{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:00:17Z","timestamp":1775307617959,"version":"3.50.1"},"reference-count":29,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1994,8]]},"abstract":"<jats:p>Variation in the phenotypic expression of Albright's hereditary osteodystrophy (AHO) determined by the parent of transmission, suggests that the human Gs alpha gene (GNAS1), in which mutations occur in AHO, may be under imprinted control. GNAS1 is also known to map to a chromosomal region (20q13.11) showing syntenic homology with the imprinted mouse region 2E1-2H3. To establish if GNAS1 is indeed imprinted, we have examined the parental origin of GNAS1 transcription in human fetal tissues. Of 75 fetuses genotyped, at gestational ages ranging from 6 to 13 weeks, 13 heterozygous for a FokI polymorphism in exon 5 of GNAS1 were identified whose mothers were homozygous for one or other allele. RNA from up to 10 different tissues from each fetus was analysed by RT-PCR. In all cases expression from both parental alleles was shown by FokI digestion of RT-PCR products and quantification of the resulting fragments. No tissue specific pattern of expression was discerned in these experiments. If genomic imprinting regulates the expression of the human GNAS1 gene, our data suggest that the effect must either be subtle and quantitative, or be confined to a small subset of specialised hormone responsive cells within the target tissues.<\/jats:p>","DOI":"10.1136\/jmg.31.8.607","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"607-614","source":"Crossref","is-referenced-by-count":91,"title":["Parental origin of transcription from the human GNAS1 gene."],"prefix":"10.1136","volume":"31","author":[{"given":"R","family":"Campbell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C M","family":"Gosden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D T","family":"Bonthron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1994,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJM199005173222002","article-title":"Mutation in the gene taken. Not only was this experiment free from possible maternal contamination effects, but it encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy","volume":"322","author":"Patten, J.L.; Johns, D.R.; Valle, D.","year":"1990","unstructured":"Patten JL, Johns DR, Valle D, et al. Mutation in the gene taken. Not only was this experiment free from possible maternal contamination effects, but it encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. N Engl J Med 1990;322:1412-19. was also performed blinded, the RT-PCR quantification being performed before the par-","journal-title":"N Engl J Med"},{"key":"ref_2","first-page":"8287","article-title":"Mutations of the Gs alpha-subunit gene in Albright's hereditary osteodystrophy detected by","volume":"87","author":"Weinstein, L.S.; Gejman, P.V.; Freidman, E.","year":"1990","unstructured":"Weinstein LS, Gejman PV, Freidman E, et al. Mutations of the Gs alpha-subunit gene in Albright's hereditary osteodystrophy detected by denaturing gel electrophoresis. Proc ental genotypes were revealed. Table 3 shows that a reproducible difference in expression Natl Acad Sci USA 1990;87:8287-90.","journal-title":"denaturing gel electrophoresis. Proc ental genotypes were; Natl Acad Sci USA; revealed. Table 3 shows that a reproducible difference in expression"},{"key":"ref_3","first-page":"464","article-title":"Studies in pseudohypoparathyroidism. Two new cases with a levels between the maternal and paternal probable selective deficiency of thyrotropin","volume":"46","author":"Zisman, E.; Lotz, M.; Jenkins, M.E.; Bartter, F.C.","year":"1969","unstructured":"Zisman E, Lotz M, Jenkins ME, Bartter FC. Studies in pseudohypoparathyroidism. Two new cases with a levels between the maternal and paternal probable selective deficiency of thyrotropin. Am J Med 1969;46:464-71. alleles was not obtained in this experiment.","journal-title":"Am J Med; alleles was not obtained in this experiment"},{"key":"ref_4","first-page":"321","article-title":"Raz-If GNAS1 imprinting is a tissue specific dan AK, Kim MH. Partial gonadotropin-resistance in pseudohypoparathyroidism","volume":"88","author":"Wolfsdorf, J.I.; Rosenfeild, R.L.; Fang, V.S.; Kobayashi, R.","year":"1978","unstructured":"Wolfsdorf JI, Rosenfeild RL, Fang VS, Kobayashi R, Raz-If GNAS1 