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Alus
Honors Genetics Lab
What is an Alu
• An Alu sequence is a short stretch of
DNA characterized by the action of the
Alu restriction endonuclease.
• Alu sequences of different kinds occur in
large numbers in primate genomes. In
fact, Alu sequences are the most
abundant mobile elements in the human
genome. Alu insertions have been
implicated in several inherited human
diseases, including various forms of
cancer, as discussed later in this article.
Restrotransposon
• “Jumping gene”
• It is able to copy itself and
insert into new locations
• Commonly called selfish DNA
Action of an Alu
• First, the inserted Alu is transcribed into
messenger RNA by the cellular RNA
polymerase.
• Then, the mRNA is converted to a
double-stranded DNA molecule by
reverse transcriptase.
• Finally, the DNA copy of Alu is
integrated into a new chromosomal locus
at the site of a single- or doublestranded break.
Why Study Alus
• The study of Alu sequences has
also been important in elucidating
human population genetics and the
evolution of primates, including the
evolution of humans. The Alu
endonuclease is so-named because
it was isolated from Arthrobacter
luteus.
Alu endonuclease
• The recognition sequence of
the Alu endonuclease is 5'
AG/CT 3'; that is, the enzyme
splits the DNA segment
between the guanine and
cytosine.
Alu characteristics
• Alu sequences are about 300 base pairs
long and are therefore classified as
short interspersed elements (SINEs)
amongst the class of repetitive DNA
elements.
• There are over 1 million Alu sequences
interspersed throughout the human
genome, and it is estimated that about
10% of the mass of the human genome
consists of Alu sequences. However less
than 0.5% are polymorphic
Defective Alus
• Alu is a "defective" transposon,
since it does not produce reverse
transcriptase and also lacks any an
enzyme to integrate itself into the
chromosome.
• However, Alu can obtain these
functions from another transposon,
called L1, a Long INterspersed
Element (LINE).
Lines and Alus
• Lines are essentially defective
retroviruses and retain many virus-like
properties. L1 produces a reverse
transcriptase with an additional
biochemical activity that produces a
single-stranded nick in DNA. The nick
created by the L1 reverse transcriptase
provides an integration site for an Alu
copy. In this sense, Alu is a parasite of
L1, which, in turn, is a relic of a
retrovirus ancestor.
Human Alus
• Most human Alu sequence
insertions can be found in the
corresponding positions in the
genomes of other primates, but
about 2,000 Alu insertions are
unique to humans.
• 500-2000 Alus are unique to the
human genome
Alus in Primates
• Alu sequences in primates form a fossil
record that is relatively easy to decipher
because Alu sequence insertion events
have a characteristic signature that is
both easy to read and faithfully recorded
in the genome from generation to
generation.
• The study of Alu sequences thus reveals
details of ancestry because individuals
will only share a particular Alu sequence
insertion if they have a common ancestor.
Alus and disease
• Alu insertions are sometimes disruptive and can
result in inherited disorders.However, most Alu
insertions act like markers since they may
segregate with a diseased allele, but the
presence of the Alu does not mean that the
person 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 [2].
PV92
• Found on Chromosome 16
• Is not associated with any disease
Two alleles
• One allele is 415 bp in size
• The other alleles is 715 bp in size
• These can be separated by agarose
gel electrophoresis
Neurofibromatosus
and Alus
• An estimated 500-2,000 Alu elements are
restricted to the human genome. The vast
majority of Alu insertions occur in non-coding
regions and are thought to be evolutionarily
neutral. However, an Alu insertion in the NF-1
gene is responsible for neurofibromatosis I, Alu
insertions in introns of genes for tissue
plasminogen activator (TPA) and angiotensin
converter enzyme (ACE) are associated with
heart disease. Alu insertions are analogous to the
insertion of a provirus in viral diseases and
certain cancers.
Genotypes
• This results in three PV92
genotypes (++, +-, or --). The +
and - alleles can be separated
by size using gel
electrophoresis.
PV 92 results