Investigation of seven proposed regions of linkage in multiple sclerosis: an American and French collaborative study.
Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA.
Margaret A
MA
Pericak-Vance
Jackie B
JB
Rimmler
Jonathan L
JL
Haines
Melissa E
ME
Garcia
Jorge R
JR
Oksenberg
Lisa F
LF
Barcellos
Robin
R
Lincoln
Stephen L
SL
Hauser
Isabelle
I
Cournu-Rebeix
Ariele
A
Azoulay-Cayla
Olivier
O
Lyon-Caen
Bertrand
B
Fontaine
Emmanuelle
E
Duhamel
Helene
H
Coppin
David
D
Brassat
Marie-Paule
MP
Roth
Michel
M
Clanet
Mehdi
M
Alizadeh
Jacqueline
J
Yaouanq
Erwann
E
Quelvennec
Gilbert
G
Semana
Gilles
G
Edan
Marie-Claude
MC
Babron
Emmanuelle
E
Genin
Francoise
F
Clerget-Darpoux
D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D002893:Chromosomes, Human, Pair 3; D003299:Cooperative Behavior; D005602:France; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D014481:United States
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen