Genetics. Published Articles Ahead of Print: April 19, 2006, Copyright © 2006
doi:10.1534/genetics.106.057406


A more recent version of this article appeared on July 1, 2006.

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Definition of a 1.06 Mb region linked to neuroinflammation in humans, rats and mice

Johan Öckinger 1*, Pablo Serrano-Fernández 2, Steffen Möller 3, Saleh M. Ibrahim 4, Tomas Olsson 1 and Maja Jagodic 1

1 Karolinska Institutet
2 International Hereditary Cancer Center
3 Institute of Neuro- and Bioinformatics
4 University of Rostock

* To whom correspondence should be addressed. E-mail: johan.ockinger{at}ki.se.

Submitted on February 24, 2006
Revised on March 23, 2006
Accepted on 14 April 2006


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 (DAxPVG.1AV1) rat advanced intercrossed line. The linkage mapping defines Eae18a to 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.

Key Words: QTL-mapping, advanced intercross line, in silico intergenomics, neuroinflammation