as LDTs)- are testing services that hospitals, academic, and clinical laboratories develop and use in patient care. These services are not commercially manufactured and marketed, but rather are designed, developed, validated, performed, and interpreted by board-certified professionals in a single laboratory. LDPs are often created in response to unmet clinical needs and are instrumental for early and precise diagnosis or monitoring and guidance of patient treatment. LDPs are not boxed and shipped medical products that are distributed across state lines rather they are validated testing protocols that are used in conjunction with the expertise of laboratory medical professionals.
Methylation- The chemical modification of DNA. When DNA is methylated, this can alter gene expression. In this process, chemical tags called methyl groups attach to a particular location within DNA where they turn a gene on or off, thereby regulating the production of proteins that the gene encodes.
Microarray Technology- A general laboratory approach that involves binding an array of thousands to millions of known DNA /RNA fragments to a solid surface, referred to as a “chip.” The chip is then bathed with DNA or RNA isolated from a patient’s study sample (such as cells or tissue). Complementary base pairing between the sample and the chip-immobilized fragments produces light through fluorescence that can be detected using a specialized machine. Microarray technology can be used for a variety of purposes in research and clinical studies, such as detecting specific DNA sequences and copy number changes.
Microscope- An optical instrument having a magnifying lens or a combination of lenses for inspecting objects too small to be seen or too small to be seen distinctly and in detail by the unaided eye. In the laboratory, the microscope is used to look at cells or chromosomes.
Mitochondrial DNA- Mitochondrial DNA is the circular chromosome found inside the cellular organelles called mitochondria. Located in the cytoplasm, mitochondria are the site of the cell’s energy production and other metabolic functions. Unlike DNA found in the cell’s nucleus, mitochondrial DNA is inherited solely from the mother.
Molecular Pathology- A discipline within pathology which is focused on the study and diagnosis of disease through the examination of molecules within organs, tissues, cells or bodily fluids.
Multiplex Testing- A method for detecting multiple pathogens or genetic alternations (i.e., gene mutations or single nucleotide polymorphisms in a single gene or across the genome) simultaneously.
Mutation- Change in the DNA sequence of an organism. Mutations can result from errors in DNA replication during cell division, exposure to mutagens or a viral infection. Germ line mutations (that occur in egg or sperm) can be passed on to offspring, while somatic mutations (present in certain cells in the body) are not passed on. Mutation and variant have the same definition; however, newer materials have begun to use the term variant due to stigma around the term mutation. You may find either term in many patient materials.
Newborn Screening- 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. If there is a positive finding, a diagnostic test will need to be ordered to determine if the newborn screening result was real.
Next Generation DNA Sequencing- DNA sequencing establishes the order of the bases that make up DNA. Next-generation DNA sequencing (abbreviated NGS) refers to the use of technologies for sequencing DNA that became available shortly after the completion of the Human Genome Project (which relied on the first-generation method of Sanger sequencing). NGS technologies can sequence an entire human genome faster and cheaper than first-generation methodologies and are used in most clinical laboratories.
Non-Invasive Prenatal Screening-Noninvasive prenatal screening (NIPS) analyze small fragments of fetal DNA, called cell-free DNA, that are circulating in a pregnant person's blood with the goal of determining the risk that the fetus has certain genetic abnormalities. If the result is high risk for a genetic abnormality, such as trisomy 21, a diagnostic test should be performed to confirm these results.
Pathogenic Variant- A genetic alteration that causes or increases an individual's susceptibility or predisposition to a certain disease or disorder.
Phenotype- The observable characteristics in an individual resulting from the expression of genes; the clinical presentation of an individual with a particular genotype.
Polymerase Chain Reaction (PCR) - 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 copied, and then multiple rounds of DNA synthesis to copy that segment.
Point Mutation- Occurs in a DNA sequence when a single base pair is changed. While most point mutations are benign, they can also have various functional consequences, including changes in gene expression or alterations in encoded proteins.
Protein- Large, complex molecules that play important roles in the cell and allow the body to function. They are critical to most of the work done by cells and are required for the structure, function and regulation of the body’s tissues and organs. A protein is made up of one or more long, folded chains of amino acids (called a polypeptide), whose sequences are determined by the DNA sequence of the protein-encoding gene.
Residual Risk- No single genetic test can detect all the possible genetic variants that could cause a disease or disorder. This means that, even if an individual tests negative, there is a chance that this individual may still be a carrier for a genetic condition.
RNA- Ribonucleic acid (abbreviated RNA) is a nucleic acid that has structural similarities to DNA and is present in living cells . However, unlike DNA, 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 Sequencing- A laboratory method used to learn the exact sequence of the RNA molecules in a cell. In a cell, RNA is copied from pieces of DNA and contains information to make proteins and perform other important functions.
Sanger Sequencing- An original method used to determine a portion of the nucleotide sequence of an individual’s genome. This technique uses polymerase chain reaction (PCR) amplification of genetic regions of interest followed by sequencing of the PCR products. This technique is accurate but is slower and more expensive than next generation sequencing methods.
