Genetics of Trimethylaminuria
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 nucleus of each cell. Chromosomes and
the genes they contain are 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.
Fish Odor Syndrome
This disorder is caused by a single nucleotide change. Early in the FMO3 gene, a guanine is substituted for a
guanine. The FMO3 gene provides instructions for making an enzyme that is part of a larger enzyme family
called flavin-containing monooxygenases (FMOs). These enzymes break down compounds that contain
nitrogen, sulfur, or phosphorus. The FMO3 enzyme, which is made chiefly in the liver, is responsible for
breaking down nitrogen-containing compounds from the foods that we eat. One of these compounds is
trimethylamine, which is the molecule that gives fish their fishy smell.
Trimethylamine is produced as bacteria in the intestine help digest certain proteins obtained from eggs, liver,
legumes (such as soybeans and peas), certain kinds of fish, and other foods. The FMO3 enzyme normally
converts fishy-smelling trimethylamine into another compound, trimethylamine-N-oxide, which has no odor.
Trimethylamine-N-oxide is then excreted from the
body in urine.
Where is the FMO3 gene located?
Cytogenetic Location: 1q24.3
The FMO3 gene is located on the long (q) arm of
chromosome 1 at position 24.3.
More precisely, the FMO3 gene is located from base pair 171,090,876 to base pair 171,117,820 on chromosome1