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At least 289 records · Page 16Linked to original sources
PubMed1996

The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family.

The three human lanosterol 14 alpha-demethylase (CYP51) genes have been mapped to human chromosomes 3, 7, and 13 using a polychromosomal somatic cell hybrid panel. Two of the genes have been cloned from human chromosome 3-specific (CYP51P1) or from human chromosome 13-containing (CYP51P2) cell hybrids. Both were found to be processed pseudogenes, the first reported in the cytochrome P450 (CYP) gene superfamily. The functional CYP51 gene resides on human chromosome 7. CYP51P1 is 96.5% identical to the human CYP51 coding sequence and is not interrupted with introns but has six in-frame stop codons resulting from point mutations. The intronless CYP51P2 gene is 97.2% identical to the CYP51 cDNA coding region. It has a 1-bp insertion leading to a change of reading frame after codon 9 and a stop codon after amino acid 81. In addition, the CYP51P2 sequence is interrupted with a 5' truncated 131-bp LINE-1 element after nucleotide 606. The element belongs to the youngest LINE subfamily Sb and is 98.2% identical to the LINE-1 element expressed in human teratocarcinoma cells. CYP51 processed pseudogenes are the only known examples of the reverse flow of genetic information during evolution of the large (more than 480 genes) CYP superfamily, suggesting expression in the germ line and a housekeeping function of the lanosterol 14 alpha-demethylase gene. CYP51 pseudogenes evolved by two independent reverse transcription events of the human CYP51 mRNA approximately 9.5 MYR (CYP51P2) and approximately 11.7 MYR (CYP51P1) ago and were inactivated soon after the insertion. The truncated L1 element was inserted into CYP51P2 approximately 6 MYR ago.

Amino Acid Sequence↗
PubMed1996

Pseudogenes for the human uracil-DNA glycosylase on chromosomes 14 and 16.

Two clones containing nonfunctional pseudogenes for the human uracil-DNA glycosylase gene have been isolated. The sequences of the two clones that are homologous to the UNG cDNA span 670 and 580 bp, respectively. In the longest of these, a full length Sx type Alu sequence interrupts the homologous sequence. Chromosomal mapping locates the clones to chromosomes 16 and 14. Comparison of the pseudogene sequences to the cDNA sequence indicates that the pseudogenes diverged from the functional gene approximately 31 and 22 million years ago, which is before the point in evolution when great apes and hominides separated.

Base Sequence↗
PubMed2000

A new gene-pseudogene fusion allele due to a recombination in intron 2 of the glucocerebrosidase gene causes Gaucher disease.

Gaucher disease is the most prevalent sphingolipid storage disorder in humans caused by a recessively inherited deficiency of the enzyme glucocerebrosidase. More than 100 mutations have been described in the glucocerebrosidase gene causing Gaucher disease. Some of them are complex alleles with several mutations due to recombination events between the gene and its highly homologous pseudogene. The generation of these recombinant alleles involves, in most cases, a crossover in the 3' end of the gene, beyond exon 8. However, in a few cases recombination took place in a more upstream location. Here we describe the analysis of a patient with type I Gaucher disease who bears a new complex allele. This allele was originated by a crossover between the gene and the pseudogene at intron 2, the most upstream recombination site described so far, which gave rise to a fusion gene. The patient was first diagnosed as homozygous for the c.1226 A --> G (N370S) mutation but the early onset of the disease prompted us to perform parental DNA analysis which showed that the mother was not a N370S carrier, suggesting deletion of at least part of the gene. Molecular analysis of the complex allele was carried out by Southern blot, PCR, and sequencing. We were able to close down the region of the recombination event to an interval of 18 nucleotides, corresponding to the last 15 nucleotides of intron 2 and the first 3 nucleotides of exon 3 of the gene. These 18 nucleotides are identical between the gene and pseudogene making any further refinement impossible. An exhaustive list of published glucocerebrosidase complex alleles, describing their recombination points, is included for comparison.

Adolescent↗
PubMed1997

Identification of a ferritin light chain pseudogene near the glycerol kinase locus in Xp21 by cDNA amplification for identification of genomic expressed sequences.

