Current gene-mapping strategies in experimental models of multiple sclerosis.
Both family-based linkage analyses and population-based association studies have failed to identify disease-regulatory non-human leucocyte antigen genes of importance in multiple sclerosis (MS). Instead, investigators have employed experimental models, which offer major advantages in genetic studies. We summarize the current main methodologies used and the status of both the human and experimental approaches. Why is it important to find genes regulating MS? There is an immense number of cellular and molecular interactions defined in the immunological field and it is very difficult to unravel those that are critical to an inflammatory disease, such as MS, by classical hypothesis-driven research. Unbiased genetics defines evolutionary conserved gene polymorphisms and pathways regulated by these genes, which are central in the pathogenesis. These, in turn, are of interest as therapeutic targets and pharmacogenetic markers.
Becanovic
K
K
Neuroimmunology Unit, Section for Neuroscience Research, Department of Clinical Neuroscience, Karolinska Institutet, CMM L8:04, Karolinska Hospital, SE-171 76 Stockholm, Sweden. kristina.becanovic@cmm.ki.se
Jagodic
M
M
Wallström
E
E
Olsson
T
T
D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D017720:Molecular Epidemiology; D009103:Multiple Sclerosis / Q000235:genetics*; D040641:Quantitative Trait Loci
D006680:HLA Antigens