{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:16:53Z","timestamp":1764688613223},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"content-version":"vor","delay-in-days":4947,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1993,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Expression of a recessive phenotype can occur by a number of different mechanisms, such as chromosomal deletion, recombination, and intragenic frameshift mutation or base substitution. To examine the contribution of different mutational events, we isolated and characterized a human fibroblast cell line heterozygous at the adenine phosphoribosyltransferase (<jats:italic>APRT<\/jats:italic>) locus. Cells that subsequently lost APRT activity were selected, cloned, and analyzed for the mechanisms contributing to the loss of APRT activity. Loss of APRT activity occurred at a rate of 7.8 x 10<jats:sup>\u20105<\/jats:sup> per allele per cell generation. Molecular analysis of DNA from 21 independent APRT<jats:sup>\u2010<\/jats:sup> clones demonstrated that 62% of mutants had lost the functional allele and that the rest had incurred intragenic mutations. Loss of the functional allele was frequently accompanied by loss of the proximal marker <jats:italic>D16S77<\/jats:italic> but not the more distant proximal marker <jats:italic>D16S4<\/jats:italic>, indicating that a high frequency of mitotic recombination or deletion occurred at the region between <jats:italic>D16S77<\/jats:italic> and <jats:italic>D16S4<\/jats:italic> on chromosome 16. Loss of APRT activity in the remaining 38% of the clones was predominantly due to point mutations. These data demonstrate that the mechanisms for loss of heterozygosity at the <jats:italic>APRT<\/jats:italic> locus are similar to those found in retinoblastoma and other tumors. The autosomal location of the <jats:italic>APRT<\/jats:italic> gene and the ease with which its phenotype can be selected make this gene useful for modeling mutational events at loci important to carcinogenesis.<\/jats:p>","DOI":"10.1002\/mc.2940080304","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:28:41Z","timestamp":1172089721000},"page":"138-144","source":"Crossref","is-referenced-by-count":13,"title":["Loss of heterozygosity: The most frequent cause of recessive phenotype expression at the heterozygous human adenine phosphoribosyltransferase locus"],"prefix":"10.1002","volume":"8","author":[{"given":"Yuan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A.","family":"Tischfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Stambrook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,19]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/305779a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3388033"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/323643a0"},{"key":"e_1_2_1_5_2","first-page":"575","article-title":"Structure of mutant alleles at the aprt locus of CHO cells","volume":"167","author":"Nalbantoglu J","year":"1983","journal-title":"J Med Biol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.7.4.1445"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.10.3499"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(89)90595-0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(85)90194-0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01570784"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01233450"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01535631"},{"key":"e_1_2_1_13_2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/genetics\/28.6.491","article-title":"Mutation of bacteria from virus sensitivity to virus resistance","volume":"28","author":"Luria SE","year":"1943","journal-title":"Genetics"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/3.9.2303"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5754"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01538655"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(91)90193-R"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/11.9.1485"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7474"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00333988"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.17.6791"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.10.3349"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)80212-D"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(91)90143-C"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.2940080304","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.2940080304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T03:32:37Z","timestamp":1698204757000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.2940080304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1993,1]]}},"alternative-id":["10.1002\/mc.2940080304"],"URL":"https:\/\/doi.org\/10.1002\/mc.2940080304","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1]]}}}