{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:07:36Z","timestamp":1791900456312,"version":"4.3.4"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,4,18]]},"abstract":"<jats:p>\n                    The identification of mutations in genes that cause human diseases has largely been accomplished through the use of positional cloning, which relies on linkage mapping. In studies of rare diseases, the resolution of linkage mapping is limited by the number of available meioses and informative marker density. One recent advance is the development of high-density SNP microarrays for genotyping. The SNP arrays overcome low marker informativity by using a large number of markers to achieve greater coverage at finer resolution. We used SNP microarray genotyping for homozygosity mapping in a small consanguineous Israeli Bedouin family with autosomal recessive Bardet\u2013Biedl syndrome (BBS; obesity, pigmentary retinopathy, polydactyly, hypogonadism, renal and cardiac abnormalities, and cognitive impairment) in which previous linkage studies using short tandem repeat polymorphisms failed to identify a disease locus. SNP genotyping revealed a homozygous candidate region. Mutation analysis in the region of homozygosity identified a conserved homozygous missense mutation in the\n                    <jats:italic>TRIM32<\/jats:italic>\n                    gene, a gene coding for an E3 ubiquitin ligase. Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci data set demonstrate that\n                    <jats:italic>TRIM32<\/jats:italic>\n                    is a BBS gene. This study shows the value of high-density SNP genotyping for homozygosity mapping and the use of expression correlation data for evaluation of candidate genes and identifies the proteasome degradation pathway as a pathway involved in BBS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0600158103","type":"journal-article","created":{"date-parts":[[2006,4,10]],"date-time":"2006-04-10T20:44:14Z","timestamp":1144701854000},"page":"6287-6292","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":367,"title":["Homozygosity mapping with SNP arrays identifies\n                    <i>TRIM32<\/i>\n                    , an E3 ubiquitin ligase, as a Bardet\u2013Biedl syndrome gene (\n                    <i>BBS11<\/i>\n                    )"],"prefix":"10.1073","volume":"103","author":[{"given":"Annie P.","family":"Chiang","sequence":"first","affiliation":[{"name":"Departments of *Electrical Engineering,"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Beck","sequence":"additional","affiliation":[{"name":"Pediatrics,"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsan-Jan","family":"Yen","sequence":"additional","affiliation":[{"name":"Pediatrics,"},{"name":"Biological Sciences, and"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan K.","family":"Tayeh","sequence":"additional","affiliation":[{"name":"Pediatrics,"},{"name":"Biological Sciences, and"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Scheetz","sequence":"additional","affiliation":[{"name":"Ophthalmology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Swiderski","sequence":"additional","affiliation":[{"name":"Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl Y.","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry A.","family":"Braun","sequence":"additional","affiliation":[{"name":"Ophthalmology,"},{"name":"Biomedical Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Youn A.","family":"Kim","sequence":"additional","affiliation":[{"name":"**Biostatistics,"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[{"name":"Statistics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Elbedour","sequence":"additional","affiliation":[{"name":"Genetic Institute, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Carmi","sequence":"additional","affiliation":[{"name":"Genetic Institute, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane C.","family":"Slusarski","sequence":"additional","affiliation":[{"name":"Biological Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Casavant","sequence":"additional","affiliation":[{"name":"Departments of *Electrical Engineering,"},{"name":"Ophthalmology,"},{"name":"Biomedical Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin M.","family":"Stone","sequence":"additional","affiliation":[{"name":"Ophthalmology,"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val C.","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Pediatrics,"},{"name":"Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,4,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1558"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198910123211503"},{"key":"e_1_3_4_3_2","volume-title":"Ph.D. thesis","author":"Bardet G.","year":"1920","unstructured":"G. Bardet Ph.D. thesis (University of Paris, Paris, 1920)."},{"key":"e_1_3_4_4_2","first-page":"1630","volume":"48","author":"Biedl A.","year":"1922","unstructured":"A. Biedl Dtsch. Med. Wschr 48, 1630 (1922).","journal-title":"Dtsch. Med. Wschr"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198809083191005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320520208"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-392"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.8.1331"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320590216"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/302301"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/79201"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20001127)95:3<208::AID-AJMG5>3.0.CO;2-J"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/88925"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.8.865"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng935"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02030"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/368204"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/423903"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1414"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00450-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/498323"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh092"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201372"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2140"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh003"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/339083"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069516"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01434"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02797"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi468"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00997"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.4.965"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","volume":"162","author":"Hoshino K.","year":"1999","unstructured":"K. Hoshino, O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, S. Akira J. Immunol 162, 3749\u20133752 (1999).","journal-title":"J. Immunol"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402354101"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405496101"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi123"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1352"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1418"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1194004"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1266"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.09.068"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/6799"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.1.109"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01629"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1453"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1086\/302836"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401692"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1552"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401702"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401710"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_3_4_52_2","author":"Stoetzel C.","year":"2006","unstructured":"C. Stoetzel, V. Laurier, E. E. Davis, J. Muller, S. Rix, J. L. Badano, C. C. Leitch, N. Salem, E. Chouery, S. Corbani, et al. Nat. Genet, 10.1038\/ng1771. (2006).","journal-title":"Nat. Genet"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0600158103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T21:22:41Z","timestamp":1683408161000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0600158103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4,18]]},"references-count":52,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2006,4,18]]}},"alternative-id":["10.1073\/pnas.0600158103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0600158103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,4,18]]},"assertion":[{"value":"2006-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-04-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}