Analysis of in Vivo Somatic Mutations at the APRT Locus
Adenine phosphoribosyltransferase (APRT; E.C.220.127.116.11) catalyzes the synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. A deficiency of this enzyme leads to 2, 8-dihydroxyadenine stone formation in the kidney. The APRT gene is located at 16q24.3 and its genomic sequence size is 2.6 kb and coding sequence 0.54 kb. It has been used extensively to examine mammalian mutagenesis (1–4). Earlier studies have focused on spontaneous and induced mutations in cultured cells. We have recently analyzed germline mutations from more than 33 patients (5, 6). Germline mutations seem to cluster at the intron 4 splice site and few other sites different than the in vitro mutagenesis results in cultured cells. These studies suggested differences in mutagenesis pathways. Therefore, it was of interest to examine another group of mutations which also arise in vivo in human cells. We initiated studies to examine the nature of in vivo somatic mutations in T lymphocytes from heterozygote (APRT +/-) individuals.
KeywordsSomatic Mutation Adenine Phosphoribosyltransferase Obligate Heterozygote Mutagenesis Assay Analyze Germline Mutation
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