Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.
By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Hills Road, Cambridge, UK. mb531@medschl.cam.ac.uk
Ban
Maria
M
Booth
David
D
Heard
Robert
R
Stewart
Graeme
G
Goris
An
A
Vandenbroeck
Koen
K
Dubois
Bénédicte
B
Laaksonen
Mikko
M
Ilonen
Jorma
J
Alizadeh
Mehdi
M
Edan
Gilles
G
Babron
Marie Claude
MC
Brassat
David
D
Clanet
Michael
M
Cournu-Rebeix
Isabelle
I
Fontaine
Bertrand
B
Semana
Gilbert
G
Goedde
Rene
R
Epplen
Jorg
J
Weber
Alexandra
A
Infante-Duarte
Carmen
C
Zipp
Frauke
F
Rajda
Cecilia
C
Bencsik
Krisztina
K
Vécsei
László
L
Heggarty
Shirley
S
Graham
Colin
C
Hawkins
Stanley
S
Liguori
Maria
M
Momigliano-Richiardi
Patricia
P
Caputo
Domenico
D
Grimaldi
Luigi M E
LM
Leone
Maurizio
M
Massacesi
Luca
L
Milanese
Clara
C
Salvetti
Marco
M
Savettieri
Giovani
G
Trojano
Maria
M
Bielecki
Bartosz
B
Mycko
Marcin P
MP
Selmaj
Krzysztof
K
Santos
Monica
M
Maciel
Patricia
P
Pereira
Clara
C
Silva
Ana
A
Silva
Berta Martins
BM
Coraddu
Francesca
F
Marrosu
Maria Giovanna
MG
Akesson
Eva
E
Hillert
Jan
J
Datta
Pameli
P
Oturai
Annette
A
Harbo
Hanne F
HF
Spurkland
Anne
A
Goertsches
Robert
R
Villoslada
Pablo
P
Eraksoy
Mefkure
M
Hensiek
Anke
A
Compston
Alastair
A
Setakis
Efrosini
E
Gray
Julia
J
Yeo
Tai Wai
TW
Sawcer
Stephen
S
D002135:Calcium-Binding Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D000072099:Serrate-Jagged Proteins; D015534:Trans-Activators / Q000235:genetics*
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C091546:POU2AF1 protein, human; D000072099:Serrate-Jagged Proteins; D015534:Trans-Activators