A polyglutamine tract or polyQ tract is a portion of a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

consisting of a sequence of several

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

units. A tract typically consists of about 10 to a few hundred such units. A multitude of

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s, in various eukaryotic species (including humans), contain a number of repetitions of the

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

triplet C A G or C A A. When the gene is translated into a protein, each of these triplets gives rise to a glutamine unit, resulting in a polyglutamine tract. Different

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

s of such a gene often have different numbers of triplets since the highly repetitive sequence is prone to contraction and expansion. Several inheritable

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s, the polyglutamine diseases, occur if a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

causes a polyglutamine tract in a specific gene to become too long. Important examples of polyglutamine diseases are spinocerebellar ataxia and

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

. Trinucleotide repeat expansion occurring in a parental

germline In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...

cell can lead to children that are more affected or display an earlier onset and greater severity of the condition. Trinucleotide repeat expansion is considered to be a consequence of slipped strand mispairing either during

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

synthesis. It is believed that cells cannot properly dispose of proteins with overlong polyglutamine tracts, which over time leads to damage in

nerve cell A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

s. The longer the polyglutamine tract, the earlier in life these diseases tend to appear.Laura Bonetta
Polyglutamine Diseases: A Devastating Genetic Stutter
,

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...

. Retrieved 30 December 2008.

History

Nucleotide sequences encoding a lengthy polyQ tract were first noted in the gene encoding the

Notch receptor __NOTOC__ __FORCETOC__ Notch proteins are a Protein family, family of type 1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in Animal, animals. The Notch extracellular domain mediates i ...

. Variation of the length of this Notch polyQ tract, as caused by triplet repeat instability, was later found to cause developmental defects. The significance of similarly expanded tracts in humans became evident when polyQ tracts were found to underlie

and several spinocerebellar ataxias. In general, several neurodegenerative disorders were found to involve nucleotide repeat expansions in

coding sequences.

References

{{reflist Peptide sequences Mutation