Open Access Highly Accessed Research article

Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia

Maristella Pitzalis1, Patrizia Zavattari2, Raffaele Murru3, Elisabetta Deidda2, Magdalena Zoledziewska1, Daniela Murru2, Loredana Moi23, Costantino Motzo1, Valeria Orrù2, Gianna Costa3, Elisabetta Solla3, Elisabetta Fadda3, Lucia Schirru3, Maria Cristina Melis3, Marina Lai3, Cristina Mancosu3, Stefania Tranquilli3, Stefania Cuccu3, Marcella Rolesu3, Maria Antonietta Secci3, Daniela Corongiu3, Daniela Contu2, Rosanna Lampis2, Annalisa Nucaro4, Gavino Pala5, Adolfo Pacifico6, Mario Maioli6, Paola Frongia7, Margherita Chessa7, Rossella Ricciardi7, Stanislao Lostia8, Anna Maria Marinaro9, Anna Franca Milia10, Novella Landis11, Maria Antonietta Zedda12, Michael B Whalen1, Federico Santoni13, Maria Giovanna Marrosu3, Marcella Devoto1415 and Francesco Cucca116*

  • * Corresponding author: Francesco Cucca

  • † Equal contributors

Author Affiliations

1 Dipartimento di Scienze Biomediche, University of Sassari, 07100 Sassari, Italy

2 Laboratorio di Immunogenetica, Ospedale Microcitemico, 09121 Cagliari, Italy

3 Centro Sclerosi Multipla, Dipartimento di Scienze Neurologiche e Cardiovascolari, University of Cagliari, 09126 Cagliari, Italy

4 Consiglio Nazionale delle Ricerche, Istituto di Neurogenetica e Neurofarmacologia, 09047 Cagliari, Italy

5 Diabetologia Ospedaliera, Dipartimento di Medicina, Ospedale San Francesco, 08100 Nuoro, Italy

6 Istituto di Clinica Medica, Servizio di Diabetologia, University of Sassari, 07100 Sassari, Italy

7 Servizio di Diabetologia Pediatrica, Ospedale Brotzu, 09100 Cagliari, Italy

8 Unità Operativa di Diabetologia, Ospedale Brotzu, 09100 Cagliari, Italy

9 Dipartimento Pediatrico e Neonatologico, University of Sassari, 07100 Sassari, Italy

10 Diabetologia Pediatrica Ospedale S. Francesco, 08100 Nuoro, Italy

11 Diabetologia Pediatrica, Ospedale Crobu, 09016 Iglesias, Italy

12 Prima Clinica Pediatrica, Unità Operativa di Diabetologia dell'Età Evolutiva, 09100 Cagliari, Italy

13 CRS4, Parco Scientifico e Tecnologico, Polaris, Edificio 1, 09010 Pula, Italy

14 The Children's Hospital of Philadelphia, Division of Human Genetics, and CCEB, University of Pennsylvania, Philadelphia, PA, USA

15 Dipartimento di Medicina Sperimentale, University La Sapienza, 00185 Rome, Italy

16 Sardegna Ricerche, Parco Scientifico e Tecnologico, Polaris, 09010 Pula, Italy

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BMC Medical Genetics 2008, 9:3  doi:10.1186/1471-2350-9-3

Published: 20 January 2008



The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis.


To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic.


In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5).


This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.