関: Alu family、Alu sequence

WordNet

a straight line that generates a cylinder or cone
one of four substances thought in ancient and medieval cosmology to constitute the physical universe; "the alchemists believed that there were four elements"
the situation in which you are happiest and most effective; "in your element"
the most favorable environment for a plant or animal; "water is the element of fishes"
the 1st letter of the Roman alphabet (同)a
the blood group whose red cells carry the A antigen (同)type_A, group A
violent or severe weather (viewed as caused by the action of the four elements); "they felt the full fury of the elements"

PrepTutorEJDIC

〈C〉(物質を構成する)元素 / 〈C〉《修飾語[句]を伴って》(…の)(基本的な)『要素』,『成分』;《しばしば複数形で》構成分子 / 〈C〉(生物に固有の)生息場所,環境;(人の)適所,本領 / 〈C〉《古》四大(しだい)[元素](自然界の基本的構成要素と考えられていた地(earth)・水(water)・風(air)・火(fire)の4大要素の一つ) / 《the elements》(雨・風・雪などの)自然力・風雨,(特に)悪天候 / 《the elements》(学問の)原理,初歩,概論
answer / ampere
aluminumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/04 19:58:01」(JST)

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An Alu element is a short stretch of DNA originally characterized by the action of the Alu (Arthrobacter luteus) restriction endonuclease.^[1] Alu elements of different kinds occur in large numbers in primate genomes. In fact, Alu elements are the most abundant transposable 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 elements, took place in the genome of an ancestor of Supraprimates.^[2]

Alu insertions have been implicated in several inherited human diseases and in various forms of cancer.

The study of Alu elements has also been important in elucidating human population genetics and the evolution of primates, including the evolution of humans.

Karyotype from a female human lymphocyte (46, XX). Chromosomes were hybridized with a probe for Alu elements (green) and counterstained with TOPRO-3 (red). Alu elements were used as a marker for chromosomes and chromosome bands rich in genes.

The Alu family

The Alu family is a family of repetitive elements in the human genome. Modern Alu elements are about 300 base pairs long and are therefore classified as short interspersed elements (SINEs) among the class of repetitive DNA elements. The typical structure is 5'Part A- A5TACA6 -Part B - PolyA Tail - 3', where Part A and Part B are similar nucleotide sequences. Expressed another way, it is believed modern Alu elements emerged from a head to tail fusion of two distinct FAMs (fossil antique monomers) over 100 mkya, hence its dimeric structure of two similar, but distinct monomers (left and right arms) joined by an A-rich linker.^[3] The length of the polyA tail varies between Alu families.

There are over one million Alu elements interspersed throughout the human genome, and it is estimated that about 10.7% of the human genome consists of Alu sequences. However, less than 0.5% are polymorphic (i.e. they occur in more than one form or morph).^[4] In 1988, Jerzy Jurka and Temple Smith discovered that Alu elements were split in two major subfamilies known as AluJ and AluS, and other Alu subfamilies were also independently discovered by several groups.^[5] Later on, a sub-subfamily of AluS which included active Alu elements was given the separate name AluY. The discovery of Alu subfamilies led to the hypothesis of master/source genes, and provided the definitive link between transposable elements (active elements) and interspersed repetitive DNA (mutated copies of active elements).^[6]

7SL RNA

The sequence of the DNA for the 299 nucleotide long 7SL RNA:^[7]

gccgggcgcg gtggcgcgtg cctgtagtcc cagctactcg ggaggctgAG GCTGgaGGAT CGcttgAGTC CAggagttct

gggctgtagt gcgctatgcc gatcgggtgt ccgcactaag ttcggcatca atatggtgac ctcccgggag cgggggacca

ccaggttgcc taaggagggg tgaaccggcc caggtcggaa acggagcagg tcaaaactcc cgtgctgatc agtagtggga

tcgcgcctgt gaatagccac tgcactccag cctgggcaac atagcgagac cccgtctct

The functional retinoic acid response element hexamer sites ^[8] are in upper case and overlap the internal transcriptional promoter. The recognition sequence of the Alu endonuclease is 5' AG/CT 3'; that is, the enzyme cuts the DNA segment between the guanine and cytosine residues (in bold above).

Alu elements

Alu elements are retrotransposons and look like DNA copies made from RNA polymerase III-encoded RNAs. Alu elements do not encode for protein products and depend on LINE retrotransposons for their replication.^[9]

Alu elements in primates form a fossil record that is relatively easy to decipher because Alu elements 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 elements thus reveals details of ancestry because individuals will only share a particular Alu element insertion if they have a common ancestor.

