Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Alu elements”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1982

Human 7SL RNA consists of a 140 nucleotide middle-repetitive sequence inserted in an alu sequence.

We have cloned and sequenced a cDNA copy of in vitro-polyadenylated 7SL RNA of HeLa cells. The cloned fragment is 303 bp long and has a composite structure. A central block of 140 bp is homologous to a new set of human middle-repetitive sequences. This block appears to be inserted in an Alu consensus sequence, 100 bp from the 5' end and 40 bp from the 3' end of the Alu monomer. Two 6 bp direct repeats are found at the junction between the Alu flanking sequences and the central element. The analysis of several clones shows the existence of sequence microheterogeneity in the 5' portion of the molecule. The 7L DNA probably represents a subset of the Alu family of DNA, highly conserved in evolution.

Base Sequence↗
PubMed2005

Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage.

Although gross insertions (>20 bp) comprise <1% of disease-causing mutations, they nevertheless represent an important category of pathological lesion. In an attempt to study these insertions in a systematic way, 158 gross insertions ranging in size between 21 bp and approximately 10 kb were identified using the Human Gene Mutation Database (www.hgmd.org). A careful meta-analytical study revealed extensive diversity in terms of the nature of the inserted DNA sequence and has provided new insights into the underlying mutational mechanisms. Some 70% of gross insertions were found to represent sequence duplications of different types (tandem, partial tandem, or complex). Although most of the tandem duplications were explicable by simple replication slippage, the three complex duplications appear to result from multiple slippage events. Some 11% of gross insertions were attributable to nonpolyglutamine repeat expansions (including octapeptide repeat expansions in the prion protein gene [PRNP] and polyalanine tract expansions) and evidence is presented to support the contention that these mutations are also caused by replication slippage rather than by unequal crossing over. Some 17% of gross insertions, all >or=276 bp in length, were found to be due to LINE-1 (L1) retrotransposition involving different types of element (L1 trans-driven Alu, L1 direct, and L1 trans-driven SVA). A second example of pathological mitochondrial-nuclear sequence transfer was identified in the USH1C gene but appears to arise via a novel mechanism, trans-replication slippage. Finally, evidence for another novel mechanism of human genetic disease, involving the possible capture of DNA oligonucleotides, is presented in the context of a 26-bp insertion into the ERCC6 gene.

Base Sequence↗
PubMed1992

Phylogenetic evidence for multiple Alu source genes.

A member of the young PV Alu subfamily is detected in chimpanzee DNA showing that the PV subfamily is not specific to human DNA. This particular Alu is absent from the orthologous loci in both human and gorilla DNAs, indicating that PV subfamily members transposed within the chimpanzee lineage following the divergence of chimpanzee from both gorilla and human. These findings and previous reports describing the transpositional activity of other Alu sequences within the human, gorilla, and chimpanzee lineages provide phylogenetic evidence for the existence of multiple Alu source genes. Sequences surrounding this particular Alu resemble known transcriptional control elements associated with RNA polymerase III, suggesting a mechanism by which cis-acting elements might be acquired upon retrotransposition.

Animals↗
PubMed1987

Recent insertion of an Alu sequence in the beta-globin gene cluster of the gorilla.

We present the nucleotide sequence of a new Alu family member that lies between the delta- and beta-globin genes in gorilla DNA. The sequence exhibits 91% similarity with a consensus sequence of the Alu family. It is flanked by a perfect repetition of a 16-nucleotide target sequence and terminates with 24 adenylic residues. As this sequence is absent at this locus in other primate DNAs, its insertion occurred less than 8 million years ago, thus supporting the idea that Alu sequences are still mobile elements in the hominoid genome.

Animals↗
PubMed1989

DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase.

Mitochondrial ADP/ATP translocase is an abundant component of the inner membrane. It carries ATP from the matrix into the intermembrane space and transports ADP back. Clones coding for two different but related forms of the protein have been characterized from bovine cDNA libraries. The corresponding genes are referred to as T1 and T2 and they are expressed at different levels in bovine tissues. The bovine cDNAs have been used to isolate clones from a human genomic library that contain the human T1 and T2 genes. Two nucleotide sequences of 9756 and 8625 base-pairs have been determined and they contain the transcribed regions of the human T1 and T2 genes which cover 4.2 and 5.9 kb of the human genome, respectively (1 kb = 10(3) base-pairs). Both genes are split into four exons. The introns in each gene are at exactly equivalent locations and interrupt sequences coding for segments of the protein that are thought to be extramembranous loops linking transmembrane segments. The proteins encoded in the genes differ in 32 amino acids out of 297, and in common with other ADP/ATP translocases, neither has a processed mitochondrial import sequence. The human T1 and T2 genes are members of a larger gene family that includes a third expressed gene T3 and also at least two spliced pseudogenes. Other studies have shown that T3 is expressed in liver and HeLa cells, and different levels of transcripts of T1 have been found in various tissues. A notable feature of the T1 and T2 genes, that may influence their expression, is that "CpG-rich islands" are associated with their 5' ends. That of the T2 gene contains numerous potential sites for binding the mammalian transcription factor SP1, but no TATA or CCAAT sequences are evident near to its 5' end, although these latter features are associated with the human T1 gene. The two DNA sequence also contain many short interspersed repetitive sequences including 11 Alu repeats, and a novel element about 236 base-pairs in length, which is repeated in a six-fold tandem array in intron B of the T2 gene.

Amino Acid Sequence↗
PubMed1997

The geographic distribution of human Y chromosome variation.

We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or "YAP" element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five "YAP haplotypes" in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 "combination haplotypes". All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.

Gene Frequency↗
PubMed1995

Characterization of the large deletion in the GALC gene found in patients with Krabbe disease.

Globoid cell leukodystrophy (GLD) of Krabbe disease results from mutations in the galactocerebrosidase (GALC) gene. Previously, we had identified a large deletion in the GALC gene together with a C to T polymorphism at cDNA position 502 in a significant number of cases of infantile Krabbe disease; however, the deletion breakpoint had not been found. In this paper we show that the deletion is approximately 30 kb starting near the middle of the 12 kb intron 10, and includes all of the coding region through exon 17 plus an additional 9 kb. The deletion junction contains a 4 bp direct repeat and is preceded by sequence identified as belonging to the Alu family of interspersed repetitive elements. Using genomic DNA and a PCR-based test to detect normal and deleted sequences at that location, a large number of patients with all clinical types of GLD were analyzed. Of 21 infantile patients found to be heterozygous for the 502T polymorphism reported previously, 15 had the deletion, one could not tested and five, including a Hmong child, did not have the deletion. Sixteen other infantile patients previously tested were found to be either homozygous (10) or heterozygous (6) for the deletion. In addition, five patients with juvenile and adult GLD were found to be heterozygous for the deletion. In every case tested, the deletion was always found on the same allele as the 502T polymorphism. However, other disease-causing mutations have been found on the 502T allele. With careful genotype analysis these families can receive improved genetic information including patient and carrier identification and preimplantation diagnosis.

Animals↗
PubMed1995

Isolation and characterization of radiation hybrids for human chromosome 12.

We have used an irradiation and fusion procedure to generate somatic cell hybrids that maintain fragments of human chromosome 12. To identify hybrids retaining human material we performed repeat element-mediated PCR (intra-ALU PCR) on DNA extracted from individual cell clones. Twenty-five of 38 hybrids tested were shown to contain human material at low passage. These were further characterized by inter-ALU and inter-LI PCR. FISH analysis, using human Cot1 DNA as a probe, revealed the presence of 1-2 fragments in 11 out of 12 hybrids. The majority of the hybrids, 8 out of 12, were found to be homogeneous. The hybrid panel was characterized by 18 markers with known locations covering the entire chromosome 12. Thirteen of the 25 hybrids were positive for at least one marker. The results indicated the following order of loci on 12q: Cen-WNTI-A2MR-RAP1B-D12S8-PTBR-ATP2B1++ +-D12S7-D12S52-IGF1-PAH-PLA2-IFNG-ALDH2-te r. Three hybrids studied in more detail were found to carry overlapping fragments from chromosome segment 12q12-->q14.

Animals↗
PubMed1995

The structure of the bovine cathepsin B gene. Genetic variability in the 3' untranslated region.

Cathepsin B is a cysteine proteinase which plays an important role in lysosomal proteolysis. We report here the characterization of a 15-kbp genomic clone of the bovine cathepsin B gene. Bovine preprocathepsin B is encoded by nine exons from translational initiation to stop codon. The last exon is sandwiched between Alu-like short interspersed nuclear elements. Alternate use of polyadenylation sites generates three transcripts encoding bovine cathepsin B. In all tissues tested, 3' end cleavage was found to occur in equal proportion at the first and second polyadenylation site, producing transcripts of 2.6-kb. Polyadenylation at the third polyadenylation site generates a 3.2-kb mRNA, only expressed at low levels and in a developmental and tissue-specific manner. Due to micro-heterogeneities between genomic and cDNA clones, sequence polymorphism was investigated in the trailer region. DNA sequencing of PCR-amplified genomic fragments revealed that, in contrast to the protein-encoding region, genetic variability exists in the 3' untranslated region. Polymorphism in the trailer was confirmed in cathepsin B mRNA by ribonuclease-protection assays. We finally emphasize that while exon-exon boundaries in mature cathepsin B are well conserved from nematodes to mammals, exons also tend to correspond to discrete units of cathepsin B structure.

