Multiple sclerosis susceptibility and the X chromosome

Multiple sclerosis (MS) is a chronic autoimmune complex trait with strong evidence for a genetic component. A female gender bias is clear but unexplained and a maternal parent-of-origin effect has been described. X-linked transmission of susceptibility has been previously proposed, based on pedigree...

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Veröffentlicht in:Multiple sclerosis Jg. 13; H. 7; S. 856 - 864
Hauptverfasser: Herrera, BM, Cader, MZ, Dyment, DA, Bell, JT, DeLuca, GC, Willer, CJ, Lincoln, MR, Ramagopalan, SV, Chao, M., Orton, S-M., Sadovnick, AD, Ebers, GC
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London, England SAGE Publications 01.08.2007
Arnold
Sage Publications Ltd
Schlagworte:
Biological and medical sciences
Chromosomes, Human, X
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Family
Female
Genetic Linkage
Genetic Predisposition to Disease - epidemiology
Genotype
Humans
Immunomodulators
Male
Medical sciences
Microsatellite Repeats
Multiple Sclerosis - epidemiology
Multiple Sclerosis - genetics
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Neurology
Pharmacology. Drug treatments
Risk Factors
Sex Characteristics
avuncular pair
exclusion
X-chromosome
linkage
multiple sclerosis
parent-of-origin
Autoimmunity
HLA-System
Multiple sclerosis
Nervous system diseases
Maternal origin
Parent
Bias
Interaction
Sex
Inflammatory disease
Chronic
Pedigree
Central nervous system disease
Genetic linkage
Surgical approach
Degenerative disease
Masking
X-Chromosome
Locus
Polymorphism
ISSN:1352-4585, 1477-0970
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Zusammenfassung:Multiple sclerosis (MS) is a chronic autoimmune complex trait with strong evidence for a genetic component. A female gender bias is clear but unexplained and a maternal parent-of-origin effect has been described. X-linked transmission of susceptibility has been previously proposed, based on pedigree, association and linkage studies. We genotyped 726 relative pairs including 552 affected sib-pairs for 22 X-chromosome microsatellite markers and a novel dataset of 195 aunt-uncle/niece-nephew (AUNN) affected pairs for 18 markers. Parent-of-origin effects were explored by dividing AUNN families into likely maternal and paternal trait transmission. For the sib-pair dataset we were able to establish exclusion at a λ s = 1.9 for all markers using an exclusion threshold of LOD ≤—2. Similarly for the AUNN dataset, we established exclusion at λAV = 1.9. For the combined dataset we estimate exclusion of λ = 1.6. We did not identify significant linkage in either the sib-pairs or the AUNN dataset nor when datasets were stratified for the presence/absence of the HLA-DRB1*15 allele or for paternal or maternal transmission. This comprehensive scrutiny of the X-chromosome suggests that it is unlikely to harbour an independent susceptibility locus or one which interacts with the HLA. Complex interactions including epigenetic ones, and masking by balanced polymorphisms are mechanisms not excluded by the approach taken. Multiple Sclerosis 2007; 13 : 856—864. http://msj.sagepub.com
Bibliographie:ObjectType-Article-1
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ISSN:1352-4585
1477-0970
DOI:10.1177/1352458507076961