Most human Alu element insertions can be found in the corresponding positions in the genomes of other primates, but about 7,000 Alu insertions are unique to humans.^[10]

Impact of Alu in humans

Alu elements are a common source of mutation in humans, but such mutations are often confined to non-coding regions where they have little discernible impact on the bearer.^[11] (That is, a given mutation may not cause any difference to exist [or, might cause only a small difference to exist] in the phenotype of the individual whose DNA contains that mutation—relative to what that phenotype would have been without that mutation, but with "other things being equal" [that is, with all other parts of the genotype being the same].) However, the variation generated can be used in studies of the movement and ancestry of human populations^{[citation needed]}, and the mutagenic effect of Alu^[12] and retrotransposons in general^[13] has played a major role in the recent 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.^[14]

The following human diseases have been linked with Alu insertions:^[15]

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

And the following diseases have been associated with single-nucleotide DNA variations in Alu elements impacting transcription levels:^[16]

Alzheimer's disease
Lung cancer
Gastric cancer

Other Alu-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^[17]
The opsin gene duplication which resulted in the re-gaining of trichromacy in Old World primates (including humans) is flanked by an Alu element,^[18] implicating the role of Alu in the evolution of three colour vision.

References

^ Schmid CW, Deininger PL (1975). "Sequence organization of the human genome". Cell 6: 345–358. doi:10.1016/0092-8674(75)90184-1. PMID 1052772.
^ Kriegs JO, Churakov G, Jurka J, Brosius J, Schmitz J (April 2007). "Evolutionary history of 7SL RNA-derived SINEs in Supraprimates". Trends Genet. 23 (4): 158–61. doi:10.1016/j.tig.2007.02.002. PMID 17307271.
^ Hasler J, Strub K, (2006). "Alu elements as regulators of gene expression". Nucleic Acids Research 34 (19): 5491–5497. doi:10.1093/nar/gkl706. PMC 1636486. PMID 17020921.
^ Roy-Engel AM, Carroll ML, Vogel E, et al. (September 2001). "Alu insertion polymorphisms for the study of human genomic diversity". Genetics 159 (1): 279–90. PMC 1461783. PMID 11560904.
^ Jurka J and Smith T' (July 1988). "A fundamental division in the Alu family of repeated sequences". Proceedings of the National Academy of Sciences 85 (July): 279–90. doi:10.1073/pnas.85.13.4775.
^ Shen MR, Batzer MA,Deininger PL (October 1991). "Evolution of the master Alu gene(s)". J. Mol. Evol. 33 (4): 311–320. doi:10.1007/bf02102862.
^ "NCBI Genbank DNA encoding 7SL RNA".
^ Vansant G and Reynolds WF (August 1995). "The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element". Proc. Natl. Acad. Sci. USA 92 (18): 8229–8233. doi:10.1073/pnas.92.18.8229. PMC 41130. PMID 7667273.
^ Kramerov DA, Vassetzky NS (2005). "Short retroposons in eukaryotic genomes". Int. Rev. Cytol. 247: 165–221. doi:10.1016/S0074-7696(05)47004-7. PMID 16344113.
^ And Analysis Consortium, The Chimpanzee Sequencing (September 2005). "Initial sequence of the chimpanzee genome and comparison with the human genome". Nature 437 (7055): 69–87. doi:10.1038/nature04072. PMID 16136131.
^ International Human Genome Sequencing Consortium (2001). "Initial sequencing and analysis of the human genome". Nature 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011.
^ Shen S, Lin L, Cai JJ, Jiang P, Kenkel EJ, Stroik MR, Sato S, Davidson BL, Xing Y (2011). "Widespread establishment and regulatory impact of Alu exons in human genes". PNAS 108 (7): 2837–42. doi:10.1073/pnas.1012834108.
^ Cordaux R, Batzer MA (2009). "The impact of retrotransposons on human genome evolution". Nature Reviews Genetics 10: 691–703. doi:10.1038/nrg2640. PMC 2884099. PMID 19763152.
^ Nyström-Lahti M, Kristo P, Nicolaides NC, et al. (November 1995). "Founding mutations and Alu-mediated recombination in hereditary colon cancer". Nat. Med. 1 (11): 1203–6. doi:10.1038/nm1195-1203. PMID 7584997.
^ Batzer MA, Deininger PL (May 2002). "Alu repeats and human genomic diversity". Nat. Rev. Genet. 3 (5): 370–9. doi:10.1038/nrg798. PMID 11988762.
^ "SNPedia: SNP in the promoter region of the myeloperoxidase MPO gene".
^ Puthucheary Z, Skipworth J, Rawal J, Loosemore M, Van Someren K, Montgomery H (2011). "The ACE Gene and Human Performance: 12 Years On". Sports Medicine 41: 433–448. doi:10.2165/11588720-000000000-00000. PMID 21615186.
^ Dulai KS, Von Dornum M, Mollon JD, Hunt DM (1999). "The Evolution of Trichromatic Color Vision by Opsin Gene Duplication in New World and Old World Primates". Genome Research 9 (7): 629–638. doi:10.1101/gr.9.7.629. PMID 10413401.