Amino Acid Sequence↗
PubMed2000

Upstream flanking sequences and transcription of SINEs.

SINEs, short interspersed repeated DNA elements, undergo amplification through retroposition and subsequent integration into a new location in the genome. Each new SINE insertion will be located in a new chromosomal environment, with different flanking sequences. Modulation of transcription by different flanking sequences may play an important role in determining which SINE elements are preferentially active in a genome. We evaluated the ability of upstream flanking sequences to regulate the transcription of three different SINEs (Alu, B2 and ID) by constructing chimeric constructs with known 5' flanking sequences of RNA polymerase III-transcribed genes. Upstream sequences from the 7SL RNA gene, U6 RNA gene, vault RNA gene, and BC1 gene increase transcription of Alu, B2 and BC1 in transient transfections of NIH3T3, HeLa, Neuro2a and C6 glioma cell lines. The 7SL sequence proved most efficient in increasing SINE transcription. The 7SL upstream fused to the BC1 RNA gene (an ID element) was used to create a transgenic mouse line. In contrast to the tissue-specific endogenous BC1 transcription, BC1 transgene transcripts were detected in all tissues tested. However, expression was much higher in those tissues that express the endogenous gene, demonstrating both transcriptional and post-transcriptional regulation. The BC1 RNA was detected in a similar ribonucleoprotein complex in the different tissues.

Alu Elements↗
PubMed1993

Structural organization of the 5' flanking region of the human corticotropin releasing hormone gene.

We have determined the nucleotide sequence of the proximal 3625 nucleotides 5' flanking the major mRNA start site of the human corticotropin releasing hormone gene (hCRH) and identified several putative regulatory elements. Interestingly, we did not detect any glucocorticoid responsive elements; we did however find five interspersed perfect half palindromic estrogen responsive elements, which might confer estrogen regulatability to the hCRH gene. We have identified a segment spanning from -2835 to -2972, which has about 72% homology to the 3' terminal half of the human Alu I family of highly repetitive elements, and another one, which spans from -2213 to -2580 and has greater than 80% homology to members of human type O family of repetitive elements. These elements may confer DNA fragility, since the loci for hCRH and the human fragile site FRA8F colocalize in human chromosome 8. The structural information reported represents a first step in the study of regulation of the hCRH gene at the molecular level.

Base Sequence↗
PubMed1997

[Nonhistone chromosome proteins HMG1 and HMG2 stabilize one of the sequence-specific complexes, formed on the promotor of human retroposons of the ALU-family of other nuclear proteins].

Human retroposons of the Alu family have an internal promoter for RNA polymerase III also present in tRNA genes, but Alu are poorly transcribed by this polymerase in somatic cells in vivo, which is probably due to an efficient system of repression of the Alu transcription. The key control promoter element of the tRNA genes, known as B-box, binds basal transcription factor TFIIIC2, which initiates assembly of the full transcription complex. Previously we identified several human nuclear factors which bind to Alu Subregion covering B-box and the adjacent sequences, which can be involved in repression of Alu transcription. In this study we identified one factor, F1, as HMF1/2 and another factor, F2, as TFIIIC2-like protein reacting with B-box. Both the factors are not alu-specific, whereas the third identified Alu-binding factor, F3, seems to be specific for the Alu-specific subsequence located just downstream from B-box and can discriminate evolutionary "young" and "old" Alu subfamilies producing different numbers of transcripts in vivo. Although HMG1/2 binds to Alu in a sequence-unspecific manner, the proteins are capable of stabilizing the sequence-specific complex F3 which can be functionally significant. We believe that the factors binding to Alu B-box subregion interfere somehow with the functions of the basal factor TFIIIC2 and, hence, can be co-repressors of Alu transcription by RNA polymerase III.

DNA-Binding Proteins↗
PubMed1999

Application of Alu-splice PCR on chromosome 21: DSCR1 and Intersectin.

