title: Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia.
abstract: 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).
  
  
  CONCLUSIONS
  This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.
authors.affiliation: Dipartimento di Scienze Biomediche, University of Sassari, 07100 Sassari, Italy. fcucca@uniss.it.
authors.forename: Maristella
authors.initials: M
authors.lastname: Pitzalis
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zavattari
authors.forename: Raffaele
authors.initials: R
authors.lastname: Murru
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Deidda
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zoledziewska
authors.forename: Daniela
authors.initials: D
authors.lastname: Murru
authors.forename: Loredana
authors.initials: L
authors.lastname: Moi
authors.forename: Costantino
authors.initials: C
authors.lastname: Motzo
authors.forename: Valeria
authors.initials: V
authors.lastname: Orrù
authors.forename: Gianna
authors.initials: G
authors.lastname: Costa
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Solla
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fadda
authors.forename: Lucia
authors.initials: L
authors.lastname: Schirru
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Melis
authors.forename: Marina
authors.initials: M
authors.lastname: Lai
authors.forename: Cristina
authors.initials: C
authors.lastname: Mancosu
authors.forename: Stefania
authors.initials: S
authors.lastname: Tranquilli
authors.forename: Stefania
authors.initials: S
authors.lastname: Cuccu
authors.forename: Marcella
authors.initials: M
authors.lastname: Rolesu
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Secci
authors.forename: Daniela
authors.initials: D
authors.lastname: Corongiu
authors.forename: Daniela
authors.initials: D
authors.lastname: Contu
authors.forename: Rosanna
authors.initials: R
authors.lastname: Lampis
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nucaro
authors.forename: Gavino
authors.initials: G
authors.lastname: Pala
authors.forename: Adolfo
authors.initials: A
authors.lastname: Pacifico
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: Paola
authors.initials: P
authors.lastname: Frongia
authors.forename: Margherita
authors.initials: M
authors.lastname: Chessa
authors.forename: Rossella
authors.initials: R
authors.lastname: Ricciardi
authors.forename: Stanislao
authors.initials: S
authors.lastname: Lostia
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marinaro
authors.forename: Anna Franca
authors.initials: AF
authors.lastname: Milia
authors.forename: Novella
authors.initials: N
authors.lastname: Landis
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zedda
authors.forename: Michael B
authors.initials: MB
authors.lastname: Whalen
authors.forename: Federico
authors.initials: F
authors.lastname: Santoni
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Marrosu
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008521:Mediterranean Islands; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics*; D040641:Quantitative Trait Loci; D018709:Statistics, Nonparametric
chemical_list: D005819:Genetic Markers