We used cDNA amplification for identification of genomic expressed sequences (CAIGES) to identify genes in the glycerol kinase region of the human X chromosome. During these investigations we identified the sequence for a ferritin light chain (FTL) pseudogene in this portion of Xp21. A human liver cDNA library was amplified by vector primers, labeled, and hybridized to Southern blots of EcoRI-digested human genomic DNA from cosmids isolated from yeast artificial chromosomes in the glycerol kinase region of Xp21. A 3.1-kb restriction fragment hybridized with the cDNA library, was subcloned and sequenced, and a 440-bp intronless sequence was found with strong similarity to the FTL coding sequence. Therefore, the FTL pseudogene that had been mapped previously to Xp22.3-21.2 was localized specifically to the glycerol kinase region. The CAIGES method permits rapid screening of genomic material and will identify genomic sequences with similarities to genes expressed in the cDNA library used to probe the cloned genomic DNA, including pseudogenes.

Base Sequence↗
PubMed1995

Cyclophilin A, the major intracellular receptor for the immunosuppressant cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map to chromosomes 3, 10, 14, and 18.

Cyclophilin A (CyP-A), the major intracellular receptor for the immunosuppressant cyclosporin A (CsA), is a member of the immunophilin class of proteins, which all possess peptidyl-prolyl cis-trans isomerase activity and, therefore, are believed to be involved in protein folding and/or intracellular protein transport. The CyP-A protein is encoded by a single gene; in addition, 15 pseudogenes have been identified. Recently, specific binding of CyP-A to the human immunodeficiency virus type 1 (HIV-1) gag protein has been reported. Interestingly, this interaction can be inhibited by the immunosuppressant CsA and also by nonimmunosuppressive, CyP-A-binding CsA derivatives, which were also shown to exhibit potent anti-HIV-1 activity. Results thus indicate that CyP-A may have an essential function in HIV-1 replication. Using a panel of somatic rodent-human cell hybrids and PCR technology, we localized the coding cyclophilin A gene (PPIA) on chromosome 7 and four pseudogenes (PPIP2, PPIP3, PPIP4, and PPIP6) on chromosomes 14, 10, 18, and 3, respectively. Using chromosome 7 and chromosome 10 deletion hybrid panels, we were able to localize further the coding gene to the region 7p11.2-p13, as confirmed by fluorescence in situ hybridization analysis, and one pseudogene (PPIP3) to the region 10q11.2-q23. This is the first report on the regional mapping of members of the CyP-A gene family.

Amino Acid Isomerases↗
PubMed1995

The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes.

Angiogenin, a homologue of pancreatic ribonuclease, is a potent inducer of blood vessel formation. As an initial step toward investigating the in vivo functional role of this protein via gene disruption, we undertook the isolation of the angiogenin gene (Ang) from the 129 strain mouse, which will be used for generating targeting constructs. Unexpectedly, screening of a genomic library with an Ang gene probe obtained previously from the BALB/c strain yielded two new genes closely similar to Ang rather than Ang itself. One of these encodes a protein with 78% sequence identity to angiogenin and is designated "Angrp" for "angiogenin-related protein." The ribonucleolytic active site of angiogenin, which is critical for angiogenic activity, is completely conserved in Angrp, whereas a second essential site, thought to bind cellular receptors, is considerably different. Thus, the Angrp product may have a function distinct from that of angiogenin. The second gene obtained by library screening is a pseudogene, designated "Ang-ps1," that contains a frameshift mutation in the early part of the coding region. Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR). Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region. PCR cloning also yielded a second Ang-like pseudogene, designated "Ang-ps2." Southern blotting of genomic DNA confirmed the presence of Ang, Angrp, and at least one of the pseudogenes in an individual mouse and suggested that the mouse Ang gene family may contain more than the four members identified here.

Amino Acid Sequence↗
PubMed1995

Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene.

G alpha q is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C beta. We report the isolation and characterization of cDNA clones from a frontal cortex cDNA library encoding human G alpha q. The encoded protein is 359 amino acids long and is identical in all but one amino acid residue to mouse G alpha q. Analysis of human genomic DNA reveals an intronless sequence with strong homology to human G alpha q cDNA. In comparison to G alpha q cDNA, this genomic DNA sequence includes several small deletions and insertions that alter the reading frame, multiple single base changes, and a premature termination codon in the open reading frame, hallmarks of a processed pseudogene. Probes derived from human G alpha q cDNA sequence map to both chromosomes 2 and 9 in high-stringency genomic blot analyses of DNA from a panel of human-rodent hybrid cell lines. PCR primers that selectively amplify the pseudogene sequence generate a product only when DNA containing human chromosome 2 is used as the template, indicating that the authentic G alpha q gene (GNAQ) is located on chromosome 9. Regional localization by FISH analysis places GNAQ at 9q21 and the pseudogene at 2q14.3-q21.

