{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:32:22Z","timestamp":1760887942036},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4512","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1981,9,4]]},"abstract":"<jats:p>The arrangement of the human insulin gene in DNA from 87 individuals was analyzed by the Southern blot hybridization technique with a cloned genomic human insulin probe. Insertions of 1.5 to 3.4 kilobase pairs in the 5\u2032-flanking region of the gene were found in DNA from 38 individuals. These insertions occurred within 1.3 kilobase pairs of the transcription initiation site. In contrast, no insertions were observed in the region 3\u2032 to the coding sequence. The prevalence of these insertions in type 2 diabetes was significantly greater than in the other groups (P &lt; .001). The limitation of this striking length polymorphism to a potential promoter region suggests that these insertions may play a role in insulin gene expression.<\/jats:p>","DOI":"10.1126\/science.6267694","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T17:45:58Z","timestamp":1160070358000},"page":"1117-1120","source":"Crossref","is-referenced-by-count":63,"title":["Polymorphism in the 5\u2032-Flanking Region of the Human Insulin Gene and Its Possible Relation to Type 2 Diabetes"],"prefix":"10.1126","volume":"213","author":[{"given":"Peter","family":"Rotwein","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University, St. Louis, Missouri 63110"},{"name":"Department of Anatomy, Washington University, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rose","family":"Chyn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University, St. Louis, Missouri 63110"},{"name":"Department of Anatomy, Washington University, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Chirgwin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University, St. Louis, Missouri 63110"},{"name":"Department of Anatomy, Washington University, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Cordell","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco 94143"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard M.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco 94143"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Alan","family":"Permut","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.2337\/diab.28.12.1039","volume":"28","year":"1979","unstructured":"DIABETES 28: 1039 (1979).","journal-title":"DIABETES"},{"key":"e_1_2_1_2_1","unstructured":"BELL G COMMUNICATION."},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/284026a0","volume":"284","year":"1980","unstructured":"BELL, G.I., SEQUENCE OF THE HUMAN INSULIN GENE, NATURE 284: 26 (1980).","journal-title":"NATURE"},{"key":"e_1_2_1_4_1","first-page":"4091","volume":"18","year":"1980","unstructured":"BELL, G. I., NUCLEIC ACIDS RESEARCH 18: 4091 (1980).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_5_1","first-page":"6","year":"1968","unstructured":"BOYUM, A, SCANDINAVIAN JOURNAL OF CLINICAL AND LABORATORY INVESTIGATION 97: 6 (1968).","journal-title":"SCANDINAVIAN JOURNAL OF CLINICAL AND LABORATORY INVESTIGATION"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0092-8674(80)90305-0","volume":"20","year":"1980","unstructured":"CALOS, M.P., TRANSPOSABLE ELEMENTS, CELL 20: 579 (1980).","journal-title":"CELL"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/0092-8674(79)90070-9","volume":"18","year":"1979","unstructured":"CORDELL, B, ISOLATION AND CHARACTERIZATION OF A CLONED RAT INSULIN GENE, CELL 18: 533 (1979).","journal-title":"CELL"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6251548"},{"key":"e_1_2_1_9_1","first-page":"1007","volume":"2","year":"1979","unstructured":"Fajans, S. S., Endocrinology 2: 1007 (1979).","journal-title":"Endocrinology"},{"key":"e_1_2_1_10_1","first-page":"2881","volume":"76","year":"1979","unstructured":"GABBAY, K.H., FAMILIAL HYPER-PROINSULINEMIA - PARTIAL CHARACTERIZATION OF CIRCULATING PROINSULIN-LIKE MATERIAL, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76: 2881 (1979).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJM198001173020301","volume":"302","year":"1980","unstructured":"GIVEN, B.D., DIABETES DUE TO SECRETION OF AN ABNORMAL INSULIN, NEW ENGLAND JOURNAL OF MEDICINE 302: 129 (1980).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_12_1","first-page":"1432","volume":"77","year":"1980","unstructured":"Grosschedl, R., Proceedings of the National Academy of Sciences of the United States of America 77: 1432 (1980).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1469-1809.1972.tb00578.x","volume":"36","year":"1972","unstructured":"HARRIS, H, AVERAGE HETEROZYGOSITY PER LOCUS IN MAN - AN ESTIMATE BASED ON INCIDENCE OF ENZYME POLYMORPHISMS, ANNALS OF HUMAN GENETICS 36: 9 (1972).","journal-title":"ANNALS OF HUMAN GENETICS"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(79)90348-9"},{"key":"e_1_2_1_15_1","first-page":"5631","volume":"75","year":"1978","unstructured":"KAN, Y.W., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 75: 5631 (1978).