{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T07:46:59Z","timestamp":1792568819906,"version":"4.5.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,8,18]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>GNAS1<\/jats:italic>\n                    gene encodes the \u03b1 subunit of the G protein G\n                    <jats:sub>s<\/jats:sub>\n                    , which couples receptor binding by several hormones to activation of adenylate cyclase. Null mutations of\n                    <jats:italic>GNAS1<\/jats:italic>\n                    cause pseudohypoparathyroidism (PHP) type Ia, in which hormone resistance occurs in association with a characteristic osteodystrophy. The observation that PHP Ia almost always is inherited maternally has led to the suggestion that\n                    <jats:italic>GNAS1<\/jats:italic>\n                    may be an imprinted gene. Here, we show that, although G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 expression (directed by the promoter upstream of exon 1) is biallelic,\n                    <jats:italic>GNAS1<\/jats:italic>\n                    is indeed imprinted in a promoter-specific fashion. We used parthenogenetic lymphocyte DNA to screen by restriction landmark genomic scanning for loci showing differential methylation between paternal and maternal alleles. This screen identified a region that was found to be methylated exclusively on a maternal allele and was located \u224835 kb upstream of\n                    <jats:italic>GNAS1<\/jats:italic>\n                    exon 1. This region contains three novel exons that are spliced into alternative\n                    <jats:italic>GNAS1<\/jats:italic>\n                    mRNA species, including one exon that encodes the human homologue of the large G protein XL\u03b1s. Transcription of these novel mRNAs is exclusively from the paternal allele in all tissues examined. The differential imprinting of separate protein products of\n                    <jats:italic>GNAS1<\/jats:italic>\n                    therefore may contribute to the anomalous inheritance of PHP Ia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.17.10038","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"10038-10043","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":226,"title":["The human\n                    <i>GNAS1<\/i>\n                    gene is imprinted and encodes distinct paternally and biallelically expressed G proteins"],"prefix":"10.1073","volume":"95","author":[{"given":"Bruce E.","family":"Hayward","sequence":"first","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Strain","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Moran","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Campbell","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Hayashizaki","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Bonthron","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Genome Science Laboratory, Tsukuba Life Science Center, Riken, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,8,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1073\/pnas.85.7.2081","volume":"85","author":"Kozasa T","year":"1988","unstructured":"T Kozasa, H Itoh, T Tsukamoto, Y Kaziro Proc Natl Acad Sci USA 85, 2081\u20132085 (1988).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1073\/pnas.85.2.617","volume":"85","author":"Levine M A","year":"1988","unstructured":"M A Levine, T G Ahn, S F Klupt, K D Kaufman, P M Smallwood, H R Bourne, K A Sullivan, C Van Dop Proc Natl Acad Sci USA 85, 617\u2013621 (1988).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJM199005173222002","volume":"322","author":"Patten J L","year":"1990","unstructured":"J L Patten, D R Johns, D Valle, C Eil, P A Grupposo, G Steele, P M Smallwood, M A Levine N Engl J Med 322, 1412\u20131419 (1990).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.1073\/pnas.87.21.8287","volume":"87","author":"Weinstein L S","year":"1990","unstructured":"L S Weinstein, P V Gejman, R M Collins, E S Gershon, A M Spiegel Proc Natl Acad Sci USA 87, 8287\u20138290 (1990).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.30.2.101","volume":"30","author":"Davies S J","year":"1993","unstructured":"S J Davies, H E Hughes J Med Genet 30, 101\u2013103 (1993).","journal-title":"J Med Genet"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1136\/jmg.31.8.607","volume":"31","author":"Campbell R","year":"1994","unstructured":"R Campbell, C M Gosden, D T Bonthron J Med Genet 31, 607\u2013614 (1994).","journal-title":"J Med Genet"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/geno.1996.0463","volume":"36","author":"Williamson C M","year":"1996","unstructured":"C M Williamson, J Schofield, E R Dutton, A Seymour, C V Beechey, Y H Edwards, J Peters Genomics 36, 280\u2013287 (1996).","journal-title":"Genomics"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/372804a0","volume":"372","author":"Kehlenbach R H","year":"1994","unstructured":"R H Kehlenbach, J Matthey, W B Huttner Nature (London) 372, 804\u2013809 (1994).","journal-title":"Nature (London)"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/ng1095-164","volume":"11","author":"Strain L","year":"1995","unstructured":"L Strain, J P Warner, T Johnston, D T Bonthron Nat Genet 11, 164\u2013169 (1995).","journal-title":"Nat Genet"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"9523","DOI":"10.1073\/pnas.88.21.9523","volume":"88","author":"Hatada I","year":"1991","unstructured":"I Hatada, Y Hayashizaki, S Hirotsune, H Komatsubara, T Mukai Proc Natl Acad Sci USA 88, 9523\u20139527 (1991).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"5610","DOI":"10.1073\/pnas.92.12.5610","volume":"92","author":"Okazaki Y","year":"1995","unstructured":"Y Okazaki, K Hirose, S Hirotsune, H Okuizumi, N Sasaki, T Ohsumi, A Yoshiki, M Kusakabe, M Muramatsu, J Kawai, et al. 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