Animals↗
PubMed1996

The bona fide mouse U7 snRNA gene maps to a different chromosome than two U7 pseudogenes.

The U7 snRNA, together with both common and unique snRNP proteins, forms the U7 snRNP particle. This particle is a major component of the 3' processing machinery that converts histone pre-mRNA into mature mRNA in the eukaryotic nucleus. The genes for many snRNAs are present in multiple copies and often have many pseudogenes. Southern blot experiments using U7 oligonucleotide and gene probes have identified only one strongly hybridizing band and three weakly hybridizing bands in mouse genomic DNA. Previously, two laboratories isolated genomic clones encoding one functional U7 gene and three presumed pseudogenes. Since all the genes were isolated on separate, nonoverlapping genomic fragments, the four genes are not tightly clustered in the mouse genome. In this study, we use fluorescence in situ hybridization to determine the chromosomal locations of these clones and their possible linkage to histone loci. Two of the pseudogenes map to mouse Chromosome 1, but are many megabases apart, whereas the active U7 gene maps to Chromosome 6. Possible mechanisms for this localization pattern are discussed.

Animals↗
PubMed1996

Characterization and genomic mapping of genes and pseudogenes of a new human protein tyrosine phosphatase.

Previously described protein tyrosine phosphatases (PTPs) are classified into three types according to their sequence homology and structural features. Here we describe the characterization of genes and pseudogenes of a member of a fourth type of PTP, designated protein tyrosine phosphatase 4A (PTP4A). The 167-amino-acid human PTP4A bears the signature active site of all PTPs, but does not show any other sequence homology to any of the previously described PTPs. Two cDNAs encoding PTP4A that differed in their noncoding regions were isolated. Another cDNA that has a high level of sequence identity with these two cDNAs and a deletion in the coding region was also isolated. Northern analysis using a probe from a common 3'-untranslated region of the cDNAs recognized mRNAs of about 2 and 4 kb. Both species of mRNA were seen in all human adult and fetal tissues tested. Fluorescence in situ hybridization mapping of the corresponding yeast artificial chromosome clones and sequence-tagged site analysis suggested that one of the PTP4A coding genes is located at 1p35 and the other is on chromosome 11. A processed pseudogene for PTP4A was found in the BRCA1 region of 17q21 and shares 96% sequence identity to one of the PTP4A coding cDNAs. Our studies also suggest the existence of another processed pseudogene on chromosome 11.

Adult↗
PubMed1997

Characterization of human SHC p66 cDNA and its processed pseudogene mapping to Xq12-q13.1.

SHC is an adapter protein in the Ras-MAPkinase pathway that is involved in the regulation of cell growth and differentiation. The p46 and p52 isoforms are thought to be produced by the use of two alternative translation initiation sites in a 3.4-kb transcript from the SHCA gene, which maps to chromosome 1q21. The p66 isoform could be encoded by a different 3.8- or 2.8-kb transcript of the same gene or alternatively by a SHC-related gene. To characterize other putative genes coding for SHC-like proteins, primers from the 3' UTR of the SHCA gene were used to screen a yeast artificial chromosome (YAC) library by polymerase chain reaction (PCR). Two YAC clones, 20D11B and 36D1D, were isolated and used as probes for fluorescence in situ hybridization analysis. Both these probes hybridized to chromosome Xq12-q13.1. This novel SHC-related sequence was characterized by direct sequencing of vectorette library PCR products produced from clone 20D11B. A transcript of 3.2 kb that was 85% identical to the mouse Shc cDNA encoding the p66 isoform was identified. Sequence analysis demonstrated the presence of multiple stop codons identifying this isoform of SHC as a processed pseudogene. Using primers designed on the basis of the nucleotide sequence of the pseudogene, we have now amplified and sequenced a human cDNA that encodes the SHC p66 protein. Thus, we have characterized the human SHC p66 isoform cDNA and identified a processed SHC pseudogene that maps to chromosome Xq12-q13.1.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The ubiquitin-homology gene PIC1: characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes.

