Intergenomic consensus in multifactorial inheritance loci: the case of multiple sclerosis.
Genetic linkage and association studies define chromosomal regions, quantitative trait loci (QTLs), which influence the phenotype of polygenic diseases. Here, we describe a global approach to determine intergenomic consensus of those regions in order to fine map QTLs and select particularly promising candidate genes for disease susceptibility or other polygenic traits. Exemplarily, human multiple sclerosis (MS) susceptibility regions were compared for sequence similarity with mouse and rat QTLs in its animal model experimental allergic encephalomyelitis (EAE). The number of intergenomic MS/EAE consensus genes (295) is significantly higher than expected if the animal model was unrelated to the human disease. Hence, this approach contributes to the empirical evaluation of animal models for their applicability to the study of human diseases.
Serrano-Fernández
P
P
Institute of Immunology, University of Rostock, Schillingallee 70, 18055 Rostock, Germany. serrano@pzr.uni-rostock.de
Ibrahim
S M
SM
Zettl
U K
UK
Thiesen
H-J
HJ
Gödde
R
R
Epplen
J T
JT
Möller
S
S
D000818:Animals; D002874:Chromosome Mapping; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009103:Multiple Sclerosis / Q000235:genetics*; D040641:Quantitative Trait Loci; D051381:Rats; D026801:Synteny / Q000235:genetics