{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:23:47Z","timestamp":1778624627404,"version":"3.51.4"},"reference-count":68,"publisher":"The Royal Society","issue":"1460","license":[{"start":{"date-parts":[[2005,7,25]],"date-time":"2005-07-25T00:00:00Z","timestamp":1122249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2005,8,29]]},"abstract":"<jats:p>\n                    Susceptibility genes for complex diseases are characterized by reduced penetrance, caused by the influence of other genes, the environment or stochastic events. Recently, positional cloning efforts have yielded several candidate susceptibility genes in different complex disorders such as Crohn's disease and asthma. Within a genetic locus, however, the identification of the effector gene may pose further challenges and require functional studies. I review two examples of such challenges: the cloning of\n                    <jats:italic>GPR154<\/jats:italic>\n                    (\n                    <jats:italic>GPRA<\/jats:italic>\n                    ) and\n                    <jats:italic>AAA1<\/jats:italic>\n                    on chromosome 7p14 at a susceptibility locus for atopy and asthma, and the study of\n                    <jats:italic>HLA-Cw6<\/jats:italic>\n                    ,\n                    <jats:italic>CCHCR1<\/jats:italic>\n                    (\n                    <jats:italic>HCR<\/jats:italic>\n                    ) and\n                    <jats:italic>CDSN<\/jats:italic>\n                    on chromosome 6p21 at\n                    <jats:italic>PSORS1<\/jats:italic>\n                    , the major susceptibility locus for psoriasis. The susceptibility locus for atopy and asthma contains two genes and only one of them is protein coding. We studied its isoform-specific expression in bronchial biopsies and in a mouse model of ovalbumin-induced inflammation of bronchial epithelia. In the\n                    <jats:italic>PSORS1<\/jats:italic>\n                    locus, strong linkage disequilibrium between genes has made it difficult to distinguish the effects of the three nearby genes. We engineered transgenic mice with either a\n                    <jats:italic>HCR<\/jats:italic>\n                    non-risk allele or the\n                    <jats:italic>HCR*WWCC<\/jats:italic>\n                    risk allele controlled by the cytokeratin-14 promoter. The results suggested that the overexpression of\n                    <jats:italic>HCR<\/jats:italic>\n                    in mouse skin was insufficient to induce a psoriasiform phenotype, but it appeared to induce allele-specific gene expression changes that were similar to those observed in psoriatic skin.\n                  <\/jats:p>","DOI":"10.1098\/rstb.2005.1684","type":"journal-article","created":{"date-parts":[[2005,7,25]],"date-time":"2005-07-25T16:40:02Z","timestamp":1122309602000},"page":"1551-1561","source":"Crossref","is-referenced-by-count":16,"title":["Mapping and identifying genes for asthma and psoriasis"],"prefix":"10.1098","volume":"360","author":[{"given":"Juha","family":"Kere","sequence":"first","affiliation":[{"name":"Department of Biosciences at Novum, Karolinska Institutet14157 Huddinge, Sweden"},{"name":"Department of Medical Genetics, University of Helsinki00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2005,7,25]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1256"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/324069"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/79216"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1533"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.589"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12483.x"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90357-U"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01381-4"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh340"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.17.1793"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01245-2.x"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-389"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/383247a0"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.5.2002113"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh178"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9494"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308250100"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/342205"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-4-14"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(03)01939-0"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35079107"},{"key":"e_1_3_2_24_1","first-page":"47","article-title":"Genetics of asthma and related phenotypes","volume":"3","author":"Illig T","year":"2002","journal-title":"Paediatr. Respir. Rev"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/377159"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1996.tb02626.x"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.1999.540501.x"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.042358"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.1938.x"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.01860.x"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2004.09.011"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200410-1312OC"},{"key":"e_1_3_2_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.4.9704041"},{"key":"e_1_3_2_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0501-87"},{"key":"e_1_3_2_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090010"},{"key":"e_1_3_2_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8091226"},{"key":"e_1_3_2_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.01977.x"},{"key":"e_1_3_2_38_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200306-877OC"},{"issue":"4","key":"e_1_3_2_39_1","first-page":"57","article-title":"Meta-analysis and retrospective collaboration: two methods to map oligogenes for atopy and asthma","volume":"29","author":"Lonjou C","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"e_1_3_2_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.20.10942"},{"key":"e_1_3_2_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/rmed.2001.1126"},{"issue":"4","key":"e_1_3_2_42_1","first-page":"27","article-title":"Candidate genes and a genome-wide search in Italian families with atopic asthmatic children","volume":"29","author":"Malerba G","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"e_1_3_2_43_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200410-1317OC"},{"key":"e_1_3_2_44_1","doi-asserted-by":"publisher","DOI":"10.1086\/302932"},{"key":"e_1_3_2_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.9.1393"},{"key":"e_1_3_2_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01323.x"},{"key":"e_1_3_2_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/35079114"},{"key":"e_1_3_2_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2165"},{"key":"e_1_3_2_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212813200"},{"key":"e_1_3_2_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101659"},{"key":"e_1_3_2_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00163.2003"},{"key":"e_1_3_2_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1339"},{"key":"e_1_3_2_53_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0330OC"},{"key":"e_1_3_2_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.03.035"},{"key":"e_1_3_2_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-223"},{"key":"e_1_3_2_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.08.003"},{"key":"e_1_3_2_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.6.1135"},{"key":"e_1_3_2_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1980.tb05690.x"},{"key":"e_1_3_2_59_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0028OC"},{"key":"e_1_3_2_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00878"},{"key":"e_1_3_2_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230374100"},{"key":"e_1_3_2_62_1","doi-asserted-by":"publisher","DOI":"10.1086\/342289"},{"key":"e_1_3_2_63_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0405OC"},{"key":"e_1_3_2_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh080"},{"key":"e_1_3_2_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.01846.x"},{"key":"e_1_3_2_66_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5806"},{"key":"e_1_3_2_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.08.005"},{"key":"e_1_3_2_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410613200"},{"key":"e_1_3_2_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1166"}],"container-title":["Philosophical Transactions of the Royal Society B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2005.1684","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rstb.2005.1684","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2005.1684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:26:22Z","timestamp":1778621182000},"score":1,"resource":{"primary":{"URL":"http:\/\/royalsocietypublishing.org\/rstb\/article\/360\/1460\/1551-1561\/20607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,25]]},"references-count":68,"journal-issue":{"issue":"1460","published-print":{"date-parts":[[2005,8,29]]}},"alternative-id":["10.1098\/rstb.2005.1684"],"URL":"https:\/\/doi.org\/10.1098\/rstb.2005.1684","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,25]]}}}