- Alu sequence
An Alu sequence is a short stretch of
DNAoriginally 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. They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle. The event, when a copy of the 7SL RNA became a precursor of the Alu sequence, took place in the genome of an ancestor of Supraprimates[Jan Ole Kriegs, Gennady Churakov, Jerzy Jurka, Jürgen Brosius, and Jürgen Schmitz (2007) Evolutionary history of 7SL RNA-derived SINEs in Supraprimates. Trends in Genetics 23 (4): 158-161 [http://dx.doi.org/10.1016/j.tig.2007.02.002] ] .
Alu insertions have been implicated in several inherited human diseases, including various forms of cancer, as discussed later in this article.
The study of Alu sequences has also been important in elucidatinghuman
population geneticsand the evolutionof primates, including the evolution of humans.The Alu endonuclease is so-named because it was isolated from " Arthrobacter luteus".
The Alu family
The Alu family is a family of repetitive elements in the
Human genome. Alu sequences are about 300 base pairs long and are therefore classified as short interspersed nuclear elements (SINEs) amongst the class of repetitive DNA elements.
There are over one million Alu sequences interspersed throughout the human genome, and it is estimated that about 10% of the human genome consists of Alu sequences. However less than 0.5% are polymorphic [A. Roy-Engel et al. "Alu Insertion Polymorphisms for the Study of Human Genomic Diversity". Genetics 159: 279–290 (September 2001).] .
The recognition sequence of the Alu endonuclease is 5' AG/CT 3'; that is, the enzyme splits the DNA segment between the
Alu sequences are
retrotransposons and look like DNA copies made from RNA polymerase III-encoded RNAs.
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 sexual ancestor.
Most human Alu sequence insertions can be found in the corresponding positions in the genomes of other primates, but about 7,000 Alu insertions are unique to humans [ [http://www.nature.com/nature/journal/v437/n7055/full/nature04072.html Chimpanzee Sequencing and Analysis Consortium. "Initial sequence of the chimpanzee genome and comparison with the human genome." Nature 437: 69-87 (September 1 2005)] ] .
Alu insertions and human 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
recombinationcausing a prevalent,inherited predisposition to cancer was a 1995report about "hereditary nonpolyposis colorectal cancer" [M. Nystrom-Lahti et al. "Founding mutations and Alu-mediated recombination in hereditary colon cancer." Nat Med. 1995 Nov;1(11):1203-6] .
In the review article referenced below [ [http://batzerlab.lsu.edu/Publications/Batzer%20and%20Deininger%202002%20Nature%20Reviews%20Genetics.pdf M. A. Batzer and P. L. Deininger. "Alu Repeats and Human Genomic Diversity." Nature Reviews: Genetics 3: 370-9 (May 2002)] ] , the authorsreport that the following human diseases have been linked with Alu insertions:
Diabetes mellitustype II
* [http://www.geneticorigins.org/ Genetic Origins - Use your own DNA variations (polymorphisms) as a means to explore our shared genetic heritage and its implications for human health and society.]
* [http://www.ColonCancerFamily.com/ ColonCancerFamily.com FREE Newsletter: topics include Lynch Syndrome, HNPCC, Genetic Testing and more]
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