The human ubiquitin-homology domain protein PIC1 interacts with the acute promyelocytic leukemia protein PML, and both proteins form part of the large, nuclear, multiprotein complexes known as PML nuclear bodies. The normal punctate immunohistochemical staining pattern of these complexes is disrupted by viral infection or interferon treatment and in blast cells from patients with acute promyelocytic leukemia. We have characterized the murine homologue of PIC1 and have found that the predicted amino acid sequences of the mouse and human proteins are identical. High levels of Pic1 mRNA were detected in a range of mouse tissues. Pic1 genomic clones were isolated, and the organization of the gene was determined. Two processed Pic1 pseudogenes were also isolated and characterized. Through FISH, the chromosomal localizations of the mouse Pic1 gene and the two pseudogenes were determined. Human PIC1 (HGMW-approved symbol UBL1)-related sequences were isolated from human genomic DNA and were shown to represent processed pseudogenes. The role of PIC1 in a variety of cellular processes is discussed.

3T3 Cells↗
PubMed2001

The MGEA6 multigene family has an active locus on 14q and at least nine pseudogenes on different chromosomes.

The meningioma expressed antigen-6 (MGEA6) was originally identified as an immunogenic antigen in meningioma patients. Somatic hybrid panel mapping and fluorescence in situ hybridization revealed MGEA6-related sequences on different human chromosomes. Here we carry out database analysis to investigate the complexity of the MGEA6-related sequences and demonstrate the existence of a multigene family. We localized the active gene (spanning over 83 kb) to chromosome 14q and elucidated its exon/intron structure. We identified and characterized 9 processed pseudogenes on 9 different chromosomes including chromosomes 2, 3, 6, 7, 9, 10, 12, 13, and 18. We performed phylogenetic analysis and concluded that the MGEA6 pseudogenes may result from more than one retrotransposition event; we calculated divergence times of the pseudogenes to be between 21.5 and 28.9 million years ago.

Alternative Splicing↗
PubMed2002

Ribonuclease H1 maps to chromosome 2 and has at least three pseudogene loci in the human genome.

We have analyzed the genomic structure of ribonuclease H1 (RNase H1) loci in the human genome. Human PAC library screening combined with database searches indicated that several loci are present. The transcribed gene is localized on chromosome 2p25. This was confirmed by RNA analysis of a monochromosomal hybrid cell line that expressed human chromosome 2. These data contradict a previous report, as well as the current Human Genome Project (HGP) annotation, which had placed the gene on chromosome 17p11.2. This location represents a pseudogene. Another highly similar pseudogene is present at a separate locus located more distal on chromosome 17p, while a third pseudogene is localized on chromosome 1q.

Base Sequence↗
PubMed1996

The presence of a pseudogene may affect the use of HPRT as an endogenous mRNA control in RT-PCR.

Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) has been used extensively as a tool to measure expression levels of mRNA species. Many commonly used endogenous mRNA control species are known to have genomic pseudogenes, which can confound RT-PCR results if not accounted for. The hypoxanthine phosphoribosyltransferase gene (HPRT) has previously been used as an mRNA control to circumvent these difficulties, since it was believed that no pseudogenes existed. The existence of a pseudogene of HPRT is reported, and researchers are warned that this gene cannot be used as an endogenous mRNA control without taking appropriate precautions.

Cell Line↗
PubMed1995

Evolution of V genes: DNA sequence structure of functional germline genes and pseudogenes.

