{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:40:20Z","timestamp":1792640420563,"version":"4.5.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,5,28]]},"abstract":"<jats:p>\n                    Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of\n                    <jats:italic>Shh<\/jats:italic>\n                    is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (\n                    <jats:italic>Ssq<\/jats:italic>\n                    ). The genetic lesions in both lie within the same respective intron of the\n                    <jats:italic>LMBR1<\/jats:italic>\n                    \/\n                    <jats:italic>Lmbr1<\/jats:italic>\n                    gene, which resides \u22481 Mb away from\n                    <jats:italic>Shh<\/jats:italic>\n                    . Genetic analysis of\n                    <jats:italic>Ssq<\/jats:italic>\n                    reveals that the\n                    <jats:italic>Lmbr1<\/jats:italic>\n                    gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of\n                    <jats:italic>Shh<\/jats:italic>\n                    . This regulator is most likely the target for generating PPD mutations in human.\n                  <\/jats:p>","DOI":"10.1073\/pnas.112212199","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:46:49Z","timestamp":1027680409000},"page":"7548-7553","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":404,"title":["Disruption of a long-range cis-acting regulator for\n                    <i>Shh<\/i>\n                    causes preaxial polydactyly"],"prefix":"10.1073","volume":"99","author":[{"given":"Laura A.","family":"Lettice","sequence":"first","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Horikoshi","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J. H.","family":"Heaney","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke J.","family":"van Baren","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herma C.","family":"van der Linde","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido J.","family":"Breedveld","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Joosse","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurten","family":"Akarsu","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben A.","family":"Oostra","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Endo","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Shibata","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Shinka","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Nakahori","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Ayusawa","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakabayashi","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Scherer","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heutink","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Hill","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumihare","family":"Noji","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-8506, Japan; Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,5,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-287"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320580208"},{"key":"e_1_3_3_3_2","first-page":"597","volume":"60","author":"Radhakrishna U","year":"1997","unstructured":"U Radhakrishna, J L Blouin, H Mehenni, U C Patel, M N Patel, J V Solanki, S E Antonarakis Am J Hum Genet 60, 597\u2013604 (1997).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_4_2","first-page":"32","volume":"36","author":"Zguricas J","year":"1999","unstructured":"J Zguricas, H Heus, E Morales-Peralta, G Breedveld, B Kuyt, E F Mumcu, W Bakker, N Akarsu, S P Kay, S E Hovius, et al. J Med Genet 36, 32\u201340 (1999).","journal-title":"J Med Genet"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5796"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/316955"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-282"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.304"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80022-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00205165"},{"key":"e_1_3_3_11_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989).","edition":"2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00222-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6225"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-010X(19981215)282:6<677::AID-JEZ4>3.0.CO;2-F"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-353"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1645"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.8457"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.21.4729"},{"key":"e_1_3_3_20_2","first-page":"253","volume":"20","author":"Toledo S P A","year":"1972","unstructured":"S P A Toledo, P H Saldanha J Genet Hum 20, 253\u2013258 (1972).","journal-title":"J Genet Hum"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320360320"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0346"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00492-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/159.2.715"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.112212199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:48:01Z","timestamp":1649796481000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.112212199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,14]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2002,5,28]]}},"alternative-id":["10.1073\/pnas.112212199"],"URL":"https:\/\/doi.org\/10.1073\/pnas.112212199","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,14]]},"assertion":[{"value":"2002-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-04-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-05-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}