imprinting is a tissue specific dan AK, Kim MH. Partial gonadotropin-resistance in pseudohypoparathyroidism. Acta Endocrinol 1978;88:321-","journal-title":"Acta Endocrinol"},{"key":"ref_5","first-page":"545","article-title":"Resistance to multiple hormones in patients with pseudohypoparathyrtissues might be involved. These would inoidism","volume":"74","author":"Levine, M.A.; Downs, R.W.; Moses, A.M.","year":"1983","unstructured":"Levine MA, Downs RW, Moses AM, et al. Resistance to multiple hormones in patients with pseudohypoparathyrtissues might be involved. These would inoidism. Am J Med 1983;74:545-56. clude PTH target tissues and other endocrine","journal-title":"Am J Med; clude PTH target tissues and other endocrine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ajmg.1320110104","article-title":"Albright's hereditary osteodystrophy: a review","volume":"11","author":"Fitch, N.","year":"1982","unstructured":"Fitch N. Albright's hereditary osteodystrophy: a review. Am J Med Genet 1982;11:11-29.","journal-title":"Am J Med Genet"},{"key":"ref_7","first-page":"496","article-title":"Differential activity of matemally and paternally derived chromosome regions in mice. tubule), thyroid, gonad, and bone","volume":"315","author":"Cattanach, B.M.; Kirk, M.","year":"1985","unstructured":"Cattanach BM, Kirk M. Differential activity of matemally and paternally derived chromosome regions in mice. tubule), thyroid, gonad, and bone. Why such Nature 1985;315:496-8.","journal-title":"Why such Nature"},{"key":"ref_8","article-title":"Autosomal and X-chromosome embryologically diverse tissues should share a imprinting","author":"Cattanach, B.M.; Beechey, C.V.","year":"1990","unstructured":"Cattanach BM, Beechey CV. Autosomal and X-chromosome embryologically diverse tissues should share a imprinting. Development Suppl 1990;63-72. common transcriptional control mechanism is, however, difficult to explain. We have been","journal-title":"Development Suppl; 63-72. common transcriptional control mechanism is, however, difficult to explain. We have been"},{"key":"ref_9","first-page":"84","article-title":"The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature unable to show a target tissue specific effect at the whole organ level, having examined kid-","volume":"349","author":"Barlow, D.; Stroger, R.; Herrman, B.; Saito, K.; Schweifer, N.","year":"1991","unstructured":"Barlow D, Stroger R, Herrman B, Saito K, Schweifer N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature unable to show a target tissue specific effect at the whole organ level, having examined kid- 1991;349:84-7."},{"key":"ref_10","first-page":"153","article-title":"Parental imprinting of the mouse H19 gene","volume":"351","author":"Bartolomei, M.; Zemel, S.; Tilghman, S.","year":"1991","unstructured":"Bartolomei M, Zemel S, Tilghman S. Parental imprinting of the mouse H19 gene. Nature 1991;351:153-5. neys from three fetuses and one pair of fetal ovaries. It remains possible, though, that","journal-title":"Nature; neys from three fetuses and one pair of fetal ovaries. It remains possible"},{"key":"ref_11","article-title":"Parental imprinting of the mouse insulin-like growth factor 2 gene. Cell 1991; 64: 849-59. imprinting is limited to a specific subset of hormone sensitive cells. If so, examining the","author":"DeChiara, T.; Robertson, E.; Efstratiadis, A.","unstructured":"DeChiara T, Robertson E, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor 2 gene. Cell 1991;64:849-59. imprinting is limited to a specific subset of hormone sensitive cells. If so, examining the"},{"key":"ref_12","first-page":"259","article-title":"Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature whole fetal kidney might not show such an effect, as the PTH sensitive proximal renal Genet","volume":"2","author":"Leff, S.E.; Brannan, C.I.; Reed, M.L.","year":"1992","unstructured":"Leff SE, Brannan CI, Reed ML, et al. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature whole fetal kidney might not show such an effect, as the PTH sensitive proximal renal Genet 1992;2:259-64."},{"key":"ref_13","article-title":"Monoallelic expression of the human H19 gene. Nature Genet 1992; 1: 40-3. tubular epithelial cells would form a tiny proportion of the total tissue","author":"Zhang, Y.; Tycko, B.","unstructured":"Zhang Y, Tycko B. Monoallelic expression of the human H19 gene. Nature Genet 1992;1:40-3. tubular epithelial cells would form a tiny proportion of the total tissue."