Some
Alu elements have been proposed to affect
gene expression and been found to contain functional
promoter regions for
steroid hormone receptors. Due to the abundant content of
CpG dinucleotides found in
Alu elements, these regions can serve as a site of
methylation, contributing to up to 30% of the methylation sites in the human genome.
Alu elements are also a common source of mutations in humans; however, such mutations are often confined to non-coding regions of pre-mRNA (
introns), where they have little discernible impact on the bearer. Mutations in the introns (or non-coding regions of RNA) have little or no effect on phenotype of an individual if the coding portion of individual's genome does not contain mutations. When Alu insertions occur in coding regions (
exons), or into mRNA after the process of splicing, they're typically detrimental to the host organism. However, the variation generated can be used in studies of the movement and ancestry of human populations, and the mutagenic effect of
Alu and retrotransposons in general has played a major role in the evolution of the human genome. There are also a number of cases where
Alu insertions or deletions are associated with specific effects in humans:
Associations with human disease Alu insertions are sometimes disruptive and can result in inherited disorders. However, most
Alu variation acts as markers that segregate with the disease so the presence of a particular
Alu allele does not mean that the carrier will definitely get the disease. The first report of
Alu-mediated
recombination causing a prevalent inherited predisposition to cancer was a 1995 report about
hereditary nonpolyposis colorectal cancer. In the human genome, the most recently active have been the 22 AluY and 6 AluS Transposon Element subfamilies due to their inherited activity to cause various cancers. Thus due to their major heritable damage it is important to understand the causes that affect their transpositional activity. The following human diseases have been linked with
Alu insertions: •
Alport syndrome •
Breast cancer •
chorioretinal degeneration •
Diabetes mellitus type II •
Ewing's sarcoma •
Familial hypercholesterolemia •
Hemophilia •
Leigh syndrome •
mucopolysaccharidosis VII •
Neurofibromatosis •
Macular degeneration And the following diseases have been associated with
single-nucleotide DNA variations in Alu elements affecting transcription levels: •
Alzheimer's disease •
Lung cancer •
Gastric cancer The following disease have been associated with repeat expansion of AAGGG pentamere in Alu element : •
RFC1 mutation responsible of
CANVAS (Cerebellar Ataxia, Neuropathy & Vestibular Areflexia Syndrome)
Associated human mutations • The
ACE gene, encoding
angiotensin-converting enzyme, has 2 common variants, one with an
Alu insertion (
ACE-I) and one with the
Alu deleted (
ACE-D). This variation has been linked to changes in sporting ability: the presence of the
Alu element is associated with better performance in endurance-oriented events (e.g. triathlons), whereas its absence is associated with strength- and power-oriented performance. • The
opsin gene duplication which
resulted in the re-gaining of
trichromacy in
Old World primates (including humans) is flanked by an
Alu element, implicating the role of
Alu in the evolution of three colour vision. == References ==