An<i>Alu</i>element retroposition in two families with Huntington disease defines a new active<i>Alu</i>subfamily

Hutchinson, Gordon B.; Andrew, Susan E.; McDonald, Helen; Goldberg, Y P; Graham, Rona; Rommens, Johanna M.; Hayden, Michael R.

doi:10.1093/nar/21.15.3379

Cited by 47 publications

(46 citation statements)

References 35 publications

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“…Although the flanking sequences of the LDLR Alu sequence show the expected evolutionary pattern throughout the pri- (18,19) and PS Alu consensus sequence (40). HS, PT, GG, PP, and CA refer to human, chimpanzee, gorilla, orangutan, and green monkey, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Though no recent de novo events of an Sb2 subfamily member have been reported, the few members that have been identified in the human genome share a relatively high degree of sequence identity (18,19), and rare Sb2 dimorphisms have been observed to be associated with acholinesteremia (32) and Huntington's disease (15). Thus, Sb2 also appears to be a very young Alu subfamily.…”

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confidence: 99%

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Gene Conversion as a Secondary Mechanism of Short Interspersed Element (SINE) Evolution

Kass

Batzer

Deininger

1995

Molecular and Cellular Biology

104

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The Alu repetitive family of short interspersed elements (SINEs) in primates can be subdivided into distinct subfamilies by specific diagnostic nucleotide changes. The older subfamilies are generally very abundant, while the younger subfamilies have fewer copies. Some of the youngest Alu elements are absent in the orthologous loci of nonhuman primates, indicative of recent retroposition events, the primary mode of SINE evolution. PCR analysis of one young Alu subfamily (Sb2) member found in the low-density lipoprotein receptor gene apparently revealed the presence of this element in the green monkey, orangutan, gorilla, and chimpanzee genomes, as well as the human genome. However, sequence analysis of these genomes revealed a highly mutated, older, primate-specific Alu element was present at this position in the nonhuman primates. Comparison of the flanking DNA sequences upstream of this Alu insertion corresponded to evolution expected for standard primate phylogeny, but comparison of the Alu repeat sequences revealed that the human element departed from this phylogeny. The change in the human sequence apparently occurred by a gene conversion event only within the Alu element itself, converting it from one of the oldest to one of the youngest Alu subfamilies. Although gene conversions of Alu elements are clearly very rare, this finding shows that such events can occur and contribute to specific cases of SINE subfamily evolution.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Gene Conversion as a Secondary Mechanism of Short Interspersed Element (SINE) Evolution

Kass

Batzer

Deininger

1995

Molecular and Cellular Biology

104

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“…While relatively few Alu sequences continue to transpose in humans, a substantial fraction of these have caused genetic variability and/or gene disruptions that have come to the at-tention of geneticists (1,14,22,25,39,42,54,73). Further characterization of human-specific Alu sequences has allowed the calculation of an Alu de novo transposition rate of 1 in 100 human births (13).…”

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confidence: 99%

A Trinucleotide Repeat-Associated Increase in the Level of Alu RNA-Binding Protein Occurred during the Same Period as the Major Alu Amplification That Accompanied Anthropoid Evolution

