The genetics of multiple sclerosis.
After many years of slow progress in the genetic analysis of complex diseases, including multiple sclerosis (MS), the past few years have eventually seen the first steps of turning a frustrating quest into a success story with the identification of a rapidly increasing number of confirmed disease promoting or protecting genetic variants. The principal reason for the change in situation is numbers: number of individuals assessed in the studies and number of genetic variations available for genotyping. In short, we now know that it takes thousands of patients to identify new genes but also to pinpoint the complex interplay of several genetic factors within the strongest genetic locus in MS, the HLA gene complex. However, the mission is not completed until the gene identification has been translated into useful understanding of disease mechanisms, and this is likely to necessitate further methodological progress as well as hard work in functional studies. Obviously, the reason for gene identification is never going to be genetic counseling or prenatal diagnosis as not even full knowledge of the genetic background on MS will allow even 30% accuracy in disease prediction, i.e., the concordance rate in female monozygotic twins. Therefore, it is only in the way that risk genes reveal details of disease triggering events, or that severity genes influence mechanisms driving the tissue damage, that genetic information is likely to be useful.
Hillert
Jan
J
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Jan.Hillert@ki.se
D001327:Autoimmune Diseases / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000235:genetics
D006680:HLA Antigens; D020395:Receptors, Interleukin-7