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 1,297 records · Page 72Linked to original sources
PubMed2000

Genomic and transcriptional characterization of the human ACHE locus: complex involvement with acquired and inherited diseases.

BACKGROUND: Abnormal levels of the acetylcholinesterase enzyme or aberrations involving the long arm of chromosome 7, harboring the ACHE gene at 7q22, occur in various diseases such as Alzheimer's, Parkinson's, and leukemias. However, the cause(s) of these abnormalities are still unknown. OBJECTIVE: To search for the genomic elements and transcriptional processes controlling ACHE gene expression and the plausible stability of its locus, by isolating, sequencing and characterizing the human (h)ACHE locus and its mRNA products. METHODS: Three clones containing the ACHE gene were isolated from a human chromosome 7 cosmid library. Two of these clones were thereafter sequenced and searched for repetitive elements, open reading frames and corresponding expressed sequence tags. Reverse transcription-polymerase chain reaction was employed to further explore these findings. RESULTS: The locus harboring the G,C-rich ACHE gene was found to be exceptionally rich in Alu repeats. It includes an additional, inversely oriented gene (ARS), tentatively associated with arsenite resistance. EST clones corresponding to both genes were found in cDNA libraries from 11 different human tissue sources, with ARS expressed in 10 additional tissues. Co-regulation of brain ACHE and ARS was suggested from their mutually increased expression following acute psychological stress. CONCLUSIONS: The abundance of Alu retrotransposones may predispose the ACHE locus to chromosomal rearrangements. Additionally, coordinated transcriptional regulation is implied from the joint ARS-AChE expression in stress insult responses. Disease-related changes in AChE may therefore reflect locus-specific regulation mechanisms affecting multiple tissues.

Acetylcholinesterase↗
PubMed2003

A patchwork interspersed sequence is present in a high copy number in the sheep genome.

We have isolated a new interspersed sequence present in a high copy number in the ovine genome. This patchwork sequence, named 3.79 AS1, is part of a larger element encompassing similarities to constant region of reverse transcriptase and to art2 shared with the Bovine Dimer Driven Family (BDDF). The 3.79 AS1 sequence includes homologies to amplification promoting sequences (APS), to a potential origin of bidirectional DNA replication (OBR), to the Alu core sequence motif GGAGGC required for RNA polymerase III promoter function and to the ATGGCTGCCAT sequence that has been shown to be able to induce amplification-dependent transformation in murine cells. Fluorescent in situ hybridization experiments using probes derived from both ends of the 3.79 AS1 sequence showed a widespread signal over all sheep chromosomes, except the Y chromosome. We propose that the structural features of the 3.79 AS1 patchwork sequence, that is likely to be a subfamily of Bov B LINE that invaded the Artiodactyl genome prior to the separation of the Bovidae species, facilitated its massive amplification and dispersion in the ovine genome.

Animals↗
PubMed1996

Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.

Over 100 distinct disease-associated mutations have been identified in the breast-ovarian cancer susceptibility gene BRCA1. Loss of the wild-type allele in > 90% of tumors from patients with inherited BRCA1 mutations indicates tumor suppressive function. The low incidence of somatic mutations suggests that BRCA1 inactivation in sporadic tumors occurs by alternative mechanisms, such as interstitial chromosomal deletion or reduced transcription. To identify possible features of the BRCA1 genomic region that may contribute to chromosomal instability as well as potential transcriptional regulatory elements, a 117,143-bp DNA sequence encompassing BRCA1 was obtained by random sequencing of four cosmids identified from a human chromosome 17 specific library. The 24 exons of BRCA1 span an 81-kb region that has an unusually high density of Alu repetitive DNA (41.5%), but relatively low density (4.8%) of other repetitive sequences. BRCA1 intron lengths range in size from 403 bp to 9.2 kb and contain the intragenic microsatellite markers D17S1323, D17S1322, and D17S855, which localize to introns 12, 19, and 20, respectively. In addition to BRCA1, the contig contains two complete genes: Rho7, a member of the rho family of GTP binding proteins, and VAT1, an abundant membrane protein of cholinergic synaptic vesicles. Partial sequences of the 1A1-3B B-box protein pseudogene and IFP 35, an interferon induced leucine zipper protein, reside within the contig. An L21 ribosomal protein pseudogene is embedded in BRCA1 intron 13. The order of genes on the chromosome is: centromere-1FP 35-VAT1-Rho7-BRCA1-1A1-3B-telomere.

Breast Neoplasms↗
PubMed1990

A transpositionally and transcriptionally competent Alu subfamily.

DNA base sequence comparisons indicate that a subfamily of recently transposed human Alu repeats are distinguished from most Alu repeats by diagnostic sequence differences. Using an oligonucleotide hybridization probe that incorporates these sequence features, we found that there was an expansion of this Alu subfamily following the divergence of humans and African apes. This oligonucleotide was used to select human genomic clones containing representatives of this subfamily. One representative member of this subfamily was evidently absent from the corresponding chimpanzee locus and was associated with a restriction fragment length polymorphism in the human genome. This apparently polymorphic member had all the diagnostic sequence features that initially predicted the existence of a newly expanding Alu subfamily. A transpositionally active sequence variant should also be transcriptionally active in at least some cell types or tissues. Northern (RNA) blot hybridization, primer extension, and RNA sequence analysis demonstrated the existence of different-length polyadenylated and nonpolyadenylated transcripts corresponding to this subfamily. Evidence for 3' processing and subcellular localization of these transcripts is discussed. Most of the nearly one million human Alu repeats are pseudogenes with respect to coding for either an RNA product or new family members; a select and identifiable subset of Alu repeats serve as transcriptionally and transpositionally competent source genes.

Base Sequence↗
PubMed1994

Amplification of distinct subfamilies of short interspersed elements during evolution of the Salmonidae.

There are at least three different kinds of short interspersed repetitive elements in salmonid genomes. Of these, members of the HpaI family are found to be most widely distributed in salmonid species. The HpaI family is present with high copy numbers in all members of the subfamily Salmoninae, such as salmon, trout and charr. In order to determine whether the amplification of the Hpa sequence occurred rapidly within a short evolutionary period or gradually, over the long term, a search was made for Hpa sequences in primitive salmonids; namely, grayling and whitefish. A grayling species has fivefold fewer copies of these sequences than the Salmoninae species, whereas several whitefish species have 200-fold to 20-fold fewer copies than the Salmoniae species. Characterization of the Hpa sequences in these species allowed us to recognize two distinct Hpa subfamilies on the basis of diagnostic substitutions as well as a new short interspersed element with an Hpa-related sequence. The distribution of these sequences revealed that distinct members of the HpaI or Hpa-related family were amplified during establishment of each subfamily lineage in a manner very similar to the amplification of the human Alu family. We provide evidence for the validity of a model that involves "multiple source genes" to explain diagnostic substitutions of the Hpa subfamilies and the timing of their appearance during evolution.

Animals↗
PubMed1998

Identification of scaffold/matrix attachment region in recurrent site of woodchuck hepatitis virus integration.

Scaffold or matrix attachment regions (S/MARs) are noncoding genomic DNA sequences displaying in vitro selective binding affinity for nuclear scaffold. They have been reported to be involved in the physical attachment of genomic DNA to the nuclear scaffold, and thus in the organization of the chromatin in functional loops or domains, and in the regulation of gene expression. In this work, we report the identification of an S/MAR in a woodchuck chromosomal locus, named b3n, previously described as a recurrent site of woodchuck hepatitis virus (WHV) DNA integration in woodchuck hepatocellular carcinoma (HCC). The 4.3-kb sequence of this locus contains several Alu-like repeats and a gag-like coding region with frameshift mutations. Computer analysis revealed the presence of a region with unusually high AT content, typical of most S/MARs, and of specific motifs (A boxes, T boxes, topoisomerase II sites, and unwinding elements) overlapping or in proximity to the region with high AT content, predicting that b3n might contain an S/MAR. Fragments of the b3n locus were isolated by conventional and inverse PCR techniques. In in vitro binding experiments with both heterologous and autologous scaffold preparations, a 592-bp fragment spanning the region rich in S/MAR features showed marked scaffold affinity, which was specific when autologous scaffolds were used. The presence of an S/MAR at the b3n locus and its nature as a recurrent WHV integration site in HCC suggest the involvement of S/MAR elements in some of the mechanisms leading to liver oncogenesis.

