A 70% reduction of HPRT- mutant frequency in radioadapted human lymphoblastoid cells has been reported, as analyzed by the Southern blot method (O. Rigaud et al., Radiat. Res., 133: 94-101, 1993). The data reported here extend the previous molecular analysis to a collection of 118 mutants. Structural rearrangements of the HPRT gene were determined using the multiplex polymerase chain reaction a...

Molecular biomarkers are becoming increasingly important tools to identify people who are at highest risk of developing cancer. For many years we have been studying residents of Qidong County, People's Republic of China, to examine the combined impact of aflatoxin exposure with other risk factors as contributors to the high liver cancer incidence rates in this region. This study was conducted t...

Somatic mutations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene are rare occurrences in T-lymphocytes of normal individuals. Lacking pathogenic significance, these events can serve as reporters for assessing environmental genotoxicity. The present molecular analyses of hprt mutations arising spontaneously in normal children show that 30-35% of the genomic hprt changes in chi...

Mutations arising in vivo in recorder genes of human blood cells provide biomarkers for molecular epidemiology by serving as surrogates for cancer-causing genetic changes. Current markers include mutations of the glycophorin-A (GPA) or hemoglobin (Hb) genes, measured in red blood cells, or mutations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) or HLA genes, measured in T-lymphoc...

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPR...

Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem (ES) cells. This technology, commonly referred to as gene targeting or knockout, is based on homologous recombination between DNA sequences residing in the chromosome and newly introduced DNA to mutate any genes of interesting in mouse genome [1]. Twenty years ago, Capec...

Over the past decade, a steady increase in the incidence of HPRT-related hyperuricemia (HRH) has been observed in Saudi Arabia. We examined all the nine exons of HPRT gene for mutations in ten biochemically confirmed hyperuricemia patients, including one female and three normal controls. In all, we identified 13 novel mutations in Saudi Arabian HPRT-related hyperuricemia patients manifesting di...

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 hyp...

The CRISPR-Cas9 system uses guide RNAs to direct the Cas9 endonuclease to cleave target sequences. It can, in theory, target essentially any sequence in a genome, but the efficiency of the predicted guide RNAs varies dramatically. If no targeted cells are obtained, it is also difficult to know why the experiment fails. We have developed a transient transfection based method to enrich successful...

A new Saccharomyces cerevisiae gene, XPT1, was isolated as a multicopy suppressor of a hypoxanthine phosphoribosyl transferase (HPRT) defect. Disruption of XPT1 affects xanthine utilization in vivo and results in a severe reduction of xanthine phosphoribosyl transferase (XPRT) activity while HPRT is unaffected. We conclude that XPT1 encodes XPRT in yeast.