Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia


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Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia
BMC Med Genet
Pitzalis M., Zavattari P., Murru R., Deidda E., Zoledziewska M., Murru D., Moi L., Motzo C., Orru V., Costa G., Solla E., Fadda E., Schirru L., Melis M. C., Lai M., Mancosu C., Tranquilli S., Cuccu S., Rolesu M., Secci M. A., Corongiu D., Contu D., Lampis R., Nucaro A., Pala G., Pacifico A., Maioli M., Frongia P., Chessa M., Ricciardi R., Lostia S., Marinaro A. M., Milia A. F., Landis N., Zedda M. A., Whalen M. B., Santoni F., Marrosu M. G., Devoto M., Cucca F.
1471-2350 (Electronic)
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Pitzalis, Maristella
Zavattari, Patrizia
Murru, Raffaele
Deidda, Elisabetta
Zoledziewska, Magdalena
Murru, Daniela
Moi, Loredana
Motzo, Costantino
Orru, Valeria
Costa, Gianna
Solla, Elisabetta
Fadda, Elisabetta
Schirru, Lucia
Melis, Maria Cristina
Lai, Marina
Mancosu, Cristina
Tranquilli, Stefania
Cuccu, Stefania
Rolesu, Marcella
Secci, Maria Antonietta
Corongiu, Daniela
Contu, Daniela
Lampis, Rosanna
Nucaro, Annalisa
Pala, Gavino
Pacifico, Adolfo
Maioli, Mario
Frongia, Paola
Chessa, Margherita
Ricciardi, Rossella
Lostia, Stanislao
Marinaro, Anna Maria
Milia, Anna Franca
Landis, Novella
Zedda, Maria Antonietta
Whalen, Michael B
Santoni, Federico
Marrosu, Maria Giovanna
Devoto, Marcella
Cucca, Francesco
Research Support, Non-U.S. Gov't
BMC Med Genet. 2008 Jan 20;9:3. doi: 10.1186/1471-2350-9-3.
BACKGROUND: 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. METHODS: 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. RESULTS: In T1D, aside from the HLA locus, we found four regions showing a lod-score > or =1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score > or =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). CONCLUSION: This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.
Adolescent, Adult, Child, Chromosome Mapping, Diabetes Mellitus, Type 1/complications/*genetics, Female, *Genetic Linkage, Genetic Markers/genetics, *Genetic Predisposition to Disease, Haplotypes, Humans, Male, Mediterranean Islands, Microsatellite Repeats/*genetics, Middle Aged, Multiple Sclerosis/complications/*genetics, Quantitative Trait Loci, Statistics, Nonparametric
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