Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the hprt gene in T-lymphocyte clones isolated from primary cultures treated with the (+)-anti enantiomer of 7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE) in vitro, and from untreated control cultures, were characterized using polymerase chain reaction and direct sequencing of hprt cDNA and genomic fragments. The spectrum of BPDE-induced mutations was very specific and clearly different from the background spectrum, which comprised many different types of mutations. Of the BPDE-induced mutations, 20/22 were transversions of GC base pairs and 18/22 were GC greater than TA transversions, which is in agreement with what has been found in other mammalian systems. While no particular 'hotspot' was observed for BPDE in the hprt gene, a sequence context specificity was detected. Ten of the 14 BPDE-induced mutations in the coding region were located in the sequence context AGG, and 2 in AG dinucleotides, which indicates that such sequences are sensitive to BPDE mutagenesis. Nine of the 22 BPDE-induced mutations and 2/12 background point mutations caused mRNA splicing errors. Six of the BPDE-induced splicing errors were caused by GC greater than TA transversions in the AG dinucleotide of different splice acceptor sites, which indicates that these sites may be frequent targets of BPDE mutagenesis. All mutated GC base pairs in the BPDE-induced spectrum were oriented so that the guanine was located on the non-transcribed strand. Assuming that the premutagenic lesion in these cases was covalent binding of BPDE to guanine and that BPDE bound randomly to both strands, the strand specificity of the BPDE-induced mutations indicates that preferential excision repair of BPDE adducts on the transcribed strand occurs in the hprt gene in human T-cells.
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PMID:Strand specificity for mutations induced by (+)-anti BPDE in the hprt gene in human T-lymphocytes. 138 65

Genetic changes in Hypoxanthine guanine phosphoribosyltransferace (HPRT1) gene can alter the expression of the dopamine neurotransmitter leads to abnormal neuron function, a disease called Lesch-Nyhan syndrome (LNS). Although different studies were conducted on LNS, information on codon usage bias (CUB) of HPRT1 gene is limited. The present study examines the genetic determinants of CUB in HPRT1 gene using twelve mammalian species. In the coding sequence of HPRT1 genes, A/T ending codons was most frequently used. A higher ENC value was observed indicating lower HPRT1 gene expression in the selected mammalian species. Correlation analysis indicates that compositional constraints under mutation pressure can involve in CUB of HPRT1 genes among the selected mammalian species. Relative synonymous codon usage (RSCU) value revealed that the codons such as ACT, AGG, ATT and AGC were over-represented in each of the mammalian species. Result from the analysis of the RSCU indicates that compositional constraint is a key driver for the variation in codon usage. Ratio of nonsynonymous (dN) and synonymous (dS) substitution further suggested that purifying selection occurs among the HPRT1 gene of studied mammals to maintain its protein function under the process of evolution. Our findings report an insight into the codon usage patterns of HPRT1 gene and will be useful for LNS management.
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PMID:Analysis of synonymous codon usage patterns of HPRT1 gene across twelve mammalian species. 3081 63