caa a22 4500 475771222 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s001250051378 doi (NATIONALLICENCE)springer-10.1007/s001250051378 Complete molecular scanning of the human Fas gene: mutational analysis and linkage studies in families with Type I diabetes mellitus [Elektronische Daten] [R. L. Nolsøe, O. P. Kristiansen, K. Sangthongpitag, Z. M. Larsen, J. Johannesen, A. E. Karlsen, F. Pociot, J. Nerup, C. F. Verge, T. Mandrup-Poulsen] Aims/hypothesis. The human Fas gene (FAS) on chromosome 10q24.1 encoding a cell surface receptor involved in apoptosis was evaluated as a candidate susceptibility gene for Type I (insulin-dependent) diabetes mellitus. Apoptosis mediated by Fas is important in maintaining peripheral self-tolerance and in down-regulating the immune response and could have a role in immune-mediated beta-cell destruction.¶Methods. We did a molecular scan of the entire human FAS (promoter, exons 1-9 including exon-intron boundaries and the 3 ′UTR) using single strand conformational polymorphism-heteroduplex analysis.¶Results. We identified 15 mutations, of which 11 are new. Of these a g-1194A→T and a g-295Ains give rise to alterations of transcription-factor-binding consensus sequences for c-Myb, SP-1 and NF-kB, respectively. A total of 1068 people from a Danish family collection comprising 138 Type I diabetic sib-pair families (289 affected and 121 unaffected offspring) and 103 Type I diabetic parent-offspring multiplex families (103 affected and 112 unaffected offspring) were typed for the three most frequent polymorphisms with high heterozygosity indices and for a FAS microsatellite. Haplotypes were established and data analysed using the extended transmission disequilibrium test, ETDT.¶Conclusion/interpretation. We found no overall evidence for linkage of the FAS polymorphisms to Type I diabetes. We conclude that it is unlikely that the Fas gene does contribute to genetic susceptibility for Type I diabetes. [Diabetologia (2000) 43: 800-808] Springer-Verlag Berlin Heidelberg, 2000 Keywords Genetics, candidate gene, apoptosis, tolerance, microsatellite, ALPS, c-Myb, SP-1, NF-kB nationallicence Nolsøe R. L. Steno Diabetes Center, Gentofte, Denmark, DK aut Kristiansen O. P. Steno Diabetes Center, Gentofte, Denmark, DK aut Sangthongpitag K. Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia, AU aut Larsen Z. M. Steno Diabetes Center, Gentofte, Denmark, DK aut Johannesen J. Steno Diabetes Center, Gentofte, Denmark, DK aut Karlsen A. E. Steno Diabetes Center, Gentofte, Denmark, DK aut Pociot F. Steno Diabetes Center, Gentofte, Denmark, DK aut Nerup J. Steno Diabetes Center, Gentofte, Denmark, DK aut Verge C. F. Sydney Children's Hospital, University of New South Wales, Sydney, Australia, AU aut Mandrup-Poulsen T. Steno Diabetes Center, Gentofte, Denmark, DK aut https://doi.org/10.1007/s001250051378 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051378 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nolsøe R. L. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Kristiansen O. P. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Sangthongpitag K. Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Larsen Z. M. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Johannesen J. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Karlsen A. E. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Pociot F. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Nerup J. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Verge C. F. Sydney Children's Hospital, University of New South Wales, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Mandrup-Poulsen T. Steno Diabetes Center, Gentofte, Denmark, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer