Alu sequence

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An Alu sequence is a short stretch of DNA originally 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.

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.

[edit] The Alu family

The Alu family is a family of polymorphisms 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 mass of the human genome consists of Alu sequences. However less than 0.5% are polymorphic ^[1]

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 residues.

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^[2].

The sequence known as Alu PV92, located in Chromosome 16, can either be present or absent (although the majority of people don't have the sequence), leading to three different genotypes:

• Presence, Presence
• Presence, Absence
• Absence, Absence

[edit] 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 recombination causing a prevalent, inherited predisposition to cancer was a 1995 report about hereditary nonpolyposis colorectal cancer ^[3].

In the review article referenced below ^[4], the authors report that the following human diseases have been linked with Alu insertions:

• Breast cancer
• Ewing's sarcoma
• Familial hypercholesterolemia
• Hemophilia
• Neurofibromatosis
• Diabetes mellitus type II

[edit] References

1. ^ A. Roy-Engel et al. Alu Insertion Polymorphisms for the Study of Human Genomic Diversity. Genetics 159: 279–290 (September 2001).
2. ^ Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69-87 (September 1 2005)
3. ^ M. Nystrom-Lahti et al. Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med. 1995 Nov;1(11):1203-6
4. ^ M. A. Batzer and P. L. Deininger. Alu Repeats and Human Genomic Diversity. Nature Reviews: Genetics 3: 370-9 (May 2002)