Down syndrome (DS) is a major cause of mental retardation and congenital heart defects, with an overall incidence of one in 700 live births. DS is caused by increases in the amounts of a number of normal gene products, the exact number and identity of which are presently unknown. Elucidating the molecular basis of DS relies on the identification of the gene products whose augmentation by 50% or more causes symptoms of the disease. With the aim of contributing to the transcriptional map of human chromosome 21 and to identify new genes with potential involvement in DS, we developed a technique to isolate expressed sequences called Alu-splice PCR, which is very simple to perform and is independent of gene expression patterns. Putative exons are PCR amplified in genomic DNA by virtue of their proximity to Alu repeats using primers designed from splice-site consensus sequences in combination with specific Alu repeat primers. The Alu repeats, which are repetitive DNA elements found exclusively and at high frequency in the genomes of primates, impart the human specificity to the method. The splice-site consensus sequences were used to direct primers to exon boundaries. Using the Alu-splice technique, we have identified at least three new genes. We trapped an exon of DSCR1 (Down Syndrome Candidate Region 1) and two different exons of a gene called human Intersectin (ITSN). Presently, we are working with another novel trapped exon to identify the corresponding gene. The major advantage of Alu-splice PCR is that the technique can be readily established in any laboratory which has the basic facilities for molecular biology because no specialised materials or expertise is required.

Adaptor Proteins, Vesicular Transport↗
PubMed1996

p53 inhibits RNA polymerase III-directed transcription in a promoter-dependent manner.

Wild-type p53 represses Alu template activity in vitro and in vivo. However, upstream activating sequence elements from both the 7SL RNA gene and an Alu source gene relieve p53-mediated repression. p53 also represses the template activity of the U6 RNA gene both in vitro and in vivo but has no effect on in vitro transcription of genes encoding 5S RNA, 7SL RNA, adenovirus VAI RNA, and tRNA. The N-terminal activation domain of p53, which binds TATA-binding protein (TBP), is sufficient for repressing Alu transcription in vitro, and mutation of positions 22 and 23 in this region impairs p53-mediated repression of an Alu template both in vitro and in vivo. p53's N-terminal domain binds TFIIIB, presumably through its known interaction with TBP, and mutation of positions 22 and 23 interferes with TFIIIB binding. These results extend p53's transcriptional role to RNA polymerase III-directed templates and identify an additional level of Alu transcriptional regulation.

Animals↗
PubMed2001

Genomic organization and chromosomal distribution of rat ID elements.

Identifier (ID) elements are members of a family of short interspersed nuclear elements (SINEs) in rodents. We investigated the genomic organization and chromosomal distribution of the ID elements in the rat, mouse and Chinese hamster. Southern blot hybridization analysis revealed that the ID elements are widespread in the rat genome, but concentrated in the mouse and Chinese hamster genomes, and that the copy of ID elements in the rat is about 5 times and 50 times that in the mouse and Chinese hamster, respectively. FISH analysis showed that the ID elements are predominantly distributed in the R-band regions of rat chromosomes. In mouse and Chinese hamster chromosomes, no specific distribution pattern of the ID elements was found. Furthermore, we found a distinct group of derivative ID elements in the rat, which contain partially repeated ID core domains, by PCR amplification using an ID core sequence. Such derivatives were not found in either the mouse or Chinese hamster. These findings suggest that explosive amplification of the ID elements in the rat has been accompanied by the occurrence of derivative ID elements and a predominant localization to the R-band regions. Similar associations found in the Alu family, one of the human SINEs, allow us to speculate that the rat ID elements and the human Alu family have analogous functions in chromosomal organization.

Animals↗
PubMed1988

Repetitive nucleotide sequence insertions into a novel calmodulin-related gene and its processed pseudogene.

A gene containing a transposon-like human repeat element, called THE 1, has been isolated and characterized. The gene, termed T+, encodes a polypeptide resembling known calcium-binding proteins. The THE 1 element is present in the 3'-untranslated region of its message. The cDNA clone corresponding to the gene's mRNA product led to the identification of this gene. A processed RNA pseudogene related to the authentic gene has also been isolated. In addition to intron processing, this pseudogene differs from the gene in that it contains an interspersed Alu repeat instead of a THE 1 element in the 3'-untranslated region. Thus, we compare a site containing a THE 1 element to an ancestrally related transposon-less target site. The comparison suggests a retroviral-related mechanism of THE 1 insertion. This system is unusual in that the parent gene is associated with three distinct retrotransposition events: the parent gene was converted to a processed RNA pseudogene, an Alu repeat inserted into the pseudogene, and a THE 1 element inserted into the parent gene.

Amino Acid Sequence↗
PubMed1985

Localization and characterization of members of a family of repetitive sequences in the goat beta globin locus.

We have characterized a family of repetitive DNA elements in the beta-globin locus of the goat. These sequences are structurally analogous to the Alu families of repeats of other mammals. Repetitive elements are located both in the intervening sequences and in the intergenic regions of the goat beta-globin locus. Nucleotide sequence analysis of five repetitive elements located within the large intervening sequence of the beta-like globin genes, and four repeats located 5' to the major developmentally regulated beta-globin genes has resulted in the definition of a consensus sequence for this family of repeats.

Animals↗