RGD Reference Report - An advanced intercross line resolves Eae18 into two narrow quantitative trait loci syntenic to multiple sclerosis candidate loci. - Rat Genome Database

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An advanced intercross line resolves Eae18 into two narrow quantitative trait loci syntenic to multiple sclerosis candidate loci.

Authors: Jagodic, M  Becanovic, K  Sheng, JR  Wu, X  Backdahl, L  Lorentzen, JC  Wallstrom, E  Olsson, T 
Citation: Jagodic M, etal., J Immunol 2004 Jul 15;173(2):1366-73.
RGD ID: 1302437
Pubmed: PMID:15240732   (View Abstract at PubMed)

Identification of polymorphic genes regulating inflammatory diseases may unravel crucial pathogenic mechanisms. Initial steps to map such genes using linkage analysis in F(2) intercross or backcross populations, however, result in broad quantitative trait loci (QTLs) containing hundreds of genes. In this study, an advanced intercross line in combination with congenic strains, was used to fine-map Eae18 on rat chromosome 10 in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Myelin oligodendrocyte glycoprotein-induced EAE is a chronic relapsing disease that closely mimics key features of multiple sclerosis. Congenic DA.ACI rat strains localized Eae18 to an approximately 30-Mb large region. Fine-mapping was then performed in an advanced intercross line consisting of a (DA x PVG.1AV1)F(7) intercross, resulting in two adjacent EAE-regulating QTLs designated Eae18a and Eae18b. The two QTLs span 5.5 and 3 Mb, respectively, and the 3-Mb Eae18b contains as few as 10 genes, including a cluster of chemokine genes (CCL1, CCL2, CCL7, and CCL11). Eae18a and Eae18b are syntenic to human chromosome 17p13 and 17q11, respectively, which both display linkage to multiple sclerosis. Thus, Eae18 consists of at least two EAE-regulating genes, providing additional evidence that clustering of disease-regulating genes in QTLs is an important phenomenon. The overlap between Eae18a and Eae18b with previously identified QTLs in humans and mice further supports the notion that susceptibility alleles in inflammatory disease are evolutionary conserved between species.

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Phenotype Values via PhenoMiner     Click to see Annotation Detail View
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Strains with Phenominer Data Strains with phenominer dataStrains with phenominer data
DA.ACI-(D10Rat12-D10Rat144) DA/ZtmKini DA.ACI-(D10Rat15-D10Rat29)
DA.ACI-(D10Rat219-D10Rat29) DA.ACI-(D10Rat2-D10Rat6) DA.ACI-(D10Rat10-D10Rat142)

Objects Annotated

Eae18a  (Experimental allergic encephalomyelitis QTL 18a)
Eae18b  (Experimental allergic encephalomyelitis QTL 18b)

Objects referenced in this article
Marker D10Kini1 D10Kini1 Rattus norvegicus
Strain DA DA Rattus norvegicus
Strain DA.PVG.1AV1-(D10Got406-D10Rat93)/Kini null Rattus norvegicus
Strain Kini:DA,PVG-G10 null Rattus norvegicus
Strain PVG.1AV1 Piebald-Virol-Glaxo Rattus norvegicus

Additional Information