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_16_1","first-page":"262","year":"1979","unstructured":"Kanazawa, Y., Proinsulin, Insulin, C-Peptide: 262 (1979).","journal-title":"Proinsulin, Insulin, C-Peptide"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1172\/JCI109790","volume":"65","year":"1980","unstructured":"KOLTERMAN, O.G., MECHANISMS OF INSULIN RESISTANCE IN HUMAN OBESITY - EVIDENCE FOR RECEPTOR AND POSTRECEPTOR DEFECTS, JOURNAL OF CLINICAL INVESTIGATION 65: 1272 (1980).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/0006-291X(81)91188-8","volume":"98","year":"1981","unstructured":"KWOK, SCM, LOSS OF A RESTRICTION ENDONUCLEASE CLEAVAGE SITE IN THE GENE OF A STRUCTURALLY ABNORMAL HUMAN INSULIN, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 98: 844 (1981).","journal-title":"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS"},{"key":"e_1_2_1_19_1","unstructured":"LEBO R.V. UNPUBLISHED."},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/287188a0","volume":"287","year":"1980","unstructured":"MCKAY, R, MOVABLE GENES, NATURE 287: 188 (1980).","journal-title":"NATURE"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0022-2836(77)90052-3","volume":"113","year":"1977","unstructured":"RIGBY, PWJ, LABELING DEOXYRIBONUCLEIC-ACID TO HIGH SPECIFIC ACTIVITY INVITRO BY NICK TRANSLATION WITH DNA-POLYMERASE I, JOURNAL OF MOLECULAR BIOLOGY 113: 237 (1977).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0002-9343(81)90418-6","volume":"70","year":"1981","unstructured":"ROTTER, J. I., AMERICAN JOURNAL OF MEDICINE 70: 116 (1981).","journal-title":"AMERICAN JOURNAL OF MEDICINE"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(75)80083-0"},{"key":"e_1_2_1_24_1","first-page":"399","volume":"17","year":"1981","unstructured":"STRATHERN, J.N., JOURNAL OF SUPRAMOLECULAR STRUCTURE AND CELLULAR BIOCHEMISTRY 17 5: 399 (1981).","journal-title":"JOURNAL OF SUPRAMOLECULAR STRUCTURE AND CELLULAR BIOCHEMISTRY"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/281122a0","volume":"281","year":"1979","unstructured":"TAGER, H, STRUCTURALLY ABNORMAL INSULIN CAUSING HUMAN DIABETES, NATURE 281: 122 (1979).","journal-title":"NATURE"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/251392a0","volume":"251","year":"1974","unstructured":"TAYLOR, J.M., GENE DELETION AS CAUSE OF ALPHA THALASSEMIA - GENETIC LESION IN HOMOZYGOUS ALPHA THALASSEMIA (HYDROPS FETALIS), NATURE 251: 392 (1974).","journal-title":"NATURE"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.6248962","volume":"209","year":"1980","unstructured":"ULLRICH, A, GENETIC-VARIATION IN THE HUMAN INSULIN GENE, SCIENCE 209: 612 (1980).","journal-title":"SCIENCE"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/283637a0","volume":"283","year":"1980","unstructured":"VANDERPLOEG, LHT, GAMMA-BETA-THALASSAEMIA STUDIES SHOWING THAT DELETION OF THE GAMMA-GENES AND DELTA-GENES INFLUENCES BETA-GLOBIN GENE-EXPRESSION IN MAN, NATURE 283: 637 (1980).","journal-title":"NATURE"},{"key":"e_1_2_1_29_1","first-page":"3683","volume":"76","year":"1979","unstructured":"WAHL, G.M., EFFICIENT TRANSFER OF LARGE DNA FRAGMENTS FROM AGAROSE GELS TO DIAZOBENZYLOXYMETHYL-PAPER AND RAPID HYBRIDIZATION BY USING DEXTRAN SULFATE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76: 3683 (1979).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0092-8674(79)90022-9","volume":"16","year":"1979","unstructured":"WEATHERALL, D.J., RECENT DEVELOPMENTS IN THE MOLECULAR GENETICS OF HUMAN-HEMOGLOBIN, CELL 16: 467 (1979).","journal-title":"CELL"},{"key":"e_1_2_1_31_1","first-page":"1577","volume":"78","year":"1981","unstructured":"WU, C, TISSUE-SPECIFIC EXPOSURE OF CHROMATIN STRUCTURE AT THE 5' TERMINUS OF THE RAT PREPROINSULIN-II GENE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 78: 1577 (1981).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES"},{"key":"e_1_2_1_32_1","first-page":"6754","volume":"77","year":"1980","unstructured":"Wyman, A. R., Proceedings of the National Academy of Sciences of the United States of America 77: 6754 (1980).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.6267694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T23:14:41Z","timestamp":1705274081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.6267694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1981,9,4]]},"references-count":32,"journal-issue":{"issue":"4512","published-print":{"date-parts":[[1981,9,4]]}},"alternative-id":["10.1126\/science.6267694"],"URL":"https:\/\/doi.org\/10.1126\/science.6267694","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1981,9,4]]}}}