Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (11)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Zavattari, P.
Right arrow Articles by Cucca, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zavattari, P.
Right arrow Articles by Cucca, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 20 2967-2972
© 2000 Oxford University Press

Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia

Patrizia Zavattari1, Rosanna Lampis1, Annapaola Mulargia1,2, Miriam Loddo1,2, Efisio Angius2, John A. Todd3 and Francesco Cucca1,+

1Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy, 2Servizio di Diabetologia Pediatrica, Ospedale G. Brotzu, Via Peretti, Cagliari 09121, Italy and 3Wellcome Trust Centre for Molecular Mechanisms in Disease, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2XY, UK

There is considerable uncertainty and debate concerning the application of linkage disequilibrium (LD) mapping in common multifactorial diseases, including the choice of population and the density of the marker map. Previously, it has been shown that, in the large cosmopolitan population of the UK, the established type 1 diabetes IDDM1 locus in the HLA region could be mapped with high resolution by LD. The LD curve peaked at marker D6S2444, 85 kb from the HLA class II gene DQB1, which is known to be a major determinant of IDDM1. However, given the many unknown parameters underlying LD, a validation of the approach in a genetically distinct population is necessary. In the present report we have achieved this by the LD mapping of IDDM1 in the isolated founder population of Sardinia. Using a dense map of microsatellite markers, we determined the peak of LD to be located at marker D6S2447, which is only 6.5 kb from DQB1. Next, we typed a large number of SNPs defining allelic variation at functional candidate genes within the critical region. The association curve, with both classes of marker, peaked at the loci DRB1-DQB1. These results, while representing conclusive evidence that the class II loci DRB1-DQB1 dominate the association of the HLA region to type 1 diabetes, provide empirical support for LD mapping.

+ To whom correspondence should be addressed. Tel: +39 070 6095681; Fax: +39 070 6095558; Email: fcucca@mcweb.unica.it


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
M. G. Marrosu, C. Motzo, R. Murru, R. Lampis, G. Costa, P. Zavattari, D. Contu, E. Fadda, E. Cocco, and F. Cucca
The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone
Hum. Mol. Genet., December 1, 2004; 13(23): 2919 - 2924.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Motzo, D. Contu, H. J. Cordell, R. Lampis, M. Congia, M. G. Marrosu, J. A. Todd, M. Devoto, and F. Cucca
Heterogeneity in the Magnitude of the Insulin Gene Effect on HLA Risk in Type 1 Diabetes
Diabetes, December 1, 2004; 53(12): 3286 - 3291.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. G. Marrosu, R. Murru, M. R. Murru, G. Costa, P. Zavattari, M. Whalen, E. Cocco, C. Mancosu, L. Schirru, E. Solla, et al.
Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia
Hum. Mol. Genet., December 1, 2001; 10(25): 2907 - 2916.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Zavattari, R. Lampis, C. Motzo, M. Loddo, A. Mulargia, M. Whalen, M. Maioli, E. Angius, J. A. Todd, and F. Cucca
Conditional linkage disequilibrium analysis of a complex disease superlocus, IDDM1 in the HLA region, reveals the presence of independent modifying gene effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1 disease loci
Hum. Mol. Genet., April 1, 2001; 10(8): 881 - 889.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.