Genetic ALS glossary

Defined below are some words and phrases commonly associated with genetic ALS. Talk with your doctor to learn more about these terms.




Defined characteristics that are measured as indicators of health, disease, or a response to an exposure or intervention, including therapeutic interventions. Biomarkers can help diagnose a disease, or predict future disease severity or outcomes.

Bulbar-onset ALS

A form of ALS in which the muscles involved in chewing, speaking, and swallowing are generally the first to be affected. Initial symptoms include speech and swallowing problems, then progress to respiratory paralysis.



The C9orf72 gene provides instructions for making a protein that is abundant in nerve cells (neurons) in the outer layers of the brain and in specialized neurons in the brain and spinal cord that control movement. Mutations in the C9orf72 gene are the most common gene mutations associated with ALS.


An organized package of DNA contained in the nucleus (center of the cell). Individual DNA segments combine to form genes, and these genes are linked together to form a chromosome. Humans inherit 23 pairs of chromosomes from their parents. Each parent contributes one chromosome to each pair, so the child receives half of their chromosomes from their mother and half from their father.

Clinical trial

Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of investigational drugs, vaccines, other therapies, or new ways of using existing treatments. Clinical trials have several phases with each phase providing different information that may include safety, tolerability, and potential effectiveness of the treatment being tested.



A molecule inside nearly every cell in the body that contains the information responsible for the cell’s development and function. DNA is made up of unique sequences of 4 chemical building blocks, called “nucleotide bases” (adenine, guanine, cytosine, and thymine). Segments of DNA form genes that are passed from parent to child, and contain information that specifies traits such as eye color, left- or right-handedness, and the ability to roll your tongue.

DNA sequencing

The act of determining the order of the 4 chemical building blocks—called “nucleotide bases” (adenine, guanine, cytosine, and thymine)—that make up the DNA molecule. The sequence tells scientists the kind of genetic information that is carried in a particular DNA segment. Sequence data can highlight changes or mutations in a gene that may cause disease.

Dominant gene

Genes come in pairs, with one version inherited from each parent. “Dominant” refers to the relationship between the 2 genes. If the versions of the gene are different, the dominant version will be expressed, while the other version, called recessive, is masked. If a disease gene is dominant, a person will develop the disease since only 1 copy is needed. For most genes associated with ALS, only 1 mutated copy is needed to cause disease.


Familial ALS

ALS cases in which the patient has a history of ALS within the family. Approximately 5%-10% of ALS cases are considered familial.

Family history

A record of medical information about an individual and their biological family that can be used to identify and measure risk for developing genetic disorders.


The FUS gene provides instructions for making a protein that is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. At least 85 mutations in the FUS gene have been found to be associated with ALS.



Segments of DNA that provide instructions, or code, required for the structure, function, and regulation of the body’s tissues and organs. Genes are contained in large, organized packages of DNA known as chromosomes. Each person has 2 copies of each gene—1 from their mother and 1 from their father.

Gene panel

A stand-alone clinical test intended for a specific clinical indication (ie, features of or a family history suggestive of a genetic condition), but not carrier screening or predictive testing (ie, testing without a clinical indication or family history).

Genetic ALS

ALS cases associated with a genetic mutation. Both sporadic ALS cases (believed to occur randomly) and familial ALS cases (when the patient has a history of ALS within the family) can be associated with a genetic mutation.


The study of genes and how certain qualities or traits are passed from parents to children as a result of changes in DNA sequence.

Genetic counseling

Services provided by healthcare professionals with specialized knowledge of genetics who can help determine whether a condition in a family may be genetic. Genetic counselors offer and interpret genetic tests and convey information in an effort to address the concerns of, and provide psychological counseling to, people with genetic diseases and their families.

Genetic mutation/

An error in the DNA, usually causing the cell to make either too little protein, too much protein, or defective protein. Any change in the normal protein can sometimes be harmful to the cell and may contribute to the development of disease.

Genetic penetrance

The proportion of people with a particular genetic variant (or gene mutation) who exhibit signs and symptoms of a genetic disorder. If some people with the variant do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance.

Genetic testing

The use of a laboratory test to look for genetic variations associated with a disease. The results of a genetic test can be used to confirm or rule out a suspected genetic condition or determine the likelihood of a person passing on a genetic mutation to their offspring.


A person’s collection of genes. The term can also refer to the 2 versions of each gene inherited from one’s parents. The genotype contributes to a person’s observable traits, which are referred to as the phenotype.



The level of influence that genes have in determining a person’s traits. Often, this term is used in reference to the traits passed down from parents to children, such as eye or hair color.


Limb-onset ALS

A form of ALS with initial symptoms including muscle weakness or breakdown in the arms and legs, and involuntary muscle contractions resulting in twitches. Around two-thirds of ALS patients have the limb-onset form of the disease.


mRNA (messenger RNA)

An intermediary, or messenger, between a gene and a protein. To make a protein, a cell first uses DNA to form an mRNA copy. That mRNA copy is then used to provide the “working instructions” to make the protein.



Structural proteins that help make up our neurons. Neurofilament levels in the blood have been shown to be an indicator of disease progression and survival in ALS.


Pedigree analysis

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


The observable expression of a person’s genes and DNA through traits such as height, eye color, blood type, and the presence or absence of a disease.


The principal component of all cells, required for the structure, function, and regulation of the body’s tissues and organs that are encoded by our genes.


Recessive gene

Genes come in pairs, with one version inherited from each parent. “Recessive” refers to the relationship between the 2 versions. If the versions are different, the effects of the recessive version will be masked and the dominant version will be expressed. Generally, in the case of a recessive genetic disorder, a person will develop the disease only if 2 copies are inherited.



The SOD1 gene provides instructions for making an enzyme called superoxide dismutase (SOD1), which is abundant in cells throughout the body. Mutations in SOD1 were first discovered in 1993, making it the first gene to be associated with ALS.

Sporadic ALS

ALS cases that are believed to occur randomly, without any known cause or family history of the disease. Ninety to 95% of ALS cases are considered sporadic, though genetic causes of disease have been discovered in people with seemingly sporadic ALS.



The TARDBP gene provides instructions for making a protein called transactive response DNA binding protein 43 kDa (TDP43). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. Mutations in TDP43 have been associated with ALS in about 4% of familial ALS and about 1% of sporadic ALS.