Originally published as Genetics Published Articles Ahead of Print on April 19, 2006.

Genetics, Vol. 173, 1539-1545, July 2006, Copyright © 2006
doi:10.1534/genetics.106.057406

Definition of a 1.06-Mb Region Linked to Neuroinflammation in Humans, Rats and Mice

Johan Öckinger*,1, Pablo Serrano-Fernández{dagger}, Steffen Möller{ddagger},§, Saleh M. Ibrahim§, Tomas Olsson*,2 and Maja Jagodic*,2

* Center for Molecular Medicine, Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, 17176 Stockholm, Sweden, {dagger} International Hereditary Cancer Center, 70115 Szczecin, Poland, {ddagger} Institute of Neuro- and Bioinformatics, University of Lübeck, 23538 Lübeck, Germany and § Institute of Immunology, University of Rostock, D-18057 Rostock, Germany

1 Corresponding author: Neuroimmunology Unit, Center for Molecular Medicine L8:04, Karolinska University Hospital, S-17176 Stockholm, Sweden.
E-mail: johan.ockinger{at}ki.se

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.