Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis
| Autor: | C, Teuscher, R J, Butterfield, R Z, Ma, J F, Zachary, R W, Doerge, E P, Blankenhorn |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Genetic Markers
Encephalomyelitis Autoimmune Experimental Polymorphism Genetic Chromosomes Human Pair 11 Molecular Sequence Data Mice Inbred Strains Monocyte Chemoattractant Proteins Mice Inbred C57BL Chemokine CCL1 Mice Quantitative Trait Heritable Chemokines CC Genes Overlapping Animals Humans Genetic Predisposition to Disease Amino Acid Sequence Chemokines Chemokine CCL2 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(4) |
| ISSN: | 0022-1767 |
| Popis: | Experimental allergic encephalomyelitis (EAE), the principal animal model of multiple sclerosis, is genetically controlled. To date, 13 disease-modifying loci have been identified in the mouse by whole genome scanning using an F2 intercross between EAE-susceptible SJL/J and EAE-resistant B10.S/DvTe mice. Two quantitative trait loci (QTL), eae6 and eae7, on chromosome 11 were identified by classical marker-specific linkage analysis and interval mapping. Both QTL were reported to be associated with severity and duration of clinical signs. eae7 was subsequently shown to be a unique locus controlling the development of monophasic remitting/nonrelapsing EAE. In this study, composite interval mapping resolved eae6 into two linked QTL: eae6a at 0-13 cM is associated with disease severity, and eae6b at 19-28 cM associated with the duration of clinical signs. Additionally, composite interval mapping significantly refined the locations of eae6a, eae6b, and eae7, thereby facilitating systematic candidate gene screening by cDNA sequencing of SJL/J and B10.S/DvTe alleles. Sequence polymorphisms were not seen in Lif and IL12 beta, candidate genes for eae6a and eae6b, respectively. Similarly, cDNA sequence polymorphisms in Nos2, Scya3, Scya4, Scya5, Scya6, Scya7, Scya9, Scya10, and Scya11 were excluded as candidates for eae7. However, multiple sequence polymorphisms resulting in significant amino acid substitutions were identified in Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5). Given the role of chemokines in EAE, these sequence polymorphisms are promising candidates for eae7, a locus associated with severity of clinical signs and susceptibility to the shorter, less severe monophasic remitting/nonrelapsing form of disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|