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Titolo:
Biased distribution of inverted and direct Alus in the human genome: Implications for insertion, exclusion, and genome stability
Autore:
Stenger, JE; Lobachev, KS; Gordenin, D; Darden, TA; Jurka, J; Resnick, MA;
Indirizzi:
NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709 ab, NIH, Res Triangle Pk, NC 27709 USA NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709 ab, NIH, Res Triangle Pk, NC 27709 USA Genet Informat Res Inst, Sunnyvale, CA 94089 USA Genet Informat Res Inst Sunnyvale CA USA 94089 t, Sunnyvale, CA 94089 USA
Titolo Testata:
GENOME RESEARCH
fascicolo: 1, volume: 11, anno: 2001,
pagine: 12 - 27
SICI:
1088-9051(200101)11:1<12:BDOIAD>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
EHLERS-DANLOS-SYNDROME; LYSYL HYDROXYLASE GENE; SACCHAROMYCES-CEREVISIAE; REPETITIVE SEQUENCE; DNA REPEATS; VI VARIANT; 7 EXONS; RECOMBINATION; DELETION; INSTABILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Resnick, MA NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Citazione:
J.E. Stenger et al., "Biased distribution of inverted and direct Alus in the human genome: Implications for insertion, exclusion, and genome stability", GENOME RES, 11(1), 2001, pp. 12-27

Abstract

Alu sequences, the most abundant class of large dispersed DNA repeats in human chromosomes, contribute to human genome dynamics. Recently we reportedthat long inverted repeats, including human Alus, can be strong initiatorsof genetic change in yeast. We proposed that the potential For interactions between adjacent, closely related Alus would influence their stability and this would be reflected in their distribution. We have undertaken an extensive computational analysis of all Alus [the database is at http://dir.niehs.nih.gov/ALU) to better understand their distribution and circumstances under which Alu sequences might affect genome stability. Alus separated by <650 bp were categorized according to orientation, length of regions sharinghigh sequence identity, distance between highly identical regions, and extent of sequence identity. Nearly 50% of all Alu pairs have long alignable regions (>275 bp), corresponding to nearly Full-length Alus, regardless of orientation. There are dramatic differences in the distributions and character of Alu pairs with closely spaced, nearly identical regions. For Alu pairs that are directly repetitive, similar to 30% have highly identical regions separated by <20 bp, but only when the alignments correspond to near full-size or half-size Alus. The opposite is found for the distribution of inverted repeats: Ala pairs with aligned regions separated by <20 bp are rare. Furthermore, closely spaced direct and inverted Alus differ in their truncation patterns, suggesting differences in the mechanisms of insertion. At larger distances, the direct and inverted Alo pairs have similar distributions. We propose that sequence identity, orientation, and distance are important Factors determining insertion of adjacent Alus, the frequency and spectrum of Alu-associated changes in the genome, and the contribution of Alu pairs to genome instability. Based on results in model systems and the presentanalysis, closely spaced inverted Alu pairs with long regions of alignmentare likely at-risk motifs (ARMs] for genome instability.

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Documento generato il 31/03/20 alle ore 10:12:05