Amino Acid Sequence↗
PubMed1984

Ruminant globin gene structures suggest an evolutionary role for Alu-type repeats.

Bovine fetal and adult globin genes were cloned and subjected to DNA sequence analysis. Both of these genes contained insertions of Alu-type repetitive DNA within their introns. Comparison of cow and goat beta-type globin genes indicates that intragenic DNA insertions played a role in their evolution. These data support the theory that Alu-type repeats maintain genetic diversity by inhibiting gene conversion.

Amino Acid Sequence↗
PubMed2004

Coding sequences of functioning human genes derived entirely from mobile element sequences.

Among all of the many examples of mobile elements or "parasitic sequences" that affect the function of the human genome, this paper describes several examples of functioning genes whose sequences have been almost completely derived from mobile elements. There are many examples where the synthetic coding sequences of observed mRNA sequences are made up of mobile element sequences, to an extent of 80% or more of the length of the coding sequences. In the examples described here, the genes have named functions, and some of these functions have been studied. It appears that each of the functioning genes was originally formed from mobile elements and that in some process of molecular evolution a coding sequence was derived that could be translated into a protein that is of some importance to human biology. In one case (AD7C), the coding sequence is 99% made up of a cluster of Alu sequences. In another example, the gene BNIP3 coding sequence is 97% made up of sequences from an apparent human endogenous retrovirus. The Syncytin gene coding sequence appears to be made from an endogenous retrovirus envelope gene.

Genome, Human↗
PubMed1983

Genomic organization of rat rDNA.

A detailed restriction map was determined for a 10.9 KB region that contains the initiation site for 45S pre-rRNA and the first 1.7 KB of the 18S rRNA coding region. When the restriction pattern of the cloned rDNA was compared with that of total rat DNA, the rDNA regions of both Sprague-Dawley and BD-9 rats were identical to each other and to that of the cloned rDNA. However, both strains exhibit a major polymorphism consisting of an insertion of 0.9 KB of DNA in the nontranscribed spacer between 0.29 KB and 1.8 KB upstream from the 45S RNA initiation site. This region consists of tandem repeats approximately 130 base pairs in length. These repeats contain large poly T tracts and are similar in sequence to analogous elements 5' to the origin of mouse rRNA transcription. Regions containing highly repetitious DNA sequences were located at sites 2.8 KB and 4.3 KB upstream from the initiation site. The repetitive sequence at 2.8 KB from the initiation site anneal to a known Alu-equivalent type 2 sequence derived from the second intron of the rat growth hormone gene.

Animals↗
PubMed1990

Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus to deleterious rearrangements.

Frequent alterations in the structure of the complement component C1 inhibitor gene have been found in patients affected by the common variant of hereditary angioedema, characterized by low plasma levels of C1 inhibitor. This control protein limits the enzymic activity of the first component of complement and of other plasma serine proteases. Sequence comparisons of a 4.6-kilobase-long segment of the normal gene and the corresponding gene segments isolated from two patients carrying family-specific DNA deletions point to unusually long clusters of tandem repeats of the Alu sequence family as a source of genetic instability in this locus. Unequal crossovers, in a variety of registers, among Alu sequences of the clusters result in deletions of variable length that encompass exon 4. In a third family, exon 4 was instead found to be duplicated along with the same tracts of flanking introns lost in one of the deletions. In addition to undergoing Alu-mediated partial deletions and duplications, the gene is also a target for more recent retroposition events. Gross alterations in the C1 inhibitor gene account for about 20% of the hereditary angioedema chromosomes and consequently make this gene a prime example of the mutagenic liability of Alu repeats.

Amino Acid Sequence↗
PubMed1994

DNA sequences tightly bound to proteins in mouse chromatin: identification of murine MER sequences.