External links

Alu Repetitive Sequences at the US National Library of Medicine Medical Subject Headings (MeSH)
AF-1(Alu Finder):A web server to find Alu elements in primate genomes.

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Staufen1 senses overall transcript secondary structure to regulate translation.

Ricci EP1, Kucukural A1, Cenik C2, Mercier BC1, Singh G1, Heyer EE1, Ashar-Patel A1, Peng L1, Moore MJ1.Author information 11] Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [2] RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA.21] Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [2] RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [4].AbstractHuman Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3' untranslated regions (UTRs) or in 'strongly distal' 3' UTRs. Stau1 also interacts with actively translating ribosomes and with mRNA coding sequences (CDSs) and 3' UTRs in proportion to their GC content and propensity to form internal secondary structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater ribosome densities, thus suggesting a general role for Stau1 in modulating translation elongation through structured CDS regions. Our results also indicate that Stau1 regulates translation of transcription-regulatory proteins.
Nature structural & molecular biology.Nat Struct Mol Biol.2014 Jan;21(1):26-35. doi: 10.1038/nsmb.2739. Epub 2013 Dec 15.
Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and dee
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Aberrant Methylation of Hypermethylated-in-Cancer-1 and Exocyclic DNA Adducts in Tobacco Smokers.

Peluso ME, Munnia A, Bollati V, Srivatanakul P, Jedpiyawongse A, Sangrajrang S, Ceppi M, Giese RW, Boffetta P, Baccarelli AA.Author information * Cancer Risk Factor Branch, Cancer Prevention and Research Institute, Florence, Italy;AbstractTobacco smoke has been shown to produce both DNA damage and epigenetic alterations. However, the potential role of DNA damage in generating epigenetic changes is largely underinvestigated in human studies. We examined the effects of smoking on the levels of DNA methylation in genes for tumor protein p53, cyclin-dependent kinase inhibitor2A, hypermethylated-in-cancer-1 (HIC1), interleukin-6, Long Interspersed Nuclear Element type1, and Alu retrotransposons in blood of 177 residents in Thailand using bisulfite-PCR andpyrosequencing. Then, we analyzed the relationship of this methylation with the oxidative DNA adduct, M1dG (a malondialdehyde adduct), measured by (32)P-postlabeling. Multivariate statistical analyses showed that HIC1 methylation levels were significantly increased in smokers compared with nonsmokers (p ≤ .05). A dose response was observed, with the highest HIC1 methylation levels in smokers of ≥ 10 cigarettes/day relative to nonsmokers and intermediate values in smokers of 1-9 cigarettes/day (p for trend ≤ .001). No additional relationships were observed. We also evaluated correlations between M1dG and the methylation changes at each HIC1 CpG site individually. The levels of this adduct in smokers showed a significant linear correlation with methylation at one of the 3 CpGs evaluated in HIC1: hypermethylation at position 1904864340 was significantly correlated with the adduct M1dG (covariate-adjusted regression coefficient (β) = .224 ± .101 [SE], p ≤ .05). No other correlations were detected. Our study extends prior work by others associating hypermethylation of HIC1 with smoking; shows that a very specific hypermethylation event can arise from smoking; and encourages future studies that explore a possible role for M1dG in connecting smoking to this latter hypermethylation.
Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2014 Jan;137(1):47-54. doi: 10.1093/toxsci/kft241. Epub 2013 Oct 23.
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Huen K, Yousefi P, Bradman A, Yan L, Harley KG, Kogut K, Eskenazi B, Holland N.Author information Center for Children's Environmental Health, School of Public Health, University of California, Berkeley, California.AbstractEpigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies. Environ. Mol. Mutagen., 2013. © 2013 Wiley Periodicals, Inc.
Environmental and molecular mutagenesis.Environ Mol Mutagen.2013 Dec 26. doi: 10.1002/em.21845. [Epub ahead of print]
Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies ha
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