Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia.
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.
Pitzalis
Maristella
M
Dipartimento di Scienze Biomediche, University of Sassari, 07100 Sassari, Italy. fcucca@uniss.it.
Zavattari
Patrizia
P
Murru
Raffaele
R
Deidda
Elisabetta
E
Zoledziewska
Magdalena
M
Murru
Daniela
D
Moi
Loredana
L
Motzo
Costantino
C
Orrù
Valeria
V
Costa
Gianna
G
Solla
Elisabetta
E
Fadda
Elisabetta
E
Schirru
Lucia
L
Melis
Maria Cristina
MC
Lai
Marina
M
Mancosu
Cristina
C
Tranquilli
Stefania
S
Cuccu
Stefania
S
Rolesu
Marcella
M
Secci
Maria Antonietta
MA
Corongiu
Daniela
D
Contu
Daniela
D
Lampis
Rosanna
R
Nucaro
Annalisa
A
Pala
Gavino
G
Pacifico
Adolfo
A
Maioli
Mario
M
Frongia
Paola
P
Chessa
Margherita
M
Ricciardi
Rossella
R
Lostia
Stanislao
S
Marinaro
Anna Maria
AM
Milia
Anna Franca
AF
Landis
Novella
N
Zedda
Maria Antonietta
MA
Whalen
Michael B
MB
Santoni
Federico
F
Marrosu
Maria Giovanna
MG
Devoto
Marcella
M
Cucca
Francesco
F
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
D005819:Genetic Markers