title: Definition of a 1.06-Mb region linked to neuroinflammation in humans, rats and mice.
abstract: Unbiased identification of susceptibility genes might provide new insights into pathogenic mechanisms that govern complex inflammatory diseases such as multiple sclerosis. In this study we fine mapped Eae18a, a region on rat chromosome 10 that regulates experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We utilized two independent approaches: (1) in silico mapping based on sequence similarity between human multiple sclerosis susceptibility regions and rodent EAE quantitative trait loci and (2) linkage mapping in an F10 (DA x PVG.AV1) rat advanced intercrossed line. The linkage mapping defines Eae18a to a 5-Mb region, which overlaps one intergenomic consensus region identified in silico. The combined approach confirms experimentally, for the first time, the accuracy of the in silico method. Moreover, the shared intersection between the results of both mapping techniques defines a 1.06-Mb region containing 13 candidate genes for the regulation of neuroinflammation in humans, rats, and mice.
authors.affiliation: Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Sweden. johan.ockinger@ki.se
authors.forename: Johan
authors.initials: J
authors.lastname: Ockinger
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernández
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Maja
authors.initials: M
authors.lastname: Jagodic
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D002874:Chromosome Mapping; D004660:Encephalitis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains