Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.5.1.3 (dihydrofolate reductase)
5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A panel of rat x mouse cell hybrids was used in the chromosomal mapping of the rat dihydrofolate reductase (DHFR) gene. It was determined that the probe hybridized to gene sequences on two different chromosomes (Nos. 2 and 4), possibly representing the active gene and a pseudogene. Hybridization of the DHFR probe to DNA from a methotrexate resistant rat cell line revealed that the gene on chromosome 2 was amplified, but not the gene on chromosome 4. This result was taken to suggest that the active DHFR gene is located on rat chromosome 2 and that the sequence on chromosome 4 is a pseudogene.
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PMID:Assignment of two rat dihydrofolate (DHFR) genes to chromosomes 2 and 4. 232 24

The human dihydrofolate reductase (DHFR) gene family comprises one functional gene and at least four intronless processed pseudogenes. The functional DHFR gene is on chromosome 5, and DHFRP4 is on chromosome 3. Using in situ hybridization, we have now localized the functional DHFR gene to the region q11.1-q13.3 on chromosome 5. By genomic DNA analysis of a panel of human X rodent somatic-cell hybrids, we determined the chromosomal assignment of the DHFRP1 pseudogene to chromosome 18 and that of the DHFRP2 pseudogene to chromosome 6. The DHFRP1 pseudogene exhibits a novel form of polymorphism in humans in that it is present in the DNA of some individuals and absent in that of others. We investigated the racial distribution of this pseudogene in five racial groups. The allelic frequency as defined by analysis of 180 chromosomes was found to be 94% in Mediterraneans, 77% in Asian Indians, 67% in Chinese, 57% in Southeast Asians, and 32% in American blacks. These data suggest that the transposition of this "perfect" pseudogene occurred prior to the inception of the human racial groups.
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PMID:Chromosomal localization and racial distribution of the polymorphic human dihydrofolate reductase pseudogene (DHFRP1). 334 83

The chromosomal location of the human dihydrofolate reductase (DHFR; EC 1.5.1.3) gene that is amplified in a methotrexate-resistant human cell line has been investigated by screening a number of human-Chinese hamster ovary cell hybrids containing terminal and interstitial deletions in human chromosome 5. A correlation of genomic blotting data with the chromosome 5 constitution of the individual hybrids has allowed the assignment of the human DHFR gene to 5q23. The present work also establishes the location of the related intronless pseudogene psi HD1 in chromosome 3.
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PMID:Assignment of human dihydrofolate reductase gene to band q23 of chromosome 5 and of related pseudogene psi HD1 to chromosome 3. 385 32

A sequence in an intron of the human HLA-DP beta 1 gene was identified by its homology to the gene encoding ribosomal protein L32 (rpL32). It lacked introns indicating that it was derived from a processed rpL32 mRNA transcript. A human cDNA clone encoding rpL32 was isolated and compared to this human pseudogene and to several related mouse sequences, one of which is contained in an intron of the murine dihydrofolate reductase gene. Comparison of these sequences revealed that they were more related within species than between, suggesting that they became inserted in the genome after man and mouse diverged.
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PMID:A processed pseudogene in an intron of the HLA-DP beta 1 chain gene is a member of the ribosomal protein L32 gene family. 386 18

The processed pseudogenes reported to date fall into three categories: those that are a complete copy of the mRNA transcribed from the functional gene, those that are only a partial copy of the corresponding mRNA, and those that contain sequences in addition to those expected to be present in the mRNA. The general structural characteristics of these processed pseudogenes include the complete lack of intervening sequences found in the functional counterparts, a poly A tract at the 3' end, and direct repeats flanking the pseudogene sequence. In all the cases studied, these pseudogenes have been found to be on a different chromosome from their functional counterpart. These characteristics have led investigators to suggest that an RNA intermediate, in many cases the mRNA of the functional gene, is involved in the production of these pseudogenes. The mechanism by which processed pseudogenes arose involves the integration of the mRNA, or its cDNA copy, into a staggered chromosome break, followed by DNA synthesis and repair. I suggest that all the transcripts that gave rise to these pseudogenes were actually produced in the germ line cell. The transcripts that gave rise to the processed pseudogenes that are direct copies of the corresponding mRNA resulted from RNA polymerase II transcription of the functional counterpart. Pseudogenes that are not a direct copy of the corresponding mRNA may have resulted from RNA polymerase III transcription. If this is indeed the case, one need not postulate the involvement of retroviruses to explain the presence of processed pseudogenes corresponding to genes that are not expressed in the germ line. Following the integration event, processed pseudogenes can no longer be transcribed to produce the functional mRNA from which they arose. This inability to be transcribed by RNA polymerase II is not surprising considering that processed pseudogenes seem to be randomly integrated into the genome. Therefore, integration of a processed pseudogene such that RNA polymerase II transcriptional promoters are correctly positioned 5' to the resultant pseudogene is an unlikely event. The presence of processed pseudogenes seems peculiar to mammals. In fact, evolutionary studies indicate that processed pseudogenes are of relatively recent origin. In fact, at least one processed pseudogene, the human DHFR psi 1, has been formed so recently that it is polymorphic.
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PMID:Processed pseudogenes: characteristics and evolution. 390 43

Three overlapping cosmid clones contain coding sequences for four HLA Class II genes, provisionally identified as two HLA-SB alpha and two HLA-SB beta genes. The genes are in the order beta, alpha, beta, alpha, inverted with respect to each other. One of the SB beta genes contains a 513 bp sequence that appears to be a processed pseudogene, flanked by direct 17 bp repeat sequences, in the intron upstream of the beta 1 exon. The pseudogene is homologous to a family of sequences of approximately 25-40 members, most of which are not on chromosome 6. A cDNA clone, highly homologous to the pseudogene, except for its 5' end, contains a normal poly(A) addition site and a poly(A) tail. The cDNA clone is homologous to a single-copy gene in both man and mouse, encoded on human chromosome 15. A search of published DNA sequences identified a mouse sequence, with about 77% similarity to the pseudogene sequence, in the negative strand of an intron in a mouse dihydrofolate reductase gene. The second SB beta gene does not contain the pseudogene sequence.
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PMID:Linkage map of two HLA-SB beta and two HLA-SB alpha-related genes: an intron in one of the SB beta genes contains a processed pseudogene. 608 68

The human dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) gene family includes a functional gene (hDHFR) and at least four intronless genes. Three intronless genes (hDHFR-psi 2, hDHFR-psi 3, and hDHFR-psi 4) are identifiable as pseudogenes because of DNA sequence divergence from the functional gene with introns, while one intronless gene (hDHFR-psi 1) is completely homologous to the coding sequences of the functional gene. Analysis of genomic DNA from two panels of somatic human-rodent cell hybrids with specific molecular probes provide insight into the chromosomal organization and assignment of these genes. The five genes are dispersed in that each one is found on a different chromosome. The functional gene hDHFR has been assigned to chromosome 5, and one pseudogene (hDHFR-psi 4), to chromosome 3. In a human cell line (HeLa) that was selected for methotrexate resistance, the functional locus became amplified, while there was no amplification of the four intronless pseudogenes. hDHFR-psi 1 was found to be present in DNA of some individuals and absent from DNA of others, consistent with a recent evolutionary origin of this gene originally suggested by its sequence identity to the coding portions of the functional gene. The presence or absence of this intronless pseudogene represents a previously unreported form of DNA polymorphism.
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PMID:Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism. 608 82

The presence of dihydrofolate reductase (DHFRase)-specific sequences that, in contrast to the normal DHFRase gene, are not amplified in a methotrexate-resistant cell line, has been detected in the DNA from human sperm and from several human cell lines. DNA fragments containing some of these sequences have been isolated from a cosmid library of human sperm DNA. One of these fragments contains a DHFRase pseudogene (psi HD1) that completely lacks introns, has 92% sequence homology to the corresponding region of normal DHFRase complementary DNA, but exhibits several alterations that make it nonfunctional. The sequence analysis of the inserts of four different plasmids containing the reading frame and varying lengths of the 3' non-coding regions of human DHFRase-specific cDNAs has revealed that the 3' non-coding segments all are colinear in their corresponding portions. Furthermore, the data indicate that the cDNA of one of the plasmids is probably derived from the smallest of the three main human DHFRase messenger RNAs, the 0.8 X 10(3) base (0.8 kb) mRNA, the cDNA of two others, from the 1.0 kb mRNA, and the cDNA of the fourth, from a longer mRNA. These results are consistent with the idea that the multiple forms of DHFRase mRNA in human cells derive from the same gene by different transcription or RNA-processing events. Moreover, the sequence comparison between the psi HD1 and the different DHFRase cDNAs clearly indicates that, if an mRNA intermediate has participated in the formation of this pseudogene, a form of mRNA larger than the 1.0 kb mRNA, probably the 3.8 kb mRNA, must have been involved.
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PMID:A human dihydrofolate reductase pseudogene and its relationship to the multiple forms of specific messenger RNA. 630 53

A dihydrofolate reductase (DHFR) pseudogene, hDHFR-psi 3 has been isolated from a human genomic DNA fragment library. Sequence analysis of this gene revealed a lack of introns and the presence of a tract of nine adenines, 90 bp downstream from the end of the coding sequence. These features suggest that hDHFR-psi 3 was derived from a processed RNA molecule that has been converted into DNA and inserted into a chromosome, analogous to the origin of three intronless human DHFR genes previously described. An interesting feature of hDHFR-psi 3 is the presence of a member of the Alu moderately repetitive DNA sequence family within the DHFR coding region. This Alu element is flanked by a 16 bp directly repeated DNA segment derived from DHFR coding sequences. The Alu element apparently has been inserted into the intronless DHFR pseudogene and thus, there have been two insertions at a single chromosomal locus. The hDHFR-psi 3 contains only the 3' half of the DHFR coding sequence. Immediately upstream from the directly repeated sequence before the Alu element is an adenine-rich tract. The DNA farther upstream is moderately repetitive and is related to neither DHFR nor Alu DNA sequence. Therefore, it seems possible that a third insertion has occurred at the same site further disrupting the hDHFR coding sequences.
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PMID:A human dihydrofolate reductase intronless pseudogene with an Alu repetitive sequence: multiple DNA insertions at a single chromosomal site. 652 69

An allele heterogeneity in a short tandem repeat at the human dihydrofolate reductase pseudogene (DHFRP2) was detected using non-denaturing gel electrophoresis and ethidium bromide staining. Sequence analysis of the allele, designated 9A, revealed the C to A substitution in the 8th AAAC repeat. A survey of 16 worldwide human populations showed that this mutation was spread through five continents at a relatively high frequency (up to p = 0.19 in Europeans). Some statistical parameters of forensic interest were also calculated (h, PD, EC and PIC) for this polymorphism. This type of heterogeneity stresses the complexity of STR variation.
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PMID:Identification of a base pair substitution at the tetranucleotide tandem repeat locus DHFRP2 (AAAC)n in a worldwide survey. 895 94


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