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.
Pericak-Vance
Margaret A
MA
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA.
Rimmler
Jackie B
JB
Haines
Jonathan L
JL
Garcia
Melissa E
ME
Oksenberg
Jorge R
JR
Barcellos
Lisa F
LF
Lincoln
Robin
R
Hauser
Stephen L
SL
Cournu-Rebeix
Isabelle
I
Azoulay-Cayla
Ariele
A
Lyon-Caen
Olivier
O
Fontaine
Bertrand
B
Duhamel
Emmanuelle
E
Coppin
Helene
H
Brassat
David
D
Roth
Marie-Paule
MP
Clanet
Michel
M
Alizadeh
Mehdi
M
Yaouanq
Jacqueline
J
Quelvennec
Erwann
E
Semana
Gilbert
G
Edan
Gilles
G
Babron
Marie-Claude
MC
Genin
Emmanuelle
E
Clerget-Darpoux
Francoise
F
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