Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cloned cDNAs representing the entire, homologous (80%) translated sequences of human phosphoribosylpyrophosphate synthetase (PRS) 1 and PRS 2 cDNAs were utilized as probes to localize the corresponding human PRPS1 and PRPS2 genes, previously reported to be X chromosome linked. PRPS1 and PRPS2 loci mapped to the intervals Xq22-q24 and Xp22.2-p22.3, respectively, using a combination of in situ chromosomal hybridization and human x rodent somatic cell panel genomic DNA hybridization analyses. A PRPS1-related gene or pseudogene (PRPS1L2) was also identified using in situ chromosomal hybridization at 9q33-q34. Human HPRT and PRPS1 loci are not closely linked. Despite marked cDNA and deduced amino acid sequence homology, human PRS 1 and PRS 2 isoforms are encoded by genes widely separated on the X chromosome.
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PMID:Cloning of cDNAs for human phosphoribosylpyrophosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes. 196 53

Studies on a cell line with amplified copies of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene and HPRT gene transfer experiments revealed the existence of a nonfunctional HPRT-related sequence in the mouse genome. This sequence was isolated and found to be a processed HPRT pseudogene. With the exception of a small internal deletion, the pseudogene is believed to comprise a complete reverse transcript of HPRT mRNA, although the 3' end of the pseudogene was lost in the cloning process. A probe from a region flanking the mouse pseudogene was used to investigate the evolutionary relationships of mammalian HPRT pseudogenes. The pseudogenes in mouse and Chinese hamster appear to have a common origin, but no homology to any of the four known human HPRT pseudogenes was detected. A pseudogene-linked restriction fragment length polymorphism was used to map the pseudogene to the distal end of mouse chromosome 17.
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PMID:Characterization, evolutionary relationships, and chromosome location of processed mouse HPRT pseudogene. 289 12

A highly conserved hypoxanthine phosphoribosyltransferase processed pseudogene (KPH) has been isolated from a female kangaroo (Macropus robustus) lambda EMBL3 genomic library. The pseudogene contains only transcribed material with all of the introns precisely removed and has possible direct repeats at either end of the message. It has a 654-nucleotide open reading frame (ORF) from the Met start codon to the stop codon that contains no additions, deletions or premature stops relative to expressed HPRT genes and, therefore, the possibility exists that it is expressed in vivo. Possible CAAT and GC boxes are present in the region 5' to the ORF and a polyadenylation signal is present in the region 3' to the ORF. If not expressed, the age of the pseudogene is estimated to be 10.7 million years. We propose that integration into the genome occurred specifically in a homocopolymeric region within a highly repeated region unique to the kangaroo genome.
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PMID:Isolation of a potentially functional HPRT processed pseudogene from the hill kangaroo Macropus robustus. 782 7

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.
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PMID:The presence of a pseudogene may affect the use of HPRT as an endogenous mRNA control in RT-PCR. 902 89

Lesch-Nyhan disease (LND) is a severe X-linked neurological disorder caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT). In contrast, HPRT-deficiency in the mouse does not result in the profound phenotypes such as self-injurious behavior observed in humans, and the genetic basis for this phenotypic disparity between HPRT-deficient humans and mice is unknown. To test the hypothesis that HPRT deficiency is modified by the presence/absence of phosphoribosyltransferase domain containing 1 (PRTFDC1), a paralog of HPRT that is a functional gene in humans but an inactivated pseudogene in mice, we created transgenic mice that express human PRTFDC1 in wild-type and HPRT-deficient backgrounds. Male mice expressing PRTFDC1 on either genetic background were viable and fertile. However, the presence of PRTFDC1 in the HPRT-deficient, but not wild-type mice, increased aggression as well as sensitivity to a specific amphetamine-induced stereotypy, both of which are reminiscent of the increased aggressive and self-injurious behavior exhibited by patients with LND. These results demonstrate that PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse and could therefore have important implications for unraveling the molecular etiology of LND.
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PMID:PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. 2181 16