The finding of stably (tightly) associated DNA-protein complexes in eukaryotic chromatin has provoked many hypotheses and speculations concerning their possible role. While the answer of this question is not envisaged yet, it is clear that elucidation of the nature of the individual components involved in such complexes is a necessary step in this direction. Here, the nature of several mouse DNA sequences in the vicinity of a putative stably attached protein is studied. Eight independently isolated clones containing such sequences were compared to known sequences in GenBank. Two clones were found to belong to different subfamilies of repetitive sequences, organized into a larger family--the L1md family. One clone harbors a sequence that is a member of the Alu-type family. Four of the cloned sequences are preset in low copy numbers, but the computer search found similar sequences in various genomic regions of different rodents. These facts, together with the finding that regions homologous to the above clones often flank other repetitive elements in the genome, suggest that the cloned sequences belong to new, not yet described families of repeats in the murine genome. It is possible that they correspond to the medium reiteration frequency sequences, MER-sequences, discovered recently in the human genome (Jurka, 1990; Kaplan and Duncan, 1990). Particularly intriguing is the homology found at the integration sites of polyoma virus in two transformed cell lines with two of these clones.

Animals↗
PubMedDate not supplied

[The coevolutionary aspects of the genome and mobile elements].

Under investigation is congruent variation of movable elements, the "genome parasites" (GP), and genome proper, as the "host". Several differential equations are studied that describe the following situations. 1. GP is able to insert in free sites only, existing in autonomous stage (outside of the genome) limited time only. 2. GP inserts in free sites only, being able to exist autonomously relatively long time. 3. GP inserts in both free and occupied sites ("molecular memory"), existing autonomously relatively short time, its prototype being Alu-like repetitions in mammals. 4. GP inserts in both free and occupied sites, and is able to live autonomously, its prototype being retrovirus. In is presumed that the genome is tolerant to "selfish" breeding of GP as long as proportion of invaded sites does not exceed some critical value. It is shown that co-evolutionary complication of GP--from the simplest one that is able to insert in free sites only, through acquiring terminal repetitions ("molecular memory"), up to complicated entities existing outside of genome--accompanied by alteration of selective co-evolutionary limitations on genome size: limitations from above--no limitations--limitations from below. Thus, genetical movable elements can be considered as intrinsic factor of progressive, co-evolutionary stipulated complication of the genome.

Animals↗
PubMed1984

Nature and origin of the RNA associated with simian virus 40 large tumor antigen.

Simian virus 40 (SV40) large tumor (T) antigen isolated from mammalian cells undergoing lytic or transforming infection is associated with small RNA fragments ("T-antigen RNA") that are protected from nuclease digestion. The rather high complexity of the ribonuclease T1 fingerprints of T-antigen RNA suggested that it is mainly derived from cellular heterogeneous nuclear RNAs. In the present study, 5'-32P-labeled T-antigen RNA was hybridized to monkey, mouse, and human Alu and SV40 DNA, and the nucleotide sequence of 37 T1 oligonucleotides was determined. The results suggest that the bulk of T-antigen RNA is derived from noncoding, double-stranded, ordered regions of cellular heterogeneous nuclear RNAs that exhibit sequence homologies with interspersed repetitive elements of the cellular genome. The possible biological implications of these results are discussed.

Animals↗
PubMed1993

Dual Alu polymerase chain reaction primers and conditions for isolation of human chromosome painting probes from hybrid cells.

A method for rapid and efficient production of chromosome- and chromosome-region specific probes for fluorescent in situ hybridization (FISH) detectable by simple fluorescent microscopy is described. The procedure is based on simultaneous use of two inter-Alu-polymerase chain reaction (PCR) primers for extraction of highly heterogeneous human DNA from interspecific somatic cell hybrids containing the chromosome regions of interest. Probes so produced do not hybridize to centromeric sequences and simultaneously band the target chromosomes, making them useful for unambiguous identification of chromosomal elements and breakpoints associated with cancer.

Animals↗
PubMed1995

MIRs are classic, tRNA-derived SINEs that amplified before the mammalian radiation.