In this review we have examined the features of germline sequences of IgV genes from a number of species in an attempt to identify the "signature" of molecular mechanisms responsible for generating and maintaining diversity in the germline repertoire (after gene duplication by meiotic unequal crossover). We now summarize the relevant features point by point: 1. Codon analysis reveals a significant deficit of stop codons below the numbers that would be expected under random point mutational change. This implies that the majority of individual V genes have each been selected for the possession of open reading frames able to encode a functional Ig molecule. There is an extraordinarily high rate of apparent rescue of potential stop codons in both V genes and pseudogenes. Other (non-Ig) pseudogene sequences studied thus far do not show this high rate of rescue of stop codons. 2. The distribution of changes is concentrated in most cases in the 5' half of CDR2 (CDR2a), and coincides with the patterns of antigen-selected mutations in B lymphocytes. It does not coincide with expected non-antigen-selected (random) changes, as exemplified by hypermutated but unexpressed passenger V transgenes in B cells in Peyer's patches of unimmunized mice (Gonzalez-Fernandez and Milstein 1993). 3. In germline V genes of mice, there is no evidence of triplet codon insertion (or multiples thereof) as a mechanism generating germline diversity. This parallels a known absence of gene conversion as a mechanism generating somatic diversity in mice. In contrast, in germline chicken pseudogenes which are known to contribute to somatic generation of diversity by gene conversion, frequent examples of triplet codon insertions and deletions in CDRs are present. 4. The pattern of unique insertions and deletions in all species with sufficient sequence data available is consistent with hyper-recombination events targeting the transcription and/or coding unit. The distribution of these events does not correlate with known inducers of gene conversion, for example, inverted or direct repeats and palindromes. Furthermore, the 5' boundaries of somatic hypermutation and the 5' peak of germline nucleotide insertions and deletions coincide in IghV (Rothenfluh et al. 1993, 1994; Rogerson 1994) and in IgkV (Rogerson 1994; Rada et al. 1994, and analyses herein). It will be interesting to see how these features relate to each other in other gene sets as data become available.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Localization of the active gene of aldolase on chromosome 16, and two aldolase A pseudogenes on chromosomes 3 and 10.

Southern blot analysis of human genomic DNA hybridized with a coding region aldolase A cDNA probe (600 bases) revealed four restriction fragments with EcoRI restriction enzyme: 7.8 kb, 13 kb, 17 kb and greater than 30 kb. By human-hamster hybrid analysis (Southern technique) the principal fragments, 7.8 kb, 13 kb, greater than 30 kb, were localized to chromosomes 10, 16 and 3 respectively. The 17-kb fragment was very weak in intensity; it co-segregated with the greater than 30-kb fragment and is probably localized on chromosome 3 with the greater than 30-kb fragment. Analysis of a second aldolase A labelled probe protected against S1 nuclease digestion by RNAs from different hybrid cells, indicated the presence of aldolase A mRNAs in hybrid cells containing only chromosome 16. Under the stringency conditions used, the EcoRI sequences detected by the coding region aldolase A cDNA probe did not correspond to aldolase B or C. The 7.8-kb and greater than 30-kb EcoRI sequences, localized respectively on chromosomes 10 and 3, correspond to aldolase A pseudogenes; the 13-kb EcoRI sequence localized on chromosome 16 corresponds to the aldolase active gene. The fact that the aldolase A gene and pseudogenes are located on three different chromosomes supports the hypothesis that the pseudogenes originated from aldolase A mRNAs, copied into DNA and integrated in unrelated chromosomal loci.

Animals↗
PubMed1989

Sublocalization of von Willebrand factor pseudogene to 22q11.22-q11.23 by in situ hybridization in a 46,X,t(X;22)(pter;q11.21) translocation.

The von Willebrand factor pseudogene, previously mapped to chromosome 22, was sublocalized by in situ hybridization using as probe a von Willebrand factor cDNA fragment completely contained in the pseudogenic region. Chromosome spreads were from a patient carrying a unique balanced de novo translocation 46,X,t(X;22)(pter;q11.21). Silver grain analysis indicated that the human von Willebrand factor pseudogene is located on 22q,11,22-q11,23, a region relevant for several somatic and constitutional chromosomal alterations.

Child, Preschool↗
PubMed1987

Evolution of pseudogenes in the immunoglobulin VH-gene family of the mouse.

A quantitative analysis of the complexity of the J558 VH-gene family in the mouse immunoglobulin heavy chain (Igh) gene locus has been performed. Considerable variations in the degree of complexity are observed in various Igh haplotypes derived from laboratory mice and wild mice. The BALB/c strain shows the highest degree of complexity of the J558 VH-gene family when all mice are compared. Multiple gene duplications seem to have occurred in the BALB/c-derived J558 VH-gene family less than 1-2 million years ago. This dating is supported by the divergence in coding and flanking regions of three strongly homologous VH-region genes. Two of these genes were generated by the duplication of a pseudogene about 1.5 X 10(5) years ago. A recent expansion of the J558 VH-gene family and therefore little time for evolutionary drift may explain why most of the pseudogenes in this family exhibit a largely intact structure. We also describe two VH-region genes which represent older pseudogenes in states of progressive disintegration.

Amino Acid Sequence↗