Genetics of ALS: What are the Genetics of ALS?
Sporadic and Familial ALS
Most cases of ALS are “sporadic,” meaning they are due to no known
cause. Approximately 5-10% of cases are due to known genetic
mutations. In most of those cases, another family member also has
ALS or a related disease. Such cases are called “familial.” Cases of
familial ALS (FALS) are presumed to be due to genes, although the
gene may not be known in all cases.
In some cases of ALS, the disease may be due to a faulty gene, but
there may be no other affected family members.
Genes and Mutations
Genes are strings of DNA that provide instructions, or code, for
making proteins. Proteins are the standard components of all types of
cells, they are used to control reactions and provide structure. Genes
are linked together to form chromosomes, which are located in the
The nucleus of a cell contains chromosomes, on
which are the genes consisting of the DNA that codes
nucleus of each cell. Chromosomes and the genes they contain are
for proteins, the main ingredients of living beings.
inherited, passing from parent to child.
The structure of each protein depends on the instructions for its assembly, spelled out in a sequence coded in the
genes. First a protein’s amino acids are strung together. Then the chain of amino acids folds up to the proper shape. A
mistake in the genetic code, that is, a mutation, places the wrong amino acid in the sequence. This can produce an
improperly folded protein that may not work, or that could have improper chemistry that disrupts cellular functions. Or a
poorly folded protein can simply be sticky, and gum up the cellular machinery. Different mutations may cause different
effects. Any change in the normal protein can be harmful to the cell, and may cause disease. The vast majority of these
mutations change the amino acid sequence at a single position.
Genes that Cause ALS
C9ORF72
This gene, discovered in 2011, is the most common genetic cause of ALS. (Its name refers its position on chromosome 9).
Mutations in this gene account for between 25% and 40% of all familial ALS cases, and also approximately 4% to 6% of
sporadic cases. A change of one nucleotide base leads to the wrong amino acid. The mutated gene codes for the amino
acid asparagine instead of the amino acid glutamine.
Cu/Zn Superoxide Dismutase 1 (SOD1)
Mutations in SOD1 were first described in 1993, and SOD1 was the first gene known for ALS. It accounts for about 10%
of familial ALS, or 1.5% to 2% of all ALS. This enzyme serves to keep cells safe from metabolic waste that can do damage
if not rendered harmless. A change of one nucleotide base leads to the wrong amino acid. The mutated gene codes for the
amino acid lysine instead of the amino acid glutamine.