Short Interspersed Nucleotide Elements (SINEs) are highly abundant in mammalian genomes. The term SINE has come to be restricted to short retroposons with internal RNA polymerase III promoter sites in a region derived from a structural RNA (usually a tRNA). Here we describe a novel, 260 bp tRNA-derived SINE, some fragments of which have been noted before to be repetitive in mammalian DNA. Unlike previously reported SINEs, which are restricted to closely related species, copies of this element can be found in all mammalian genomes, including marsupials. It is therefore called MIR for mammalian-wide interspersed repeat. Their high divergence and their presence at orthologous sites in different mammals indicate that MIRs, at least in part, amplified before the mammalian radiation. Next to Alu, MIRs are the most common interspersed repeat in primates with an estimated 300,000 copies still discernible, which account for 1 to 2% of our DNA. Interestingly, a small, central region of MIR appears to be much better conserved in the genomic copies than the rest of the sequence.

Animals↗
PubMed1992

Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a result of an Alu insertion/deletion event.

Polymerase chain reaction and direct sequencing were used to investigate an amplified DNA fragment containing the suspected polymorphic site of all known intragenic restriction fragment length polymorphisms (RFLPs) within the human tissue-type plasminogen activator (TPA) gene. Sequence data obtained showed that these RFLPs were all generated by the presence or absence of one of the two Alu sequences located in intron h of the human TPA gene. Furthermore, one of the direct repeats flanking this Alu sequence was absent in the minor allele. In addition to indicating the presence of an Alu insertion in an ancestral human TPA gene, these findings suggest a slip-replication mechanism for the deletion of this Alu repeat, once inserted into the gene. As both alleles have been observed in similar frequencies among different ethnic groups, the insertion or subsequent deletion of this Alu sequence in the human TPA gene must have occurred early in human evolution.

Alleles↗
PubMed1995

Sequence analysis of the 5.34-kb 5' flanking region of the human rhodopsin-encoding gene.

In order to define elements which may be involved in regulating human rhodopsin expression, we have isolated and sequenced a clone containing 5.34 kb of the 5'-upstream region of the human rhodopsin-encoding gene. The 5.34-kb human segment contains multiple potential transcription factor-binding sites and a subfamily of Alu repeats. The same subfamily of Alu repeats is found 5.8 kb upstream from the human red/green visual pigment-encoding gene.

Animals↗
PubMed1986

Chromosome-specific subfamilies within human alphoid repetitive DNA.

Nucleotide sequence data of about 20 X 10(3) base-pairs of the human tandemly repeated alphoid DNA are presented. The DNA sequences were determined from 45 clones containing EcoRI fragments of alphoid DNA isolated from total genomic DNA. Thirty of the clones contained a complete 340 base-pair dimer unit of the repeat. The remaining clones contained alphoid DNA with fragment lengths of 311, 296, 232, 170 and 108 base-pairs. The sequences obtained were compared with an average alphoid DNA sequence determined by Wu & Manuelidis (1980). The divergences ranged from 0.6 to 24.6% nucleotide changes for the first monomer and from 0 to 17.8% for the second monomer of the repeat. On the basis of identical nucleotide changes at corresponding positions, the individual repeat units could be shown to belong to one of several distinct subfamilies. The number of nucleotide changes defining a subfamily generally constitutes the majority of nucleotide changes found in a member of that subfamily. From an evaluation of the proportion of the total amount of alphoid DNA, which is represented by the clones studied, it is estimated that the number of subfamilies of this repeat may be equal to or exceed the number of chromosomes. The expected presence of only one or a few distinct subfamilies on individual chromosomes is supported by the study, also presented, of the nucleotide sequence of 17 cloned fragments of alphoid repetitive DNA from chromosome 7. These chromosome-specific repeats all contain the characteristic pattern of 36 common nucleotide changes that defines one of the subfamilies described. A unique restriction endonuclease (NlaIII) cleavage site present in this subfamily may be useful as a genetic marker of this chromosome. A family member of the interspersed Alu repetitive DNA was also isolated and sequenced. This Alu repeat has been inserted into the human alphoid repetitive DNA, in the same way as the insertion of an Alu repeat into the African green monkey alphoid DNA.

Base Sequence↗