Chang

Sasaki-Tozawa

Green

et al. 1995

Molecular and Cellular Biology

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Nearly 1 million Alu elements in human DNA were inserted by an RNA-mediated retroposition-amplification process that clearly decelerated about 30 million years ago. Since then, Alu sequences have proliferated at a lower rate, including within the human genome, in which Alu mobility continues to generate genetic variability. Initially derived from 7SL RNA of the signal recognition particle (SRP), Alu became a dominant retroposon while retaining secondary structures found in 7SL RNA. We previously identified a human Alu RNA-binding protein as a homolog of the 14-kDa Alu-specific protein of SRP and have shown that its expression is associated with accumulation of 3-processed Alu RNA. Here, we show that in early anthropoids, the gene encoding SRP14 Alu RNA-binding protein was duplicated and that SRP14-homologous sequences currently reside on different human chromosomes. In anthropoids, the active SRP14 gene acquired a GCA trinucleotide repeat in its 3-coding region that produces SRP14 polypeptides with extended C-terminal tails. A C3G substitution in this region converted the mouse sequence CCA GCA to GCA GCA in prosimians, which presumably predisposed this locus to GCA expansion in anthropoids and provides a model for other triplet expansions. Moreover, the presence of the trinucleotide repeat in SRP14 DNA and the corresponding C-terminal tail in SRP14 are associated with a significant increase in SRP14 polypeptide and Alu RNA-binding activity. These genetic events occurred during the period in which an acceleration in Alu retroposition was followed by a sharp deceleration, suggesting that Alu repeats coevolved with C-terminal variants of SRP14 in higher primates.Ample evidence indicates that amplification of short interspersed elements (SINEs) occurred via reverse transcription of small RNA intermediaries in a process termed retroposition (52). The SINEs of many organisms are related to one or another tRNA, and these have been found widely distributed in nature, including in plants, fish, and mammals (see references 13, 43, and 44 and references therein). The Alu family of SINEs was derived from the terminal portions of the 7SL RNA component of the signal recognition particle (SRP), a small ribonucleoprotein involved in intracellular protein trafficking (6,24,27,70,71,74,77). In contrast to tRNA-like SINEs, and despite the ubiquity of 7SL SRP RNAs, Alu-related SINEs are for unknown reasons mostly limited to rodents and primates (for a recent review, see reference 13).Evolution of Alu-related SINEs apparently occurred in two major phases: an ancient period during which Alu sequences emerged as monomeric elements followed by a period of remodelling and proliferation (see reference 50 and references therein). The discovery of fossil Alu sequences provided evidence that an Alu monomer originated in an ancestor common to rodents and primates (50). The monomeric Alu-equivalent SINE referred to as B1 has since undergone substantial divergence from 7SL during its amplification to ϳ50,000 to 80,000 copies per haploid genom...

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“…It was new AluY member that had direct repeats at the flanking region which called tandem site duplication (TSD). The TSD sites could be useful marker for the confirmation of recent integration event by retrotransposition mechanism apart from conversion event (Hutchinson et al, 1993;Jurka and Klonowski, 1996;Roy-Engel et al, 2002). The Alu Yj4 element (AL163282) had TSD sites (GAAAATAGAACTGA) obviously (see Table 1).…”

Section: Discussionmentioning

confidence: 99%

Analysis of newly identified low copy AluYj subfamily

et al. 2005

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Human specific Alu Y elements were investigated by comparative analysis between human chromosome 21 and chimpanzee chromosome 22. Human specific Alu Y element was identified on human chromosome 21q22 (accession no. AL163282), and then that was a new member of Alu Yj subfamily. From the bioinformatic analysis, Alu Yj subfamily was investigated in human whole genome using Alu Yj4 consensus sequence (accession no. AL163282). Thirteen members of the Alu Yj4 elements (4 diagnostic mutations) and eight members of the Alu Yj3 elements (3 diagnostic mutations) were identified with distinct diagnostic mutation from Alu Y consensus sequence. The results of the molecular clock calculation of non-CpG region substitution indicated that, Alu Yj4 elements (2.1 million years old) may be proliferated more recent time than Alu Yj3 elements (14.1 million years old). For the verification of recent insertion time, four of Alu Yj4 elements (ch2-AC017101, ch10-AC044786, ch12-AC007656 and ch21-AL163282) from human chromosomes 2, 10, 12, 21 were analyzed by PCR amplification using various human and primate DNA samples. Though, no polymorphism was detected in human population, we identified the new Alu Yj4 subfamily as the human specific elements.

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AnAluelement retroposition in two families with Huntington disease defines a new activeAlusubfamily

Cited by 47 publications

References 35 publications

Gene Conversion as a Secondary Mechanism of Short Interspersed Element (SINE) Evolution

Gene Conversion as a Secondary Mechanism of Short Interspersed Element (SINE) Evolution

A Trinucleotide Repeat-Associated Increase in the Level of Alu RNA-Binding Protein Occurred during the Same Period as the Major Alu Amplification That Accompanied Anthropoid Evolution

Analysis of newly identified low copy AluYj subfamily

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