},{"issue":"1","key":"ref_14","first-page":"13","article-title":"Imprinting of human H19. Allele-specific CpG methylation, loss of the active allele in Wilms tumour, and In summary, we have found no compelling experimental evidence that GNAS1 is under potential for somatic allele switching","volume":"53","author":"Zhang, Y.; Shields, T.; Crenshaw, T.; Hao, Y.; Moulton, T.; Tycko, B.","year":"1993","unstructured":"Zhang Y, Shields T, Crenshaw T, Hao Y, Moulton T, Tycko B. Imprinting of human H19. Allele-specific CpG methylation, loss of the active allele in Wilms tumour, and In summary, we have found no compelling experimental evidence that GNAS1 is under potential for somatic allele switching. Am J Hum Genet 1993;53:1 13-24.","journal-title":"Am J Hum Genet"},{"key":"ref_15","first-page":"94","article-title":"IGF2 is imprinted control, despite the strong clinical evidence supporting such an effect. Prospectparentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome","volume":"4","author":"Ohlsson, R.; Nystrom, A.; Pfeifer-Ohlsson, S.","year":"1993","unstructured":"Ohlsson R, Nystrom A, Pfeifer-Ohlsson S, et al. IGF2 is imprinted control, despite the strong clinical evidence supporting such an effect. Prospectparentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome. Nature Genet 1993;4:94-7. ive study of further AHO pedigrees, combined with mutational analysis, may shed further","journal-title":"Nature Genet; ive study of further AHO pedigrees, combined with mutational analysis, may shed further"},{"key":"ref_16","first-page":"98","article-title":"Parental genomic imprinting of the human IGF2 gene","volume":"4","author":"Giannoukakis, N.; Deal, C.; Paquette, J.; Goodyer, C.G.; Polychronakos, C.","year":"1993","unstructured":"Giannoukakis N, Deal C, Paquette J, Goodyer CG, Polychronakos C. Parental genomic imprinting of the human IGF2 gene. Nature Genet 1993;4:98-101. light on the underlying postulate of imprinted inheritance of PHP and PPHP.","journal-title":"Nature Genet; light on the underlying postulate of imprinted inheritance of PHP and PPHP"},{"key":"ref_17","first-page":"2001","article-title":"Functional imprinting and epigenetic modification of the human SNRPN gene","volume":"12","author":"Glenn, C.C.; Porter, K.A.; Jong, M.T.C.; Nicholls, K.D.; Driscoll, D.J.","year":"1993","unstructured":"Glenn CC, Porter KA, Jong MTC, Nicholls KD, Driscoll DJ. Functional imprinting and epigenetic modification of the human SNRPN gene. Hum Mol Genet 1993;12:2001-5.","journal-title":"Hum Mol Genet"},{"key":"ref_18","first-page":"74","article-title":"The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nature We thank Alison Rae for operation of the ALF machine","volume":"5","author":"Kalscheuer, V.M.; Mariman, E.C.; Schepens, M.T.; Rehder, H.; Ropers, H.H.","year":"1993","unstructured":"Kalscheuer VM, Mariman EC, Schepens MT, Rehder H, Ropers HH. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nature We thank Alison Rae for operation of the ALF machine, and Genet 1993;5:74-8."},{"key":"ref_19","first-page":"156","article-title":"Single step method of RNA EDfodrimJnebHdu.rBgTrhhoic(skCawinoncrewkrhwRoaessseejauornicintthlyFthusenudpe)pxoparentrdeidmtehbneytaMtlehdewioUcrnaiklveRwreasssietapyrecroh-f isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski, P.; Sacchi, N.","year":"1987","unstructured":"Chomczynski P, Sacchi N. Single step method of RNA EDfodrimJnebHdu.rBgTrhhoic(skCawinoncrewkrhwRoaessseejauornicintthlyFthusenudpe)pxoparentrdeidmtehbneytaMtlehdewioUcrnaiklveRwreasssietapyrecroh-f isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156-9.","journal-title":"Anal Biochem"},{"key":"ref_20","first-page":"2081","article-title":"RC is an MRC research training fellow","volume-title":"characterisation of the human Gsa gene. Proc Natl Acad Sci","volume":"85","author":"Kozasa, T.; Itoh, H.; Tsukamoto, T.; Isolation, Kaziro Y.; Council","year":"1988","unstructured":"Kozasa T, Itoh H, Tsukamoto T, Kaziro Y. Isolation and Council. RC is an MRC research training fellow. characterisation of the human Gsa gene. Proc Natl Acad Sci USA 1988;85:2081-5."