Deletion of entire <i>HLA‐A </i>gene accompanied by an insertion of a retrotransposon

Takasu, Masako; Hayashi, Ryosuke; Maruya, Etsuko; Ôta, Masao; Imura, Kohei; Kougo, K.; Kobayashi, Chie; Saji, Hiroo; Ishikawa, Yoshihide; Asai, Tatsuhiko; Tokunaga, Katsushi

doi:10.1111/j.1399-0039.2007.00870.x

Cited by 37 publications

(35 citation statements)

References 39 publications

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“…To date, SVA elements have been reported to contribute to human genome evolution through insertional mutagenesis (Kobayashi et al 1998;Rohrer et al 1999;Wilund et al 2002;Ostertag et al 2003;Conley et al 2005;Makino et al 2007;Takasu et al 2007), by constituting alternative exons (Damert et al 2004) and by exon and gene shuffling mediated by 39 transduction (Xing et al 2006). Similar to 39 transduction events, the process of 59 transduction entails the juxtaposition of two previously unlinked host genomic segments.…”

Section: Exon Shuffling Mediated By Sva 59 Transductionmentioning

confidence: 99%

5′-Transducing SVA retrotransposon groups spread efficiently throughout the human genome

Damert

Raiz²,

Horn³

et al. 2009

Genome Res.

111

184

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SVA elements represent the youngest family of hominid non-LTR retrotransposons, which alter the human genome continuously. They stand out due to their organization as composite repetitive elements. To draw conclusions on the assembly process that led to the current organization of SVA elements and on their transcriptional regulation, we initiated our study by assessing differences in structures of the 116 SVA elements located on human chromosome 19. We classified SVA elements into seven structural variants, including novel variants like 39-truncated elements and elements with 59-flanking sequence transductions. We established a genome-wide inventory of 59-transduced SVA elements encompassing ;8% of all human SVA elements. The diversity of 59 transduction events found indicates transcriptional control of their SVA source elements by a multitude of external cellular promoters in germ cells in the course of their evolution and suggests that SVA elements might be capable of acquiring 59 promoter sequences. Our data indicate that SVA-mediated 59 transduction events involve alternative RNA splicing at cryptic splice sites. We analyzed one remarkably successful human-specific SVA 59 transduction group in detail because it includes at least 32% of all SVA subfamily F members. An ancient retrotransposition event brought an SVA insertion under transcriptional control of the MAST2 gene promoter, giving rise to the primal source element of this group. Members of this group are currently transcribed. Here we show that SVA-mediated 59 transduction events lead to structural diversity of SVA elements and represent a novel source of genomic rearrangements contributing to genomic diversity.

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Section: Exon Shuffling Mediated By Sva 59 Transductionmentioning

confidence: 99%

5′-Transducing SVA retrotransposon groups spread efficiently throughout the human genome

Damert

Raiz²,

Horn³

et al. 2009

Genome Res.

111

184

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“…For the approximate localization of the deleted region, the strategy from Takasu et al [30] was used. In brief, five different fragments in the close proximity of HLA-A, known to be highly polymorphic, were amplified and sequenced.…”

Section: Localization Of Deleted Region Around Hla-a Genementioning

confidence: 99%

Inactivation of a functional HLA-A gene: A 4-kb deletion turns HLA-A*24 into a pseudogene

2010

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“…Analysis of the deletion site identified an SVA insertion, hereafter referred to as SVA HLA-A . Using the SVA HLA-A DNA sequence, we located an SVA insertion on chromosome 3p21.31 as the likely progenitor of the SVA HLA-A insertion (Takasu et al 2007). Further analysis of SVA HLA-A and its progenitor revealed several interesting details.…”

Section: Identification Of Mast2-svamentioning

confidence: 99%

“…To date, experiments to characterize the SVA promoter have led to ambiguous results. Recently, we reexamined an SVA insertion on CH6 associated with a genomic deletion including the entire HLA-A gene that resulted in leukemia in three Japanese individuals (Takasu et al 2007). The HLA-A insertion led to several interesting findings, including the identification of a new SVA subfamily formed by alternative splicing from the first exon of the MAST2 gene on CH1 into an SVA, and the identification of a SVA master element on CH10.…”

mentioning

confidence: 99%

“…SVAs are currently active in the human genome, as indicated by the identification of de novo SVA insertions associated with disease (Hassoun et al 1994;Rohrer et al 1999;Makino et al 2007). SVA disease insertions are associated with exon-skipping (Hassoun et al 1994;Rohrer et al 1999), deletion of genomic DNA (Takasu et al 2007), and reduced or absent mRNA expression (Kobayashi et al 1998;Wilund et al 2002;Makino et al 2007). In a manner similar to L1, SVAs have been shown to transduce 39 flanking sequences to new genomic locations (Moran et al 1999;Ostertag et al 2003;Xing et al 2006).…”

mentioning

confidence: 99%

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Exon-trapping mediated by the human retrotransposon SVA

Hancks¹,

Ewing²,

Chen³

et al. 2009

Genome Res.

104

138

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Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genomes. After molecular and computational experiments, we found a number of functional 39 splice sites within many different transcribed SVAs across the human and chimpanzee genomes. Using a minigene splicing construct containing an SVA, we observed splicing in cell culture, along with SVA exonization events that introduced premature termination codons (PTCs). These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species.[Supplemental material is available online at http://www.genome.org. The 59 RACE sequence data from this study have been submitted to dbEST (http://www.ncbi.nlm.nih.gov/dbEST) under accession nos. Most eukaryotic genomes harbor retrotransposable elements (Malik et al. 1999). About 35% of the human genome is derived from retrotransposed sequences such as LINE-1, Alu, SVA, endogenous retroviruses, and processed pseudogenes (Lander et al. 2001). Although most human retroelement copies are no longer mobile, both active and inactive human elements have been shown to drive genome evolution and influence gene expression (Moran et al. 1999;Han et al. 2004; for reviews, see Belancio et al. 2008;Goodier and Kazazian 2008).SVA RNAs are hominid-specific noncoding RNAs, which vary in size from 700-4000 bp, and are likely mobilized by the human LINE-1 in trans (Ono et al. 1987;Shen et al. 1994;Ostertag et al. 2003;Wang et al. 2005), similar to the human Alu (Dewannieux et al. 2003). There are roughly 2700 SVA copies in the human genome (Wang et al. 2005). A canonical full-length SVA (Fig. 1A) contains a number of sequence features proceeding from its 59 end: (1) a CCCTCT hexameric repeat, ranging in repeat number from a few to as many as 71; (2) a sequence that shares homology with two antisense Alu fragments; (3) a variable number of tandem repeat sequence (VNTR); and (4) a sequence derived from the ENV gene and right LTR of an extinct HERV-K, hereafter referred to as SINE-R. SVAs typically terminate at their own polyA signal, with genomic insertions usually containing a number of adenines at the 39 end. A target site duplication common to other LINE-1-driven retroelements (6-20 bp) flanks the inserted element (Ostertag et al. 2003).Little is known about the biology of SVA apart from its structure. SVAs are c...

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Deletion of entire HLA‐A gene accompanied by an insertion of a retrotransposon

Cited by 37 publications

References 39 publications

5′-Transducing SVA retrotransposon groups spread efficiently throughout the human genome

5′-Transducing SVA retrotransposon groups spread efficiently throughout the human genome

Inactivation of a functional HLA-A gene: A 4-kb deletion turns HLA-A*24 into a pseudogene

Exon-trapping mediated by the human retrotransposon SVA

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