SARS-CoV-2- The virus that causes a respiratory disease called coronavirus disease 19 (COVID-19). SARS-CoV-2 is a member of a large family of viruses called coronaviruses. These viruses can infect people and some animals. SARS-CoV-2 was first known to infect people in 2019
Sensitivity- The frequency with which a test shows a true positive result among individuals who actually have the disease or the genetic variant in question. A test with high sensitivity has a low false-negative rate, which means it does a good job of correctly identifying affected individuals or carriers of a genetic variant.
Sex Chromosome- 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 Cell- An egg cell in females or sperm cell in males. Each mature sex cell contains 23 chromosomes.
Sex Linked- Refers to characteristics (or traits) that are influenced by genes carried on the sex chromosomes. In humans, the term often refers to traits or disorders influenced by genes on the X-chromosome, as it contains many more genes than the smaller Y-chromosome. Males, who have only a single copy of the X-chromosome, are more likely to be affected by a sex-linked disorder than females, who have two copies. In females, the presence of a second, non-mutated copy may cause different, milder, or no symptoms of a sex-linked disorder. An example of a sex-linked disorder is Fragile X syndrome.
Single Nucleotide Polymorphisms (SNP)- 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. The frequency of SNPs may differ between populations.
Single Nucleotide Variation (SNV)- A genomic variant at a single base position in the DNA. Scientists study if and how SNVs in a genome influence health, disease, drug response and other traits. A SNV may be unique to an individual. A SNV may be unique to an individual and may be the cause of a disease or disorder in that individual.
Somatic cells- Any cell of a living organism other than the reproductive cells.
Specificity- The frequency with which a test shows a true negative result among individuals who do not have the disease or the genetic variant in question. A test with high specificity has a low false-positive rate, which means it does a good job of correctly identifying unaffected individuals or noncarriers of a genetic variant.
Unaffected Individual- An individual who does not have a particular trait or disease.
Vaccine- A preparation that is used to stimulate the body’s immune response against specific diseases. Vaccines are usually administered through needle injections, but some can be administered by mouth or sprayed into the nose.
Variant- Change in the DNA sequence caused by errors in DNA replication during cell division, exposure to mutagens or a viral infection. Variant and mutation have the same definition; however, newer materials have begun to use the term variant due to stigma around the term mutation. You may find either term in many patient materials.
Variant of Unknown Significance- When analysis of a patient’s genome identifies a variant, but it is unclear whether that variant is actually connected to a health condition, the finding is called a variant of uncertain significance (abbreviated VUS or VOUS). In many cases, these variants are so rare in the population that little information is available about them. Typically, more information is required to determine if the variant is disease related. Such information may include more extensive population data, functional studies, and tracing the variant in other family members who have or do not have the same health condition.
Virus -A virus is an infectious microbe consisting of a segment of nucleic acid (either DNA or RNA) surrounded by a protein coat. A virus cannot replicate alone; instead, it must infect cells and use components of the host cell to make copies of itself. Often, a virus ends up killing the host cell in the process, causing damage to the host organism. Well-known examples of viruses causing human disease include acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV), coronavirus disease (COVID-19) caused by SARS-CoV-2, measles caused by morbillivirus and smallpox caused by variola virus.
Whole Exome Sequencing- A laboratory process that sequences all coding regions (exomes) of an individual's complete DNA sequence.
Whole Genome Sequencing- A laboratory process that sequences all 3 billion bases of an individual’s complete DNA sequence, including non-coding sequence.
X-Chromosome- The X chromosome is one of the two sex chromosomes that are 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.
X-Chromosome Inactivation- This is the normal process of one of the X chromosomes being randomly inactivated in a female’s cells. This process equalizes dosage of gene products from the X chromosome between XX females and XY males.
X-linked dominant- One of the ways a genetic trait or genetic condition can be inherited. X-linked means that the disease gene or region is located on the X-chromosome (one of the sex chromosomes). Dominant means that only one copy of the mutated gene or region (from a biological parent) is required to cause the disease/disorder. XX females and XY males will have the disease/disorder if they have the mutated gene. Sometimes the mutation/disorder is so detrimental to life that XY males may not survive because they only have the mutated copy. Whereas an XX female has the mutated copy but also has a normal copy which may allow for survival. An example of an X-linked condition is Rett syndrome.
X-Linked recessive- One of the ways a genetic trait or a genetic condition can be inherited. X-linked means that the disease gene or region is located on the X-chromosome (one of the sex chromosomes). Recessive means that two copies of the mutated gene or region (one from the father and one from the mother) are required to cause the disorder/disease in a XX female. In XY males, only one copy of the mutated gene or region is required to cause the disorder/disease and this individual may inherited that copy from their biological mother. The mother is likely to be unaffected (does not have the disease) because she carries only one copy of the mutated gene. An example of an X-linked condition is red-green color blindness.
Y-Chromosome- The Y chromosome is one of the two sex chromosomes that are 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.
AMP would like to thank the National Human Genome Research Institute, National Cancer Institute for their contributions to a unified glossary available for all patients.
Created: 3/2023