DESCRIPTION:

QTL Associated with Brain/spinal cord inflammation. On Chromosome 10 with a LOD score= 5.8, p-value =0.03. From a(n) Intercross of

LABEL:

QTL-Eae18b-Rat-Chr 10

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Jagodic M, Becanovic K, Sheng JR, Wu X, Bäckdahl L, Lorentzen JC, Wallström E, Olsson T

TITLE:

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

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) None None, Vol 173, pp. 1366-73

ABSTRACT:

1. J Immunol. 2004 Jul 15;173(2):1366-73. An advanced intercross line resolves Eae18 into two narrow quantitative trait loci syntenic to multiple sclerosis candidate loci. Jagodic M(1), Becanovic K, Sheng JR, Wu X, Bäckdahl L, Lorentzen JC, Wallström E, Olsson T. Author information: (1)Department of Clinical Neuroscience, Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Maja.Jagodic@cmm.ki.se 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. PMID: 15240732 [PubMed - indexed for MEDLINE] PUBMED: 15240732
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