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 F 10 (DA 3 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.

Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barré Syndrome

“…We identified five QTLs overlapping already described loci for the chronic inflammatory and thus EAN-related models EAE and EA (17,19,(27)(28)(29). This indicates a number of shared mechanisms between these complex inflammatory disease models converging at common inflammatory key events, despite their differences in etiology.…”

A Genetic Relationship between Phosphorus Efficiency and Photosynthetic Traits in Soybean As Revealed by QTL Analysis Using a High-Density Genetic Map

“…In this study, overlapped or adjacent QTLs with less than 5 Mb were classified into the same loci (Visscher et al, 1996 ; Öckinger et al, 2006 ; Swanson-Wagner et al, 2009 ; Wang et al, 2012 ). Base on this rule, 172 QTLs were classified into 29 genomic regions (loci; Table 3 ).…”

Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis

“…The AIL was produced as previously described. 34 Inbred DA rats were originally obtained from the Zentralinstitut fü r Versuchstierzucht (Hannover, Germany) and PVG.av1 rats from Harlan UK (Blackthorn, UK). Animals were bred and housed at the Karolinska University Hospital (Stockholm, Sweden), in polystyrene cages containing aspen wood shavings with free access to water and standard rodent chow and a 12 h light-dark cycle.…”

“…The incidence of EAE was 29%, affecting 152 females and 72 males, as previously described. 34 The region analyzed in the G10 AIL includes the Eae18b region previously linked to MOG-EAE. 19 The 7.93 Mb region delimited by markers D10Arb27 and D10Rat27 was genotyped with 10 microsatellite markers (Proligo, Paris, France).…”