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6967","DOI":"10.1093\/nar\/19.24.6967","article-title":"Polymerase chain reaction (PCR) for detection of Apal polymorphism at the insulin-like growth factor II gene (IGF2)","volume":"19","author":"Tadokoro, K.; Fujii, H.; Inoue, T.; Yamada, M.","year":"1991","unstructured":"Tadokoro K, Fujii H, Inoue T, Yamada M. Polymerase chain reaction (PCR) for detection of Apal polymorphism at the insulin-like growth factor II gene (IGF2). Nucleic Acids Res 1991;19:6967.","journal-title":"Nucleic Acids Res"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1101\/gad.6.10.1843","article-title":"Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (IGF2) gene","volume":"6","author":"Sasaki, H.; Jones, P.A.; Chaillet, JR, etal","year":"1992","unstructured":"Sasaki H, Jones PA, Chaillet JR, etal. Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (IGF2) gene. Genes Devel 1992;6:1843-56.","journal-title":"Genes Devel"},{"key":"ref_23","first-page":"1096","article-title":"Oppositely imprinted genes H19 and insulin-like growth factor II are co-expressed in human androgenetic trophoblast","volume":"53","author":"Mutter, G.L.; Stewart, C.L.; Chaponot, M.L.; Pomponio, R.J.","year":"1993","unstructured":"Mutter GL, Stewart CL, Chaponot ML, Pomponio RJ. Oppositely imprinted genes H19 and insulin-like growth factor II are co-expressed in human androgenetic trophoblast. Am Hum Genet 1993;53:1096-102.","journal-title":"Am Hum Genet"},{"key":"ref_24","first-page":"369","article-title":"Steroid sulfatase gene in XX males","volume":"46","author":"Mohandas, T.K.; Stem, H.J.; Meeker, C.A.","year":"1990","unstructured":"Mohandas TK, Stem HJ, Meeker CA, et al. Steroid sulfatase gene in XX males. Am Hum Genet 1990;46:369-76.","journal-title":"Am Hum Genet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF00278971","article-title":"X-linked steroid sulfatase: evidence for different gene-dosage in males and females","volume":"54","author":"Muller, C.R.; Migl, B.; Traupe, H.; Ropers, H.H.","year":"1980","unstructured":"Muller CR, Migl B, Traupe H, Ropers HH. X-linked steroid sulfatase: evidence for different gene-dosage in males and females. Hum Genet 1980;54:197-9.","journal-title":"Hum Genet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0140-6736(81)90503-1","article-title":"Sex specific difference in placental steroid sulphatase activity","volume":"ii:","author":"Lykkesfeldt, G.; Bock, J.E.; Lykkesfeldt, A.E.","year":"1981","unstructured":"Lykkesfeldt G, Bock JE, Lykkesfeldt AE. Sex specific difference in placental steroid sulphatase activity. Lancet 1981;ii:255-6.","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF00291559","article-title":"Steroid sulphatase in man: a non inactivated X-locus with partial gene dosage compensation","volume":"65","author":"Lykkesfeldt, G.; Lykkesfeldt, A.E.; Skakkebaek, N.E.","year":"1984","unstructured":"Lykkesfeldt G, Lykkesfeldt AE, Skakkebaek NE. Steroid sulphatase in man: a non inactivated X-locus with partial gene dosage compensation. Hum Genet 1984;65:355-7.","journal-title":"Hum Genet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0378-1119(81)90062-7","article-title":"New restriction endonucleases from Flavobacterium okeanokoites (FokI) and Micrococcus luteus (MluI)","volume":"16","author":"Sugisaki, H.; Kanazawa, S.","year":"1981","unstructured":"Sugisaki H, Kanazawa S. New restriction endonucleases from Flavobacterium okeanokoites (FokI) and Micrococcus luteus (MluI). Gene 1981;16:73-8.","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/362749a0","article-title":"Relaxation of insulinlike growth factor II gene imprinting implicated in Wilms tumour","volume":"362","author":"Ogawa 0, Eccles MR, Szeto J","year":"1993","unstructured":"Ogawa 0, Eccles MR, Szeto J, et al. Relaxation of insulinlike growth factor II gene imprinting implicated in Wilms tumour. Nature 1993;362:749-51.","journal-title":"Nature"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.31.8.607","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:19:21Z","timestamp":1760761161000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.31.8.607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,8]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[1994,8,1]]},"published-print":{"date-parts":[[1994,8]]}},"alternative-id":["10.1136\/jmg.31.8.607"],"URL":"https:\/\/doi.org\/10.1136\/jmg.31.8.607","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,8]]}}}